HLA-Identical Sibling Compared With 8/8 Matched and Mismatched Unrelated Donor Bone Marrow Transplant for Chronic Phase Chronic Myeloid Leukemia

Abstract

A B S T R A C T PurposeTransplantation of hematopoietic stem cells from an unrelated donor (URD) is an option for many patients who do not have an HLA-identical sibling donor (MSD). Current criteria for the selection of URDs include consideration for HLA alleles determined by high resolution typing methods, with preference for allele-matched donors. However, the utility and outcome associated with transplants from URDs compared with those from MSDs remains undefined. Patients and MethodsWe examined clinical outcome after patients received bone marrow transplants (BMTs) from MSDs; HLA-A, -B, -C, and DRB1 allele-matched URDs (8/8); and HLA-mismatched URDs in a homogeneous population of patients with chronic myeloid leukemia (CML) in first chronic phase (CP1) where a strong allogeneic effect and hence a lower risk of relapse is anticipated. Transplantation outcomes were compared between 1,052 URD and 3,514 MSD BMT recipients with CML in CP1. ResultsFive-year overall survival and leukemia-free survival (LFS) after receipt of BMTs from 8/8 matched URDs were worse than those after receipt of BMTs from MSDs (5-year survival, 55% v 63%; RR, 1.35; 95% CI, 1.17 to 1.56; P Ͻ .001; LFS, 50% v 55%; RR, 1.21; 95% CI, 1.06 to 1.40; P ϭ .006). Survival was progressively worse with greater degrees of mismatch. Similar and low risk of relapse were observed after receipt of transplant from either MSD or URD. ConclusionIn this homogeneous cohort of good risk patients with CML in CP1, 5-year overall survival and LFS after receipt of transplant from 8/8 allele-matched donors were modestly though significantly worse than those after receipt of transplant from MSDs. Additive adverse effects of multilocus mismatching are not well tolerated and should be avoided if possible.

How to select the best available related or unrelated donor of hematopoietic stem cells?

“…21 In a large CIBMTR study on patients with chronic myeloid leukemia no significant difference in overall survival was noted between patients transplanted with HLA class I or class II mismatched grafts. 22 With regards to HLA class II disparities, several studies indicated that HLA-DQB1 disparities are not associated with mortality. 5,11,20 Because of the high priority given to HLA-DRB1 matching and the strong DRB1-DQB1 linkage disequilibrium, studies are often underpowered to reveal the clinical relevance of DQB1 disparities.…”

Unrelated cord blood transplantation in adults with myelodysplasia or secondary acute myeloblastic leukemia: a survey on behalf of Eurocord and CLWP of EBMT

“…In acute or chronic leukemia, transplantation from an HLA-matched or one HLA allelemismatched unrelated donor is associated with 5-10 and 10-15% lower survival rates, respectively, when compared with transplantation from an HLA-matched sibling donor, despite high resolution HLA typing. 39,40 With respect to the source of unrelated stem cells, HLA-mismatched bone marrow or cord blood transplants have been shown to give similar outcome in adults with acute leukemia. 2 Furthermore, outcomes with cord blood transplantation have been reported to be similar to that of HLA-matched bone marrow by Rocha et al 3 but this was not confirmed by Laughlin et al 2 In patients with MDS, DFS appears to be similar to that achieved using other unrelated hematopoietic stem cell sources, but comparative studies are required to better determine the role of UCBT for this group of patients.…”

The impact of HLA matching on long-term transplant outcome after allogeneic hematopoietic stem cell transplantation for CLL: a retrospective study from the EBMT registry

“…[7][8][9][10][11] Only 30% of patients in need of allo-HSCT will have a suitable human leukocyte antigen (HLA)-matched family member, and in the remainder an unrelated donor (UD) may be sought. 12 Although studies on large homogeneous samples in standard-risk hematopoietic malignancy (that is, chronic myeloid leukemia) suggest inferior results for UD compared with sibling transplants, 13,14 disadvantages of UD have not emerged in the trials on RIC allo-HSCT in CLL performed to date. 9,[15][16][17][18][19] However, analyses on donor effects in CLL have been hampered by small patient numbers, and generally disregarded the potentially important impact of HLA class-I allele and HLA C mismatch.…”