Abstract

It is unclear how related donor transplants in which the donor-recipient pair is mismatched in one locus (1AgMM) compare to transplants performed using a fully matched unrelated donor (MUD), matching at HLA-A, B, C, DRB1 and DQB1. Here, we performed such a comparison.

Methods: We studied 83 consecutive patients (pts) with acute leukemias and myeloproliferative/myelodysplasia syndromes receiving grafts considered to be “1-antigen mismatched related” (1AgMM) and compared their outcomes to that of 134 MUD HSCT performed from 1992 to 2006. Among 83 1AgMM transplants, 40 had prospectively or retrospectively performed high-resolution HLA typing (Hires), of which 6 pts were 8/10 matched, and 43 had only low resolution (Lowres) typing. 8/10 Hires pts were excluded from this analysis. All MUD donor-recipient pairs were typed by Hires. Median age, gender, cytogenetic risk, disease status at transplant and stem cell source were similar. Diagnosis were ALL in 5% of the Hires group, 28% of the Lowres and 0 in the MUD group; AML/MDS cases were 76%, 60% and 87%, respectively; and CML cases were 19%, 12% and 13%, respectively(p< 0.001). Preparative regimens were of reduced intensity for 22% of Hires, 21% of Lowres patients and 40% of MUD patients (p=0.02). High-resolution typing was performed for HLA-A, B, DRB1, DQB1 and DPB1, and SBT/SSOP for HLA-C. Cumulative incidence of NRM, acute and chronic GVHD was estimated accounting for death in the absence of event as a competing risk. The Cox’s proportional hazards model was used to compare outcomes beteween groups.

Results: With a median follow-up of 15 mo for MUD pts, 27 mo for Hires patients and 33 mo for Lowres pts, OS at 18 mo is 52%, 46% and 22% (p= 0.002 for the comparison of MUD vs Lowres; P=NS for the comparison of MUD vs Hires); NRM is 23%, 26% and 54%(p=0.001 for the comparison of MUD vs Lowres; P=NS for the comparison of MUD vs Hires). Primary graft failure occurred in 1% of MUD, 5% of MOL and 12% of SER (p=0.003). Cumulative incidence of grade II-IV aGVHD is 34% for MUD pts, 48% for Hires and 49% for Lowres(p= 0.07); cGVHD: 34%, 40% and 54%(p=0.01 for the comparison of MUD vs Lowres). We divided the Hires related group according to presence of Class I or Class II mismatches, and compared their outcomes to the MUD group (Table). 23 pts had Class I and 11 pts had Class II mismatches; median follow-up is 26 and 62 mo, respectively. Distribution of gender, diagnosis, cytogenetic risk, dis. status at transplant, ablative/RIC regimens and stem cell source was similar between the 2 groups. Pts with class I mismatches had the worse survival.

Conclusion: Cumulative incidence of grade II-IV aGVHD and cGVHD, non-relapse mortality and overall survival of 1AgMM (allele level typing) patients was similar to that observed in a cohort of recipients of molecularly matched, HLA 10/10 MUD transplants.

OS at 18 moHR (95%CI) PC. Incid. gd II-IV aGVHDHR (95% CI) PC. Incid. chronic GVHDHR (95% CI) P
C. Incid= cumulative incidence 
MUD n=134 52% Reference 34% Reference 34% Reference 
Class I n=23 34% 1.8 (1–3.1) P=0.05 40% 1.3 (0.6–2.9) P=0.4 35% 1.1 (0.5–2.5) P=0.7 
Class II n=11 73% 0.6 (0.2–1.9) P=0.4 64% 2.8 (1.3–6.3) P=0.01 48% 2.3 (0.9–5.7) P=0.08 
OS at 18 moHR (95%CI) PC. Incid. gd II-IV aGVHDHR (95% CI) PC. Incid. chronic GVHDHR (95% CI) P
C. Incid= cumulative incidence 
MUD n=134 52% Reference 34% Reference 34% Reference 
Class I n=23 34% 1.8 (1–3.1) P=0.05 40% 1.3 (0.6–2.9) P=0.4 35% 1.1 (0.5–2.5) P=0.7 
Class II n=11 73% 0.6 (0.2–1.9) P=0.4 64% 2.8 (1.3–6.3) P=0.01 48% 2.3 (0.9–5.7) P=0.08 

Author notes

Disclosure: No relevant conflicts of interest to declare.