Nifakos v. Secretary of Health and Human Services ( 2021 )

In the United States Court of Federal Claims
OFFICE OF SPECIAL MASTERS
No. 14-236V
Filed: March 4, 2021
************************* *
*
VICTORIA NIFAKOS, *
*
* TO BE PUBLISHED
Petitioner, *
*
v. *
* Dismissal; Hepatitis A Vaccine;
* Meningococcal Vaccine; Varicella
SECRETARY OF HEALTH AND * Vaccine; Human Papillomavirus (HPV)
HUMAN SERVICES, * Vaccine; Primary Mediastinal Large B-
*
* Cell Lymphoma (PMBCL); Non-
Respondent. * Hodgkin’s Lymphoma.
*
************************
Mark Theodore Sadaka, Mark T. Sadaka, LLC, Englewood, NJ, for Petitioner
Ida Nassar, U.S. Department of Justice, Washington, DC, for Respondent
DECISION ON ENTITLEMENT1
Oler, Special Master:
On March 27, 2014, Victoria Nifakos (“Petitioner”) filed a petition for compensation under
the National Vaccine Injury Compensation Program, 42 U.S.C. § 300aa-10, et seq.2 (the “Vaccine
Act” or “Program”). Petitioner alleges that she developed primary mediastinal large B-cell
lymphoma (“PMBCL”) which was caused-in-fact or was significantly aggravated by the Hepatitis
A (“Hep A”), meningococcal, varicella, and human papillomavirus (“HPV”) vaccines3 she
1
This Decision will be posted on the United States Court of Federal Claims’ website, in accordance with
the E-Government Act of 2002, 44 U.S.C. § 3501 (2012). This means the Decision will be available to
anyone with access to the internet. As provided in 42 U.S.C. § 300aa-12(d)(4)(B), however, the parties
may object to the Decision’s inclusion of certain kinds of confidential information. To do so, each party
may, within 14 days, request redaction “of any information furnished by that party: (1) that is a trade secret
or commercial or financial in substance and is privileged or confidential; or (2) that includes medical files
or similar files, the disclosure of which would constitute a clearly unwarranted invasion of privacy.”
Vaccine Rule 18(b). Otherwise, this Decision will be available to the public in its present form. Id.
2
National Childhood Vaccine Injury Act of 1986, Pub. L. No. 99-660, 100 Stat. 3755. Hereinafter, for ease
of citation, all “§” references to the Vaccine Act will be to the pertinent subparagraph of 42 U.S.C. § 300aa
(2012).
3
Petitioner identifies the meningococcal and varicella vaccines she received by their tradenames, Menactra
and Varivax. Menactra is a meningococcal polysaccharide diphtheria toxoid conjugate vaccine
1
received on June 29, 2011. Petition at 1, ¶¶ 2, 23, ECF No. 1.
Upon review of the evidence in this case, I find that Petitioner has failed to show that the
vaccines she received on June 29, 2011 caused or significantly aggravated her PMBCL. The
petition is accordingly dismissed.
I. Procedural History
Victoria Nifakos filed her Petition on March 27, 2014.4 Over the subsequent six-month
period, she filed the affidavit and medical records required by the Vaccine Act. Exs. 1-10, ECF
Nos. 6, 14, 18-19, 23 (Notice of Filing by CD);5 see Section 11(c). On November 7, 2014,
Respondent filed a Rule 4(c) Report, setting forth his objections to compensation. ECF No. 24.
During a status conference held telephonically on November 18, 2014, Petitioner expressed
her intention to provide expert reports from an immunologist and/or oncologist to support her
claim. ECF No. 25. On October 21, 2015, Petitioner filed an expert report from Yehuda
Shoenfeld, M.D. Ex. 11, ECF No. 45. More than two months later, she filed medical literature
said to “represent Petitioner’s vaccine related injury.” Notice of Filing at 1 (describing Exs. 12-
58, 60-77),6 filed Jan. 4, 2016, ECF No. 51. On March 8, 2016, Petitioner filed an expert report
and curriculum vitae (“CV”) from Jeffrey Alan Gordon, M.D. Exs. 78-79, ECF No. 57.
In response, Respondent filed an expert report and CV from Kenneth McClain, M.D. Exs.
A-B, filed June 6, 2016, ECF No. 59. In this first expert report, Dr. McClain addressed several of
the points made by Dr. Shoenfeld. Ex. A at 8-10. Approximately two months later, Respondent
filed medical literature and a supplemental expert report from Dr. McClain which focused on the
opinion provided by Dr. Gordon. Exs. A.1-A.7, C, filed Aug. 15, 2016, ECF No. 62. During this
time, Petitioner filed updated medical records. Ex. 80, filed June 30, 2016, ECF No. 60.
Thereafter, the parties discussed potential dates for an entitlement hearing with Special
Master Hastings, but the case was reassigned before a hearing could be scheduled. Status Report,
manufactured by Sanofi Pasteur, Inc. https://www.fda.gov/vaccines-blood-biologics/vaccines/menactra
(last visited Jan. 22, 2021). Varivax is a live virus varicella vaccine manufactured by Merck Corp.
https://www.fda.gov/vaccines-blood-biologics/vaccines/varivax (last visited Jan. 22, 2021).
4
Initially assigned to Special Master Moran, this case was reassigned to now-retired Special Master George
Hastings on March 1, 2016. ECF No. 54. It was reassigned to my docket on December 5, 2017. ECF No.
69.
5
Exhibit 10, which was filed by CD in early September 2014, was refiled electronically on December 14,
2020 at ECF No. 134.
6
When labeling and filing her exhibits, Petitioner mistakenly skipped the number 59. Thus, there is no
Exhibit 59 in the record of this case. See, e.g., Exhibit List, filed June 13, 2019, at 7, ECF No. 100.
Additionally, Ex. 72 was filed a second time as Ex. 73. Exhibit List at 8. Approximately 20 percent of the
medical literature filed by Petitioner contains only the article title or title and abstract. See Exs. 23-25, 32,
37-39, 43-44, 50, 52-54, 56-58, 64-65, 74, 90. Exhibits 12-58 and 60-77, which were filed by CD in early
January 2016, were refiled electronically on December 14, 2020 at ECF Nos. 135-137.
2
filed Apr. 18, 2017, ECF No. 65. After the case was assigned to my docket, an in-person
entitlement hearing was set for June 18-19, 2019. See Non-pdf Scheduling Order, issued Apr. 9,
2018. On July 24, 2018, I established a schedule for pre-hearing submissions. ECF No. 75.
After several requests for additional time, Petitioner filed her pre-hearing brief and
additional medical literature on May 10, 2019. Petitioner’s Prehearing Submission (referred to
hereinafter as “Pet. Pre-Hearing Brief”), ECF No. 86; Exs. 81-87, ECF No. 85. She filed a
supplemental expert report from Dr. Shoenfeld approximately one week later. Ex. 88, filed May
16, 2019, ECF No. 88.
On May 30, 2019, I held a telephonic status conference with the parties to address
Respondent’s concerns regarding the timing of Dr. Shoenfeld’s supplemental expert report, filed
approximately one month before the entitlement hearing. Scheduling Order at 1, ECF No. 89.
Respondent’s counsel indicated that Respondent’s expert, Dr. McClain believed he could provide
a third expert report, filed with Respondent’s pre-hearing submissions, if allowed several
additional weeks. In response to questioning from Respondent’s counsel, Petitioner’s counsel
indicated Petitioner planned no further filings. Id. at 1-2. Respondent’s counsel then requested
that Petitioner file textbook chapters referenced by Dr. Shoenfeld and an affidavit from Petitioner’s
mother. Id. at 2.
On June 4, 2019, the parties confirmed agreement regarding the following: 1) the timeliness
of Petitioner’s claim, 2) the accuracy of vaccines received, and 3) the accuracy of Petitioner’s
PMBCL diagnosis. Joint Status Report at 1, ECF No. 91. The parties added that, although they
generally agreed with the events and treatment as set forth in the medical records, their experts
“may disagree over the medical significance to be placed on the medical facts.” Id. As expected,
Petitioner maintained she has established causation, and Respondent disputed that assertion. Id.
On June 12, 2019, Petitioner filed the textbook excerpts and affidavit from Petitioner’s
mother which were requested by Respondent, as well as additional medical literature. Exs. 89-
100, ECF Nos. 93-95. The same day, Respondent filed his pre-hearing briefing and Dr. McClain’s
third expert report, updated CV, and referenced medical literature. Respondent’s Pre-Hearing
Brief (“Res. Pre-Hearing Brief”), ECF No. 96; Exs. D, D.1-D.13, E, filed June 12, 2019, ECF Nos.
96-97. The next day, he filed an additional article and his exhibit list. Ex. D.14, Exhibit List, filed
June 13, 2019, ECF Nos. 98-99.
The first day of the entitlement hearing, Petitioner filed two additional articles. Exs. 101,
102, filed June 18, 2019, ECF No. 101. During the two-day entitlement hearing, I heard testimony
from Petitioner, her experts Dr. Shoenfeld and Dr. Gordon, and Respondent’s expert Dr. McClain.
Approximately one month later, Respondent filed additional medical literature. Exs. F-H,
filed July 19, 2019, ECF No. 106. On August 2, 2019, the parties indicated that they believed the
record was complete. Joint Status Report, ECF No. 107.
Despite this representation, Petitioner filed an additional article on December 2, 2019. Ex.
103, ECF No. 110. The next day, he filed his post-hearing brief. Petitioner’s Post-Hearing Brief
(“Pet. Post-Hearing Brief”), filed Dec. 3, 2019, ECF No. 113. Four months later, Respondent filed
3
his post-hearing brief. Respondent’s Post-Hearing Brief (“Res. Post-Hearing Brief”), filed Apr.
10, 2020, ECF No. 117.
In early May 2020, Petitioner filed a CV for Dr. Schoenfeld and reply to Respondent’s
post-hearing brief. Ex. 104, filed May 7, 2020, ECF No. 118; Petitioner Reply Brief (“Pet. Reply
Brief”), filed May 8, 2020, ECF No. 119. On May 28, 2020, both parties filed additional briefs.
Respondent’s Sur-Reply in Support of His Post-Hearing Briefing (“Res. Sur-Reply Brief”), ECF
No. 122; Petitioner’s Sur-Sur Reply in Support of Her Post-Hearing Brief (“Pet. Sur-Sur Reply
Brief”), ECF No. 123. On July 10, 2020, the parties filed a joint status report indicating that the
record is complete for a ruling on the record. ECF No. 125.
This matter is now ripe for adjudication.
II. Factual History
As stated in the joint status report filed prior to the entitlement hearing, the parties generally
agree that the events and treatment set forth in Petitioner’s medical records are accurate. Although
specific details may be disputed, for example the exact weight lost by Petitioner in the year prior
to vaccination, these differences do not impact my analysis in this case. Thus, there is no factual
issue about Petitioner’s health which requires adjudication.
A. Medical Records
Petitioner was born in early 1994. E.g., Ex. 2 at 13. Prior to 2011, she was a healthy child
who suffered the usual childhood illnesses. Id. Medical records from her well child visits reveal
she was consistently in the upper 50th percentile for weight and height. Id. at 26-30.
Approximately one month prior to vaccination, Petitioner was seen by a dermatologist for
a growth on her left knee, tag on her neck, and mole on her back which were either removed,
shaved, or treated with cryotherapy.7 Ex. 6 at 1, 3. In a follow-up phone call on June 14, 2011,
the dermatologist recommended removal of the left knee growth by a plastic surgeon. Id. at 2; see
Ex. 2 at 24 (additional notation regarding this phone call in pediatric records).
At her well child visit on June 29, 2011, Petitioner received the vaccinations alleged as
causal. Ex. 2 at 31-33. At this visit, it was noted that Petitioner’s potassium was low, and she had
lost 50 pounds in the past year. Id. at 31-32. Petitioner requested a referral to a plastic surgeon
who could excise the growth on her knee. Id. at 31; see id. at 25 (referral provided on July 1,
2011).
Petitioner returned to her pediatrician on August 3, 2011, complaining of facial swelling,
nausea, dizziness, and an itchy throat which began one day earlier. Ex. 2 at 34. She also reported
that she had experienced lower back, neck, and shoulder pain for the last month. Petitioner’s
7
Cryotherapy is “the therapeutic use of cold.” DORLAND’S ILLUSTRATED MEDICAL DICTIONARY
(hereinafter “DORLAND’S”) at 438 (32th ed. 2012).
