Effect of peptide-binding motif on survival of HLA-haploidentical transplantation with post-transplant cyclophosphamide.

HLA HLA‐haploidentical haematopoietic cell transplantation with post‐transplant cyclophosphamide peptide‐binding motif

Journal

British journal of haematology
ISSN: 1365-2141
Titre abrégé: Br J Haematol
Pays: England
ID NLM: 0372544

Informations de publication

Date de publication:
07 Jul 2024
Historique:
received: 13 04 2024
accepted: 24 06 2024
medline: 8 7 2024
pubmed: 8 7 2024
entrez: 7 7 2024
Statut: aheadofprint

Résumé

Peptide-binding motif (PBM) model, a hierarchical clustering of HLA class I based on their binding specificity, was developed to predict immunopeptidome divergence. The effect of PBM mismatches on outcomes is unknown in HLA-haploidentical haematopoietic cell transplantation with post-transplant cyclophosphamide (PTCy-haplo). We therefore conducted a retrospective study using national registry data in PTCy-haplo. Overall, 1352 patients were included in the study. PBM-A bidirectional mismatch was associated with an increased risk of overall mortality in multivariable analysis (hazard ratio, 1.26; 95% confidence interval, 1.06 to 1.50; p = 0.010). None of relapse, non-relapse mortality (NRM) and graft-versus-host disease showed significant differences according to PBM-A bidirectional mismatch status in the entire cohort. The impact of PBM-A bidirectional mismatch on overall survival (OS) was preserved within the HLA-A genotype bidirectional mismatch population, and their lower OS stemmed from higher relapse rate in this population. The worse OS due to high NRM with PBM-A bidirectional mismatch was prominent in lymphoid malignancies receiving reduced-intensity conditioning. The PBM model may predict outcomes more accurately than HLA genotype mismatches. In conclusion, this study demonstrated that the presence of PBM-A bidirectional mismatch elevated the risk of mortality of PTCy-haplo. Avoiding PBM-A bidirectional mismatch might achieve better outcomes in PTCy-haplo.

Identifiants

pubmed: 38972374
doi: 10.1111/bjh.19630
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : Japan Society for the Promotion of Science
ID : JP23K06746

Informations de copyright

© 2024 British Society for Haematology and John Wiley & Sons Ltd.

