1.
Mother donors improve outcomes after HLA haploidentical transplantation: A Study by the Cellular Therapy and Immunobiology Working Party of the EBMT
Ruggeri, L., Eikema, D. J., Bondanza, A., Noviello, M., van Biezen, A., de Wreede, L. C., Crucitti, L., Vago, L., Ciardelli, S., Bader, P., et al
Transplantation and cellular therapy. 2022
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Abstract
BACKGROUND Trans-placental trafficking of maternal and foetal cells during pregnancy establishes long-term, reciprocal micro-chimerism in both mother and child. As a consequence, the immune system of the mother may become sensitized to paternal histocompatibility antigens. It has been hypothesized that mother's "exposure" to paternal HLA haplotype antigens during pregnancy may affect transplantation outcomes when the mother acts as donor for the child. In T-cell depleted HLA haploidentical hematopoietic transplants, maternal donors have been shown to improve transplantation outcomes (Stern et al. Blood, 2008;112: 2990-2995). OBJECTIVES AND STUDY DESIGN The present retrospective multicenter study was conducted on behalf of Cellular Therapy and Immunobiology Working Party of the EBMT. It involved 409 patients (102 pediatric and 307 adult) with acute leukemia who were given HLA-haploidentical hematopoietic transplants. The goal of the study was to evaluate the role of maternal donors in a large cohort of haploidentical transplants. RESULTS Transplants from maternal donors were associated with lower relapse incidence in T-cell depleted (HR: 2.13 (1.16-3.92), p= 0.018) as well as in a limited series of unmanipulated, in vivo T-cell depleted transplants (HR: 4.15 (0.94-18.35), P=0.06) and also better graft-vs-host disease/relapse-free survival in T-cell depleted transplants (HR: 1.67 (1.02-2.73), p = 0.04). CONCLUSION These results indicate that the mother should be the preferred donor in order to provide better graft-vs-host disease/relapse-free survival in T-cell depleted HLA-haploidentical transplants for acute leukemia.
PICO Summary
Population
Adults and children with acute leukemia who underwent HSCT from a haploidentical family donor and were reported to the EBMT registry (n=409; 102 paediatric and 307 adult)
Intervention
Maternal donor (n=96)
Comparison
Other family donor (n=313)
Outcome
Transplants from maternal donors were associated with lower relapse incidence in T-cell depleted (HR: 2.13 (1.16-3.92) as well as in a limited series of unmanipulated, in vivo T-cell depleted transplants (HR: 4.15 (0.94-18.35) and also better graft-vs-host disease/relapse-free survival in T-cell depleted transplants (HR: 1.67 (1.02-2.73).
2.
Human leukocyte antigen evolutionary divergence influences outcomes of paediatric patients and young adults affected by malignant disorders given allogeneic haematopoietic stem cell transplantation from unrelated donors
Merli, P., Crivello, P., Strocchio, L., Pinto, R. M., Algeri, M., Del Bufalo, F., Pagliara, D., Becilli, M., Carta, R., Gaspari, S., et al
British journal of haematology. 2022
Abstract
High genetic heterogeneity in the human leukocyte antigen (HLA) increases the likelihood of efficient immune response to pathogens and tumours. As measure of HLA diversity, HLA evolutionary divergence (HED) has been shown to predict the response of tumours to immunotherapy and haematopoietic stem cell transplantation (HSCT) in adults. We retrospectively investigated the association of HED with outcomes of 153 paediatric/young adults patients, treated for malignant disorders with HSCT from 9-10/10 HLA-matched unrelated donors. HED was calculated as pairwise genetic distance between alleles in patient HLA-A, -B, -C, -DRB1, -DQB1 and -DPB1, using the locus median to stratify patients with 'high' or 'low' HED. Patients with high HED-B and -DRB1 showed significantly improved disease-free survival (DFS), especially when combined (70.8% vs 53.7% p = 0.008). High HED-B + -DRB1 was also associated with improved overall survival (OS) (82.1 vs 66.4% p = 0.014), and concomitant reduction of non-relapse-mortality (5.1% vs 21.1% p = 0.006). The impact on OS and DFS of combined HED-B + -DRB1 was confirmed in multivariate analysis [hazard ratio (HR) 0.39, p = 0.009; and HR 0.45, p = 0.007 respectively]. Only high HED scores for HLA-DPB1 were associated, in univariate analysis, with reduced incidence of relapse (15.9% vs 31.1%, p = 0.03). These results support HED as prognostic marker in allogeneic HSCT and, if confirmed in larger cohorts, would allow its use to inform clinical risk and potentially influence clinical practice.
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The European Society for Blood and Marrow Transplantation (EBMT) consensus recommendations for donor selection in haploidentical hematopoietic cell transplantation
Ciurea, S. O., Al Malki, M. M., Kongtim, P., Fuchs, E. J., Luznik, L., Huang, X. J., Ciceri, F., Locatelli, F., Aversa, F., Castagna, L., et al
Bone marrow transplantation. 2019
Abstract
The number of HLA-haploidentical hematopoietic cell transplants continues to increase worldwide due to recent improvements in outcomes, allowing more patients with hematological malignancies and non-malignant disorders to benefit from this procedure and have a chance to cure their disease. Despite these encouraging results, questions remain as multiple donors are usually available for transplantation, and choosing the best HLA-haploidentical donor for transplantation remains a challenge. Several approaches to haploidentical transplantation have been developed over time and, based on the graft received, can be grouped as follows: T-cell depleted haploidentical transplants, either complete or partial, or with T-cell replete grafts, performed with post-transplant cyclophosphamide-based graft-versus-host disease (GVHD) prophylaxis, or G-CSF-primed bone marrow graft and enhanced GVHD prophylaxis. Carefully selecting the donor can help optimize transplant outcomes for recipients of haploidentical donor transplants. Variables usually considered in the donor selection include presence of donor-specific antibodies in the recipient, donor age, donor/recipient gender and ABO combinations, and immunogenic variables, such as natural killer cell alloreactivity or KIR haplotype. Here we provide a comprehensive review of available evidence for selecting haploidentical donors for transplantation, and summarize the recommendations from the European Society for Blood and Marrow Transplantation (EBMT) on donor selection for different transplant platforms.