Impact of Postremission Consolidation Chemotherapy On Outcome After Reduced-Intensity Conditioning (RIC) Allogeneic Stem Cell Transplantation (allo-SCT) for AML in First Complete Remission (CR1): A Report From the Acute Leukemia Working Party of EBMT.

Abstract 3098

The role of consolidation therapy after successful remission induction is well established in the treatment paradigm of patients with AML in the non-transplant setting. Most contemporary treatment protocols for young AML patients not transplanted in CR1 include repetitive cycles of high-dose cytarabine. However, in the standard myeloablative allo-SCT setting, consolidation therapy prior to transplant did not prove to have a beneficial impact on overall survival (OS), leukemia free survival (LFS) or relapse incidence (RI) as shown in 2 previous studies from the IBMTR and EBMT. In the context of RIC and non-myeloablative (NMA) allo-SCT, this picture might be different since one may speculate that consolidation therapy prior to transplantation may allow for reducing the incidence of relapse while waiting for the GVL effect. Nevertheless, the value of consolidation prior to RIC and NMA allo-SCT in AML in CR1 has not yet been explored.

Thus, this multicenter retrospective analysis aimed to assess the role of consolidation prior to RIC/NMA allo-SCT in a cohort of AML CR1 patients (n=789) who received HLA-identical (n=564) or MUD (n=225) peripheral blood stem cell grafts between 2000 and 2010 and who were reported to the EBMT registry. Patients who required more than 2 cycles of induction to achieve CR were excluded. In this cohort, 591 patients received at least one course of consolidation and 198 patients did not receive any consolidation before SCT. With a median follow-up of 40 months (range, 1–140), the Kaplan-Meier estimates of OS and LFS at 3 years were 55% (95%CI, 52–59%) and 52% (95%CI, 48–55%), respectively. The cumulative incidence of relapse was 33% (95%CI, 29–36%). The median time from CR to allo-SCT was longer among patients who received consolidation compared with patients who received no consolidation (4.7 vs. 2.2 months; p<0.001). Of note, patients who received consolidation and who were transplanted beyond the median time between CR and transplantation, had an improved 3-year LFS compared with patients who received consolidation and transplanted within the median time (58+/−2 vs. 47+/−3, p=0.002). This was due to a lower RI in the group of patients transplanted beyond the median time (28+/−2% vs. 38+/−3%, p=0.009), irrespective of the number of consolidations they received, suggesting a possible selection bias of patients surviving longer without relapse before allo-SCT.

With this background, we elected to focus on the group of 373 patients who were transplanted within the median time frame between CR achievement and allo-SCT (3 months for sibling donors and 4 months for MUDs). In this subgroup, 151 did not receive any consolidation and 222 received ≥1 consolidation (1 course, n=164, ≥ 2 courses, n=58).Patients who did not receive any consolidation were older (58 vs. 56 y, p=0.03), had a shorter time from CR to transplantation (56 vs. 71 days, p<0.001), needed more often 2 induction cycles to achieve CR (80% vs. 35%, p<0.001), and received more often TBI based conditioning (57% vs. 23%, p<0.001). Factors such as transplantation year, patient gender, cytogenetics risk group, donor type (MUD vs. sibling), and female donor to male recipient, were not significantly different between groups. With a median follow-up of 40 months (range, 1–140), the 3-year cumulative incidences of relapse were not significantly different between groups: 36±4% for patients with no consolidation and 38±3% for patients with consolidation (p=0.89). In addition, LFS was similar between groups, 45±4% and 47±3%, respectively (p=0.41). Doses of cytarabine given as consolidation had no influence on RI. By multivariate analysis adjusting for patient age, cytogenetics risk group, number of induction cycles, time from CR to transplantation, donor type, and conditioning regimen category, performing pre-transplant consolidation (0 vs. ≥1 cycle) had no significant impact on RI (HR=1.12, 95%CI, 0.74–1.70, p=0.58), or LFS (HR= 0.90; 95%CI, 0.64–1.27, p=0.90).

In all, this retrospective study did not find any impact of postremission consolidation on outcome of patients with AML in CR1 who underwent allo-SCT with reduced-intensity or NMA conditioning. However, further investigation of high-risk subpopulations and well designed prospective controlled studies are warranted.