A Prospective Study of Allogeneic Transplant for Older Patients with Acute Myelogenous Leukemia (AML) Indicates That Unrelated Donor Transplants Are As Efficacious As Related Donor, with Favorable Outcomes for Intermediate Risk Disease

Hematopoietic stem cell transplants (HCT) for older patients with AML have increased significantly over the past decade, associated with the use of reduced intensity conditioning (RIC) regimen.  Transplant outcome based upon disease status (high vs intermediate risk) and donor source (related vs unrelated) is now examined. METHODS: Between 2007-2012, 50 patients (55-70 years, median 61) with AML in CR1 (n=41) or >CR1 (n=9) were prospectively enrolled on an IRB-approved clinical trial using a RIC regimen.  Donor sources included either a related (RD) (n=23) or unrelated donor (UD)(n=27), if a suitable RD was not available. All patients were conditioned with fludarabine (160 mg/m²) + busulfan (6.4 mg/m²) [FluBu2]; UD recipients additionally received 200cGy TBI on day -1 pre-transplant. GVHD prophylaxis was tacrolimus and mycophenolate.  No anti-thymocyte globulin (ATG) was administered pre-HCT. Patients exhibited high risk (n=21) or intermediate risk (n=29) disease at initial diagnosis, as defined by cytogenetic and molecular criteria.  Patients with good risk disease were excluded from analysis.  RESULTS: For the entire cohort, the 1y and 3y relapse free survival (RFS) was 56% (95% CI: 43-69) and 43% (95% CI: 28-58) respectively, with 1y and 3y overall survival (OS) rates 58% (95% CI:46-74) and 44% (95% CI: 27-62%).  Patients with intermediate risk disease experienced 1y and 3y RFS of 74±8.5% and 3y RFS 62±10.5%.  By comparison, transplant outcomes were poor for patients with high risk disease, with 1y and 3y RFS only 31±10% and 13±10% (Figure). There was no significant difference in 1y RFS between UD and RD recipients [62±9.5% vs 48±11%] or 3y RFS [44±11% vs 40±12%], p = 0.42 (Figure). There was no difference in outcome by age, with 3y RFS 42.5±11% for patients 55-59 yrs (n=20) and 40±12% for patients 60-70 yrs (n=30), p =0.54. The median donor age was 37 yrs (range 19-50) for UD and 58 yrs (range 42-70) for RD recipients.  The median CD34 cell dose infused was 5.0 x 10(6)/kg in both cohorts [range UD: 1.2 -8.3 x 10(6), RD: 1.9 -9.8 x 10(6)].  There was no difference in time to neutrophil engraftment, with both cohorts engrafting a median 12 days post-transplant.  Primary graft failure occurred in 1 (3.4%) UD recipient, who received an HLA mismatched graft.  No secondary graft failure occurred in either cohort.  Day 100 CD33 chimerism was all donor in all UD cases, and in 75% of RD recipients. Grade 2-4 acute GVHD developed in 44% URD and 30% RD respectively, with grade 3-4 acute GVHD in 7% UD and 10% RD.  CONCLUSION: Reduced intensity transplants for older patients with intermediate risk AML are associated with high RFS rates. In contrast, transplant outcomes for older patients presenting with high risk disease are poor using a reduced intensity regimen. No survival advantage is noted by donor source (RD or UD).   Donor stem cell yield and hematologic recovery were equivalent in RD and UD transplants for older AML patients.