4
pediatrician ordered testing and instructed her to drink fluids and to take antipyretics.8 Ex. 2 at 35.
When seen again by her pediatrician on August 5, 2011, Petitioner reported that her facial
swelling had decreased, but that she continued to experience “general aches, muscle soreness, [a]
deep, productive cough, [and] mid sternal chest pain.” Ex. 2 at 36. Petitioner was diagnosed with
acute bronchitis and prescribed a Zithromax Tri-Pak. Id. at 37.
Petitioner returned on August 10, 2011, complaining of abdominal and mid sternal pain
and difficulty breathing, especially when laying down. Ex. 2 at 38. Petitioner’s sore throat had
improved but she continued to cough and was sleeping all day. Id. Assessed as having a slight
fever and elevated heart rate with increased trouble breathing, Petitioner’s pediatrician instructed
her to go directly to the emergency room (“ER”). Id. at 39; see also Ex. 5 at 148.
After she visited the ER at Palms West Hospital, Petitioner was diagnosed with pleural
effusion9 and admitted to the PICU10 that evening. Ex. 5 at 148, 156-57. Testing was ordered to
rule out pericardial effusion.11 Ex. 5 at 157. Results of testing revealed an elevated C-reactive
protein level of 11.2 milligrams per liter.12 Ex. 5 at 148. According to the history provided,
Petitioner had experienced chest pain and difficulty breathing for two days. Id. at 148, 157. Her
facial swelling and nausea began a week ago. Id. at 156.
By the time Petitioner was assessed in the PICU, test results revealed she also was suffering
from pericardial effusion. Ex. 5 at 238. “[A] chest tube was placed, and the fluid was sent for
culture.” Id. at 148. Petitioner received temporary relief from fluid drainage from chest and
pericardial tubes. E.g., id. at 149. A CT scan, performed on August 11, revealed a large
mediastinal mass, indicative of lymphoma and measuring 13 x 6 x 10.4 centimeters. Id. at 421.
When no diagnosis was obtained from the cytology of the pleural fluid, a CT-guided biopsy under
local anesthesia was performed. Id. at 239. The biopsy results confirmed the mass was “a large
B-cell lymphoma of the mediastinum.” Id. at 240. Imaging performed on August 18, 2011
revealed thrombosis13 in Petitioner’s left jugular and subclavian veins, and Petitioner was
transferred to a larger facility to begin chemotherapy. Ex. 5 at 240.
8
Antipyretics are agents which reduce or relieve fever. DORLAND’S at 109.
9
Pleural effusion is “the presence of fluid in the in the pleural space.” DORLAND’S at 596. Pleural is an
adjective referring to “the serous membrane investing the lungs and lining the thoracic cavity, completely
enclosing a potential space known as the pleural cavity.” DORLAND’S at 1460.
10
PICU stands for “pediatric intensive care unit.” MEDICAL ABBREVIATIONS at 468 (16th ed. 2020).
Pericardial effusion is “the accumulation of more than 50 mL of pericardial fluid in the pericardium.”
11
DORLAND’S at 596. Pericardium is “the fibroserous sac that surrounds the heart.” DORLAND’S at 1412.
12
C-reactive protein “is the most predominant of the acute phase proteins.” DORLAND’S at 1532. Acute
phase proteins are “any of the non-antibody proteins, produced mainly in the liver, found in increased
amounts in serum during the acute phase response.” DORLAND’S at 1531.
13
Thrombosis is “the formation, development, or presence of a thrombus” which is “a stationary blood clot
along the wall of a blood vessel.” DORLAND’S at 1923.
5
Petitioner was admitted to the Arnold Palmer Hospital for Children from August 19
through September 8, 2011. Ex. 10 at 6. The histories found in the medical records from this
facility are consistent with information contained in prior records. Regarding the weight loss she
experienced prior to vaccination, Petitioner “reported a 20-pound intentional weight loss from
January to July with exercise and appropriate dietary modification.” Id. In a later record, it was
noted that Petitioner was “a fit and trained athlete who works out regularly.” Id. at 13.
On August 22, 2011, prior to the start of her chemotherapy, Petitioner underwent another
CT scan which showed the anterior mediastinal mass “[wa]s overall not significantly changed in
size, . . . measuring approximately 13.8 centimeters at the level of the carina.[14]” Ex. 10 at 533.
The same day, Petitioner received a PICC15 line in her left arm. Ex. 10 at 242. On August 23,
2011, she began chemotherapy which included multiple compounds including prednisone.16
Following chemotherapy, she remained on prednisone. Ex. 10 at 242.
Petitioner’s pericardial tube was removed on August 26, and her chest tube was removed
on August 28. Ex. 10 at 6. She was moved to the hematology and oncology floor to continue her
chemotherapy and given salt and soda mouth rinses for mouth care and a sore throat. Id. at 6, 244.
X-rays performed on September 6 revealed the “mediastinal mass had decreased in size.” Id. at 6-
7. An ultrasound of Petitioner’s left jugular and subclavian veins showed no thrombosis.
Petitioner was discharged home on September 8, 2011. Id. at 7.
Petitioner returned to the Arnold Palmer Hospital for Children for three more rounds of
chemotherapy in September, October, and November 2011. Ex. 1 at 6-20; Ex. 3 at 1-79. Between
rounds of chemotherapy, Petitioner was seen by her local hematologist and oncologist. See
generally, Ex. 4.
When Petitioner was seen on January 16, 2012, she was told she was in remission. Ex. 3
at 81. It was determined that Petitioner would undergo a PET scan and echocardiogram in
February 2012 and could have her port removed if all test results were normal. Id. Petitioner’s
PET scan was normal, and she was instructed to follow-up in three months. Id. at 83-84.
Throughout the remainder of 2012, Petitioner had follow-up visits at the Arnold Palmer Hospital
for Children and with her local hematologist and oncologist. Id. at 85-93; Ex. 7 at 1-18. While
physically well, Petitioner continues to experience panic attacks which are triggered by doctor
visits. E.g., Ex. 80 at 12 (medical record from June 29, 2016 visit).
B. Petitioner’s Affidavit and Testimony
In her affidavit and testimony, Petitioner echoed the history contained in her medical
14
Carina is “a ridge or ridgelike structure.” DORLAND’S at 296.
15
PICC stands for “peripherally inserted central catheter.” MEDICAL ABBREVIATIONS at 468.
16
Prednisone is “a synthetic glucocorticoid derived from cortisone, administered orally as an inflammatory
immunosuppressant in a variety of disorders.” DORLAND’S at 1509.
6
records, adding additional detail regarding the difficulties she experienced throughout her illness.
Ex. 9 at ¶¶ 6-53; Transcript (“Tr.”) at 147-68. She described headaches beginning on July 10,
2011 and increasing neck and back pain and dizziness throughout the month. Ex. 9 at ¶¶ 9-11.
When asked about the June 29, 2011 entry indicating she lost 50 pounds in the year prior to
vaccination, Petitioner characterized her weight loss as closer to 30 pounds. Tr. at 148. She also
provided information regarding the reason for her weight loss, attributing it to a concerted effort
to exercise and eat healthier. Id. at 148-49; see also Ex. 9 at ¶ 6.
Petitioner’s assertions regarding her efforts to exercise and to eat a healthy diet are
supported by entries in the contemporaneously created medical records. E.g., Ex. 10 at 6 (an
August 2011 medical record chronicling a 20-pound weight loss from exercise and healthy eating
during the prior six months). Thus, it appears Petitioner lost approximately 20 pounds in the six
months prior to her illness and between 30 to 50 pounds during the full year. An exact finding
regarding the amount of weight lost by Petitioner prior to her illness is not germane to the issue of
causation in this case.
C. Affidavit from Petitioner’s Mother
In her affidavit, Mary Nifakos contrasted her daughter’s good health prior to vaccination
with the deterioration of her health thereafter. Ex. 89 at ¶¶ 4-7. Like her daughter, she accurately
recounted specific events, providing additional information regarding the effects of her daughter’s
illness on her life. Id. at ¶¶ 6-10. Ms. Nifakos indicated that her daughter continues to see
“multiple doctors including a therapist for her anxiety, which is an ongoing thing.” Id. at ¶ 9.
III. Expert Opinions
Petitioner submitted two expert reports from Dr. Yehuda Shoenfeld, an internist and
immunologist, and one expert report from Dr. Jeffrey Alan Gordon, a hematologist and oncologist.
Exs. 11, 88, 104 (hereinafter “First Shoenfeld Rep.”, “Second Shoenfeld Rep.”, and “Shoenfeld
CV”); Exs. 78-79 (hereinafter “Gordon Rep.” and “Gordon CV”). In response, Respondent’s
submitted three expert reports from Dr. Kenneth McClain, a pediatric hematologist and oncologist.
Exs. A-D (hereinafter “First McClain Rep.”, “McClain CV”, “Second McClain Rep.”, and “Third
McClain Rep.”). All experts testified at the entitlement hearing.
A. Qualifications
1. Petitioner’s Expert: Dr. Yehuda Shoenfeld
Dr. Shoenfeld received his medical training at Hadassah Medical School, Hebrew
University and Medical School, Tel-Aviv University. Shoenfeld CV at 2. Following fellowships
in the United States, he returned to Israel where he concentrated on research and teaching. Id.; Tr.
at 6. In 1985, he founded the Center for Autoimmune Diseases. First Shoenfeld Rep. at 1; Tr. at
6. He continues to see patients and teach as an emeritus professor at the Tel-Aviv University. Tr.
at 6. Additionally, he is the Incumbent of the Laura Schwarz-Kipp Chair for Research of
Autoimmune Diseases at Tel-Aviv University. Shoenfeld CV at 6; First Shoenfeld Rep. at 2. He
is certified in internal medicine, clinical immunology, and allergy. First Shoenfeld Rep. at 1.
7
A member of numerous professional societies and editorial boards, Dr. Shoenfeld has
helped organize numerous meetings and has received multiple awards. Shoenfeld CV at 4-11.
Focusing on autoimmune and rheumatic diseases, he has performed extensive research and has
authored chapters, books, and over 1800 peer reviewed papers. Id. at 21-129; First Shoenfeld Rep.
at 2. In his first expert report, Dr. Shoenfeld emphasized the 15 articles he has published on
vaccines and autoimmunity and 11 articles on lymphomas. First Shoenfeld Rep. at 3-5. He
indicated he formulated the theory of Autoimmune Syndrome Induced by Adjuvants (known by
the acronym ASIA)17 in 2011. First Shoenfeld Rep. at 3.
2. Petitioner’s Expert: Dr. Jeffrey Alan Gordon
Dr. Gordon received his M.D. from the University of Massachusetts Medical School in
1993. Gordon CV at 2; Tr. at 176. After a residency in internal medicine, he received fellowship
training in hematology and oncology. Gordon CV at 2; Tr. at 176. He is board certified in
hematology and oncology and has practiced medicine at the New London Cancer Center since
2012. Gordon CV at 1-2; Tr. at 176.
Having previously held teaching positions, Dr. Gordon testified that currently “nearly all
of [his] time is spent on clinical care.” Tr. at 177; accord. Gordon CV at 3. In his 20-year practice,
he treats patients “with blood disorders, blood cancers, or what they call solid cancers, other types
of cancers.” Tr. at 193-94. Dr. Gordon explained that he performed the lung cancer research
indicated on his CV during his fellowship because that was the focus of the work being performed
by his mentor in the program. Tr. at 194; see Gordon CV at 4-5.
3. Respondent’s Expert: Dr. Kenneth McClain
Dr. McClain attended the dual M.D./Ph.D program at the University of Chicago School of
Medicine from 1963 to 1973. McClain CV at 1; Tr. at 208. While a predoctoral trainee, he worked
in the Department of Pathology, focusing on tumor biology, specifically viral cause of cancers. Id.
He earned his Ph.D. in 1972 and his M.D. in 1973. McClain CV at 1; Tr. at 209. He completed a
pediatric residency at The Johns Hopkins Hospital in 1976, postdoctoral training at the National
Institutes of Health in 1979, and a Hematology/Oncology Fellowship at the Department of
Pediatrics, University of Minnesota in 1981. McClain CV at 1; Tr. at 209-10.
