A novel clofarabine bridge strategy facilitates allogeneic transplantation in patients with relapsed/refractory leukemia and high-risk myelodysplastic syndromes. | Aplastic Anemia & MDS International Foundation Return to top.

A novel clofarabine bridge strategy facilitates allogeneic transplantation in patients with relapsed/refractory leukemia and high-risk myelodysplastic syndromes.

Journal Title: 
Bone Marrow Transplant
Primary Author: 
Locke F
Author(s): 
Locke F, Agarwal R, Kunnavakkam R, van Besien K, Larson RA, Odenike O, Godley LA, Liu H, Le Beau MM, Gurbuxani S, Thirman MJ, Sipkins D, White C, Artz A, Stock W.
Original Publication Date: 
Monday, June 17, 2013

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/m2/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.Bone Marrow Transplantation advance online publication, 17 June 2013; doi:10.1038/bmt.2013.79.

Bone Marrow Disease(s): 
  • myelodysplastic syndromes (MDS)
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