Feasibility of clofarabine cytoreduction followed by haploidentical hematopoietic stem cell transplantation in patients with relapsed or refractory advanced acute leukemia.
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.
Department of Medicine III, Hematopoietic stem cell transplantation, Ludwig-Maximilians University of Munich, Campus Grosshadern, Munich, Germany.
Johanna
J
Tischer
Hans Joachim
HJ
Stemmler
Nicole
N
Engel
Max
M
Hubmann
Susanne
S
Fritsch
Dusan
D
Prevalsek
Christoph
C
Schulz
Anna K
AK
Zoellner
Veit
V
Bücklein
Wolfgang
W
Hill
Georg
G
Ledderose
Andreas
A
Hausmann
D000227:Adenine Nucleotides / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D001087:Arabinonucleosides / Q000627:therapeutic use*; D000077866:Clofarabine; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000628:therapy*; D012189:Retrospective Studies; D055815:Young Adult
D000227:Adenine Nucleotides; D001087:Arabinonucleosides; D007166:Immunosuppressive Agents; D000077866:Clofarabine