Certified in general pediatrics with a specialty in hematology-oncology, Dr. McClain is
currently a Professor of Pediatrics in the Pediatric Hematology Oncology section at the Texas
Children’s Cancer Center. McClain CV at 3; Tr. at 211. He is the clinical director of the
17
To date, the ASIA theory has not been found to be a valid theory, sufficient to satisfy Althen prong one.
See D’Angiolini v. Sec’y of Health & Hum. Servs., 122 Fed. Cl. 86, 101 (affirming the special master’s
rejection of the theory as “still developing and currently incomplete”), aff’d, 645 Fed.Appx. 1002 (Fed. Cir.
2016); Garner v. Sec’y of Health & Hum. Servs., No. 15-0063V, 2017 WL 1713184, at *15 (Fed. Cl. Spec.
Mstr. Mar. 24, 2017); Johnson v. Sec’y of Health & Hum. Servs., No. 10-0578V, 2016 WL 4917548, at *8-
9 (Fed. Cl. Spec. Mstr. Aug. 18, 2016) (describing this theory as overbroad, generalized, and vague and
finding this expansive theory logically unpersuasive); Rowan v. Sec’y of Health & Hum. Servs., No. 10-
0272V, 2014 WL 7465661, at *12 (Fed. Cl. Spec. Mstr. Dec. 8, 2014).
8
histiocytosis program and co-director of the lymphoma program. Tr. at 211. Dr. McClain testified
that the Texas Children’s Cancer Center is the largest pediatric cancer center in the United States
and one of the largest referral centers. Id. at 213. The lymphoma program is “the only designated
lymphoma program among the pediatric oncology centers in the United States.” Id. at 212. Dr.
McClain estimated he spends 75 percent of his time seeing patients and 25 percent of his time
performing clinical research. Id. at 214. Dr. McClain has published almost 200 articles, many
regarding non-Hodgkin’s and Hodgkin’s lymphoma. McClain CV at 13-28. In his first expert
report, Dr. McClain indicated he “ha[s] been especially interested in the care of children with
lymphomas and those who have lymphoproliferative diseases caused by Epstein Barr Virus.” First
McClain Rep. at 1. He listed the 26 articles and book chapters he has authored on the topic of
lymphomas. Id. at 1-3.
B. Expert Reports
1. Dr. Shoenfeld’s First Expert Report
In his first report, Dr. Shoenfeld postulated the two theories of causation relied upon by
Petitioner. Noting that Petitioner received four vaccinations on June 29, 2011, two of which
contain an aluminum adjuvant, he posited that Petitioner’s PMBCL “was caused by consistent
stimulation of her immune system caused by the adjuvant, a cross reaction, or likely a combination
of the two.” First Shoenfeld Rep. at 25. He also theorized a cross reaction at the molecular level
could have occurred between the HPV L1 protein and human proteins, damaging human proteins
which play a role in suppressing the formation of lymphomas. Id. at 30-31.
Regarding his first theory, Dr. Shoenfeld described two stages he believes are involved in
this process. The first stage consists of the attraction of lymphocytes to the stimulation provided
by the adjuvants. First Shoenfeld Rep. at 28. Dr. Shoenfeld labeled this stage “pseudo
lymphoma.” Id. He then theorized “[t]he pseudo lymphoma (a benign condition) . . . can progress
into a malignant condition, named lymphoma.” Id. (emphasis in original removed). While Dr.
Shoenfeld provided extensive medical literature regarding the development of cutaneous pseudo
lymphoma at the site of vaccination, the first stage of this theory,18 none of the medical literature
filed by Petitioner addresses the second stage. When asserting “pseudolymphomas . . . can be
transformed in time to malignant condition,” he cited one article which was not filed by Petitioner.
Id. at 30 (citing reference 15: Arai, et al., A review of 55 cases of cutaneous lymphoid hyperplasia:
reassessment of the histopathologic findings leading to reclassification of 4 lesions as cutaneous
marginal zone lymphoma and 19 as pseudolymphomatous folliculitis, 36 HUM. PATHOL. 505-11
(2005) (hereinafter “Arai”)). This article was later filed by Respondent. See Arai (filed as Exhibit
A.6). As the title suggests, the Arai article addresses only instances of incorrect classification. Id.
at 6.
When discussing his second theory, Dr. Shoenfeld theorized that peptide matching between
18
E.g., Cerroni et al., Cutaneous B-cell Pseudolymphoma at the Site of Vaccination, 29 AM J
DERMATOPATHO 538-42 (2007) (filed as Ex. 19); Hernandez et al., B-cell Pseudolymphoma Caused by
Aluminium Hydroxide Following Hyposensitization therapy, 99 ACAD. DERMOSIFILIOGR. 213-16 (2008)
(filed as Ex. 20). Petitioner did not present evidence that she experienced a pseudolymphoma.
9
different HPV L1 proteins and lymphoma-associated proteins in humans may trigger cross-
reactions which suppress or alter the human proteins, interfering with their ability to prevent the
formation of lymphoma or lymphomagenesis. First Shoenfeld Rep. at 24. This specific theory
involves the process of molecular mimicry.19 First Shoenfeld at 21-24. Dr. Shoenfeld then
provided specific examples of human proteins, which if affected, could allow lymphomagenesis
and listed multiple peptides which are shared by both HPV L1 and those and other human proteins.
First Shoenfeld Rep. at 21-25. He provided numerous articles regarding human proteins whose
mutation may be related to the formation of lymphoma or other cancers. E.g. Shin, et al.,
Inactivating mutations of CASP10 gene in non-Hodgkin lymphomas, 99 BLOOD, 11: 4094-99, 2002
(filed as Ex. 36).
To support both theories that vaccines can cause lymphoma through adjuvant stimulation
and/or molecular mimicry, Dr. Shoenfeld relied upon what he described as the well-established
association between autoimmune disease and lymphoma. First Shoenfeld Rep. at 20. He
referenced several articles which discuss this association.20 However, in at least one of the articles
offered by Dr. Shoenfeld, the authors stated, “it may be hard to determine whether the autoimmune
disease preceded the malignancy.” Goldin at 1501. “[I]t could be that immune-related disorders
are reflections of a pre-ceding precursory state on the pathway to full-blown malignancy.” Id.Furthermore, when discussing the possible mechanisms involved in any causal relationship
between autoimmune diseases and lymphoma, factors provided by the autoimmune disease which
may not be present for a vaccine, such as a sustained antigen drive, are required. See Cuttner at
793-94. Presumably to address this deficiency, on several occasions Dr. Shoenfeld quoted an
online article stating that “[a] wide spread belief has been that alum exerts a depot effect whereby
the emulsion retains antigen at the site of injection and releases it slowly to promote sustained
antigen presentation.” First Shoenfeld Rep. at 20-21, 27 (quoting B. Pulendran, Immunological
mechanisms of vaccination, 12 NATURE IMMUNOLOGY, 6: 511, 509-17 (filed as Ex. 72) (hereinafter
19
“[M]olecular mimicry has been suggested to explain the etiology of some autoimmune diseases. The
molecular mimicry hypothesis posits that autoimmune diseases arise when the structure of the foreign
invader resembles (or mimics) the structure of cells in the body. This similarity confuses the adaptive
immune system and leads antibodies produced by B cells and/or T cells to attack the host, a process
sometimes known as ‘breaking tolerance.’” Tullio v. Sec’y of Health & Hum. Servs., No. 15-0051V, 2019
WL 7580149, at *12 (Fed. Cl. Spec. Mstr. Dec. 19, 2019), aff'd, 149 Fed. Cl. 448 (2020); Special masters
have recognized molecular mimicry as the method by which streptococcus bacteria can develop into
Sydenham's chorea and c. jejuni infection can cause Guillain-Barré syndrome. W.C. v. Sec'y of Health &
Hum. Servs., No. 07-456V, 2011 WL 4537877, at *11 (Fed. Cl. Spec. Mstr. Feb. 22, 2011), mot. for rev.
denied in relevant part, 100 Fed. Cl. 440, 451-53 (2011), aff'd, 704 F.3d 1352 (Fed. Cir. 2013); Isaac v.
Sec'y of Health & Hum. Servs., No. 08-601V, 2012 WL 3609993, at *4 (Fed. Cl. Spec. Mstr. July 30, 2012),
mot. for rev. denied, 108 Fed. Cl. 743 (2013), aff'd without op., 540 Fed. App'x 999 (Fed Cir. 2013).
20
First Shoenfeld Rep. at 20 (citing J. Cuttner, Autoimmune Disease Is a Risk Factor for the Development
of Non-Hodgkin’s Lymphoma, 32 THE JOURNAL OF RHEUMATOLOGY, 10: 1884-87 (2005) (filed as Ex. 69)
(hereinafter “Cuttner”); Mackay & Rose, Autoimmunity and lymphoma: tribulations of B cells, 2 NATURE
IMMUNOLOGY 9: 793-95 (filed as Ex. 70) (hereinafter “Mackay”); Goldin & Landgren, Autoimmunity and
lymphomagenesis, 124 INT. J. CANCER 1497-1502 (2009) (filed as Ex. 71) (hereinafter “Goldin”).
10
“Pulendran”)).21 Relying on this sentence, he postulated that vaccines can cause a “[s]ustained
antigen drive” similar to that created by autoimmune diseases and sufficient to create lymphoma.
First Shoenfeld Rep. at 20, 26.
When opining that the four vaccines Petitioner received in this case caused her PMBCL,
Dr. Shoenfeld relied upon Petitioner’s lack of symptoms prior to vaccination, the temporal
relationship between vaccination and Petitioner’s first symptoms, and existence of the two theories
he proposed. First Shoenfeld Rep. at 25-26. He concluded that “[t]he lack of prior disease, the
time sequence and the plausible mechanism in which vaccine can induce pseudolymphoma and
the later can progress to a malignant lymphoma (as in Sjogren’s syndrome[22]) point to the fact that
mo[re] probabl[y] than not that the four vaccine[s] were the sole cause to the emergence of the B
cell lymphoma in Victoria.” Id. at 32. He also theorized that, prior to vaccination, Petitioner
“might have harbored a benign lymphoproliferation in her anterior chest, which did not cause any
inconvenience” but developed into a malignancy “[u]pon being ‘bombarded’ by four vaccines,
with all their constituents (adjuvant i.e. Aluminum), synthetic ingredients of the vaccines, diluents,
yeast (i.e. saccharomyces).” Id.
2. Dr. Gordon’s Expert Report
In his expert report, Dr. Gordon relied upon the theory of antigen stimulation postulated by
Dr. Shoenfeld. Gordon Rep. at 5-7. After describing abnormalities in lymphocytes which occur
with low levels of antigen stimulation over time, Dr. Gordon posited that “[s]ometimes, a potent
exposure, such as a virus or a vaccination, can cause enough of an antigen stimulation that
abnormalities within a lymphocyte occur quickly.” Id. at 6. He provided examples when “[a]
number of viruses have been implicated in lymphomagenesis, such as human immunodeficiency
virus (HIV), hepatitis C (HCV), Epstein Barr virus (EBV), cytomegalovirus (CMV), human T-cell
leukemia virus (HTLV), and Kaposi’s sarcoma herpes virus (KSHV).” Id. While observing that
it is more unusual for bacteria to contribute to the formation of lymphomas, Dr. Gordon noted that
the Helicobacter pylori bacteria “ha[s] been implicated in the development of certain types of
lymphomas.” Id. He also theorized that pseudolymphomas “can over time become true
lymphomas if continued antigen stimulation occurs or potent antigen stimulation occurs” (id.) but
provided no evidence to support that assertion.
Regarding causation in this case, Dr. Gordon relied upon one of the factors mentioned by
Dr. Shoenfeld, specifically Petitioner’s lack of symptoms prior to vaccination, and the alleged
21
This article was filed twice as Exs. 72 and 73. Supra at note 6.
22
Sjogren’s syndrome is “a symptom complex of unknown etiology usually occurring in middle-aged or
older women” implicating “an abnormal immune response.” DORLAND’S at 1848. Dr. Shoenfeld filed
several exhibits regarding Sjogren’s syndrome. Exs. 22-24. Two exhibits consist of only the article title.
