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/m 2 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,o20% cellularity with o10% blasts) in 10 of 17 patients (59%). Ineffective cytoreduction correlated with lower PFS (3.8 vs 6.4 months; HR ¼ 2.7, 95% CI ¼ 1.10-14.29, P ¼ 0.035) and OS (5.1 vs 16.6 months; HR ¼ 2.5, 95% CI ¼ 0.98-12.17, P ¼ 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.

Low efficacy and high mortality associated with clofarabine treatment of relapsed/refractory acute myeloid leukemia and myelodysplastic syndromes

“…Additional studies have also supported use of clofarabine either for cytoreduction or conditioning purposes [23][24][25][26][27][28]. Concerns for increased post-transplant hepatotoxicity in clofarabine-treated patients, given the hepatotoxicity of the drug, have thus far not been substantiated [29].…”

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

“…Importantly, clofarabine extrame-dullary toxicities were non-overlapping with those of conditioning regimens and patients were able to proceed to transplant. 17 Based upon these observations we designed a prospective study of clofarabine induction followed by transplant conditioning for relapsed/refractory leukemia and MDS patients, to test the feasibility of proceeding to transplant and reducing disease burden.…”

Control of relapsed or refractory acute myeloid leukemia by clofarabine in preparation for allogeneic stem cell transplant

“…Moreover, clofarabine has been successfully tested as component of a preparative regimen prior to allo-SCT in patients with relapsed or refractory leukemia and high risk myelodysplastic syndromes [28,29].…”