doi: 10.18282/amor.v2.i3.

65

CASE REPORT

Hodgkin’s lymphoma associated with hemophagocytic lymphohistio-

cytosis: A challenging combination
Arif Alam1, Fatima AlKendi2, Jihad Kanbar1, Mohammad Jaloudi1*
1
Department of Hematology/Oncology, Tawam Hospital, Al-Ain, Abu Dhabi, United Arab Emirates
2
Department of Internal Medicine, Tawam Hospital, Al-Ain, Abu Dhabi, United Arab Emirates

Abstract: Hemophagocytic lymphohistiocytosis (HLH) is a hyper inflammatory disorder. In this case report, we de-
scribed our experience with an associated diagnosis of Hodgkin’s lymphoma (HL) and a therapeutic course using
“bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone” (BEACOPP) chem-
otherapy to treat both HLH and HL.
Keywords: hemophagocytic lymphohistiocytosis; Hodgkin’s lymphoma
Citation: Alam A, AlKendi F, Kanbar J, Jaloudi M. Hodgkin’s lymphoma associated with hemophagocytic lymphohis-
tiocytosis: A challenging combination. Adv Mod Oncol Res 2016; 2(3): xx–xx; http://dx.doi.org/10.18282/
amor.v2.i3.65.

*Correspondence to: Mohammad Jaloudi, Department of Hematology/Oncology, Tawam Hospital, Al-Ain, Abu Dhabi, United Arab
Emirates; mjaloudi@seha.ae

Received: 20th October 2015; Accepted: 03rd February 2016; Published Online: 11th May 2016

Introduction derlying malignancies[2]. The most common are the T-

Hemophagocytic lymphohistiocytosis (HLH) is a rare but
potentially life-threatening hyper inflammatory disorder.
It is characterized by the systemic activation of macro-
phages resulting in the phagocytosis of hematopoietic
cells. It was first described by pediatricians Scott and
Robb-Smith in 1939[1]. The syndrome is usually ob-
served in children (from birth till 18 months of age);
however, adult cases are being reported in greater fre-
quency.
HLH can be either primary (due to genetic defects in
the cytotoxic functions of T lymphocytes) or secondary
(due to malignancies, infections, and immune disorders).
Clinical manifestations include prolonged fever of un-
known origin and organomegaly, while laboratory evalu-
ations usually show cytopenia, altered liver function tests,
increased ferritin and triglycerides, low fibrinogen, as
well as low natural killer (NK) cell functions and CD25
levels in serum. Histologically, there is evidence of he-
mophagocytosis in the bone marrow, lymph node, or
spleen.
In adults, at least half of the cases are linked to un-
and B-cell lymphomas, followed by Hodgkin’s Lym-
phoma (HL). Although the link between HLH and HL is
uncommon, it has been especially described in the setting
of the Epstein-Barr virus (EBV) infection (94%)[3-8]. In
this case report, we described our experience with this rare
phenomenon and its management at Tawam Hospital.
Case report
Case 1: A 35-year-old male was admitted with lower
limb edema, hepato-splenomegaly, and inguinal lym-
phadenopathy. Laboratory evaluation showed pancyto-
penia, high ferritin, lactate dehydrogenase (LDH)
and bilirubin, on top of low fibrinogen level. Lymph
node biopsy showed classical HL. He also had classical
HL, along with hemophagocytosis in the bone marrow
(BM). EBV levels in the serum were not analyzed while
EBV-in situ hybridization (EBV-ISH) was negative in the
BM. He was diagnosed with classical Hodgkin’s Lym-
phoma (cHL) stage IV-B and was subsequently treated
with “bleomycin, etoposide, doxorubicin, cyclophos-
phamide, vincristine, procarbazine, and prednisone”