Exs. 23-24. The other involves a case study of a 74-year old patient with Sjogren’s syndrome complicated
by cutaneous tumors. Y. Horiuchi, Massive cutaneous follicular lymphoid hyperplasia in a patient with the
Sjogren syndrome: 7-year follow-up and immunohistochemical study, 26 RHEUMATOL INT. 1044-49 (2006)
(filed as Ex. 22) (hereinafter “Horiuchi”). However, the patient’s condition was deemed to be benign and
the lesions disappeared after several months of topical steroid treatment. Horiuchi at 1044.
11
absence of a cause other than her vaccinations. Gordon Rep. at 6-7. To account for the short time
period between vaccination and Petitioner’s first symptoms, Dr. Gordon emphasized that PMBCL
is an aggressive lymphoma. Id. at 6. He concluded that “the lymphoma experienced by
[Petitioner] was caused more probably than not by a strong, immune mediated, antigen response
from the multiple vaccinations she received.” Id. at 7.
In forming this opinion, Dr. Gordon did not provide or cite to any medical literature. He
indicated he had reviewed Petitioner’s affidavit and medical records filed to date (Exs. 1-3, 5-10)23
and Dr. Shoenfeld’s first expert report. Id. at 1.
3. Dr. McClain’s First Expert Report
In his first expert report, Dr. McClain opined “[t]he progression of [Petitioner’s] symptoms
[wa]s characteristic of all young people who have large mediastinal masses from lymphoma and
[he] believe[s] there is no data to suggest the vaccinations had anything to do with the onset of her
lymphoma.” First McClain Rep. at 6. Stressing the amount of weight loss Petitioner experienced
in the year prior to vaccination, he suggested the weight loss could have been an early sign of
Petitioner’s lymphoma. He indicated that he believes the back, neck, and shoulder pain which
Petitioner experienced in July 2011, the month following vaccination, “may have been secondary
to the mediastinal mass which could have been developing.” Id.
Stating that PMBCL is no longer considered a subset of diffuse large B-cell lymphomas
(“DLBCL”) but rather a distinct entity, Dr. McClain described the differences in these lymphoma
types. First McClain Rep. at 7. He explained that DLBCLs “have surface markers which identify
the malignant cells as originating in the germinal center of a lymph node.” Id. In contrast, PMBCL
“arises from thymic B-cells in the mediastinum.” Id. Dr. McClain provided several articles
indicating PMBCL is “demographically, clinically, and ecologically distinct from other DLBCL
[(diffuse large B-cell lymphoma)] subtypes [with] clinical and biological features more closely
resemble[ing] those of nodular sclerosing Hodgkin lymphoma (NSHL) arising in the
mediastinum.” K. Dunleavy, Primary mediastinal B-cell lymphoma: biology and evolving
therapeutic strategies, AMERICAN SOCIETY OF HEMATOLOGY EDUCATION BOOK 2017(1): 298-303
(2017) (filed as Ex. D.5) (hereinafter “Dunleavy”). According to Dr. McClain, “[t]he cause of
PMBCL is rooted in characteristic DNA mutations and rearrangements . . . [and] [t]here is no
known connection with viral infections, environmental exposure, or vaccines.” Id.
Dr. McClain also delivered a critique of the theories posited by Dr. Shoenfeld. First
McClain Rep. at 8-10. Stressing “a fundamental lack of knowledge of the biology of lymphoma”
on the part of Dr. Shoenfeld, he maintained that Dr. Shoenfeld’s opinion is “built upon an unsound
foundation of faulty biologic associations that he incorrectly claims support a conclusion of
vaccine causation. Id. at 8. He characterized Dr. Shoenfeld’s theories as “only confabulations of
loosely associated, and often misquoted ‘facts’ which make no biologic sense.” Id. (internal quotes
in original).
23
When identifying the medical records which he reviewed in this case, Dr. Gordon did not include records
from the local hematologist and oncologist who treated Petitioner following her initial hospitalization in
late August through early September 2011, Ex. 4. From his description of Petitioner’s medical history, it
appears he has not seen these records. See Gordon Rep. at 1-4.
12
Specifically, Dr. McClain criticized Dr. Shoenfeld’s reliance on a connection between
autoimmune disease and lymphoma, proclaiming it irrelevant in this case as Petitioner has no
history of autoimmune disease. First McClain Rep. at 8. He also criticized Dr. Shoenfeld’s claim
that the expected collection of lymphocytes at the site of vaccination (a normal event) and
development of the benign inflammatory response of pseudolymphoma can progress to the
malignant condition of lymphoma as untrue. Id. at 9-10 (observing that the Arai article cited by
Dr. Shoenfeld does not support this assertion). He stressed that “pseudo lymphomas are NOT real
lymphomas.” Id. at 9 (emphasis in original).
Regarding Dr. Shoenfeld’s theory of molecular mimicry, Dr. McClain insisted it “is totally
without experimental support.” First McClain Rep. at 9. He declared “[m]olecular similarity does
NOT mean the presence of these peptides would CAUSE cancer.” Id. (emphasis in original). He
posited Dr. Shoenfeld’s theory as another example of true but unrelated occurrences. Id.
4. Dr. McClain’s Second Expert Report
In his second expert report, Dr. McClain criticized Dr. Gordon’s opinion as lacking detail
and scientific proof. Dr. McClain’s Second Expert Report (“Second McClain Rep.”) filed as Ex.
C at 1. Regarding Dr. Gordon’s discussion of a relationship between autoimmune disease and
lymphoma, he reiterated his observation, made when critiquing Dr. Schoenfeld’s expert report,
that Petitioner had no history of autoimmune disease. Id. He opined that there is no connection
between the PMBCL Petitioner suffered and the vaccines she received. Id. at 2.
5. Dr. Shoenfeld’s Second Expert Report
In his second expert report, Dr. Shoenfeld characterized the opinions expressed by Dr.
McClain as a denial of a causal link between immune attacks and the formation of lymphomas.
Second Shoenfeld Rep. at 1. Regarding Dr. McClain’s discussion of the differences in
lymphomas, he criticized this act of “meticulously classifying the disease” as distracting from a
discussion of the “root cause(s) of the disease.” Id.
In response to Dr. McClain’s criticism of his theories, Dr. Shoenfeld argued that Dr.
McClain misunderstood and misrepresented those theories. He characterized Dr. McClain’s use
of the term “upregulation” as a misrepresentation of the suppression he described. Second
Shoenfeld Rep. at 2. He stressed that he “used NFKB2 protein as an example but obviously cross-
reactive mechanism can apply to all the lymphoma-related proteins sharing peptides with the
viruses contained in vaccines.” Id. at 3. Noting that Dr. McClain described his theory as “a very
wordy discussion of correlations without proof of causation,” Dr. Shoenfeld again stressed the
“high extent of peptide identities between Gardasil HPV L1s and human proteins that are related,
when altered, to lymphoma.” Id. at 3 (quoting First McClain Rep. at 10). He provided a table of
multiple shared peptides (Table 1) and asserted this data showed that “a potentiating cross-reactive
synergy appears more than possible.” Second Shoenfeld Rep. at 4. After providing tables
regarding the matching peptides contained in Hep A and Varicella virus (Table 2-3), he maintained
these tables showed “scientific data that actually do represent the concrete possibility that HPV
13
cross-reactivity [along with that of Hep A and varicella viruses] may well have implemented a
powerful and unfortunately successful lymphomatogenic synergy.” Id. at 5.
Regarding Dr. McClain’s opinion that Petitioner’s PMBCL most likely had a genetic
etiology, he insisted “cancer is not exclusively a genetic disease.” Second Shoenfeld Rep. at 6.
He accused Dr. McClain of refusing to accept the fact that Petitioner’s lymphoma could have had
multiple etiologies including an autoimmune etiology. Id. at 6. To support his assertion that it
did, he cited the remission obtained by the chemotherapy drugs Petitioner received which he
described as “among the most potent known inhibitors of the immune response.” Id. at 7. He
claimed Dr. McClain’s opinion that PMBCL had a genetic cause would not account for the
remission Petitioner experienced in January 2012, stating this would have to be caused by the
“DNA alterations . . . magically disappear[ing].” Id. at 10.
To further support his opinion, Dr. Shoenfeld provided a list of more than 40 cases in which
a VAERS24 report was filed alleging lymphoma following receipt of one or more vaccines. Second
Shoenfeld Rep. at 8-10.
6. Dr. McClain’s Third Expert Report
In his third expert report, Dr. McClain responded to Dr. Shoenfeld’s latest assertions.
Regarding his use of the term “upregulation,” he explained that “inactivating the repressor domain
is the same as upregulation.” Third McClain Rep. at 1 (internal quotations omitted). He observed
that none of the medical literature cited by Dr. Shoenfeld related to the type of cancer Petitioner
suffered, PMBCL. Id. He maintained “the underlying premise of Dr. Shoenfeld’s arguments that
an antibody response can induce PMBCL has no reliable foundation in the scientific literature.”
Id. at 2.
Regarding the tables of shared peptides provided by Dr. Shoenfeld, Dr. McClain asserted
they are irrelevant for several reasons. Third McClain Report at 2. First, he explained that
“vaccines induce antibodies to the entire 485 amino acid HPV L1 protein, NOT to just the 7 amino
acid SLVDTYR peptide.” Id. He insisted Dr. Shoenfeld had provided no experimental proof that
the vaccine would specifically bind to the seven amino acids identified or “even if it did, that such
binding would induce a mutation that would trigger the onset of the particular type of lymphoma
Victoria has.” Id.
Observing that “the degree of homology overlap identified by Dr. Shoenfeld is not unique,”
Dr. McClain offered a paper which found that the overlap between viral and human proteomes
was rarely less than 90 percent. Third McClain Rep. at 2 (citing Kanduc, et al., Massive peptide
sharing between viral and human proteomes, 29 PEPTIDES 1755-66 (2008) (filed as Ex. D.8)
(hereinafter “Kanduc”). He maintained the authors of this paper as well as one discussing
comparing bacteria to the human proteome, concluded their research undermines any role of
24
“Established in 1990, the Vaccine Adverse Event Reporting System (VAERS) is a national early warning
system to detect possible safety problems in U.S.-licensed vaccines, . . . co-managed by the Centers for
Disease Control and Prevention (CDC) and the U.S. Food and Drug Administration (FDA).”
https://vaers.hhs.gov/about.html (last visited on Feb. 19, 2021). Although healthcare providers are required
to report certain events, “[a]nyone can report an adverse event to VAERS.” Id.
14
molecular mimicry in the genesis of autoimmunity because, due to the extensive instance of
overlap, the incidence of autoimmunity should occur at a rate of almost 100 percent. Id. (citing
Kanduc at 1765; B. Trost, Bacterial peptides are intensively present throughout the human
proteome, 1 SELF/NONSELF 1: 73, 71-41).
Noting that Dr. Shoenfeld criticized his lack of evidence of the specific genetic mutation,
Dr. McClain observed that Dr. Shoenfeld, likewise, had performed no DNA sequencing to show
the lack of DNA mutation. Third McClain Rep. at 4. He stressed that “it is generally accepted in
the oncology community that the types of genomic abnormalities in a given type of lymphoma are
caused by spontaneous mutations.” Id.
Regarding Dr. Shoenfeld’s discussion of Petitioner’s treatment and remission, Dr. McClain
argued that remission was obtained because all lymphoma cells, which were the only ones carrying
the DNA mutation, were destroyed by chemotherapy. Third McClain Rep. at 4. While
acknowledging that the chemotherapy drugs Petitioner received are immune-suppressive, he
explained that “those same medications are used in chemotherapy protocols in lymphoma because
they kill lymphoma cells.” Id. (emphasis in original). He added that Dr. Shoenfeld had not
provided nor was he aware of any literature to explain that these medications play a different role
in this instance. Id. at 5. He again reiterated that there was no evidence indicating Petitioner had
an autoimmune disease and stressed that VAERS reports have not been found to be evidence of
causation. Id. at 4-5.
C. Testimony
1. Dr. Shoenfeld
During his direct testimony, Dr. Shoenfeld repeated the theories he advanced in his first
expert report. Tr. at 4-46. He confirmed that, other than the mechanisms he described, he
continued to rely on Petitioner’s lack of symptoms prior to vaccination and the temporal
association between vaccination and Petitioner’s PMBCL. Id. at 144-45.
