Further Evidence to Not Delay Transplant for Continued ARA-C Consolidation in Patients with Intermediate or High Risk AML

Background: Allogeneic stem cell transplant (alloSCT) is indicated for patients with acute myeloid leukemia (AML) with high-risk disease on presentation or in relapsed or refractory cases. Durable elimination of leukemic burden after achieving a complete remission (CR) is thought to be an important prerequisite for successful transplant. Typically, this is achieved with consolidation treatments with cytarabine (ARA-C) in repeated cycles in non-refractory cases. Previous reports have suggested there is no apparent advantage for post-remission consolidation chemotherapy before reduced intensity transplant, provided a donor is readily available.

Aim: To study the impact of the total cumulative dose of ARA-C in the pre-transplant setting before alloSCT either with reduced-intensity conditioning (RIC) or full myeloablative conditioning (MAC).

Methods: We conducted a retrospective chart review at the University of Oklahoma and affiliated hospitals in patients with AML in complete remission from October 2006 to December 2014. Appropriate IRB approval was obtained in accordance with Helsinki declaration. Simple descriptive statistics were created for all covariates [mean, SD for continuous covariates and n (%) for categorical variables]. A Cox proportional hazards model was used to assess the association of each covariate with overall survival.

Results: Sixty five patients were identified through our local leukemia registry with a mean age of 43, 57 (87.7%) were white, and 42 (64.6%) were male. Based on cytogenetics and molecular markers, 36 patients (55.3%) were intermediate risk and 20 patients (30.7%) were unfavorable risk status. For transplant preparative regimen, MAC was utilized in 50 cases (76.9%) and RIC was utilized in the other 15 (23.0%). Bone marrow stem cells were used in 28 cases (43.0%), peripheral blood cells were used in 26 cases (40.0%), and cord blood cells were used in the remaining 11 cases (16.9%). The mean dose of ARA-C given in consolidation was 43 g/m² with standard deviation 31.5 g/m². After adjusting for age and risk status, ARA-C consolidation was not associated with increased overall survival (OS) in the patients (p-value = 0.1776). When only considering those patients with myeloablative conditioning, ARA-C consolidation was still not associated with increased OS (p-value = 0.7533).

Conclusions: Prior published data indicates that further ARA-C therapy given during consolidation does not correlate with improved outcomes post-transplant in patients with AML who received a reduced intensity preparative regimen. However, we attempted to expand this data to include patients who received a full myeloablative preparative regimen. Our experience using our single institution retrospective data suggests further ARA-C therapy given in consolidation does not benefit patients who underwent either RIC or MAC in terms of post-transplant survival. This provides further evidence that there should be no delay in moving patients to transplant, provided a suitable donor is available.