Standardizing Definitions of Hematopoietic Recovery, Graft Rejection, Graft Failure, Poor Graft Function, and Donor Chimerism in Allogeneic Hematopoietic Cell Transplantation: A Report on Behalf of the American Society for Transplantation and Cellular Therapy

Mohamed A. Kharfan-Dabaja, Ambuj Kumar, Ernesto Ayala, Mahmoud Aljurf, Taiga Nishihori, Rebecca Marsh, Lauri M. Burroughs, Navneet Majhail, A. Samer Al-Homsi, Zaid S. Al-Kadhimi, Merav Bar, Alice Bertaina, Jaap J. Boelens, Richard Champlin, Sonali Chaudhury, Zachariah DeFilipp, Bhagirathbhai Dholaria, Areej El-Jawahri, Suzanne Fanning, Ellen FraintUsama Gergis, Sergio Giralt, Betty K. Hamilton, Shahrukh K. Hashmi, Biljana Horn, Yoshihiro Inamoto, David A. Jacobsohn, Tania Jain, Laura Johnston, Abraham S. Kanate, Ankit Kansagra, Adetola Kassim, Leslie S. Kean, Carrie L. Kitko, Jessica Knight-Perry, Joanne Kurtzberg, Hien Liu, Margaret L. MacMillan, Zahra Mahmoudjafari, Marco Mielcarek, Mohamad Mohty, Arnon Nagler, Eneida Nemecek, Timothy S. Olson, Betul Oran, Miguel Angel Perales, Susan E. Prockop, Michael A. Pulsipher, Iskra Pusic, Marcie L. Riches, Cesar Rodriguez, Rizwan Romee, Gabriela Rondon, Ayman Saad, Nina Shah, Peter J. Shaw, Shalini Shenoy, Jorge Sierra, Julie Talano, Michael R. Verneris, Paul Veys, John E. Wagner, Bipin N. Savani, Mehdi Hamadani, Paul A. Carpenter

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

Abstract

Allogeneic hematopoietic cell transplantation (allo-HCT) is potentially curative for certain hematologic malignancies and nonmalignant diseases. The field of allo-HCT has witnessed significant advances, including broadening indications for transplantation, availability of alternative donor sources, less toxic preparative regimens, new cell manipulation techniques, and novel GVHD prevention methods, all of which have expanded the applicability of the procedure. These advances have led to clinical practice conundrums when applying traditional definitions of hematopoietic recovery, graft rejection, graft failure, poor graft function, and donor chimerism, because these may vary based on donor type, cell source, cell dose, primary disease, graft-versus-host disease (GVHD) prophylaxis, and conditioning intensity, among other variables. To address these contemporary challenges, we surveyed a panel of allo-HCT experts in an attempt to standardize these definitions. We analyzed survey responses from adult and pediatric transplantation physicians separately. Consensus was achieved for definitions of neutrophil and platelet recovery, graft rejection, graft failure, poor graft function, and donor chimerism, but not for delayed engraftment. Here we highlight the complexities associated with the management of mixed donor chimerism in malignant and nonmalignant hematologic diseases, which remains an area for future research. We recognize that there are multiple other specific, and at times complex, clinical scenarios for which clinical management must be individualized.

Original languageEnglish (US)
Pages (from-to)642-649
Number of pages8
JournalTransplantation and Cellular Therapy
Volume27
Issue number8
DOIs
StatePublished - Aug 1 2021