Copyright © 2016 Alam A, et al. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0
International License (http://creativecommons.org/licenses/by-nc/4.0/), permitting all non-commercial use, distribution, and reproduction in any me-
dium, provided the original work is properly cited.
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Hodgkin’s lymphoma associated with hemophagocytic lymphohistiocytosis: A challenging combination
(BEACOPP) chemotherapy. He achieved complete re-
mission after four cycles with the normalization of liver
function tests and normalization of blood counts. He
subsequently received another two cycles of BEACOPP
and remains in remission 19 months post-diagnosis.
Case 2: A 39-year-old male had fever, night sweats,
hepato-splenomegaly, as well as cervical and para-aortic
lymphadenopathy. Laboratory evaluation revealed ane-
mia, thrombocytopenia, elevated ferritin, elevated tri-
glyceride, and low fibrinogen levels. Tests also revealed
elevated liver functions. Lymph node (LN) and BM bi-
opsy showed cHL. Serum EBV levels were not analyzed
and EBV-ISH was positive in the LN biopsy. He was
diagnosed with stage IV-B cHL and HLH, and was sub-
sequently treated with BEACOPP chemotherapy. Hospi-
tal course was complicated by acute kidney injury due to
tumor lysis syndrome and septic shock, along with E.
coli bacteremia and seizures. Cerebrospinal fluid (CSF)
was clear. His condition dramatically improved with
modified BEACOPP chemotherapy. He also achieved
complete remission after six cycles of chemotherapy and
this was confirmed by positron emission tomography-
computed tomography (PET-CT). A repeat BM biopsy
was not performed. He was unfortunately diagnosed with
fever of unknown origin and experienced headaches
within four weeks upon completing the last cycle of
BEACOPP. Magnetic resonance imaging (MRI) did not
reveal any lesions, while lumbar puncture showed only
pleocytosis. Other than increased ferritin, there was no
other evidence of HLH. Patient’s condition rapidly dete-
riorated, developing seizures and cerebral edema, and the
patient finally deceased. The cause of death was sus-
pected to be HLH recurrence.
Discussion
Hodgkin’s lymphoma associated with HLH is rare but
has been linked to a high mortality rate (15%–60%).
Figure 2. BEACOPP regimen with 1500 mg/m2 etoposide and a cumulative dose of 900 mg/m2 over nine weeks
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HLH is typically treated with etoposide and dexametha-
sone based on the HLH-94 protocol. Although the diag-
nostic criteria for HLH include clinical, laboratory, and
histopathologic findings, the initiation of therapy re-
quires three of four clinical findings (fever, splenomegaly,
cytopenias, hepatitis) and one of four immune markers
(hemophagocytosis, increased ferritin, hypofibrino-
genemia, absence or decreased NK cell functions).
The standard therapy for cHL is a systemic chemo-
therapy with or without radiation, depending on the stage
and bulk of the disease. Based on institutional experience,
the “Adriamycin, Bleomycin, Vinblastine, and Dacarba-
zine” (ABVD), escalated BEACOPP, or Stanford V
regimens are typically used[9,10]. The exact management
of HLH in the case of lymphoma is not well-defined.
Some clinicians advocate the use of etoposide and dex-
amethasone to initially suppress the immune system
storm. This is followed by a definitive therapy of the
underlying disease. However, a recent paper by Schram
and Berliner suggested a therapy directed at the underly-
ing disease, with a regimen containing etoposide[11].
In our case, using BEACOPP chemotherapy to treat
advanced HL (stages III–IV) and HLH was based on the
rationale of using agents that are active in both cHL and
HLH (etoposide and steroids). Over a nine-week course
of HLH-94, the cumulative dose of etoposide was 1500
mg/m2 (Figure 1), while the dose of standard BEA-
COPP used was at 900 mg/m2 (Figure 2).
Figure 1. Management of hemophagocytic lymphohistiocyto-
sis (adapted from Jordan et al.[1])
doi: 10.18282/amor.v1.i3.65

Despite this difference, both patients responded rap-
idly to therapy. Using an escalated BEACOPP regimen
(three cycles), etoposide dosage would reach the
HLH-94 regimen (1800 mg/m2) over a nine-week course.
This may be the best option. However, it would require
close monitoring and precautionary administration of
filgrastim owing to toxicity. Another theoretical ad-
vantage of using BEACOPP in both patients was that the
regimen contained cyclophosphamide that did not re-
quire dose modification in the setting of hepatic insuffi-
ciency (present in both patients), and could target the
underlying cHL. High clinical suspicion and early diag-
nosis of HLH with underlying HL is of paramount im-
portance. Initiating BEACOPP (standard or escalated)
chemotherapy may improve the prognosis of
HL-associated HLH.
Conflict of interest
The authors declare no potential conflict of interest with
respect to the research, authorship, and/or publication of
this article.
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