Dr. Shoenfeld also discussed two articles filed earlier that day.25 He claimed the second
article, which involved biopsies of cats showing the presence of cutaneous lymphomas at
commonly used injection sites (Roccabianca at 832), was evidence that pseudolymphoma can
transform into lymphoma. Tr. at 51. Dr. Shoenfeld also discussed the list of VAERS reports
25
The first article was a population-based study which indicated the herpes zoster infection is an
independent risk marker for subsequent lymphoid malignancies. Lui, et al., Herpes zoster is associated
with an increased risk of subsequent lymphoid malignancies – A nationwide population-based matched-
control study in Taiwan, posted on an Open Access website (filed as Ex. 101). The second article purported
to show an increased presence of cutaneous lymphomas arising in areas commonly used for injection.
Roccabianca, et al., Cutaneous Lymphoma at Injection Sites: Pathological, Immunophenotypical, and
Molecular Characterization in 17 Cats, 53 VETERINARY PATHOLOGY 4: 823-32 (2016) (filed as Ex. 102)
(hereinafter “Roccabianca”). Respondent’s counsel objected to any consideration of these articles as they
were published in 2012 and 2016 but only introduced into the record the morning of the first day of the
entitlement hearing. Tr. at 47, 50. I indicated I would consider the articles but allowed Respondent’s counsel
time to first review the articles with her expert. Tr. at 47-48.
15
included in his second expert report, claiming these were proof of vaccine included lymphomas.
Id. at 54
During cross examination, Respondent’s counsel attempted to elicit, from Dr. Shoenfeld,
an estimate of the percentage of time he spends diagnosing patients with cancer, specifically
PMBCL. Tr. at 61-65. She also questioned him about his relationship to Claire Dwoskin, the
founder of Children’s Medical Safety Research Institute, considered an anti-vaccine
organization.26 Id. at 66-67. While acknowledging that he is listed as a member of the Scientific
Advisory Board for this organization, Dr. Shoenfeld testified that he “never attended a board
[meeting], and . . . was not involved in any decision of the board.” Id. at 76. When asked about
funding from Ms. Dwoskin and her organization, Dr. Shoenfeld acknowledged that one of his
colleagues and co-authors, Miri Blank, had received funding from this source but denied accepting
any such financial support himself. Id. at 67, 70-73.
Regarding Petitioner’s case, Dr. Shoenfeld confirmed that Petitioner’s diagnosis was
PMBCL and that she had never been diagnosed with an autoimmune disease, pseudolymphoma,
or any other type of lymphoma. Tr. at 85. When asked about his extensive discussion regarding
autoimmune disease in his expert reports and testimony, despite the lack of autoimmune disease
in this case, Dr. Shoenfeld testified that the purpose of these discussions was to provide examples
of the mechanism by which lymphomagenesis occurs. Id. at 88-90. He stated, “I brought [up]
Sjogren’s disease as an example to show how chronic stimulation can stimulate and increase
lymphocyte infiltration, progress to pseudolymphoma and then also develop lymphoma.” Id. at
90. When related to stimulation by vaccines, as opposed to autoimmune diseases, Dr. Shoenfeld
testified that “chronic means intensive stimulation,” . . . not necessarily the timing, but the
intens[ity] of the stimulation.” Id. at 92.
Dr. Shoenfeld often provided confusing and conflicting testimony. When asked to provide
the appropriate timing between vaccination and tumor formation under his theories of causation,
Dr. Shoenfeld based his answer on the specific facts in this case. He stated “[i]n this case, in my
opinion, due to the facts, which are very clear, one month.” Tr. at 97. He attributed the facial
swelling Petitioner experienced on August 3 to her tumor but not the neck and back pain she
experienced in July. Id. at 96-99. He theorized that these July symptoms may have been due to a
vaccine site injury but then admitted there was no evidence of such an injury in the medical records.
Id. at 97-99. He then seemed to reverse his opinion on this point, indicating that while “not directly
related,” these symptoms would have drawn the attention of a treating physician “that something
unusual [wa]s going [on] there.” Id. at 98-99. He then reiterated his claim that Petitioner’s facial
swelling would have been the first symptom of her PMBCL. Id. at 99.
Throughout his testimony, Dr. Shoenfeld continued to insist that the only difference
between PMBCL and other lymphomas was its location. He testified that “B large cell lymphoma
26
Children’s Medical Safety Research Institute is a 501(c)(3) non-profit organization which highlights what
it deems to be “serious concerns raised by the scientific and medical community about the acknowledged
significant increases in immune and inflammatory diseases in children and adults during the past three
decades” and advocates that the study of “[t]he effect of vaccines on the immune and neurological systems
must also be assessed in association with cognitive function as it is related to academic performance and
systemic effects on the educational system.” https://www.cmsri.org/about (last visited Feb. 17, 2021).
16
[in] the mediastinum is the same if it appears in the abdomen” (Tr. at 109) and that “the location
in lymphoma is not important,” [l]ymphoma is lymphoma” Id. at 136. He claimed his theories of
causation would apply to “any kind of lymphoma.” Id. at 89.
2. Dr. Gordon
During his testimony, Dr. Gordon explained that he is not a researcher, but a clinician
involved in direct patient care. Tr. at 177. Describing PMBCL, he testified “it is a distinct
lymphoma entity . . . recognized as its own subcategory of lymphoma.” Id. at 179. However, he
added that as a subcategory of non-Hodgkin’s lymphoma, “it does have a lot of similarities in
general to non-Hodgkin’s lymphoma with regard to certain etiologies . . . and some commonality
in the types of treatments that we general[ly] consider.” Id. at 181.
When discussing the two-stage theory of sustained antigen simulation advanced by Dr.
Shoenfeld, Dr. Gordon was asked if “there is a reason to believe that a pseudolymphoma could not
eventually progress to lymphoma.” Tr. at 186. He initially replied, “Classically, it’s not described
as an entity that in and of itself has a high risk of turning into a lymphoma.” Id. After being asked,
however, if it could happen, he replied in the affirmative. Id.
Regarding the timing of Petitioner’s PMBCL, Dr. Gordon testified that a 30-day period
between vaccination and the symptoms Petitioner experienced would be “consistent with an
abnormal response to one or more of the vaccinations” she received. Tr. at 189. In reaching this
conclusion, he emphasized that “it is an aggressive, fast-growing type of lymphoma.” Id.
Regarding a comparison of the CT scans performed on August 11 and 22, 2011, Dr. Gordon noted
that the results of the second CT scan listed only the tumor’s two dimensional measurement of
13.8 centimeters, which still was .8 centimeters greater than the largest of the three dimensional
measurements reported on August 11. Id. at 280-82. Upon cross-examination, Dr. Gordon
admitted that he had no information regarding the doubling rate of PMBCL. Id. at 200.
During cross-examination, Dr. Gordon also testified that “to a certain degree,” he agreed
with the scientific community’s belief that the development of PMBCL “is triggered by genetic
mutations in the cells.” Tr. at 195. He also acknowledged that he could point to nothing atypical
about the presentation of Petitioner’s PMBCL. Id. at 201.
In closing, Dr. Gordon confirmed that the bases for his opinion in this case, that the
vaccines Petitioner received caused her PMBCL, was the lack of an alternative cause and the
timing of her symptoms and diagnosis. Tr. at 204-06.
3. Dr. McClain
During the first portion of his direct testimony, Dr. McClain described the two major
categories (Hodgkin’s and non-Hodgkin’s) and various types of lymphomas. Tr. at 220-30. He
testified that PMBCL “was once thought to be a part of the diffuse large B cell lymphomas but is
now understood through genetic research to be a separate category.” Id. at 222. He then discussed
an article showing the DNA characteristics which he indicated showed, “in a very dramatic way, .
. . the complete uniqueness of PMB[C]L versus the other type of lymphoma.” Id. at 227
17
(discussing Wessendorf et al., Further delineation of chromosomal consensus regions in primary
mediastinal B-cell lymphomas: an analysis of 37 tumor samples using high-resolution genomic
profiling (array-CGH), LEUKEMIA 21: 2463-69, (2007)) (filed as Ex. D-10).
When asked about the connection between autoimmune disease and lymphoma, Dr.
McClain opined that he was unaware of any autoimmune disease linked to the formation of
PMBCL. Tr. at 234. He acknowledged, however, that this could be due, in part, to the rarity of
PMBCL. Id.
Discussing further this theory of chronic stimulation, Dr. McClain emphasized the need for
and correlation between the constant stimulation over time, like that provided by autoimmune
disease. He noted that rheumatoid arthritis patients with the highest disease activity were at
greatest risk of developing lymphoma. Tr. at 235-36. He explained that the type of inflammation
produced by an autoimmune disease can occur for weeks and months. In contrast, inflammation
at the site of vaccination “might happen for a few days or a week or two at most.” Id. at 237.
Dr. McClain also stressed the importance of the location of a tumor in relationship to the
chronic stimulation. He explained that any lymphoma caused by inflammation would occur close
to the origin of the inflammation. Tr. at 253. As examples, he discussed the lymphoma which
develops in the parotid gland in response to the accumulation of lymphocytes due to Sjogren’s
disease and the lymphoma which develops in the stomach in reaction to the Helicobacter pylori,
bacteria which causes constant stimulation, inflammation, and ulcers in that area. Id. at 238-39.
He maintained that the location of Petitioner’s tumor undermined the possibility that it was caused
by the vaccinations she received as any related lymphoma would have formed physically much
closer to the site of vaccination. Id. at 253.
Regarding the theory of cross reactivity posited by Dr. Shoenfeld, Dr. McClain testified
that molecular mimicry had been debunked as a cause of cancer. Tr. at 176-77. When asked about
the human proteins identified by Dr. Shoenfeld as lymphoma-related, he testified that he was
unaware of any association between these protein sequences and the development of PMBCL. Id.
at 240-41. He also explained that any antibody attack would be against the whole protein not just
the smaller groups of peptides identified by Dr. Shoenfeld. Id. at 246-47.
Dr. McClain also disagreed with Dr. Gordon’s characterization of PMBCL as an aggressive
and therefore fast-growing lymphoma. He testified that the term aggressive does not automatically
equate to fast-growing. Tr. at 256. While asserting that the neck and back pain Petitioner
experienced in July 2011 could have been related to her PMBCL, he theorized that Petitioner’s
tumor could have been there for quite a long time before it actually caused [any] . . . symptoms.”
Id. at 255. Dr. McClain acknowledged that a fast-growing lymphoma, like Burkitt’s27 could have
produced a tumor the size seen on the August 11, 2011 CT scan within a month. Id. at 256-57.
However, he pointed to the results of Petitioner’s second CT scan performed on August 22, 2011
27
Burkitt’s lymphoma is a type of non-Hodgkin’s lymphoma that is further classified as a mature B-cell
lymphoma. First McClain Rep. at 6. Dr. McClain described as Burkitt’s lymphoma as “the fastest growing
lymphoma that we know.” See Tr. at 254.
18
which showed no significant change in size from what was observed on the August 11 CT scan,
to show that the growth of Petitioner’s tumor was slow. Id. at 258-59.
IV. Applicable Law
A. Overall Burden in Vaccine Program Cases
Under the Vaccine Act, a petitioner may prevail on her claim if she has “sustained, or
endured the significant aggravation of any illness, disability, injury, or condition” set forth in the
Vaccine Injury Table (the Table). § 11(c)(1)(C)(i). The most recent version of the Table, which
can be found at 42 C.F.R. § 100.3, identifies the vaccines covered under the Program, the
corresponding injuries, and the time period in which the particular injuries must occur after
vaccination. § 14(a). If a petitioner establishes that she has suffered a “Table Injury,” causation
is presumed.
If, however, a petitioner suffered an injury that either is not listed in the Table or did not
occur within the prescribed time frame, she must prove that the administered vaccine caused injury
to receive Program compensation. § 11(c)(1)(C)(ii) and (iii). In such circumstances, petitioner
asserts a “non-Table or [an] off-Table” claim and to prevail, a petitioner must prove her claim by
preponderant evidence. § 13(a)(1)(A). This standard is “one of . . . simple preponderance, or
‘more probable than not’ causation.” Althen v. Sec’y of Health & Hum. Servs., 418 F.3d 1274,
1279-80 (Fed. Cir. 2005) (referencing Hellebrand v. Sec’y of Health & Hum. Servs., 999 F.2d
1565, 1572-73 (Fed. Cir. 1993). The Federal Circuit has held that to establish an off-Table injury,
a petitioner must “prove . . . that the vaccine was not only a but-for cause of the injury but also a
substantial factor in bringing about the injury.” Shyface v. Sec’y of Health & Hum. Servs., 165
F.3d 1344, 1351 (Fed. Cir 1999). Id. at 1352. The received vaccine, however, need not be the
predominant cause of the injury. Id. at 1351.