Bibliographical note

Funding Information:
Financial disclosure: Please refer to conflicts of interest statement which lists financial disclodures whenever applicable. Conflict of interest statement: M.A.K-D. reports consultancy for Daiichi Sankyo and Pharmacyclics. L.M.B. has received support for a clinical trial conducted through the Fred Hutchinson Cancer Research Center by Medac, including supply of the study drug treosulfan; is a member of the data safety and monitoring boards (DSMB) for a clinical trial with Rocket Pharmaceuticals and another clinical trial with Jasper Therapeutics. N.M. has served as a consultant for Anthem and has received honoraria from Incyte and Nkarta, M.B. reports employment by Bristol Myers Squibb. J.J.B. reports consultancy for Race Oncology, Takeda, Avrobio, Bluerock, Omeros, and Advanced Clinical. S.C. serves on an advisory board for bluebird bio. Z.D. has received research support from Inctye and RegImmuneCorp and has served as a consultant for Syndax Pharmaceuticals. B.D. has received research support from Takeda, Janssen, Angiocrine, Poseida, and Celgene and serves on consultancy/advisory boards for Jazz Pharmaceuticals and Celgene. S.F. serves on speakers bureaus for TG Pharma, Sanofi, BMS, and Takeda and as a consultant for Genentech. U.G. serves as a consultant for Jazz, Incyte, Astellas, Mesoblast, and Gamida Cell. S.G. serves on consultancy/advisory boards for Amgen, Celgene, Janssen, Quintiles, Pfizer, CSL Behring, Sanofi, Adiene, Kite Pharma, Jazz Pharmaceuticals, and Actinuum. Y.I. serves as a consultant for Novartis, Meiji Seika, and Janssen Pharmaceutical. T.J. serves as a consultant for Targeted Oncology and on advisory boards for CareDx and Bristol Myers Squibb. H.L. serves on the speakers bureau for Sanofi. B.O. has received research funding from ASTEX and AROG Pharmaceuticals. M-A.P. has received honoraria from Abbvie, Bellicum, Celgene, Bristol-Myers Squibb, Incyte, Kite/Gilead, Merck, Novartis, Nektar Therapeutics, Omeros, and Takeda. He serves on DSMBs for Cidara Therapeutics, Servier, and Medigene and on the scientific advisory boards of MolMed and NexImmune. He has received research support for clinical trials from Incyte, Kite/Gilead, and Miltenyi Biotec. He serves in a volunteer capacity as a member of the Board of Directors of Be The Match (National Marrow Donor Program), as well as on the CIBMTR Cellular Immunotherapy Data Resource Executive Committee. S.E.P. receives support for the conduct of sponsored trials from Atara Biotherapeutics, Mesoblast, and Jasper and is an inventor of IP licensed to Atara Biotherapeutics by Memorial Sloan Kettering Cancer Center (MSKCC) (assigned all rights to MSKCC and has no financial interest in Atara Biotherapeutics). I.P. serves on advisory boards for Kadmon, Incyte, and Syndex. M.L.R. serves on an advisory board for BioIntellect. C.R. serves as a consultant for Amgen, Bristol Myers Squibb, Takeda, and Sanofi. R.R. has received research funding from Crispr Therapeutics and serves on a scientific advisory board for Glycostem. A.S. serves as a consultant for Magenta, Incyte Pharmaceuticals, and CareDx and receives research support from Amgen, Kadmon, and OrcaBio. N.S. has received research funding from Celgene/Bristol Myers Squibb, Janssen, bluebird bio, Sutro Biopharma, Teneobio, Poseida, Nektar, and has served as an advisor for GSK, Amgen, Indapta Therapeutics, Sanofi, CareDx, Kite Pharma, Karyopharm, Oncopeptides, and CSL Behring. J.S. reports personal fees from Astellas, Jazz Pharmaceuticals, Abbvie, Daiichi Sankyo, Pfizer, and grants and personal fees from Novartis. M.R.V. reports advisory board participation for Jazz Pharmaceuticals and Novartis and consultancy with Fate Therapeutics and Terumo. J.E.W. serves as a clinical advisor to Magenta Therapeutics and Rocket Pharmaceuticals. M.H. reports receiving research support/funding from Takeda Pharmaceutical, Spectrum Pharmaceuticals, and Astellas Pharma; serving as a consultant for Janssen, Incyte, ADC Therapeutics, Celgene, Omeros, Verastem, and MorphoSys; and serving on the speakers bureau for Sanofi Genzyme, AstraZeneca, and BeiGene. E.A. A. Kumar, M.A. T.N. R.M. A.S.A. Z.S.A. A.B. R.C. A.E-J. E.F. B. Hamilton, S.K.H. B. Horn, D.A.J. L.J. A.S.K. A. Kansagra, A. Kassim, L.S.K. C.L.K. J.K-P. J.K. M.L.M. Z.M. M. Mielcarek, M. Mohty, A.N. E.N. T.S.O. M.A.P. G.R. P.J.S. S.S. J.T. P.V. B.N.S. and P.A.C. declare no conflicts of interest. Financial disclosure: See Acknowledgments on page 648.

