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Conditioning Regimens

Feasibility of clofarabine cytoreduction before allogeneic transplant conditioning for refractory AML

Abstract

To control disease before allogeneic hematopoietic cell transplantation (HCT) for relapsed/refractory AML, we used clofarabine cytoreduction. Seventeen patients received clofarabine 30–40 mg/m2 i.v. daily for 5 days with plans to initiate conditioning during the nadir, 14 days later. Bone marrow biopsy 12 days after clofarabine showed effective cytoreduction (that is,<20% cellularity with <10% blasts) in 10 of 17 patients (59%). Ineffective cytoreduction correlated with lower PFS (3.8 vs 6.4 months; HR=2.7, 95% CI=1.10–14.29, P=0.035) and OS (5.1 vs 16.6 months; HR=2.5, 95% CI=0.98–12.17, P=0.053). Significant toxicities before HCT, attributable to clofarabine, were grade 1–2 hyperbilirubinemia (18%); grade 1–2 (59%) or grade 3–4 (18%) transaminitis; and grade 1–2 (18%) creatinine elevation. Sixteen patients proceeded to HCT infusion 22 days (median) after initiation of clofarabine. Day 100 and 2-year transplant-related mortality were 6 and 36%. Nine patients relapsed. One year PFS and OS were 25 and 38%, respectively. Two patients are alive in remission at 18 and 52 months. Clofarabine cytoreduction followed by immediate HCT is feasible with acceptable toxicity and TRM. Outcomes for this cohort of patients with refractory AML remain poor and we are studying this approach in a prospective manner.

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Correspondence to F L Locke.

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Dr Stock, Dr van Beisien and Dr Rich receive financial research support from Genzyme. Dr Locke, Dr Artz and Dr Zhang report no conflict of interest.

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Locke, F., Artz, A., Rich, E. et al. Feasibility of clofarabine cytoreduction before allogeneic transplant conditioning for refractory AML. Bone Marrow Transplant 45, 1692–1698 (2010). https://doi.org/10.1038/bmt.2010.32

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