Références

McDonald GB, Sandmaier BM, Mielcarek M, Sorror M, Pergam SA, Cheng GS, et al. Survival, nonrelapse mortality, and relapse‐related mortality after allogeneic hematopoietic cell transplantation: comparing 2003–2007 versus 2013–2017 cohorts. Ann Intern Med. 2020;172(4):229–239.
Gagelmann N, Bacigalupo A, Rambaldi A, Hoelzer D, Halter J, Sanz J, et al. Haploidentical stem cell transplantation with posttransplant cyclophosphamide therapy vs other donor transplantations in adults with hematologic cancers: a systematic review and meta‐analysis. JAMA Oncol. 2019;5(12):1739–1748.
Nakamae H, Okamura H, Hirose A, Koh H, Nakashima Y, Nakamae M, et al. A prospective study of an HLA‐haploidentical peripheral blood stem cell transplantation regimen based on modification of the dose of posttransplant cyclophosphamide for poor prognosis or refractory hematological malignancies. Cell Transplant. 2022;31:9636897221112098.
Luznik L, O'Donnell PV, Symons HJ, Chen AR, Leffell MS, Zahurak M, et al. HLA‐haploidentical bone marrow transplantation for hematologic malignancies using nonmyeloablative conditioning and high‐dose, posttransplantation cyclophosphamide. Biol Blood Marrow Transplant. 2008;14(6):641–650.
Bolanos‐Meade J, Hamadani M, Wu J, Al Malki MM, Martens MJ, Runaas L, et al. Post‐transplantation cyclophosphamide‐based graft‐versus‐host disease prophylaxis. N Engl J Med. 2023;388(25):2338–2348.
Maurer K, Ho VT, Inyang E, Cutler C, Koreth J, Shapiro RM, et al. Posttransplant cyclophosphamide vs tacrolimus‐based GVHD prophylaxis: lower incidence of relapse and chronic GVHD. Blood Adv. 2023;7(15):3903–3915.
Kharfan‐Dabaja MA, Labopin M, Ayala E, Bazarbachi A, Blaise D, Vydra J, et al. Significance of degree of HLA disparity using T‐cell replete peripheral blood stem cells from haploidentical donors with posttransplantation cyclophosphamide in AML in first complete hematologic remission: a study of the acute leukemia working party of the EBMT. HemaSphere. 2023;7(7):e920.
Fuchs EJ, McCurdy SR, Solomon SR, Wang T, Herr MR, Modi D, et al. HLA informs risk predictions after haploidentical stem cell transplantation with posttransplantation cyclophosphamide. Blood. 2022;139(10):1452–1468.
Solomon SR, Aubrey MT, Zhang X, Jackson KC, Morris LE, Holland HK, et al. Class II HLA mismatch improves outcomes following haploidentical transplantation with posttransplant cyclophosphamide. Blood Adv. 2020;4(20):5311–5321.
Meurer T, Crivello P, Metzing M, Kester M, Megger DA, Chen W, et al. Permissive HLA‐DPB1 mismatches in HCT depend on immunopeptidome divergence and editing by HLA‐DM. Blood. 2021;137(7):923–928.
Buhler S, Baldomero H, Ferrari‐Lacraz S, Mamez AC, Masouridi‐Levrat S, Heim D, et al. Analysis of biological models to predict clinical outcomes based on HLA‐DPB1 disparities in unrelated transplantation. Blood Adv. 2021;5(17):3377–3386.
Pidala J, Lee SJ, Ahn KW, Spellman S, Wang HL, Aljurf M, et al. Nonpermissive HLA‐DPB1 mismatch increases mortality after myeloablative unrelated allogeneic hematopoietic cell transplantation. Blood. 2014;124(16):2596–2606.
Fleischhauer K, Shaw BE, Gooley T, Malkki M, Bardy P, Bignon JD, et al. Effect of T‐cell‐epitope matching at HLA‐DPB1 in recipients of unrelated‐donor haemopoietic‐cell transplantation: a retrospective study. Lancet Oncol. 2012;13(4):366–374.
Klobuch S, Lim JJ, van Balen P, Kester MGD, de Klerk W, de Ru AH, et al. Human T cells recognize HLA‐DP‐bound peptides in two orientations. Proc Natl Acad Sci USA. 2022;119(49):e2214331119.
Gfeller D, Bassani‐Sternberg M. Predicting antigen presentation‐what could we learn from a million peptides? Front Immunol. 2018;9:1716.
Crivello P, Arrieta‐Bolaños E, He M, Wang T, Fingerson S, Gadalla SM, et al. Impact of the HLA Immunopeptidome on survival of leukemia patients after unrelated donor transplantation. J Clin Oncol. 2023;41(13):2416–2427.
Mehta RS, Petersdorf EW, Spellman SR, Lee SJ. Combined effect of unrelated donor age and HLA peptide‐binding motifs (PBM) match status on HCT outcomes. Blood Adv. 2024;8:2235–2242. https://doi.org/10.1182/bloodadvances.2024012669
Atsuta Y. Introduction of transplant registry unified management program 2 (TRUMP2): scripts for TRUMP data analyses, part I (variables other than HLA‐related data). Int J Hematol. 2016;103(1):3–10.
Atsuta Y, Suzuki R, Yoshimi A, Gondo H, Tanaka J, Hiraoka A, et al. Unification of hematopoietic stem cell transplantation registries in Japan and establishment of the TRUMP system. Int J Hematol. 2007;86(3):269–274.
CIBMTR. PBM Matching Tool. https://pbm‐matching‐tool.b12x.org/
Przepiorka D, Weisdorf D, Martin P, Klingemann HG, Beaty P, Hows J, et al. Consensus conference on acute GVHD grading. Bone Marrow Transplant. 1995;15(6):825–828.
Shulman HM, Sullivan KM, Weiden PL, McDonald GB, Striker GB, Sale GE, et al. Chronic graft‐versus‐host syndrome in man. A long‐term clinicopatholigic study of 20 Seattle patients. Am J Med. 1980;69(2):204–217.
Giralt S, Ballen K, Rizzo D, Bacigalupo A, Horowitz M, Pasquini M, et al. Reduced‐intensity conditioning regimen workshop: defining the dose spectrum. Report of a workshop convened by the center for international blood and marrow transplant research. Biol Blood Marrow Transplant. 2009;15(3):367–369.
Fuji S, Sugita J, Najima Y, Konishi T, Tanaka T, Ohigashi H, et al. Low‐ versus standard‐dose post‐transplant cyclophosphamide as GVHD prophylaxis for haploidentical transplantation. Br J Haematol. 2023;204:959–966.
Dulery R, Goudet C, Mannina D, Bianchessi A, Granata A, Harbi S, et al. Reduced post‐transplant cyclophosphamide doses in haploidentical hematopoietic cell transplantation for elderly patients with hematological malignancies. Bone Marrow Transplant. 2023;58(4):386–392.
Gooley TA, Leisenring W, Crowley J, Storer BE. Estimation of failure probabilities in the presence of competing risks: new representations of old estimators. Stat Med. 1999;18(6):695–706.
Fine JP, Gray RJ. A proportional hazards model for the subdistribution of a competing risk. J Am Stat Assoc. 1999;94(446):496–509.
Kanda Y. Investigation of the freely available easy‐to‐use software “EZR” for medical statistics. Bone Marrow Transplant. 2013;48(3):452–458.
Kanda J, Ichinohe T, Fuji S, Maeda Y, Ohashi K, Fukuda T, et al. Impact of HLA mismatch direction on the outcome of unrelated bone marrow transplantation: a retrospective analysis from the Japan Society for Hematopoietic Cell Transplantation. Biol Blood Marrow Transplant. 2015;21(2):305–311.
Sasazuki T, Juji T, Morishima Y, Kinukawa N, Kashiwabara H, Inoko H, et al. Effect of matching of class I HLA alleles on clinical outcome after transplantation of hematopoietic stem cells from an unrelated donor. N Engl J Med. 1998;339(17):1177–1185.
Nunes NS, Kanakry CG. Mechanisms of graft‐versus‐host disease prevention by post‐transplantation cyclophosphamide: an evolving understanding. Front Immunol. 2019;10:2668.
Wachsmuth LP, Patterson MT, Eckhaus MA, Venzon DJ, Gress RE, Kanakry CG. Posttransplantation cyclophosphamide prevents graft‐versus‐host disease by inducing alloreactive T cell dysfunction and suppression. J Clin Invest. 2019;129(6):2357–2373.
McCurdy SR, Luznik L. Relapse after allogeneic transplantation with post‐transplant cyclophosphamide: shattering myths and evolving insight. Blood Rev. 2023;62:101093.
Gooptu M, Romee R, St Martin A, Arora M, Al Malki M, Antin JH, et al. HLA‐haploidentical vs matched unrelated donor transplants with posttransplant cyclophosphamide‐based prophylaxis. Blood. 2021;138(3):273–282.

