Impact of Donor Source and Match on Outcome of Allogeneic Hematopoietic Cell Transplantation with Reduced Intensity Conditioning
Authors: Federmann Birgit , Faul Christoph , Vogel Wichard , Kanz Lothar , Bethge Wolfgang A. 
Published: October 2019

Abstract
Abstract 3539
The introduction of reduced intensity conditioning (RIC) regimens in allogeneic hematopoietic cell transplantation (HCT) allows the use of this treatment option even in older, comorbid or heavily pretreated patients. The impact of donor source and match on outcome of HCT after RIC remains to be evaluated. We retrospectively analyzed 254 consecutive adult patients (f=104, m=150) who received allogeneic HCT using RIC treated at our institution between 2000–2010. Median age of patients was 58 years (range, 18–76). Diagnoses were acute leukemia (AML, n=127, ALL, n=9), Non-Hodgkin lymphoma (n=30), multiple myeloma (n=29), myelodysplastic syndrome (n=27), osteomyelofibrosis (n=19), chronic myeloid leukemia (n=5), chronic lymphatic leukemia (n=5) and Hodgkin lymphoma (n=3). 91 patients were transplanted in complete remission (CR), 163 in partial remission (PR). 49 patients were transplanted from a matched related donor (MRD), 93 from a matched unrelated donor (MUD), 68 from a mismatched unrelated donor (MMUD, up to 2 allel/antigen mismatches), 3 from a mismatched related donor and 41 from a haploidentical donor (haplo). Remission status at time of HCT in patients transplanted from haplo donors (21 CR, 20 PR) was balanced, whereas patients transplanted from MRD (10 CR, 39 PR), MUD (36 CR, 57 PR) or MMUD (24 CR, 47 PR) were predominantly in PR. 82 of the patients were high-risk because of preceding autologous or allogeneic HCT (MRD=19, MUD=27, MMUD=11, haplo=25). Kaplan-Meier estimated 3-year overall survival (OS) for all patients was 45%, 47% with MRD, 46% with MUD, 53% with MMUD and 29% with haplo (p=0.07). Kaplan Meier estimated 3-year-OS and statistical analysis by univariate log-rank test in different subgroups are described in table 1.
Table 1 3-year OS (in %) MRD p MUD p MMUD p Haplo p Remission CR 39 49 62 29 0.30 PR 49 45 49 28 0.19 NRM 22 34 28 39 0.24 aGVHD 3II 100 0.49 13 0.001 53 0.91 25 0.91 no aGVHD 3II 40 51 50 23 cGVHD no 48 0.97 40 0.07 56 0.93 16 0.03 limited 75 39 50 50 extensive 35 66 57 53
Donor source and match had no significant impact on OS in the different subgroups. Non-relapse mortality was 31% without a difference between different donors. 3-year OS in the biggest diagnostic group AML was 47% with MUD, 51% with MMUD, 30% with MRD and 31% with haplo, respectively (p=0.38). Incidence of acute GVHD (aGVHD) ≥II was 14% (4% with MRD, 15% with MUD, 15% with MMUD and 17% with haplo) with a lower incidence of acute GVHD with MRD compared to haplo (p=0.02). Incidence of chronic GVHD (cGVHD) was 37% (33% with MRD, 45% with MUD, 33% with MMUD and 34% with haplo). Presence of aGVHD ≥II was associated with an inferior outcome (3-year OS 30 vs. 45%, p=0.02) while presence of limited or extensive cGVHD was associated with an improved OS (52% and 50% vs. 39% without cGVHD, p= 0.25). cGVHD had a positive impact on OS especially after HCT with MUD (p=0.07) or haplo (p=0.03) Thus, RIC for allogeneic HCT in elderly or heavily pretreated patients shows promising results irrespective of donor source. The lack of a MRD should not preclude MUD or MMUD allogeneic HCT using RIC in elderly patients.

Disclosures:
No relevant conflicts of interest to declare.