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01.10.2013 | Original Article

Feasibility of clofarabine cytoreduction followed by haploidentical hematopoietic stem cell transplantation in patients with relapsed or refractory advanced acute leukemia

verfasst von: Johanna Tischer, Hans Joachim Stemmler, Nicole Engel, Max Hubmann, Susanne Fritsch, Dusan Prevalsek, Christoph Schulz, Anna K. Zoellner, Veit Bücklein, Wolfgang Hill, Georg Ledderose, Andreas Hausmann

Erschienen in: Annals of Hematology | Ausgabe 10/2013

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Abstract

Clofarabine is a novel purine nucleoside analogue with immunosuppressive and anti-leukemic activity in acute lymphoblastic and myeloid leukemia (AML, ALL). This retrospective study was performed to evaluate the feasibility and anti-leukemic activity of a sequential therapy using clofarabine for cytoreduction followed by conditioning for haploidentical hematopoietic stem cell transplantation (HSCT) in patients with non-remission acute leukemia. Patients received clofarabine (5 × 30 mg/m² IV) followed by a T cell replete haploidentical transplantation for AML (n = 15) or ALL (n = 3). Conditioning consisted of fludarabine, cyclophosphamide plus either melphalan, total body irradiation or treosulfan/etoposide. High-dose cyclophosphamide was administered for post-grafting immunosuppression. Neutrophil engraftment was achieved in 83 % and complete remission in 78 % at day +30. The rate of acute graft versus host disease (GvHD) grade II–IV was 22 %, while chronic GvHD occured in five patients (28 %). Non-relapse mortality (NRM) after 1 year was 23 %. At a median follow-up of 19 months, estimated overall survival and relapse-free survival at 1 year from haploidentical HSCT were 56 and 39 %, respectively. Non-hematological regimen-related grade III–IV toxicity was observed in ten patients (56 %) and included most commonly transient elevation of liver enzymes (44 %), mucositis (40 %), and skin reactions including hand-foot syndrome (17 %), creatinine elevation (17 %), and nausea/vomiting (17 %). The concept of a sequential therapy using clofarabine for cytoreduction followed by haploidentical HSCT proved to be feasible and allows successful engraftment, while providing an acceptable toxicity profile and anti-leukemic efficacy in patients with advanced acute leukemia. NRM and rate of GvHD were comparable to results after HSCT from HLA-matched donors.

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Titel: Feasibility of clofarabine cytoreduction followed by haploidentical hematopoietic stem cell transplantation in patients with relapsed or refractory advanced acute leukemia
verfasst von: Johanna Tischer
Hans Joachim Stemmler
Nicole Engel
Max Hubmann
Susanne Fritsch
Dusan Prevalsek
Christoph Schulz
Anna K. Zoellner
Veit Bücklein
Wolfgang Hill
Georg Ledderose
Andreas Hausmann
Publikationsdatum: 01.10.2013
Verlag: Springer Berlin Heidelberg
Erschienen in: Annals of Hematology / Ausgabe 10/2013
Print ISSN: 0939-5555
Elektronische ISSN: 1432-0584
DOI: https://doi.org/10.1007/s00277-013-1862-6

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