Successful mobilization with plerixafor and autologous hematopoietic SCT in a patient with refractory Hodgkin's lymphoma and Gaucher disease.

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UNCORRECTED PROOF
infiltration by Gaucher cells, without any evidence of
involvement by HL. Therefore, the clinical stage was IIIB.
She was treated with six cycles of ABVD
and achieved a
PR, with residual disease at the cervical areas. Local
radiotherapy of 36cGy was then offered, and a CR was
attained. However, cervical lymphadenopathy reappeared
LETTER TO THE EDITOR
Successful mobilization with plerixafor and autologous hematopoietic SCT
in a patient with refractory Hodgkin’s lymphoma and Gaucher disease
Bone Marrow Transplantation (2010) 0, 000–000.
doi:10.1038/bmt.2010.263
Patients with Gaucher disease (GD) are prone to manifest
various lymphoproliferative disorders (LPDs), and parti-
cularlynon-Hodgkin’slymphoma,
(MM) and monoclonal gammopathy of undetermined
significance. The occurrence of Hodgkin’s lymphoma
(HL) is rare. Among 137 and 126 cases of various
malignancies identified in two large registries of 1525 and
2472 patients with GD, respectively, there were only two
cases of HL,1,2and additional five cases of coexistent GD
and HL have been previously described in the literature.3–6
Moreover, only two cases of high-dose therapy and auto-
SCT in patients with GD and MM or refractory/relapsed
non-Hodgkin’s lymphoma have been reported.7,8We
describe here the first case of successful mobilization with
the anti-CXCR4 chemokine plerixafor, after initial mobi-
lization failure, and the first reported case of successful
high-dose therapy and auto-SCT in a patient with multiply
relapsed HL and type-I GD.
The patient was a female, diagnosed with type-I GD at
the age of 15 years, during investigation for massive
splenomegaly. She exhibited the N370S/N370S genotype
and was homozygous for a deletional mutation of the
chitotriosidase gene. As a consequence, we used serum
levels of the chemokine CCL18/PARC, to evaluate the GD
burden. She was splenectomized 3 years later, and started
regular enzyme replacement therapy at the age of 28 years.
When she was 38 years old, she presented with painless,
hard, left cervical lymph node enlargement, fever and
sweats. An initial lymph node biopsy was interpreted as
reactive lymphadenopathy with many Gaucher cells.
Because of clinical deterioration and manifestation of
inguinal lymph nodes, a second biopsy confirmed the
diagnosis of nodular-sclerosing classical HL. During that
period, her median serum CCL18/PARC levels were
623ng/mL (normal range 10–72ng/mL), compared with a
baseline level of 1837ng/mL, estimated 8 years previously.
She was profoundly anemic (Hb 8.5gper100mL, serum
ferritin 623ng/mL, CRP 12.5gper100mL) with leukocy-
tosis (19.2?109cells per L, neutrophils 82%), but platelet
count was normal. The BM was normocellular, with 15%
multiple myeloma
Q1
18 months later. Treatment with four cycles of DHAP was
unsuccessful. At 7 months after her first relapse, she was
referred to our department for further evaluation and
treatment. She complained of fatigue and sweats and
exhibited moderate hepatomegaly, anemia, leukocytosis,
but no manifestation of bone or neurological involvement.
A new lymph node biopsy confirmed the presence of
refractory HL of stage IIIB, with an international prog-
nostic score of 2. Treatment with three cycles of DICE
(dexamethasone, ifosfamide, carboplatin, etoposide) re-
sulted in a second CR, with a negative positron emission
tomography scan. An effort to mobilize and collect
hematopoietic progenitor cells with the fourth cycle of
DICE yielded 0.5?106CD34þ cells per kg of body
weight. A second effort for mobilization 2 months later
with CY plus G-CSF was again unsuccessful. Meanwhile,
findings of a new relapse at the supraclavicular area
appeared. Chemotherapy with three cycles of GVD
(gemcitabine, vinorelbine and liposomal doxorubicin) was
given and a third CR was achieved. A third mobilization
course, this time by adding two s.c. doses of 240mg per kg
of body weight of the anti-CXCR4 chemokine, plerixafor
(Mozobil, Genzyme
), one administered soon after the last
G-CSF dose (10mg/kg ?5 days), that is, 14h before
collection and the second 2h before starting collection,
yielded a total of 3.61?106CD34þ cells per kg in 2
consecutive days. The patient was then administered high-
dose therapy with BEAM and was supported by her
autologous graft. The post transplant period was unevent-
ful. She engrafted well (day þ13 neutrophils 41?109cells
per L, day þ14 platelets 420?109cells per L). At 17
months after auto-SCT, she remains in CR with a negative
Positron emission tomography computed tomography and
continues enzyme replacement therapy. It is the first
described case of successful auto-SCT in a patient with
GD and multiply relapsed HL, as well as the first case of
successful mobilization and hematopoietic progenitor cell
collection using plerixafor in a patient with GD in whom
the standard process was unsuccessful, suggesting that
plerixafor may be effective in similar cases of patients
with GD.
