Clinical Outcome of Allogeneic SCT with a RIC Regimen in Young Adults with AML in CR1; Impact of Prior Consolidation Therapy

The role of reduced intensity conditioning regimen and impact of prior consolidation therapy with such regimens for young adults with AML in CR1 remains controversial. At our center from July 2005 to April 2012 we have done 52 allogeneic stem cell transplants for patients with acute myeloid leukemia in CR1 using a well reported RIC regimen consisting of Fludarabine and Melphalan. Majority of the donors (94.2%) were HLA identical related donors. All patients received a peripheral blood stem cell graft with a median CD34 cell dose of 11x10⁶/Kg. GVHD prophylaxis consisted of cyclosporine combined with short course methotrexate. The median age of the patients was 34 years (range: 11-63) and there were 34 (65%) males. Majority (73%) were intermediate risk patients. One patient died prior to engraftment while all other cases engrafted with a median time to ANC>500/mm³ of 14 days and platelet count>20,000/mm³ was 16 days. 19 (36%) received an allogeneic SCT without any consolidation therapy while the rest had consolidation therapy consisting of either high dose cytarabine or cytarabine with an anthracycline given for one, two or three cycles prior to transplant. Repeated cycles of consolidation chemotherapy were given in some cases mainly due to lack of a transplant slots in the program, with intention to buy time prior to the intended transplant. The treatment related mortality at 100 days was 3(5.7%) and at one year was 11(21%). Acute GVHD grade II-IV was seen in 20(38%) and was grade III-IV in 10(19%). Chronic GVHD was seen in 29(55%) which was extensive in 8(27%). Deaths attributable to GVHD (GVHD or infection resulting from treatment of GVHD) occurred in 11 (21%). The 3 year KM-estimate of OS and EFS was 66.4±7.4% and 61.9±7.5% respectively. Comparison of patients who did not receive any consolidation therapy prior to transplant (n=19) versus those that received one or more consolidation courses revealed that there was a significantly improved OS and a trend to improved EFS among those that received some consolidation therapy (46.3±12.7%  Vs.79.9±7.5% and 46.3±12.7% Vs.71.7±8.7%; P-value = 0.049 and 0.114 respectively). This data compared favorably with our historical controls that received a conventional myeloablative conditioning regimen (100 day and one year TRM = 16 % and 51% respectively). The OS and EFS was also significantly superior with the RIC conditioning regimen compared to our myeloablative historical controls.

In conclusion allogeneic SCT with RIC regimens for young adults with AML in CR1 results in clinical outcomes comparable with those achieved by myeloablative regimens. However, it would appear that some consolidation therapy prior to RIC SCT is likely to improve the clinical outcome. The optimal number and intensity of consolidation therapy needs to be evaluated further in larger and prospective clinical trials.