The Federal Circuit has indicated that a petitioner “must show ‘a medical theory causally
connecting the vaccination and the injury’” to establish that the vaccine was a substantial factor in
bringing about the injury. Shyface, 165 F.3d at 1352-53 (quoting Grant v. Sec’y of Health & Hum.
Servs., 956 F.2d 1144, 1148 (Fed. Cir. 1992)). The Circuit Court added that "[t]here must be a
‘logical sequence of cause and effect showing that the vaccination was the reason for the injury.’”
Id. The Federal Circuit subsequently reiterated these requirements in its Althen decision. See 418
F.3d at 1278. Althen requires a petitioner demonstrate by preponderant evidence that the
vaccinations she received caused her injuries by providing: “(1) a medical theory causally
connecting the vaccination and the injury; (2) a logical sequence of cause and effect showing that
the vaccination was the reason for the injury; and (3) a showing of a proximate temporal
relationship between vaccination and injury.” Id. All three prongs of Althen must be satisfied. Id.“Unlike an on-Table case, proof of causation in an off-Table case must comprise more than just a
literal temporal association between the onset of the injury and the vaccination.” Pafford v. Sec’y
of Health & Hum. Servs., 64 Fed. Cl. 19, 24 (Fed. Cl. 2005); see also Grant, 956 F.2d at 1148.
The Federal Circuit has instructed that a petitioner may satisfy her evidentiary burden by
relying either on “medical records or medical opinion.” Althen, 418 F.3d at 1279 (emphasis in
original). Any offered expert testimony must be scientifically reliable and may be analyzed using
19
the four factors enumerated by the Supreme Court in Daubert. Terran v. Sec’y of Health & Hum.
Servs., 195 F.3d 1301, 1316 (Fed. Cir. 1999) (referring to Daubert v. Merrell Dow Pharm., Inc.,
509 U.S. 579 (1993)). Circumstantial evidence also might be used. Capizzano v. Sec’y of Health
& Hum. Servs., 440 F.3d 1317, 1325-26 (Fed. Cir. 2006). Evidence that satisfies one prong might
assist in proving another prong as well. Id. at 1326.
Petitioner is not required to eliminate alternative causes when establishing his prima facie
case. Doe 11 v. Sec’y of Health & Hum. Servs., 601 F.3d 1349, 1357-58 (Fed. Cir. 2010); de Bazan
v. Sec’y of Health & Hum. Servs., 539 F.3d 1347, 1352 (Fed. Cir. 2008). To support an argument
regarding causation, a petitioner may, however, introduce evidence of the lack of an alternative
cause. Walther v. Sec’y of Health & Hum. Servs., 485 F.3d 1146, 1149-50 (Fed. Cir. 2007).
Respondent also may introduce evidence of the presence of an alternative cause to rebut evidence
regarding causation. Doe 11, 601 F.3d at 1358; de Bazan, 639 F.3d at 1353.
Once a petitioner has established a prima facie case, the burden shifts to respondent to show
by preponderant evidence that petitioner’s injury was “due to factors unrelated to the
administration of the vaccine.” § 13(a)(1); see also DeBazan, 639 F.3d at 1352-54; Walther, 486
F.3d at 1150.
B. Analysis of Expert Testimony
Establishing a sound and reliable medical theory connecting the vaccine to the injury often
requires a petitioner to present expert testimony in support of her claim. Lampe v. Sec’y of Health
& Hum. Servs., 219 F.3d 1357, 1361 (Fed. Cir. 2000). Vaccine Program expert testimony is
usually evaluated according to the factors for analyzing scientific reliability set forth in Daubert,
509 U.S. at 594-96. See Cedillo v. Sec’y of Health & Hum. Servs., 617 F.3d 1328, 1339 (Fed. Cir.
2010) (citing Terran, 195 F.3d at 1316). “The Daubert factors for analyzing the reliability of
testimony are: (1) whether a theory or technique can be (and has been) tested; (2) whether the
theory or technique has been subjected to peer review and publication; (3) whether there is a known
or potential rate of error and whether there are standards for controlling the error; and (4) whether
the theory or technique enjoys general acceptance within a relevant scientific community.”
Terran, 195 F.3d at 1316 n.2 (citing Daubert, 509 U.S. at 592-95).
The Daubert factors play a slightly different role in Vaccine Program cases than they do
when applied in other federal judicial fora. Daubert factors are employed by judges to exclude
evidence that is unreliable and potentially confusing to a jury. In Vaccine Program cases, these
factors are used in the weighing of the reliability of scientific evidence. Davis v. Sec’y of Health
& Hum. Servs., 94 Fed. Cl. 53, 66-67 (2010) (“uniquely in this Circuit, the Daubert factors have
been employed also as an acceptable evidentiary-gauging tool with respect to persuasiveness of
expert testimony already admitted”). The flexible use of the Daubert factors to evaluate
persuasiveness and reliability of expert testimony has routinely been upheld. See, e.g., Snyder, 88
Fed. Cl. at 743. In this matter, (as in numerous other Vaccine Program cases), Daubert has not
been employed at the threshold to determine what evidence should be admitted, but instead to
determine whether expert testimony offered is reliable and/or persuasive.
20
Respondent frequently offers one or more experts of his own in order to rebut a petitioner’s
case. Where both sides offer expert testimony, a special master’s decision may be “based on the
credibility of the experts and the relative persuasiveness of their competing theories.”
Broekelschen v. Sec’y of Health & Hum. Servs., 618 F.3d 1339, 1347 (Fed. Cir. 2010) (citing
Lampe, 219 F.3d at 1362). However, nothing requires the acceptance of an expert’s conclusion
“connected to existing data only by the ipse dixit of the expert,” especially if “there is simply too
great an analytical gap between the data and the opinion proffered.” Snyder, 88 Fed. Cl. at 743
(quoting Gen. Elec. Co. v. Joiner, 522 U.S. 136, 146 (1997)). A “special master is entitled to
require some indicia of reliability to support the assertion of the expert witness.” Moberly v. Sec’y
of Health & Hum. Servs., 592 F.3d 1315, 1324 (Fed. Cir. 2010). Weighing the relative
persuasiveness of competing expert testimony, based on a particular expert’s credibility, is part of
the overall reliability analysis to which special masters must subject expert testimony in Vaccine
Program cases. Id. at 1325-26 (“[a]ssessments as to the reliability of expert testimony often turn
on credibility determinations”); see also Porter v. Sec’y of Health & Hum. Servs., 663 F.3d 1242,
1250 (Fed. Cir. 2011) (“this court has unambiguously explained that special masters are expected
to consider the credibility of expert witnesses in evaluating petitions for compensation under the
Vaccine Act”).
C. Consideration of Medical Literature
Although this decision discusses some but not all of the medical literature in detail, I
reviewed and considered all of the medical records and literature submitted in this matter. See
Moriarty v. Sec’y of Health & Hum. Servs., 844 F.3d 1322, 1328 (Fed. Cir. 2016) (“We generally
presume that a special master considered the relevant record evidence even though [s]he does not
explicitly reference such evidence in h[er] decision.”); Simanski v. Sec’y of Health & Hum. Servs.,
115 Fed. Cl. 407, 436 (2014) (“[A] Special Master is ‘not required to discuss every piece of
evidence or testimony in her decision.’” (citation omitted)), aff’d, 601 F. App’x 982 (Fed. Cir.
2015).
V. Analysis
A. Credibility of the Experts
I will note at the outset that while all of the experts were qualified to testify in this
proceeding, I found Dr. McClain to possess the best qualifications with respect to the disease at
issue in this case: PMBCL. Dr. McClain serves as the clinical director of the histiocytosis program
and co-director of the lymphoma program at Texas Children’s Hospital. Tr. at 211-12. This
facility is the only designated lymphoma program among the pediatric oncology centers in the
United States. Id. at 212. Further, Dr. McClain has seen or consulted with over 300 lymphoma
patients during his lengthy career. Id. at 215. He has numerous publications relevant to this field.
See McClain CV. These impressive qualifications render him especially qualified to opine on the
issues germane to this case. Special masters may consider the relative expertise of testifying
experts when weighing the value of their opinion. See Depena v. Sec’y of Health & Hum. Servs.,
No. 13-675V, 2017 WL 1075101 (Fed. Cl. Spec. Mstr. Feb. 22, 2017), mot. for rev. denied, 133
Fed. Cl. 535, 547-48 (2017), aff’d without op., 730 Fed. App’x 938 (Fed. Cir. 2018); Copenhaver
21
v. Sec’y of Health & Hum. Servs., No. 13-1002V, 2016 WL 3456436 (Fed. Cl. Spec. Mstr. May
31, 2016), mot. for rev. denied, 129 Fed. Cl. 176 (2016).
B. Three-Pronged Althen Test
In order to receive compensation under the Vaccine Act, a petitioner must prove causation
by satisfying the three-pronged test set forth in Althen by the preponderance of evidence standard
required in the Vaccine Act. 418 F.3d at 1278. In Althen, the Federal Circuit described this
standard “as one of proof by a simple preponderance, of ‘more probable than not’ causation.” Id.
at 1279.
Although the first and second prongs of Althen appear to be similar, these analyses involve
different inquiries. See Doe 93 v. Sec’y of Health & Hum. Servs., 98 Fed. Cl. 553, 566-67 (2011).
The first prong focuses on general causation, whether the administered vaccine can cause the
particular injury suffered by the petitioner, and the second prong focuses on specific causation,
whether the administered vaccine did cause the injury. Pafford v. Sec'y of Health & Hum. Servs.,
451 F.3d 1352, 1355-56 (Fed. Cir. 2006). This distinction “has been described as the ‘can cause’
vs. ‘did cause’ distinction.” Stapleton v. Sec’y of Health & Hum. Servs., No. 03-234V, 2009 WL
1456441, at *18 (Fed. Cl. Spec. Mstr. May 1, 2009).
1. Althen Prong One
Under the first prong of Althen, petitioners must provide a “reputable medical theory,”
demonstrating that the vaccine received can cause the type of injury alleged. Pafford, 451 F.3d at
1355-56 (citations omitted). To satisfy this prong, a petitioner’s theory must be based on a “sound
and reliable medical or scientific explanation.” Knudsen v. Sec’y of Health & Hum. Servs., 35
F.3d 543, 548 (Fed. Cir. 1994). Proof that the proffered medical theory is reasonable, plausible,
or possible does not satisfy a petitioner’s burden. Boatmon v. Sec’y of Health & Hum. Servs., 941
F.3d 1351, 1359-60 (Fed. Cir. Nov. 7, 2019).
Petitioners may satisfy the first Althen prong without resort to medical literature,
epidemiological studies, demonstration of a specific mechanism, or a generally accepted medical
theory. Andreu v. Sec’y of Health & Hum. Servs., 569 F.3d 1367, 1378-79 (Fed. Cir. 2009) (citing
Capizzano, 440 F.3d at 1325-26). However, special masters are “entitled to require some indicia
of reliability to support the assertion of the expert witness.” Boatmon, 941 F.3d at 1360, quoting
Moberly, 592 F.3d at 1324. Special Masters, despite their expertise, are not empowered by statute
to conclusively resolve what are complex scientific and medical questions, and thus scientific
evidence offered to establish Althen prong one is viewed “not through the lens of the laboratorian,
but instead from the vantage point of the Vaccine Act’s preponderant evidence standard.” Id. at
1380. Accordingly, special masters must take care not to increase the burden placed on petitioners
in offering a scientific theory linking vaccine to injury. Contreras v. Sec’y of Health & Hum.
Servs., 121 Fed. Cl. 230, 245 (2015), vacated on other grounds, 844 F.3d 1363 (Fed. Cir. 2017);
see also Hock v. Sec’y of Health & Hum. Servs., No. 17-168V, 2020 U.S. Claims LEXIS 2202 at
*52 (Fed. Cl. Spec. Mstr. Sept. 30, 2020).
