Bone Marrow Transplantation
https://doi.org/10.1038/s41409-018-0297-z
FEATURE
Graft-versus-leukaemia effect post fludarabine, melphalan and
alemtuzumab reduced intensity allogeneic stem cell transplant
in HIV-infected patient with acute myeloid leukaemia
A. Kanellopoulos
1
●
M. Kaparou
1
●
E. Xenou
1
●
S. Paneesha
1
●
B. Kishore
1
●
R. Lovell
1
●
K. Holder
1
●
J. Suhr
1
●
L. Baker
1
●
L. Ryan
1
●
E. Nikolousis
1
Received: 24 September 2017 / Revised: 5 June 2018 / Accepted: 21 July 2018
© Springer Nature Limited 2018
Allogeneic stem cell transplantation (Allo-HSCT) is sine qua non to cure high-risk acute myeloid leukaemia (AML). In spite
the advent of highly active antiretroviral treatment, HIV-infected patients display a remarkable risk for haematological
neoplasms such as non-Hodgkin lymphomas, Hodgkin lymphoma and acute leukaemia. Several case series have confirmed
the efficacy of the autologous stem cell transplantation for the treatment of non-Hodgkin lymphomas in the HIV setting.
Nonetheless, there is a paucity of data for the role of the Allo-HSCT in HIV-infected individuals with haematological
malignancies. Herein, we presented the successful long-term outcome of a HIV-infected patient who received reduced
intensity conditioned, matched unrelated donor transplant with alemtuzumab as graft-versus-host disease prophylaxis for
therapy-related acute myeloid leukaemia. We propose that Allo-HSCT in HIV patients is safe and that alemtuzumab-based
conditioning could further work to eradicate HIV in those whose donor is not CCR5 homozygous.
A 29-year-old man was diagnosed in May 2003 with Ph
negative, normal karyotype B-cell acute lymphoblastic leu-
kemia (B-ALL) amid Mycobaterium avium intracellulare
septicaemia (Table 1). In tandem with ALL, HIV-C3
infection was identified. At the time, CD4+ T-lymphocyte
count was only 2 cells/mm
3
. Complete remission was
attained post induction and central nervous system intensi-
fication phases of the UKALL chemotherapy protocol.
Consolidative autologous stem cell transplantation (auto-
HSCT) conditioned with total body irradiation (TBI) ensued.
In parallel, HIV infection was successfully treated with
highly active antiretroviral treatment (HAART) (tenofovir,
lamivudine and efavirenz) [1–3]. Interestingly delayed CD4
+ T-cell reconstitution followed the first transplant as their
count surpassed 200 cells/mm
3
only in 2006. In 2013, pro-
gressive pancytopenia became evident: Hb 80 g/L white
blood cells 5.1 × 109/L, platelets 48 × 10
9
/L, neutrophils
1.35 × 10
9
/L, mean corpuscular volume 115 fL. Bone mar-
row biopsy exhibited dysplastic megakaryopoiesis and
erythropoiesis, atypical eosinophils, myeloid maturation
arrest, and significant excess of CD34+ blasts (~ 20% CD34
+ CD117+ CD33+ blast cells at immunophenotyping).
Karyotype analysis revealed complex abnormal karyotype
including monosomy 7 and abnormal 17p in line with
diagnosis of therapy-related acute myeloid leukaemia
(AML). Patient was administered FLAG × 2 cycles (fludar-
abine, high-dose cytarabine). Morphological remission was
attained albeit the aberrant cytogenetic clone was present at
the time of the human leukocyte antigen (10/10) matched
unrelated donor allogeneic stem cell transplantation (Allo-
HSCT) in February 2014. Transplant protocol consisted of
fludarabine (30 mg/m
2
for 5 days), melphalan (140 mg/m
2
—
single dose). Alemtuzumab (25 mg—2 doses on days -2
and -1) and Ciclosporin (day-1 until 2 months post trans-
plant) were used for graft-versus-host disease (GVHD)
prophylaxis. CD34+ stem cell dose was 6.03 × 10
6
/kg with
the patient engrafting neutrophils and platelets day +15 and
+13 respectively. Early post-transplant course was compli-
cated from Hickman-line associated thrombosis and pneu-
monia. Day +100 bone marrow demonstrated complete
morphological and cytogenetic remission. At the time,
whole blood and T-cell compartment showed chimerism
91% and 16% donor respectively, necessitating two donor
lymphocyte infusions with the CD3+ -cell dose reaching
5 × 10
6
/kg. Full donor chimerism was achieved as of
* E. Nikolousis
emelni@hotmail.com
1
Haematology and Stem Cell Transplantation Department Heart of
England NHS Trust, Birmingham, United Kingdom
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