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

作者：Locke F; Agarwal R; Kunnavakkam R; van Besien K; Larson R A; Odenike O; Godley L A; Liu H; Le Beau M M; Gurbuxani S; Thirman M J; Sipkins D; White C; Artz A; Stock W^*

来源：Bone Marrow Transplantation, 2013, 48(11): 1437-1443.

DOI：10.1038/bmt.2013.79

• allo-SCT
• relapsed leukemia
• AML
• bridge therapy
• myelodysplastic syndrome

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. x 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 %26lt;20% and blasts %26lt;10%). Marrow cellularity (P%26lt;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.

• 出版日期2013-11