Reduced Intensity Conditioning (RIC) Transplantation In Acute Leukemia: The Effect of Source of Unrelated Donor Stem Cells on Outcomes
Authors: Brunstein Claudio , Eapen Mary , Ahn Kwang w , Appelbaum Frederick R. , Ballen Karen K , Champlin Richard , Kan Fangyu , Laughlin Mary J. , Soiffer Robert J , Weisdorf Daniel J. , Woolfrey Ann , Horowitz Mary M. , Wagner John E. 
Published: October 2019

Abstract
Abstract 908
Peripheral blood progenitor cells (PBPC) are the preferred graft source for RIC transplantation. As in other settings, if a suitable unrelated adult donor is not available, primarily HLA mismatched unrelated cord blood (CB) is increasingly utilized, including the co-infusion of two CB units to overcome the cell dose limitation. We here report the relative efficacy of double CB (dCB, n=161) transplantation vs. PBPC whether from an 8/8 HLA matched (MUD, n=313) vs. 1 allele mismatched (MMUD, n=111) unrelated donor in patients with acute myeloid (AML, n=523) and lymphoblastic leukemia (ALL, n=62) transplanted between 2000 and 2009. Patients were aged 21 – 69 years. dCB recipients were more likely to be younger (median age: 54 vs. MUD 59 vs. MMUD 58 years, p<0.001), to have ALL (20% vs. MUD 6% vs. MMUD 10%, p<0.001) and to be in 1st or 2nd complete remission (83% vs. MUD 74% vs. MMUD 65%, p<0.001). Transplant conditioning regimens differed between dCB and PBPC transplants. Approximately 75% of dCB recipients received TBI 200 cGy + cyclophosphamide + fludarabine (TCF) ± ATG, 20% received melphalan or busulfan (Bu) or cyclophosphamide (Cy) + fludarabine ± ATG and the remaining 5%, TBI + fludarabine ± alkylating agent ± ATG. In contrast, approximately 75% of PBPC recipients received melphalan or Bu or Cy + fludarabine ± ATG. While there were no differences in overall survival by conditioning regimen in PBPC recipients, conditioning regimen influenced survival in recipients of dCB with the best survival in those treated with TCF. Therefore, 4 groups were created for multivariate analysis comparing transplant outcomes: dCB after TCF, dCB after other RIC regimens, MUD and MMUD; results are shown in the Table below. Compared to dCB after TCF, grade 2–4 but not grade 3–4 acute GVHD was lower in those with a MUD and chronic GVHD was higher in those with either a MUD or MMUD. Compared to dCB after other RIC regimens, transplant-related mortality (TRM) and overall mortality were lower after MUD and dCB after TCF transplants but similar to those after MMUD transplants. The 2-year probabilities of TRM in recipients of dCB after TCF, dCB after other RIC regimens, MUD and MMUD transplants are 19%, 52%, 21% and 28%, respectively. The corresponding probabilities for overall survival, adjusted for disease status and performance score were 38%, 19%, 44% and 37%. These data support dCB after TCF for adults with acute leukemia where a transplant is indicated but a suitably HLA matched unrelated adult donor is not available or when transplant is needed urgently. Although a center-effect could not be demonstrated statistically (p=0.2), a substantial proportion of dCB patients treated with TCF were done at a single center. Results of an ongoing multi-center phase II trial evaluating dCB after TCF will verify the reproducibility of these results.
Grade 2–4 Acute GVHD* Chronic GVHD* TRM Relapse† Treatment failureμ Overall mortalityμ MUD vs. dCB after TCF HR 0.52 p=0.0001 HR 2.33 p=0.0001 HR 1.09 p=0.72 HR 0.79 p=0.15 HR 0.89 p=0.37 HR 0.93 p=0.60 MMUD vs. dCB after TCF HR 0.70 p=0.06 HR 2.22 p=0.0002 HR 1.77 p=0.04 HR 0.87 p=0.49 HR 1.14 p=0.43 HR 1.15 p=0.41 dCB after TCF vs. dCB after other RIC HR 1.64 p=0.09 HR 0.61 p=0.11 HR 0.34 p<0.0001 HR 1.37 p=0.29 HR 0.77 p=0.22 HR 0.60 p=0.02 MUD vs. dCB after other RIC HR 0.87 p=0.62 HR 1.41 p=0.22 HR 0.37 p=0.0001 HR 1.09 p=0.76 HR 0.68 p=0.05 HR 0.56 p=0.004 MMUD vs. dCB after other RIC HR 1.15 p=0.65 HR 1.35 p=0.33 HR 0.59 p=0.07 HR 1.20 p=0.55 HR 0.88 p=0.52 HR 0.69 p=0.09 * adjusted for transplant period † adjusted for disease status μ adjusted for disease status and performance score

Disclosures:
No relevant conflicts of interest to declare.