Petitioner in this case proposed two theories of causation which she maintained establish,
22
either separately or collectively, that the multiple vaccines she received can cause PMBCL. In her
pre-hearing brief, she averred “[t]here is considerable overlap between our two positions as they
both deal with stimulation brought about by vaccination.” Pet. Pre-Hearing Brief at 7. Both
theories are described in detail in Dr. Shoenfeld’s first expert report and discussed in further detail
in Petitioner’s pre- and post- hearing briefs. In his expert report, Dr. Gordon advanced the first of
Dr. Shoenfeld’s theories but added no accompanying evidence.
When presenting both theories, Dr. Shoenfeld provided evidence of associations which do
not equate to a causal relationship. Additionally, much of his discussion was not relevant to
Petitioner’s case but was presented only to illustrate how Dr. Shoenfeld’s theories are potentially
substantiated in other circumstances. He focused on the validity of his theories in these other
circumstances but failed to establish how they translate to the facts of Petitioner’s case.
Both theories offered by Dr. Shoenfeld are unsupported and incomplete. While petitioners
are not required to provide the exact mechanism involved in any general theory of causation, there
must be some support for their assertions. Knudsen, 35 F.3d at 548-49. When discussing his
theories, Dr. Shoenfeld provides details based upon assumptions and conjecture.
a. Chronic Stimulation
With respect to his first theory, Dr. Shoenfeld posited that vaccines can cause PMBCL in
the same manner that autoimmune disease has been shown to cause non-Hodgkin’s lymphoma,
through chronic stimulation. When advancing this theory, he sometimes focused on the aluminum
adjuvant alone and, at other times, the vaccine antigen supported by the included adjuvant. First
Shoenfeld Rep. at 28-30. In forming his opinion of causation, Dr. Gordon relied upon the same
theory, referring to the chronic stimulation provided by vaccine antigens. Gordon Rep. at 5-7.
However, there are several problems with this theory.
Dr. Shoenfeld described chronic stimulation as follows:
What I mean by chronic stimulation, it's a strong repetitive stimulation. There are
two kinds of strong stimulations. One is repetitive with small amounts, and one
which is repetitive with huge amounts with different kinds of antigens. This case is
unique. There are four different vaccines given at the same day, at the same
injection, with huge amounts of aluminum. So in this case, the chronic means
intensive stimulation.
Tr. at 91-92.
First, none of the evidence Dr. Shoenfeld provided to support the relationship between
autoimmune disease and non-Hodgkin’s lymphoma pertains to the specific type of lymphoma
Petitioner suffered, PMBCL. As Dr. McClain testified, PMBCL “is a very unique form of
lymphoma.” Tr. at 227. According to literature supplied by Dr. McClain, PMBCL actually more
closely resembles a subtype of Hodgkin’s lymphoma. Dunleavy at 298.
23
Second, even if applicable to the formation of PMBCL, Petitioner has not provided
sufficient evidence to show that the vaccines Petitioner received would have resulted in the chronic
stimulation induced by autoimmune disease. The medical literature provided by Dr. Shoenfeld
discussed sustained antigen drive. Mackay at 793-94. Citing the Pulendran article, Dr. Shoenfeld
seemed to theorize that the inclusion of alum adjuvant would increase the duration of the effect of
the vaccine antigen. First Shoenfeld Rep. at 20-21, 27; see Pulendran at 511. He further testified
as followed regarding aluminum: “So the aluminum, being a strong stimulant of the immune
system, is toxic to many organs in our body, including the brain. So in this case, she got one gram
in one shot with multiple antigens. This is a strong stimulation which lasted -- in this case didn't
need more than one month to arise or to stimulate to get the emergence of the aggressive
lymphoma.” Tr. at 93. Dr. Shoenfeld later conceded that Petitioner received one milligram of
aluminum in the four vaccines and not one gram. Id. at 94. However, he continued to call this
dose “a huge amount.” Id. Dr. Shoenfeld acknowledged that he had not submitted evidence in
this case that the amount of aluminum in vaccines constitutes a toxic amount. See Tr. at 94-95.
Dr. McClain contrasted the autoimmune stimulation provided by vaccines which is lesser
in duration than what would be provided by autoimmune disease, calling them “markedly
different”. Tr. at 237; First McClain Rep. at 8. Specifically, Dr. McClain stated that “inflammation
that happens at the site of an injection might happen for a few days or a week or two at most”
whereas the inflammation from an autoimmune condition can go on for “months and months and
months.” Tr. at 237.
Finally, as discussed by Dr. McClain, it is illogical to assume that chronic stimulation
provided at the site of vaccination would cause the type and location of tumor Petitioner
experienced. During his testimony, Dr. McClain stressed the importance of the location of a tumor
in relationship to the chronic stimulation, explaining that any lymphoma caused by inflammation
would occur close to the origin of the inflammation. Tr. at 253. I find Dr. McClain’s testimony
on this point to be persuasive.
Examining the two-stage explanation advanced by Dr. Shoenfeld further underscores the
weakness of this theory. While Dr. Shoenfeld supplied extensive medical literature showing that
benign lymphomas can form at the site of vaccination, he provided no support for the proposition
that these benign pseudolymphomas can progress to cutaneous lymphomas. Dr. Shoenfeld
claimed the Roccabianca article regarding biopsies in cats supported this assertion, but that article
only indicates cutaneous lymphomas can form at common injection sites. It does not suggest a
transformation from benign to malignant tumor occurs. Furthermore, there is no evidence
Petitioner experienced cutaneous pseudo lymphoma in this case. Certainly, there is no support for
the proposition that any response which occurred at the site of vaccination would affect
lymphocytes in the chest cavity.
Petitioner has failed to provide preponderant evidence that this theory of chronic
stimulation is a reliable medical theory applicable to Petitioner’s case.
24
b. Cross Reactivity - Molecular Mimicry
Dr. Shoenfeld next proposed a theory of cross reactivity following the process of molecular
mimicry. In additional to being an accepted means by which certain viral and bacterial infections
can cause autoimmune disease (see supra note 19), the theory of molecular mimicry has been used
to persuasively show a causal link between the HPV and MMR vaccines and immune
thrombocytopenic purpura (“ITP”). Johnson v. Sec'y of Health & Hum. Servs., No. 14–113V,
2017 WL 772534 (Fed. Cl. Spec. Mstr. Jan. 6, 2017) (finding petitioner presented sufficient
evidence to conclude the HPV vaccine can cause ITP); Ebenstein v. Sec'y of Health & Hum. Servs.,
No. 06–573V, 2010 WL 5113185, at *21 (Fed. Cl. Spec. Mstr. Sept. 1, 2010) (accepting that
molecular mimicry links the MMR vaccine and ITP). However, the fact that these theories have
been found to provide sufficient evidence of prong one general causation, does not equate to an
acceptance of the theory of molecular mimicry in every instance. As the special master in Isaac
stated,
The fact that molecular mimicry exists as a biological phenomenon does not
automatically mean that vaccines can cause autoimmune disease by that process.
Applicable law instructs that special masters need not accept unsupported theories
of vaccine causation without some indicia of reliability, and that a temporal
association is not sufficient in itself. I accept the theory of molecular mimicry in
some cases and reject it in others, depending on the particular vaccine, the injury,
the reliability of the expert testimony supporting and opposing causation, and the
weight of the other evidence in the record.
2012 WL 3609993, at *4; accord. Caves v. Sec’y of Health & Hum. Servs., 100 Fed. Cl. 119, 135
(June 24, 2011) (indicating the theory of molecular mimicry must be held applicable to the specific
case at hand), aff. per curiam, 463 Fed. Appx. 932 (Fed. Cir. 2012). To date, the theory of
molecular mimicry has not been accepted as a reputable theory of general causation when used to
link vaccines to cancers, including lymphoma.
I will note that lymphoma is not an autoimmune disease and is not considered to be an
antibody-mediated condition. Tr. at 246. Based on that, Dr. McClain testified that the vaccines
that Petitioner received could not have triggered an autoantibody response that in turn caused
PMBCL. Id. Dr. McClain further testified that there is no evidence in the scientific community
that PMBCL has an infectious or an autoimmune etiology. Id. at 250. There is additionally no
evidence in the scientific community that PMBCL can be caused by vaccination. Id. Further, Dr.
McClain, in his 42 years of treating cancer patients, has not seen a case of vaccination causing a
lymphoma. First McClain Rep. at 7.
In this case, Dr. Shoenfeld relied solely upon the similarities between the proteins found in
the HPV, Hep A, and Varicella-Zoster vaccines and human proteins which he theorized are
involved in lymphomagenesis. First Shoenfeld Rep. at 20-25, 30-31; Second Shoenfeld Rep. at 2-
5. The medical literature Petitioner filed addressed these similarities but provided no evidence to
show these vaccines would initiate the cross reactivity (molecular mimicry) Dr. Shoenfeld
presumes would occur. Neither does he provide any evidence to establish that alteration or
mutation of these human proteins would result in the formation of lymphoma.
25
Dr. McClain succinctly described the flaws in Dr. Shoenfeld’s theory when he wrote
“[m]olecular similarity does NOT mean the presence of these peptides would CAUSE cancer.”
First McClain Rep. at 9 (emphasis in original). He emphasized the lack of scientific evidence
showing that the antibodies induced by vaccines would bind to the specific peptides identified by
Dr. Shoenfeld as proposed or that such binding would produce a mutation that would trigger the
type of lymphoma Petitioner had, PMBCL. Third McClain Report at 2. Dr. McClain also asserted
that if the similarity that Dr. Shoenfeld relied upon were sufficient by itself to ensure the cross-
reactivity Dr. Shoenfeld described, the expected outcome, be it autoimmune disease or lymphoma
would occur much more often. First McClain Rep. at 2 (citing Kanduc at 1765; Trost at 73). I
find Dr. McClain’s criticisms to be persuasive.
I will also note that Petitioner has provided no medical literature which supports a
connection between the vaccines at issue in this case and the development of PMBCL. As Dr.
McClain observed, there is no evidence that wild type HPV infection, Hepatitis A infection, or
Varicella infection cause PMBCL. Third McClain Rep. at 2. “Thus, if the antigens associated
with these viral infections had any capacity to induce PMBCL, it would have likely been noted in
the scientific literature as PMBCL is an extensively studied disease.” Id. While support in the
medical literature is not required in order for Petitioner to establish a reputable prong one theory,
the absence of such evidence does not serve to advance Petitioner’s case. “[A] scientific theory
that lacks any empirical support will have limited persuasive force.” Caves, 100 Fed. Cl. at 134.
Petitioner has failed to provide preponderant evidence that her theory of cross reactivity or
molecular mimicry is a reputable medical theory connecting vaccinations to the formation of
PMBCL.
2. Althen Prong Two
To satisfy the second prong of the Althen test, a petitioner must establish a “logical
sequence of cause and effect showing that the vaccination was the reason for the injury.” Althen,
418 F.3d at 1278. The sequence of cause and effect need only be “logical and legally probable,
not medically or scientifically certain.” Knudsen, 35 F.3d at 548-49; accord. Capizzano, 440 F.3d
at 1326. In establishing that a vaccine did cause the injury in question, the opinions and views of
treating physicians are entitled to some weight. Andreu, 569 F.3d at 1367; Capizzano, 440 F.3d
at 1326 (“treating physicians are likely to be in the best position to determine whether a ‘logical
sequence of cause and effect show[s] that the vaccination was the reason for the injury’”) (quoting
Althen, 418 F.3d at 1280).
A review of the medical records in this case reveals no entry which supports Petitioner’s
claim that the vaccines she received on June 29, 2011 caused her PMBCL. None of her treating
physicians implicated, or even discussed the possibility of a causal link, and Petitioner does not
argue that this evidence exists.
Additionally, the medical records themselves do not provide evidence linking Petitioner’s
PMBCL to her vaccination. Dr. Shoenfeld testified that after vaccination “I believe that the
stimulant will go immediately at the same very day, which will be exemplified quite often by fever,
26
by feeling unwell, et cetera, which quite often the vaccinee would complain.” Tr. at 95. Yet as
Dr. McClain points out in his report, “from June to early August [Petitioner] had no fevers or
cervical or axillary adenopathy, which one would expect if an injection in the deltoid muscles of
both arms were to excessively activate the immune system.” First McClain Rep. at 6. Indeed,
there is no evidence in Petitioner’s medical records that she developed an aberrant immune
response to her vaccinations.
