Clofarabine Does Not Impact Negatively the Outcomes of Patients with Acute Myeloid Leukemia (AML) Undergoing Allogeneic Stem Cell Transplantation and Is Not Associated with Higher Liver Toxicity Rates Compared with Standard Chemotherapy

The purine nucleoside analog clofarabine is currently being actively investigated at the M.D. Anderson Cancer Center (MDACC) in combination with idarubicin and cytarabine (CIA) as frontline therapy for younger patients with newly diagnosed acute myeloid leukemia (AML). Hepatotoxicity (i.e. elevation of transaminases and/or bilirubin) is one of the primary adverse events associated with clofarabine and rare instances of severe hepatotoxicity as well as veno-occlusive disease (VOD) have been reported. Allogeneic stem cell transplant (allo-SCT) is indicated for younger AML patients with poor risk features (i.e. adverse cytogenetics, diploid karyotype with FLT3 mutations) in first complete remission (CR). Allo-SCT also places the patient at risk of liver toxicity and VOD. Therefore, we investigated whether pre-transplant clofarabine-containing chemotherapy regimens adversely impacted the outcomes of younger patients with AML compared with those of patients pre-treated with non-clofarabine containing chemotherapy.

We conducted a retrospective review comparing patients who underwent allo-SCT after receiving CIA (clofarabine 20 mg/m² IV daily for 5 days, idarubicin 10 mg/m² IV daily for 3 days, cytarabine 1,000 mg/m² IV daily for 5 days) versus a non-clofarabine containing chemotherapy regimen (IA, idarubicin 12 mg/m² IV daily for 3 days, cytarabine 1,500 mg/m² via IV continuous infusion over 24 hours daily for 4 days). Consolidation cycles contained the same agents given according to an attenuated schedule. Patients were all receiving CIA or IA as their frontline regimen for AML. Variables that were extracted from the medical record include age, number of cycles of chemotherapy, CR rate, allo-SCT in CR, stem cell source, conditioning regimen, engraftment day, incidence of VOD, incidence of acute hepatotoxicity post-transplant, incidence of graft versus host disease (GVHD), early death, and early relapse.

Overall, 42 younger patients with AML undergoing allo-SCT were identified (n = 20 CIA, n = 22 IA). Patient age in both groups was similar, and there were more females in the IA group. Other patient and transplant characteristics were comparable between cohorts. Most patients underwent a matched related donor or matched unrelated donor allo-SCT (CIA 80% versus IA 82%), and the majority received busulfan-fludarabine based conditioning (CIA 70% versus IA 82%). Two patients in each group received clofarabine as part of their conditioning program. In general, there was not any appreciable difference in acute post-transplant hepatotoxicity or in the incidence of VOD (table 1). Moreover, early mortality, early relapse, and the incidence of GVHD were not increased in the pretransplant clofarabine group compared to the IA group.

The use of clofarabine does not appear to impact negatively the outcome of younger patients with AML undergoing allo-SCT. There does not appear to be an increased risk of delayed engraftment, hepatotoxicity, VOD, GvHD, early relapse, or early mortality among patients with AML undergoing allo-SCT who receive pretransplant clofarabine.

No relevant conflicts of interest to declare.