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Background Allogeneic hematopoietic cell transplantation (HCT) from human leukocyte antigen (HLA) matched related donors (RD) and matched unrelated donors (URD) produce similar outcomes in patients with acute myelogenous leukemia, while donor source has been reported as a predictor of outcomes in myelodysplastic syndrome. Methods Post-HCT outcomes in 1458 ALL patients from 2000-2011 were analyzed, comparing RD versus URD transplants. Results Median age was 37 years (range, 18-69). In multivariate analysis, HLA 8/8 allele matched URD recipients had similar transplant-related mortality (TRM) and all-cause mortality (hazard ratio [HR] 1.16 [95% CI 0.91-1.48] and HR 1.01 [95% CI 0.85-1.19], respectively) compared to RD recipients; 7/8 URD had greater risk of TRM and all-cause mortality compared to RD (HR 1.92 [95% CI 1.47-2.52] and HR 1.29 [95% CI 1.05-1.58], respectively). Risk of TRM and all-cause mortality was also greater comparing 7/8 to 8/8 URD. Compared to RD, both 8/8 and 7/8 URD had lower risk of relapse (HR 0.77 [95% CI 0.62-0.97] and HR 0.75 [95% CI 0.56-1.00], respectively). Both 8/8 and 7/8 URD had greater risk of acute GVHD (HR 2.18 [95% CI 1.76-2.70] and HR 2.65 [95% CI 2.06-3.42], respectively) and chronic GVHD (HR 1.28 [95% CI 1.06-1.55] and HR 1.46 [95% CI 1.14-1.88], respectively) compared to RD. Conclusions In the absence of RD, 8/8 URD is a viable alternative with similar survival outcomes, while 7/8 URD transplantation is associated with poorer overall survival.

Allogeneic hematopoietic cell transplantation (HCT) is a potentially life-saving treatment for patients with acute lymphoblastic leukemia (ALL). About one-third of patients have a human leukocyte antigen (HLA) matched related donor (MRD), while the remaining two-thirds have either a fully HLA-matched (HLA-A, -B, -C, -DRB1 [8/8]) unrelated donor (MUD) or a MUD with a single HLA mismatch (7/8). Previous analyses by the CIBMTR have shown that MRD and MUD transplants produce similar survival outcomes for patients with acute myelogenous leukemia (AML) (Blood 2012; 119(17):3908-16), while donor source was an important predictor of outcomes in patients with myelodysplastic syndrome (MDS) (Blood 2013; 122(11):1974-82). Given that ALL represents the second most common indication for HCT, and recognizing the disease-specific nature of the impact of donor source on post-HCT outcomes previously described, we performed an analysis of outcomes after MRD versus MUD HCT in 1458 patients with ALL who underwent allogeneic HCT from 2000-2011 (MRD n=440, 8/8 MUD n=729, 7/8 MUD n=289). Median age was 37 years (18-69). Thirty-four percent were Philadelphia chromosome positive.Ten percent received reduced intensity conditioning (RIC). Twenty-three percent were transplanted in second complete remission (CR2).Seventy-four percent received peripheral blood stem cells. At 100 days post-HCT, the incidence of acute GVHD Grade B-D was significantly lower in MRD recipients than in 8/8 MUD or 7/8 MUD recipients (26%, 45%, 50%, respectively; p<0.001). In multivariate analysis, 8/8 MUD recipients had similar rates of transplant-related mortality (TRM) and overall survival (OS) (hazard ratio [HR] 1.16, p=0.225and HR 1.01, p=0.93, respectively) compared to MRD recipients; 7/8 MUD recipients had inferior TRM and OS when compared to both MRD recipients (HR 1.92, p<0.001 and HR 1.29, p=0.01, respectively) and 8/8 MUD recipients (HR 1.66, p<0.001 and HR 1.28, p=0.008, respectively).Recipients of peripheral blood transplants had inferior long-term survival (>24 months post-HCT) (HR=2.13, p=0.003) compared to bone marrow transplants. Compared to MRD, 8/8 MUD recipients had superior relapse rates (HR 0.77, p=0.02), while 7/8 MUD recipients had no difference (HR 0.75, p=0.05). There were no differences in leukemia-free survival (LFS) comparing 8/8 MUD recipients (HR 0.95, p=0.55) and 7/8 MUD recipients (HR 1.20, p=0.07) to MRD recipients (Table 2, Figure 1).Differences in survival were likely due to higher rates of acute GVHD and TRM in the 7/8 MUD group. We conclude that MRD and 8/8 MUD recipients have similar survival outcomes post-HCT, while 7/8 MUD recipients suffer inferior survival, demonstrating that donor source plays a large role in the quality of outcomes. While MRD remains the ideal donor source due to its lower incidence of acute GVHD,HCT from an 8/8 MUD is a good alternative to MRD transplant, given its comparable long-term survival outcomes. Figure 1. 100-day Cumulative Incidence of Acute GVHD; 5-year Cumulative Incidence of chronic GVHD, relapse, and TRM; 5-year Probabilities of LFS and OS in Adult ALL Patients Receiving MRD, 8/8 MUD, or 7/8 MUD HCT from 2000-2011 *Overall point-wise comparison † Point-wise pair-wise comparison Figure 1. 100-day Cumulative Incidence of Acute GVHD; 5-year Cumulative Incidence of chronic GVHD, relapse, and TRM; 5-year Probabilities of LFS and OS in Adult ALL Patients Receiving MRD, 8/8 MUD, or 7/8 MUD HCT from 2000-2011 *Overall point-wise comparison † Point-wise pair-wise comparison Figure 2. Multivariate Analysis for Relapse, TRM, Treatment Failure (Inverse of LFS), and All-Cause Mortality (Inverse of Overall Survival) in Adult ALL Patients Receiving MRD, 8/8 MUD, or 7/8 MUD HCT from 2000-2011. Figure 2. Multivariate Analysis for Relapse, TRM, Treatment Failure (Inverse of LFS), and All-Cause Mortality (Inverse of Overall Survival) in Adult ALL Patients Receiving MRD, 8/8 MUD, or 7/8 MUD HCT from 2000-2011. Figure 3. Adjusted Overall Survival Estimatesfor Adult ALL Patients Receiving MRD, 8/8 MUD, or 7/8 MUD HCT Figure 3. Adjusted Overall Survival Estimatesfor Adult ALL Patients Receiving MRD, 8/8 MUD, or 7/8 MUD HCT Disclosures Sandmaier: Gilliad: Honoraria; ArevaMed: Honoraria; Jazz Pharmaceutical: Honoraria; Seattle Genetics: Honoraria; Abmit: Research Funding; Bellicum: Research Funding.