Further, during his testimony, Dr. McClain stressed the importance of the location of a
tumor in relationship to the chronic stimulation, explaining that any lymphoma caused by
inflammation would occur close to the origin of the inflammation. Tr. at 253. Dr. McClain
testified as follows:
If a person has some inflammatory infectious condition of the shoulder, the lymph
nodes of the armpit, the axilla, would be the recipients of that information, whether
it's cancer cells or inflammation. So if she had had inflammation from, or if the
lymphoma had started in her vaccine site, it would have gone to her axillary lymph
nodes. She did not have axillary lymphadenopathy....
Id. Petitioner’s medical records make it clear that her PMBCL did not develop close to the origin
of her purported vaccine-induced inflammation. In short, Petitioner’s medical records are bereft
of evidence connecting her June 29, 2011 vaccinations to her subsequent development of PMBCL.
When asserting that causation-in-fact has been proven, Petitioner and her experts relied
upon her lack of symptoms prior to vaccination, the timing of her symptoms post-vaccination,
along with a lack of an alternative cause. First Shoenfeld Rep. at 32; Gordon Rep. at 6-7; Tr. at
144-45, 204-06; Pet. Brief at 12; Pet. Post-Hearing brief at 9-12. Although presented as two
separate bases, the first two assertions (made by Dr. Shoenfeld) are simply variations of the
argument that the timing of Petitioner’s symptoms is temporally appropriate to vaccination, in
essence the focus of Althen prong three. Proper timing may be considered as evidence to establish
the second Althen prong, but timing alone is not sufficient. Grant, 956 F.2d 1148 (Fed. Cir. 1992).
Furthermore, as discussed below, I do not find the temporal relationship between Petitioner’s
PMBCL and the vaccines she received to be medically appropriate.
In his expert report, Dr. Gordon also discussed the lack of an alternative cause. Gordon
Rep. at 6-7. He maintained that “[n]o other plausible etiology has been identified in the provided
medical records.” Id. at 7. At the end of her post-hearing brief, Petitioner argued that Respondent
failed to provide “a cogent argument for alternative cause.”28 Pet. Post-Hearing Brief at 12.
In this case, Dr. Gordon claimed there was no alternative cause for petitioner’s PMBCL
but offers no evidence to support that assertion. Gordon Rep. at 7. In contrast, Dr. McClain
asserted PMBCL has a genetic etiology. Tr. at 225. In his expert report, Dr. McClain stated that
28
To support causation, a petitioner may introduce evidence of the lack of an alternative cause. Walther,
485 F.3d at 1149-50. Respondent is not required to provide preponderant evidence of a viable alternative
cause until Petitioner has established her prima facie case. Walther, 485 F.3d at 1150; see § 13(a)(1).
27
“[t]he cause of PMBCL is rooted in characteristic DNA mutations and rearrangements.” First
McClain Rep. at 7; accord. Third McClain Rep. at 3. Petitioner’s other expert, Dr. Shoenfeld,
does not dispute this fact but rather asserts that Dr. McClain failed to recognize that multiple
etiologies could be involved. Second Shoenfeld Rep. at 6. During his testimony, Dr. Gordon
expressed a level of agreement asked when about the scientific community’s view that PMBCL
has a genetic basis. Tr. at 195. Even combined with Petitioner’s assertions regarding appropriate
timing, this assertion of the lack of an alternative cause is not sufficient to satisfy Althen prong
two, especially when considered in the context of her medical records and the lack of treater
support for vaccine causation.
Petitioner has not provided preponderant evidence of a logical sequence of cause and effect
between the vaccines she received and the PMBCL she developed. She has therefore failed to
sustain her burden under the second prong of Althen.
3. Althen Prong Three
The third Althen prong requires establishing a “proximate temporal relationship” between
the vaccination and the injury alleged. Althen, 418 F.3d at 1281. That term has been equated to
the phrase “medically-acceptable temporal relationship.” Id. The timing prong contains two parts.
First, a petitioner must establish the “timeframe for which it is medically acceptable to infer
causation” and second, she must demonstrate that the onset of the disease occurred in this period.
Shapiro v. Secʼy of Health & Hum. Servs., 101 Fed. Cl. 532, 542-43 (2011), recons. denied after
remand on other grounds, 105 Fed. Cl. 353 (2012), aff’d without op., 503 F. App’x 952 (Fed. Cir.
2013). The explanation for what is a medically acceptable timeframe must also coincide with the
theory of how the relevant vaccine can cause an injury (Althen prong one’s requirement). Shapiro,
101 Fed. Cl. at 542; Koehn v. Sec’y of Health & Hum. Servs., No. 11-355V, 2013 WL 3214877(Fed. Cl. Spec. Mstr. May 30, 2013), mot. for review den’d (Fed. Cl. Dec. 3, 2013), aff’d, 773 F.3d
1239 (Fed. Cir. 2014).
a. The Timeframe for which it is Medically Appropriate to Infer Causation
Petitioner and her experts posited that a 30-day time frame between vaccination and
Petitioner’s first symptoms constituted a medically appropriate temporal relationship under the
theories they advanced. Pet. Pre-Hearing Rep. at 12; Tr. at 97, 189. They did not, however,
provide a persuasive explanation regarding why this is the case or what supported this temporal
window. In fact, the experts all acknowledged that the doubling rate for a PMBCL tumor is
unknown. See e.g., Tr. at 100, 200, 254, 283. Given this point, it is difficult to understand how
Petitioner’s experts could opine that preponderant evidence establishes the development and
growth of Petitioner’s tumor in this case is medically appropriate.
b. The Onset of Petitioner’s Disease
Focusing on the facial swelling and dizziness that Petitioner reported on August 3, 2011,
Petitioner’s experts maintained that the onset of Petitioner’s symptoms was consistent with that
30-day time frame. Pet. Pre-Hearing Brief at 1; Tr. at 101-02; see Ex. 2 at 34 (report from August
3, 2011 visit). However, they ignore the lower back and shoulder pain Petitioner reported
28
experiencing throughout July. See Ex. 2 at 34. Moreover, in her affidavit, Petitioner indicated
that her dizziness occurred, along with headaches and back and neck pain earlier, in July 2011.
Petitioner stated, “Around July 10, I started getting frequent headaches. As the month progressed,
I also started having neck and back pains, and I felt dizzy a lot.” Ex. 9 at 9.
Dr. McClain stated that in July 2011, Petitioner “noted back, neck, and shoulder pain which
I believe may have been secondary to the mediastinal mass”. First McClain Rep. at 6. He also
testified that “the tumor could have been there for quite a long time before it actually caused any
pain symptoms.” Tr. at 255. In her affidavit, Petitioner indicated the dizziness she reported on
August 3, 2011 began in July 2011, prior to the facial swelling she had experienced for a few
days. Ex. 9 at ¶ 9.
Dr. Gordon does not address these earlier occurring symptoms, but Dr. Shoenfeld appears
to consider they could be connected to Petitioner’s PMBCL. In his testimony, he stated these
earlier symptoms “would have to draw the attention of the physician, the treating physician, that
something unusual is going [on] there.” Tr. at 98-99. Additionally, Petitioner included the
symptoms of back and chest pain which occurred in July 2011, as symptoms of PMBCL in her
post-hearing brief. Post-Hearing Brief at 9-11. However, when doing so, she shortened the
medically appropriate time frame previously supplied, stating “within 30-days after exposure is
within the timeframe the medical community would expect from an aggressive tumor like
PMBCL.” Id. at 10 (emphasis added); see Pet. Pre-Hearing Brief at 12 (describing “the
development of symptoms a little over 30-days after exposure” as appropriate for comparison
(emphasis added)).
Petitioner offers little support for the 30-day time frame she initially proposed. And the
evidence she did supply is less potent when applied to the shorter window, less than 30 days.
Despite being asked to “set[] Petitioner’s clinical course aside” and provide a timeline for tumor
formation under the theories he advanced, Dr. Shoenfeld referenced the facts in Petitioner’s case
to opine that a one-month time frame was appropriate. Tr. at 97. Dr. Gordon offered at least some
additional basis for his opinion when he described PMBCL as an aggressive cancer, and Petitioner
echoed this argument in her briefs. Gordon Rep. at 6; Tr. at 189; Pet. Pre-Hearing Brief at 12; Pet.
Post-Hearing Brief at 10-11. Dr. Gordon theorized that Petitioner’s tumor could have grown to
the size observed in a CT, performed on August 11, 2011, even if it originated after vaccination in
late June 2011. Tr. at 204-06.
Respondent’s expert, Dr. McClain agreed that a fast-growing tumor, such as a Burkitt
tumor, could grow to the size observed on August 11, 2011 even if formed six weeks earlier. Tr.
at 255-57. However, he also testified that labeling a cancer as aggressive did not mean it was fast
growing. Id. at 256.
However, there is evidence in the medical records showing Petitioner’s tumor was not fast-
growing. A CT performed on August 11 showed the tumor measured 13 x 6 x 10.4 centimeters at
that time. Ex. 5 at 421. While a second CT scan performed on August 22 was only two
dimensional, the report indicated the “anterior mediastinal mass [wa]s overall not significantly
29
changed in size.” Ex. 10 at 533. Dr. McClain surmised from these CT scans that Petitioner’s
tumor had a “very slow” growth rate.29 Tr. at 259-60.
Ultimately, there is persuasive evidence that Petitioner’s first symptoms of PMBCL
occurred, at latest two weeks after vaccination, and there is some evidence that Petitioner’s tumor
formed prior to vaccination. Ultimately, it is unnecessary for me to determine the precise onset of
Petitioner’s disease because she has failed to establish that a time frame of 30 days or less between
vaccination and the first symptoms of PMBCL is medically appropriate to infer vaccine causation.
Accordingly, Petitioner has failed to provide the preponderant evidence needed to satisfy the third
prong of Althen.
C. Significant Aggravation
In her petition, Ms. Nifakos advanced claims of both causation-in-fact and significant
aggravation. Petition at 1. However, other than that one mention, she provided no further
discussion of or evidence for a claim of significant aggravation.
Petitioner’s expert Dr. Shoenfeld briefly mentioned that Petitioner’s mass may have been
present prior to vaccination. First Shoenfeld Rep. at 32. However, he then hypothesized that the
mass was benign until “bombarded” by the four vaccines Petitioner received. Id. Thus, his
discussion was still focused on a causation-in-fact claim.30
If Petitioner had pursued a significant aggravation claim further, it would be appropriate to
discuss the legal standards for such a claim as articulated in Loving ex rel. Loving v. Sec'y of Health
& Hum. Servs., 86 Fed. Cl. 135, 144 (2009). Because Petitioner effectively abandoned this
argument by not discussing significant aggravation in her briefs, no further discussion is required.31
VI. Conclusion
Upon careful evaluation of all the evidence submitted in this matter, including the medical
records, the testimony, as well as the experts’ opinions and medical literature, I conclude that
Petitioner has not shown by preponderant evidence that she is entitled to compensation under the
29
Although Dr. Gordon’s disagreed with this position because three-dimensional imaging had not been
performed on August 22, I find that argument unpersuasive. Tr. at 281-82. Dr. McClain effectively testified
that when a tumor changes in one dimension, it generally changes in the other dimensions as well. Tr. at
262. Conversely, when one dimension of a tumor “doesn’t change, you have to assume that it’s not
changing in other dimensions, also.” Id.30
Even assuming that Petitioner had advanced a significant aggravation theory, I find that theory would
have been unpersuasive for the reasons articulated earlier in this decision. Namely, any significant
aggravation theory would have necessarily relied on the same unpersuasive causal mechanism articulated
in Petitioner’s causation-in-fact claim.
31
In fact, in her brief, Petitioner stated “There is absolutely no evidence that petitioner had large B cell
lymphoma prior to the development of facial swelling, back, and chest pain within 30-days of
administration of 4 biologic products.” Pet. Post-Hearing Brief at 9.
30
Vaccine Act. The petition is therefore DISMISSED. The clerk shall enter judgment
accordingly.32
IT IS SO ORDERED.
s/ Katherine E. Oler
Katherine E. Oler
Special Master
32
Pursuant to Vaccine Rule 11(a), the parties may expedite entry of judgment by each filing (either jointly
or separately) a notice renouncing their right to seek review.
31