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

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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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The authors declare no conflict of interest with regard to the data presented in this article.

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Authors and Affiliations

  1. Department of Medicine III, Hematopoietic stem cell transplantation, Ludwig-Maximilians University of Munich, Campus Grosshadern, Munich, Germany

    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

  2. Department of Medicine III (Hematology & Oncology), Ludwig-Maximilians University of Munich, Campus Grosshadern Marchioninistr. 15, 81377, Munich, Germany

    Hans Joachim Stemmler

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  1. Johanna Tischer
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Tischer, J., Stemmler, H.J., Engel, N. et al. Feasibility of clofarabine cytoreduction followed by haploidentical hematopoietic stem cell transplantation in patients with relapsed or refractory advanced acute leukemia. Ann Hematol 92, 1379–1388 (2013). https://doi.org/10.1007/s00277-013-1862-6

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