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The effect of NIMA matching in adult unrelated mismatched hematopoietic stem cell transplantation – a joint study of the Acute Leukemia Working Party of the EBMT and the CIBMTR

Bone Marrow Transplantation volume 54, pages 849–857 (2019)Cite this article

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Abstract

Hematological malignancies can be cured by unrelated donor allogeneic HSCT and outcomes are optimized by high-resolution HLA matching at HLA-A, -B, -C, -DRB1 and -DQB1 (10/10 match). If a 10/10 match is unavailable, 9/10 matches may be suitable. Fetal exposure to non-inherited maternal antigens (NIMA) may impart lifelong NIMA tolerance modulating the immune response, as shown in adult haploidentical transplantation. In cord blood transplantation, NIMA matching lowered rates of aGvHD and TRM; in haploidentical transplantation, sibling donors with non-shared maternal antigens showed less grade II-IV aGvHD. This retrospective analysis examined if 9/10 matched unrelated donor HSCT benefits from NIMA matching. DKMS contacted 1,735 donors and obtained 733 (42%) maternal samples. NIMA-matched and -mismatched cases with a minimum follow-up of 1 year were compared by univariate and multivariate analyses adjusted for co-variates for OS, DFS, relapse, TRM and a/cGvHD. The study population (N = 445) comprised 31 NIMA-matched and 414 NIMA-mismatched cases. No significant differences between NIMA-matched and NIMA-mismatched groups were found for any outcomes with similar OS and TRM rates within both groups. This study provides the proof of principle that NIMA matching is possible in the unrelated donor HSCT setting; larger studies may be able to provide significant results.

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Acknowledgements

We thank Carlheinz Müller from the German National Bone Marrow Donor Registry ZKRD for providing additional HLA information for patients, Jon van Rood for his persistence in moving HSCT forward with his dedication and research for NIMA matching and related topics. Without his initiative, scientific directions and valuable advice, this study would not have been possible. We thank Christina Peters from the pediatric working group of EBMT for granting access to data from the pediatrics working group of the EBMT for this study and Cladd Stevens for revisions of our NIMA match assignments, as well as the donors and their mothers for their participation and cooperation in this study. The CIBMTR is supported primarily by Public Health Service Grant/Cooperative Agreement 5U24CA076518 from the National Cancer Institute (NCI), the National Heart, Lung and Blood Institute (NHLBI) and the National Institute of Allergy and Infectious Diseases (NIAID); a Grant/Cooperative Agreement 4U10HL069294 from NHLBI and NCI; a contract HHSH250201200016C with Health Resources and Services Administration (HRSA/DHHS); two Grants N00014-17-1-2388 and N0014-17-1-2850 from the Office of Naval Research; and grants from *Actinium Pharmaceuticals, Inc.; *Amgen, Inc.; *Amneal Biosciences; *Angiocrine Bioscience, Inc.; Anonymous donation to the Medical College of Wisconsin; Astellas Pharma US; Atara Biotherapeutics, Inc.; Be the Match Foundation; *bluebird bio, Inc.; *Bristol Myers Squibb Oncology; *Celgene Corporation; Cerus Corporation; *Chimerix, Inc.; Fred Hutchinson Cancer Research Center; Gamida Cell Ltd.; Gilead Sciences, Inc.; HistoGenetics, Inc.; Immucor; *Incyte Corporation; Janssen Scientific Affairs, LLC; *Jazz Pharmaceuticals, Inc.; Juno Therapeutics; Karyopharm Therapeutics, Inc.; Kite Pharma, Inc.; Medac, GmbH; MedImmune; The Medical College of Wisconsin; *Mediware; *Merck & Co, Inc.; *Mesoblast; MesoScale Diagnostics, Inc.; Millennium, the Takeda Oncology Co.; *Miltenyi Biotec, Inc.; National Marrow Donor Program; *Neovii Biotech NA, Inc.; Novartis Pharmaceuticals Corporation; Otsuka Pharmaceutical Co, Ltd. – Japan; PCORI; *Pfizer, Inc; *Pharmacyclics, LLC; PIRCHE AG; *Sanofi Genzyme; *Seattle Genetics; Shire; Spectrum Pharmaceuticals, Inc.; St. Baldrick’s Foundation; *Sunesis Pharmaceuticals, Inc.; Swedish Orphan Biovitrum, Inc.; Takeda Oncology; Telomere Diagnostics, Inc.; and University of Minnesota. The views expressed in this article do not reflect the official policy or position of the National Institute of Health, the Department of the Navy, the Department of Defense, Health Resources and Services Administration (HRSA) or any other agency of the U.S. Government. *Corporate Members

