Outcome of unrelated bone marrow donor searches in 174 children resulting in 45 patients transplanted in the HLA-matched and -mismatched situation

Abstract

Summary:The aim of the study was to evaluate the outcome of unrelated bone marrow donor (UBMD) searches initiated for 174 children between 1986 and 1997. Seven patients were registered twice so that a total of 181 UBMD searches took place. At the time of registration, patients suffered from hematological malignancies (n = 121), non-malignant hemopathies (n = 26) and inborn errors (n = 34). Forty-five of the patients (26%) were given transplants from unrelated donors of whom 26 (58%) were HLA-mismatched transplants. Our strategy accepted HLA mismatches at the time of donor selection, using Thymoglobuline as part of the conditioning regimen. Of the 45 patients given unrelated donor transplants, overall survival was 60% at 3 years and concerned 27 patients of whom 14 were from HLAmismatched donors. Disease-free survival for hematological malignancies was 65% in HLA-matched transplants and 50% in HLA-mismatched transplants. For some patients (16%) urgency led us to use alternative options: non-identical related donor (n = 14), autograft (n = 10), related cord blood transplant (n = 4). For others, UBMD searches were stopped because of favorable evolution (n = 29), death (n = 24), disease progression (n = 22) or other reasons (n = 21). By the end of the follow-up period, 88 patients had died (50%), 75 (43%) are currently alive with or without being transplanted of whom eight are still having active searches and 11 are no longer contactable. In conclusion, in severe disease in children, an immediate transplant from a partially matched donor might be preferable to a prolonged search for a full match. Consequently, this strategy increases the number of patients for whom a suitable donor can be found. We have chosen this option in order not to delay BMT; in so doing we have obtained encouraging results which include high overall survival, low incidence of acute GVHD grade III-IV and low percentage of relapse even in mismatched pairs. Bone Marrow Transplantation (2000) 26, 31-43.

Impact of marrow unrelated donor search duration on outcome of children with acute lymphoblastic leukemia in second remission

“…26,27 This improvement is mainly due to refinements in HLA typing, GvHD prophylaxis, timing of SCT, and supportive care. It has recently been reported that matching HLA class I and class II alleles of the donor and recipient can significantly improve outcome after UD BMT, 28 but, in keeping with Souillet et al, 29 the aim of the search strategy should be to carry out a transplant within 3 months from search activation. In the absence of a fully compatible donor, a one-antigen mismatched unrelated volunteer donor can be considered.…”

“…In the absence of a fully compatible donor, a one-antigen mismatched unrelated volunteer donor can be considered. 29 In this study, the outcome of the cohort of patients undergoing other types of SCT should be considered with caution, due to the heterogeneity of transplants and to the small number of analyzed patients. About half of these alternative transplants were performed during a more advanced phase, at a median time of 10.6 months after search activation.…”

Common genomic HLA haplotypes contributing to successful donor search in unrelated hematopoietic transplantation

“…The disease-free survival rate appears similar in young patients for which HLA incompatibility is limited to one HLA class I locus. 32 Therefore, for pediatric patients with advanced disease, finding one HLA class I-mismatched donor within a short time would be preferable to searching for a perfectly matched donor for a longer time. In this regard, it seems appropriate to search in a donor pool with one HLA broad mismatch when analysis of patient HLA genotype reveals that matching at the genomic level will be unlikely.…”

Relationship between CsA trough blood concentration and severity of acute graft-versus-host disease after paediatric stem cell transplantation from matched-sibling or unrelated donors

“…The stem cell source was: unmanipulated bone marrow for related donor-SCT (n ¼ 39); peripheral blood stem cells (n ¼ 2), cord blood stem cells (n ¼ 2) and unmanipulated bone marrow (n ¼ 51) for unrelated donor-SCT. Methods of HLA typing for patients and donors are described in detail by Souillet et al 7 Patient and donor characteristics are described in Table 1.…”