Open AccessA novel clofarabine bridge strategy facilitates allogeneic transplantation in patients with relapsed/refractory leukemia and high-risk myelodysplastic syndromes
Author(s) -
Frederick L. Locke,
Rajiv Agarwal,
Rangesh Kunnavakkam,
Koen van Besien,
Richard A. Larson,
Olatoyosi Odenike,
Lucy A. Godley,
H Liu,
Michelle M. Le Beau,
Sandeep Gurbuxani,
Michael J. Thirman,
Dorothy A. Sipkins,
Carol White,
Andrew S. Artz,
Wendy Stock
Publication year - 2013
Publication title -
bone marrow transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.609
H-Index - 127
eISSN - 1476-5365
pISSN - 0268-3369
DOI - 10.1038/bmt.2013.79
Subject(s) - medicine , clofarabine , myelodysplastic syndromes , refractory (planetary science) , transplantation , leukemia , oncology , bone marrow , cytarabine , physics , astrobiology
Patients with relapsed/refractory leukemias or advanced myelodysplastic syndrome (MDS) fare poorly following allogeneic hematopoietic cell transplant (HCT). We report prospective phase II study results of 29 patients given clofarabine 30 mg/m(2)/day i.v. × 5 days followed immediately by HCT conditioning while at the cytopenic nadir. A total of 15/29 patients (52%) were cytoreduced according to pre-defined criteria (cellularity <20% and blasts <10%). Marrow cellularity (P<0.0001) and blast% (P=0.03) were reduced. Toxicities were acceptable, with transient hyperbilirubinemia (48%) and gr3-4 infections (10%). In all, 28/29 proceeded to transplant; 27 received ATG or alemtuzumab. Post HCT, 180 day non-relapse mortality (NRM) was 7% (95% confidence interval (CI): 1-21), relapse was 29% (95% CI: 13-46) and OS was 71% (95% CI: 51-85), comparing favorably to published data for high-risk patients. Two-year graft vs host disease incidence was 40% (95% CI: 21-58) and 2 year OS was 31% (95% CI: 14-48). Disease at the nadir correlated with inferior OS after HCT (HR=1.22 for each 10% marrow blasts, 95% CI: 1.02-1.46). For AML/MDS patients, there was a suggestion that successful cytoreduction increased PFS (330 vs 171 days, P=0.3) and OS (375 vs 195 days, P=0.31). Clofarabine used as a bridge to HCT reduces disease burden, is well tolerated, and permits high-risk patients to undergo HCT with acceptable NRM. Late relapses are common; thus, additional strategies should be pursued. NCT-00724009.