Fludarabine and Melphalan Conditioning Regimen in Young Patients with Acute Myeloid Leukemia in CR1 Undergoing a Matched Related Allogeneic Stem Cell Transplant: A Single Center Experience.
Authors: Chandy Mammen , Mathews Vikram , Rajasekar T. , Lakshmi Kavitha M. , Viswabandya Auro , John Joseph M. , George Biju , Srivastava Alok 
Published: October 2019

Abstract
Allogeneic SCT remains the most effective anti-leukemic therapy. However, due to the associated TRM with conventional myeloablative regimens, this has often not translated to a significant improvement in EFS or OS. Since October 2005, at our center, we offered a RIC regimen consisting of fludarabine 30mg/m2 x 5days followed by one dose of melphalan 140mg/m2 for young adults with AML in CR1 after induction chemotherapy. GVHD prophylaxis consisted of cyclosporine with a low dose short course methotrexate. The graft source was a PBSC harvest. The clinical outcomes were compared with a historical control who received a conventional Bu/Cy regimen. Since October 1992, 55 of patients with AML in CR1 (constituted 47% of all AML transplants done at our center) underwent a matched related allogeneic SCT. Among these 11 received a Flu/Mel conditioning regimen while 41 received a conventional Bu/Cy conditioning regimen (3 patients excluded from analysis since they received other conditioning regimens), the clinical outcomes of these two groups were compared. All, except for one donor (one antigen mismatch) in the Bu/Cy group, were complete 6/6 HLA identical related donors. The age (mean±SD) of patients in the Flu/Mel and the Bu/Cy group was 39±14 and 27±11 respectively. The baseline characteristics of these two groups were comparable for sex, donor age, female to male transplants, AML subtypes and requirement of two course of chemotherapy to achieve CR1. Four (36.4%) of patients among the Flu/Mel group and 28 (68.3%) in the Bu/Cy group received one or two cycles of consolidation chemotherapy prior to SCT. All patients in the Flu/Mel group received a PBSC graft while only 26 (41%) among the Bu/Cy group received a PBSC graft (P=0.05). One patient in the Bu/Cy group failed to engraft. All other cases engrafted. All 11 (100%) cases in the Flu/Mel group had a complete donor chimerism documented on day 30. Prophylactic donor lymphocyte infusion was not administered for any patient. There were no treatment related deaths in the Flu/Mel group up to day 100. One patient died on day 299 following pulmonary GVHD and septicemia. In comparison, the day 100 TRM was 8 (19.5%), going up to a one year all cause mortality of 21 (51%) in the Bu/Cy group. Acute GVHD grade 2–4 occurred in 5 (45.5%) and in 14 (34.1%) among patients conditioned with Flu/Mel and Bu/Cy, respectively. Chronic GVHD occurred in 4 (36.4%) of patients conditioned with Flu/Mel and was similar to the incidence seen in the Bu/Cy group. During the period of follow up none of the patients in the Flu/Mel group have relapsed while 11 (26.8%) patients had relapsed in the Bu/Cy group. The 2 year Kaplan-Meier estimate of EFS and OS for the Flu/Mel and Bu/Cy group (mean follow up 19 and 71 months, respectively) was 85.71±13.23 vs. 43.19±7.82 (P=0.0176) and 85.71±13.23 vs. 45.59±7.86 (P=0.027) respectively. A conditioning regimen of fludarabine and melphalan in young adults with AML in CR1 is associated with a low TRM with a potential to translate into improved EFS and OS.
Figure 1: Kaplan-Meier estimate of Event Free Survival among patients who received Flu/Mel conditioning (n=11) versus those that received a Bu/Cy conditioning regimen (n=41) Figure 1:. Kaplan-Meier estimate of Event Free Survival among patients who received Flu/Mel conditioning (n=11) versus those that received a Bu/Cy conditioning regimen (n=41)