Authorship contributions

JvR: Study design and interpretation of the results. JP: Study design, data collection, interpretation of results, manuscript preparation, revision and approval. TW: Statistical analysis, interpretation of results, manuscript preparation, manuscript revision and approval. MDH: Data collection, statistical analysis, manuscript preparation, manuscript revision and approval. SRS: Study design, data collection, interpretation of results, manuscript writing, manuscript revision and approval. YH: HLA allele frequency data and comparisons, manuscript preparation, manuscript revision and approval. CJH-F: Data collection, results interpretation, manuscript revision and approval. AN: Study design, data contributions, results interpretation, manuscript revision and approval. MM: Study design, data contributions, results interpretation, manuscript revision and approval. KF: Study design, manuscript revision and approval. KCH: Study design, manuscript revision and approval. MRV: Study design, manuscript revision and approval. SJL: Study design, results interpretation, manuscript revision and approval. EP: Study design, data management, data collection, manuscript revision and approval. AHS: Study design, data collection, results interpretation, manuscript revision and approval

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Authors and Affiliations

  1. DKMS, Tübingen, Germany

    Julia Pingel, Yvonne Hagenlocher, Camila J. Hernández-Frederick & Alexander H. Schmidt

  2. Center for International Blood and Marrow Transplant Research, Medical College of Wisconsin, Milwaukee, WI, USA

    Tao Wang & Stephanie J. Lee

  3. Division of Biostatistics, Institute for Health and Society, Medical College of Wisconsin, Milwaukee, WI, USA

    Tao Wang

  4. Sheba Medical Center, Sheba Cord Blood Bank, Tel-Hashomer, Israel

    Arnon Nagler

  5. Center for International Blood and Marrow Transplant Research, Minneapolis, MN, USA

    Michael D. Haagenson & Stephen R. Spellman

  6. Institute for Experimental Cellular Therapy, University Hospital Essen, Essen, Germany

    Katharina Fleischhauer

  7. Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Katharine C. Hsu

  8. University of Colorado - Children’s Hospital, Aurora, CO, USA

    Michael R. Verneris

  9. Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA

    Stephanie J. Lee

  10. Department of Haemotology, Saint Antoine Hospital, Paris, France

    Mohamad Mohty

  11. EBMT (European Society for Blood and Marrow Transplantation), Department of Haematology, Saint Antoine Hospital, Université Pierre et Marie Curie, INSERM UMR 938, Paris, France

    Emmanuelle Polge

  12. Matchis Foundation, Leiden, The Netherlands

    Jon J. van Rood

  13. Department of Immunohematology and Blood Transfusion, Leiden University Medical Centre, Leiden, The Netherlands

    Jon J. van Rood

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  1. Julia Pingel
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Correspondence to Stephen R. Spellman.

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Pingel, J., Wang, T., Hagenlocher, Y. et al. The effect of NIMA matching in adult unrelated mismatched hematopoietic stem cell transplantation – a joint study of the Acute Leukemia Working Party of the EBMT and the CIBMTR. Bone Marrow Transplant 54, 849–857 (2019). https://doi.org/10.1038/s41409-018-0345-8

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