Journal Article

DKFZ-2026-01557

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Donor Selection and Human Leukocyte Antigen Loss Leukemia Relapse After Hematopoietic Cell Transplantation.

Fleischhauer, K.DKFZ* ; Toffalori, C. ; Cugnata, F. ; Hofmann, J. A. ; Orofino, G. ; Lorentino, F. ; Ahci-Hanci, M. ; Lange, V. ; Müller, C. R. ; Kunadt, D. ; Bornhäuser, M.DKFZ* ; Sanz, G. ; Soiffer, R. ; Waterhouse, M. ; Giaccone, L. ; Ali, H. ; Nachtkamp, K. ; Bacigalupo, A. ; Bonifazi, F. ; Luznik, L. ; Facchini, L. ; Bramanti, S. ; Nagler, A. ; Saccardi, R. ; Milano, F. ; Zallio, F. ; Pierini, A. ; Mohty, M. ; Flomenberg, N. ; Takaori-Kondo, A. ; Vey, N. ; Teshima, T. ; Kröger, N. ; Laperche, C. M. ; Andreani, M. ; Lupo Stanghellini, M. T. ; Peccatori, J. ; Di Serio, C. ; Kobbe, G. ; Al Malki, M. M. ; Bruno, B. ; Zeiser, R. ; Lindsley, R. C. ; Sanz, J. ; Beelen, D. ; Stölzel, F. ; Sauter, J. ; Schmidt, A. H. ; Ciceri, F. ; Vago, L. ; Consortium, H. (Collaboration Author) ; Montoro, J. (Contributor) ; Jan, M. (Contributor) ; Wehr, C. (Contributor) ; Busca, A. (Contributor) ; Gendzekhadze, K. (Contributor) ; Schuler, E. (Contributor) ; Putke, K. (Contributor) ; Zanussi, M. (Contributor) ; Mazzi, B. (Contributor) ; Crivello, P. (Contributor) ; Betke, L. (Contributor) ; Arrieta-Bolaños, E. (Contributor) ; Turki, A. T. (Contributor) ; Picardi, A. (Contributor) ; Kwon, M. (Contributor) ; Ayuk, F. (Contributor) ; Onozawa, M. (Contributor) ; Devillier, R. (Contributor) ; Kanda, J. (Contributor) ; Grosso, D. (Contributor) ; Malard, F. (Contributor) ; Ruggeri, L. (Contributor) ; Altmann, H. (Contributor) ; Such, E. (Contributor) ; Ritz, J. (Contributor) ; Wäsch, R. (Contributor) ; Brunello, L. (Contributor) ; Arslan, S. (Contributor) ; Cadeddu, R. P. (Contributor) ; Pini, M. (Contributor) ; Hadland, B. (Contributor) ; Rombolà, G. (Contributor) ; Danylesko, I. (Contributor) ; Mannina, D. (Contributor) ; Imovilli, A. (Contributor) ; Gojo, I. (Contributor) ; Ursi, M. (Contributor) ; Chiusolo, P. (Contributor) ; Cerretti, R. (Contributor) ; Buño, I. (Contributor) ; Badbaran, A. (Contributor) ; Goto, H. (Contributor) ; Blaise, D. (Contributor) ; Watanabe, M. (Contributor) ; Wang, Z. (Contributor) ; Brissot, E. (Contributor) ; Carotti, A. (Contributor) ; Caravagna, G. (Contributor)

2026
American Society of Clinical Oncology Alexandria, Va.

Abstract: For patients with hematologic malignancies, relapse is the leading cause of death after allogeneic hematopoietic cell transplantation (allo-HCT). Frequently, relapses are explained by immune evasion through alterations of human leukocyte antigens (HLAs), but determinants and clinical consequences remain poorly defined.We analyzed 533 relapses of hematologic cancers after allo-HCT from different donor types, conducted at 27 centers worldwide. Genomic loss of mismatched HLA (HLA loss) was assessed using a newly developed next-generation sequencing pipeline. Clinical and immunogenetic factors associated with HLA loss were evaluated. Using HLA data from approximately 5 million individuals, a web-based tool to infer HLA incompatibility phasing was developed.HLA loss occurred in 15.6% of relapses, with significant variation according to donor type (28.7% haploidentical family, 7.2% unrelated adult, 2.7% cord blood, P < .0001). The distribution of HLA mismatches across the patient's haplotypes, predicted through the phasing tool, was strongly associated with HLA loss, with an incidence of 27.6% when HLA mismatches were in the same haplotype, compared with 5.4% if present on different haplotypes (P < .0001). HLA loss affected postrelapse outcomes, abrogating the efficacy of original donor lymphocyte infusions, with significant survival advantage by second allo-HCT from a different donor.The likelihood of HLA loss varies significantly according to the number and positioning of HLA mismatches between patient and donor. A newly developed phasing tool enables reliable prediction of its risk, supporting informed donor selection. Routine assessment of HLA loss at relapse is warranted, as it critically affects the success of immunologic salvage therapies.

Note: #DKTKZFB26# / #NCTZFB26# / epub

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Contributing Institute(s):

1. DKTK Koordinierungsstelle Essen/Düsseldorf (ED01)
2. Koordinierungsstelle NCT Dresden (DD04)

Research Program(s):

1. 899 - ohne Topic (POF4-899) (POF4-899)

Appears in the scientific report 2026

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Database coverage:
; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; Essential Science Indicators ; IF >= 40 ; JCR ; Nationallizenz ; PubMed Central ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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