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Purpose: To investigate the influence of donor type (human leukocyte antigen [HLA] -identical sibling donor versus HLA-A-, HLA-B-, HLA-Cw-, HLA-DRB1-, and HLA-DQB1-identical unrelated donors, or so-called 10/10) on the outcome of patients who underwent allogeneic stem-cell transplantation (alloSCT), adjusting for other prognostic factors, in patients with standard-risk hematologic malignancy., Patients and Methods: Between March 2000 and January 2003, we prospectively investigated the outcome of 236 consecutive patients with standard-risk malignancy from 12 French centers. Fifty-five patients underwent alloSCT from an unrelated HLA-identical donor at the allelic level, whereas 181 patients received an alloSCT from an HLA-identical sibling. Diagnoses included acute leukemia (n = 175), chronic myeloid leukemia (n = 43), and myelodysplastic syndrome (MDS; n = 18). All patients received unmodified marrow graft following myeloablative conditioning with cyclophosphamide and total-body irradiation. Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine and short-course methotrexate in all patients., Results: In multivariable analysis, overall survival and transplantation-related mortality were adversely influenced by recipient cytomegalovirus (CMV) -positive serology, age of donor older than 37 years, and the occurrence of acute grade > or = II GVHD. Event-free survival rates were lower for patients with recipient CMV-positive serology. Acute grades II to IV GVHD rates were higher for patients with chronic myeloid leukemia (CML). No factor was found to influence either relapse or acute grades III to IV GVHD. The effect of donor type was nonsignificant for all criteria., Conclusion: In patients with standard-risk malignancy, transplantation from unrelated HLA-allellically matched donors led to outcomes similar to those from HLA-identical sibling donors.

An introduction is presented in which the editors discuss various topics within the issue including genetic and non-genetic factors which affect the outcome of the hematopoietic stem cell transplantation (HSCT).

Given their antileukemic activity, natural killer (NK) cells can alter the outcome of hematopoietic stem cell transplantation (HSCT). The physiologic functions of NK cells are regulated by the interaction of killer immunoglobulin-like receptors (KIR) with specific HLA class I ligands. In the literature, different models based on HLA class I and/or KIR donor (D)/recipient (R) gene disparities are considered as predictors of NK cell alloreactivity. In this retrospective and multicentric French study, we analyzed the clinical impact of the different NK-alloreactivity models in 264 patients who underwent T repleted unrelated HSCT. First, we did not observe that the “KIR ligand-ligand” model had a significant clinical impact on unrelated HSCT outcome, whereas the “missing KIR ligand” model had a significant but limited effect on unrelated HSCT, because only the absence of C1 ligand in patients with myelogenous diseases was associated with a decreased overall survival (OS) (hazard ratio=2.17, P =.005). The “KIR receptor-receptor” and the “KIR receptor-ligand” models seemed the most capable of predicting NK alloreactivity because they had a significant impact on acute graft-versus-host disease (aGVHD) occurrence, OS, and relapse incidence in D/R unrelated pairs. In particular, KIR3DL1 gene mismatches in the GVH direction (D+R−) and the D KIR3DL1+/3DS1+ and R Bw4− combination were respectively correlated with the lowest OS in HLA identical pairs (HR=1.99, P =.02) and the highest incidence of relapse in HLA nonidentical D/R unrelated pairs (HR=4.72, P =.03). Overall, our results suggest a detrimental effect of KIR3DL1+/3DS1+ donor NK cells transplanted into HLA-Bw4− patients in the absence of an educational process via KIR3DL1/HLA-Bw4 interactions. [Copyright &y& Elsevier]

Abstract: Human leukocyte antigen (HLA) matching remains a key issue in the outcome of transplantation. In hematopoietic stem cell transplantation with unrelated donors, the matching for compatible donors is based on the HLA phenotype information. In familial transplantation, the matching is achieved at the haplotype level because donor and recipient share the block-transmitted major histocompatibility complex region. We present a statistical method based on the HLA haplotype inference to refine the HLA information available in an unrelated situation. We implement a systematic statistical inference of the haplotype combinations at the individual level. It computes the most likely haplotype pair given the phenotype and its probability. The method is validated on 301 phase-known phenotypes from CEPH families (Centre d’Etude du Polymorphisme Humain). The method is further applied to 85,933 HLA-A B DR typed unrelated donors from the French Registry of hematopoietic stem cells donors (France Greffe de Moëlle). The average value of prediction probability is 0.761 (SD 0.199) ranging from 0.26 to 1. Correlations between phenotype characteristics and predictions are also given. Homozygosity (OR = 2.08; [2.02–2.14] p <10−3) and linkage disequilibrium (p <10−3) are the major factors influencing the quality of prediction. Limits and relevance of the method are related to limits of haplotype estimation. Relevance of the method is discussed in the context of HLA matching refinement. [Copyright &y& Elsevier]