Abstract

Strict HLA-match using high resolution typing for HLA-A,B,C,DRB1 improves unrelated volunteer donor (URD) hematopoietic stem cell (HSC) transplant outcome but limits the number of suitable donors. In contrast, CB transplantation (CBT) is associated with a greatly reduced HLA-match requirement which may extend the donor pool. Therefore, we prospectively evaluated donor availability in 309 patients [median age 46 (range 1–71 years)] with high-risk hematologic malignancies between 10/05–5/08 with the hypothesis that CB would extend transplant access. Adequate donor-recipient HLAmatch was ≥/10 HLA-A,B,C,DRB1,DQ alleles for a T cell depleted or ≥9/10 alleles for an unmodified URD graft. Adequate CB units were ≥4/6 HLA-A,B antigen, DRB1 allele matched and ≥1.5 × 107/nucleated cells/kg/unit and double unit grafts were used to augment engraftment. URDs had priority as HSC source; CB was chosen if no suitable URD was available in the required time period. While 28 patients with suitable URDs had no CB search, the results of the 281 patients with both URD and CB formal search/confirmatory typing are shown in Table 1. This combined search group had highly diverse ancestry with only 60 (21%) of northwestern (NW) European origin and 99 (35%) were non-European. 9–10/10 URDs were available for the majority of NW, Eastern and mixed Europeans but not for Southern or non-European patients. Notably, CB extended HSC availability to all and especially Southern European, Asian, African, and Hispanic patients with no Asian patient being without a CB graft.

Table 1: Comparison of Formal Search for Both URD and CB by Patient Ancestry

Best URD NW Europe (n=60) East Europe (n=40) South Europe (n=39) Mix: Europe (n=43) Asian (n=19) African (n=33) Hispanic (n=36) Middle East (n=6) Mix: Non-Europe (n=5) 
9–10/10 53 (88%) 33 (82%) 23 (59%) 31 (72%) 4 (21%) 14 (42%) 16 (44%) 5 (83%) 3 (60%) 
≤8/10 7 (12%) 7 (18%) 16 (41%) 12 (28%) 15 (79%) 19 (58%) 20 (56%) 1(17%) 2 (40%) 
Best CB          
5–6/6 48 (80%) 30 (75%) 20 (51%) 30 (70%) 14 (74%) 19 (58%) 22 (61%) 4 (67%) 4 (80%) 
4/6 11 (18%) 8 (20%) 13 (33%) 12 (28%) 5 (26%) 6 (18%) 10 (28%) 2 (33%) 0 (0%) 
No CB 1 (2%) 2 (5%) 6 (16%) 1 (2%) 0 (0%) 8 (24%) 4 (11%) 0 (0%) 1 (20%) 
Best URD NW Europe (n=60) East Europe (n=40) South Europe (n=39) Mix: Europe (n=43) Asian (n=19) African (n=33) Hispanic (n=36) Middle East (n=6) Mix: Non-Europe (n=5) 
9–10/10 53 (88%) 33 (82%) 23 (59%) 31 (72%) 4 (21%) 14 (42%) 16 (44%) 5 (83%) 3 (60%) 
≤8/10 7 (12%) 7 (18%) 16 (41%) 12 (28%) 15 (79%) 19 (58%) 20 (56%) 1(17%) 2 (40%) 
Best CB          
5–6/6 48 (80%) 30 (75%) 20 (51%) 30 (70%) 14 (74%) 19 (58%) 22 (61%) 4 (67%) 4 (80%) 
4/6 11 (18%) 8 (20%) 13 (33%) 12 (28%) 5 (26%) 6 (18%) 10 (28%) 2 (33%) 0 (0%) 
No CB 1 (2%) 2 (5%) 6 (16%) 1 (2%) 0 (0%) 8 (24%) 4 (11%) 0 (0%) 1 (20%) 

The ancestry of the 201 patients who were transplanted and the 15 not transplanted due to lack of suitable graft is shown in Table 2. The remaining 93 patients were not transplanted for other reasons.

Table 2: Patient Ancestry if Transplanted or No Graft

 8–10/10 URD (n=149) 4–6/6 CB (n=52) No graft (n=15) 
NW Europe 47 (32%) 4 (8%) 1 (7%) 
East Europe 27 (18%) 6 (12%) 0 (0%) 
South Europe 15 (10%) 8 (15%) 3 (20%) 
Mix:Europe 27 (18%) 8 (15%) 1 (7%) 
Asian 6 (4%) 7 (13%) 0 (0%) 
African 11 (7%) 10 (19%) 6 (40%) 
Hispanic 10 (7%) 8 (15%) 3 (20%) 
Middle East 5 (3%) 1 (2%) 0 (0%) 
Mix:Non-Europe 1 (1%) 0 (0%) 1 (7%) 
 8–10/10 URD (n=149) 4–6/6 CB (n=52) No graft (n=15) 
NW Europe 47 (32%) 4 (8%) 1 (7%) 
East Europe 27 (18%) 6 (12%) 0 (0%) 
South Europe 15 (10%) 8 (15%) 3 (20%) 
Mix:Europe 27 (18%) 8 (15%) 1 (7%) 
Asian 6 (4%) 7 (13%) 0 (0%) 
African 11 (7%) 10 (19%) 6 (40%) 
Hispanic 10 (7%) 8 (15%) 3 (20%) 
Middle East 5 (3%) 1 (2%) 0 (0%) 
Mix:Non-Europe 1 (1%) 0 (0%) 1 (7%) 

URD transplant recipients were predominantly (68%) NW, Eastern, or mixed European with Asian, African and Hispanic patients combined accounting for only 18%. In contrast, only 4 (8%) of CBT recipients were NW European. While these patients received CB due to urgency (n=1), patient preference (n=1), or MD preference over mismatched URD (n=2), the remaining 48 (92%) of CBT recipients including 15% Southern Europeans and 49% non-Europeans (13% Asian, 19% African, 15% Hispanic, 2% Middle Eastern) did not have other donor options. Of 15 patients (5% of the 309 total) not transplanted due to lack of any HSC source 10 were non-European including 6 of African ancestry. Notably, the median weight of this “no graft” group [87kg (range 66–151)] was significantly higher than CBT [70kg (range 13–109)] recipients (p<0.01) partially accounting for their lack of suitable CB grafts. In summary, URD transplantation predominantly serves patients of NW, Eastern and mixed European ancestry with many Southern and non-Europeans having no suitable URD. In contrast, CB significantly extends transplant access to all but especially to both Southern and non-Europeans. Patients of African ancestry are the most challenged to secure a suitable HSC source. This data is compelling support for increased funding of public CB banking and suggests that CB has the greatest potential to fulfill the promise of being able to offer allograft to all regardless of race.

Disclosures: No relevant conflicts of interest to declare.

Author notes

Corresponding author