Auteurs

Kentaro Ido (K)

Department of Hematology, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan.

Hirohisa Nakamae (H)

Department of Hematology, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan.

Norimichi Hattori (N)

Division of Hematology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan.

Minoru Kanaya (M)

Blood Disorders Center, Aiiku Hospital, Sapporo, Japan.

Kaoru Morita (K)

Division of Hematology, Department of Medicine, Jichi Medical University, Shimotsuke, Japan.

Masayuki Hino (M)

Department of Hematology, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan.

Hiroyuki Ohigashi (H)

Department of Hematology, Hokkaido University Hospital, Sapporo, Japan.

Takahiro Fukuda (T)

Department of Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital, Tokyo, Japan.

Tetsuya Eto (T)

Department of Hematology, Hamanomachi Hospital, Fukuoka, Japan.

Koji Nagafuji (K)

Division of Hematology and Oncology, Department of Medicine, Kurume University Hospital, Kurume, Japan.

Nobuhiro Hiramoto (N)

Department of Hematology, Kobe City Medical Center General Hospital, Kobe, Japan.

Yumiko Maruyama (Y)

Department of Hematology, University of Tsukuba Hospital, Tsukuba, Japan.

Shuichi Ota (S)

Department of Hematology, Sapporo Hokuyu Hospital, Sapporo, Japan.

Ken-Ichi Matsuoka (KI)

Department of Hematology and Oncology, Okayama University Hospital, Okayama, Japan.

Toshihiko Ando (T)

Division of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine, Faculty of Medicine, Saga University, Saga, Japan.

Takashi Akasaka (T)

Department of Hematology, Tenri Hospital, Nara, Japan.

Yasuo Mori (Y)

Hematology, Oncology & Cardiovascular Medicine, Kyushu University Hospital, Fukuoka, Japan.

Tomohiko Kamimura (T)

Department of Hematology, Harasanshin Hospital, Fukuoka, Japan.

Toshiro Kawakita (T)

Department of Hematology, NHO Kumamoto Medical Center, Kumamoto, Japan.

Koji Kawamura (K)

Division of Clinical Laboratory Medicine, Department of Multidisciplinary Internal Medicine, Tottori University, Tottori, Japan.

Junya Kanda (J)

Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.

Makoto Onizuka (M)

Department of Hematology/Oncology, Tokai University School of Medicine, Isehara, Japan.

Yoshiko Atsuta (Y)

Japanese Data Center for Hematopoietic Cell Transplantation, Nagakute, Japan.
Department of Registry Science for Transplant and Cellular Therapy, Aichi Medical University School of Medicine, Nagakute, Japan.

Makoto Murata (M)

Department of Hematology, Shiga University of Medical Science, Otsu, Japan.

Classifications MeSH