The occurrence of HL in patients with GD is uncommon,
and to date, only six to seven cases have been reported. The
diagnosis of HL may be difficult or delayed in view of the
lymph node infiltration by GD macrophages, as was the
case in our patient. BM infiltration, splenomegaly and
chronic inflammation, which are typically present in
patients with GD, may adversely affect hematopoiesis,
leading to greater chemotherapy-induced myelosuppres-
sion, delays in chemotherapy administration and dose
Q2
Bone Marrow Transplantation (2010), 1–2
& 2010 Macmillan Publishers Limited All rights reserved 0268-3369/10
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UNCORRECTED PROOF
modifications,
treatment failure.
The application of high-dose therapy and auto-SCT
has been previously reported only in two patients with GD
and MM.7,8
Inone of
failure was observed.7Secondary allograft failure has
also been reported after allo-SCT in patients with GD.9
Finally, difficulties in obtaining sufficient PBSC number
has been reported in GD patients, accrued to gene
therapy protocols.10The great majority of GD patients,
who have developed a LPD, have been treated with
conventional chemotherapy. Our patient, although neither
elderly nor overtreated with chemotherapy and having
received only stem cell sparing regimens (six cycles of
ABVD, four cycles of DHAP and three cycles of DICE),
was unable to effectively mobilize CD34þ cells. The
possible contribution of GD per se in this inability,
inducing an inflammatory marrow microenvironment and
impairing the growing potential of multipotent stem cells
cannot be ruled out. Therefore, the insufficient stem
cell yield of our patient might at least in part be attributed
to GD.
The administrationof
plerixafor led to effective mobilization and collection of
sufficient number of PBSCs, more than seven times higher,
compared with the number of previous mobilization
products. Plerixafor is a stem-cell adherence inhibitor and
results in their easy detachment from the BM matrix. It has
been used in many cases in which standard mobilization
procedures are ineffective, particularly as a result of
chemotherapy overtreatment or previous exposure to
purine analogs. This is the first time that plerixafor was
used in a patient with GD. As LPDs, and particularly MM
and non-Hodgkin’s lymphoma, are commonly encountered
among patients with GD, and the optimal treatment
strategy has not been outlined, this drug may permit the
application of more effective strategies and particularly of
high-dose therapy and auto-SCT.
In conclusion, our case shows that auto-SCT can be
feasible in patients with GD who develop LPDs, and when
mobilization is ineffective, plerixafor may help to overcome
the problem, mobilizing sufficient number of PBSCs.
therebyincreasing thelikelihoodof
them, secondaryautograft
the mobilization enhancer
Conflict of interest
The authors declare no conflict of interest.
Acknowledgements
We would like to thank Dr Helen Michelakakis, head of the
laboratory of Metabolic Disorders, Institute of Child’s Health,
‘St Sophia’ Children’s Hospital of Athens, for her excellent
support in monitoring the Gaucher disease burden of the
patient. We also wish to thank Dr Panayiotis Tsaftaridis, Laikon
Hospital of Athens and Dr George Katrinakis, University
Hospital of Heraclion, Crete, for their contribution in the care of
our patient.
A Symeonidis, M Liga, E Triantafyllou, A Kouraklis,
M Tiniakou, M Karakantza, A Spyridonidis
and N Zoumbos
Hematology Division, Department of Internal Medicine,
University of Patras Medical School, Patras, Greece
E-mail: Argiris.Symeonidis@Yahoo.Gr
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NPG_BMT_BMT2010263
Letter to the Editor
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Bone Marrow Transplantation