Funding Information:
Conflict of interest statement: M.A.K-D. reports consultancy for Daiichi Sankyo and Pharmacyclics. L.M.B. has received support for a clinical trial conducted through the Fred Hutchinson Cancer Research Center by Medac, including supply of the study drug treosulfan; is a member of the data safety and monitoring boards (DSMB) for a clinical trial with Rocket Pharmaceuticals and another clinical trial with Jasper Therapeutics. N.M. has served as a consultant for Anthem and has received honoraria from Incyte and Nkarta, M.B. reports employment by Bristol Myers Squibb. J.J.B. reports consultancy for Race Oncology, Takeda, Avrobio, Bluerock, Omeros, and Advanced Clinical. S.C. serves on an advisory board for bluebird bio. Z.D. has received research support from Inctye and RegImmuneCorp and has served as a consultant for Syndax Pharmaceuticals. B.D. has received research support from Takeda, Janssen, Angiocrine, Poseida, and Celgene and serves on consultancy/advisory boards for Jazz Pharmaceuticals and Celgene. S.F. serves on speakers bureaus for TG Pharma, Sanofi, BMS, and Takeda and as a consultant for Genentech. U.G. serves as a consultant for Jazz, Incyte, Astellas, Mesoblast, and Gamida Cell. S.G. serves on consultancy/advisory boards for Amgen, Celgene, Janssen, Quintiles, Pfizer, CSL Behring, Sanofi, Adiene, Kite Pharma, Jazz Pharmaceuticals, and Actinuum. Y.I. serves as a consultant for Novartis, Meiji Seika, and Janssen Pharmaceutical. T.J. serves as a consultant for Targeted Oncology and on advisory boards for CareDx and Bristol Myers Squibb. H.L. serves on the speakers bureau for Sanofi. B.O. has received research funding from ASTEX and AROG Pharmaceuticals. M-A.P. has received honoraria from Abbvie, Bellicum, Celgene, Bristol-Myers Squibb, Incyte, Kite/Gilead, Merck, Novartis, Nektar Therapeutics, Omeros, and Takeda. He serves on DSMBs for Cidara Therapeutics, Servier, and Medigene and on the scientific advisory boards of MolMed and NexImmune. He has received research support for clinical trials from Incyte, Kite/Gilead, and Miltenyi Biotec. He serves in a volunteer capacity as a member of the Board of Directors of Be The Match (National Marrow Donor Program), as well as on the CIBMTR Cellular Immunotherapy Data Resource Executive Committee. S.E.P. receives support for the conduct of sponsored trials from Atara Biotherapeutics, Mesoblast, and Jasper and is an inventor of IP licensed to Atara Biotherapeutics by Memorial Sloan Kettering Cancer Center ( MSKCC) (assigned all rights to MSKCC and has no financial interest in Atara Biotherapeutics). I.P. serves on advisory boards for Kadmon, Incyte, and Syndex. M.L.R. serves on an advisory board for BioIntellect. C.R. serves as a consultant for Amgen, Bristol Myers Squibb, Takeda, and Sanofi. R.R. has received research funding from Crispr Therapeutics and serves on a scientific advisory board for Glycostem. A.S. serves as a consultant for Magenta, Incyte Pharmaceuticals, and CareDx and receives research support from Amgen, Kadmon, and OrcaBio. N.S. has received research funding from Celgene/Bristol Myers Squibb, Janssen, bluebird bio, Sutro Biopharma, Teneobio, Poseida, Nektar, and has served as an advisor for GSK, Amgen, Indapta Therapeutics, Sanofi, CareDx, Kite Pharma, Karyopharm, Oncopeptides, and CSL Behring. J.S. reports personal fees from Astellas, Jazz Pharmaceuticals, Abbvie, Daiichi Sankyo, Pfizer, and grants and personal fees from Novartis. M.R.V. reports advisory board participation for Jazz Pharmaceuticals and Novartis and consultancy with Fate Therapeutics and Terumo. J.E.W. serves as a clinical advisor to Magenta Therapeutics and Rocket Pharmaceuticals. M.H. reports receiving research support/funding from Takeda Pharmaceutical, Spectrum Pharmaceuticals, and Astellas Pharma; serving as a consultant for Janssen, Incyte, ADC Therapeutics, Celgene, Omeros, Verastem, and MorphoSys; and serving on the speakers bureau for Sanofi Genzyme, AstraZeneca, and BeiGene. E.A., A. Kumar, M.A., T.N., R.M., A.S.A., Z.S.A., A.B., R.C., A.E-J., E.F., B. Hamilton, S.K.H., B. Horn, D.A.J., L.J., A.S.K., A. Kansagra, A. Kassim, L.S.K., C.L.K., J.K-P., J.K., M.L.M., Z.M., M. Mielcarek, M. Mohty, A.N., E.N., T.S.O., M.A.P., G.R., P.J.S., S.S., J.T., P.V., B.N.S., and P.A.C. declare no conflicts of interest.

Publisher Copyright:
© 2021 The American Society for Transplantation and Cellular Therapy

Keywords

  • Allogeneic hematopoietic cell transplantation
  • Donor chimerism
  • Graft failure
  • Graft rejection
  • Hematopoietic recovery

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