Sibling versus unrelated donor allogeneic hematopoietic cell transplantation for chronic myelogenous leukemia: Refined HLA matching reveals more graft-versus-host disease but not less relapse

Daniel J. Weisdorf; Gene Nelson; Stephanie J. Lee; Michael Haagenson; Stephen Spellman; Joseph H. Antin; Brian Bolwell; Jean Yves Cahn; Francisco Cervantes; Edward Copelan; Robert Gale; Alois Gratwohl; H. Jean Khoury; Philip McCarthy; David I. Marks; Jeff Szer; Ann Woolfrey; Jorge Cortes-Franco; Mary M. Horowitz; Mukta Arora

doi:10.1016/j.bbmt.2009.06.016

Sibling versus unrelated donor allogeneic hematopoietic cell transplantation for chronic myelogenous leukemia: Refined HLA matching reveals more graft-versus-host disease but not less relapse

Daniel J. Weisdorf, Gene Nelson, Stephanie J. Lee, Michael Haagenson, Stephen Spellman, Joseph H. Antin, Brian Bolwell, Jean Yves Cahn, Francisco Cervantes, Edward Copelan, Robert Gale, Alois Gratwohl, H. Jean Khoury, Philip McCarthy, David I. Marks, Jeff Szer, Ann Woolfrey, Jorge Cortes-Franco, Mary M. Horowitz, Mukta Arora

Research output: Contribution to journal › Article › peer-review

37 Scopus citations

Abstract

Unrelated donor (URD) hematopoietic cell transplantation (HCT) can eradicate chronicmyelogenous leukemia (CML). It has been postulated that greater donor-recipient histoincompatibility can augment the graft-versus-leukemia (GVL) effect. We previously reported similar, but not equivalent, outcomes of URD versus sibling donor HCT for CML using an older, less precise classification of HLA matching. Here, we used our recently refined HLA-matching classification, which is suitable for interpretation when complete allele-level typing is unavailable, to reanalyze outcomes of previous HCT for CML. We found that using our new matching criteria identifies substantially more frequent mismatching than older, less precise "6 of 6 antigen-matched" URD-HCT. Under the new criteria, only 37% of those previously deemed "HLA- matched" were HLA well matched, and 44% were partially matched. Using our refined matching criteria confirms the greater risk of graft failure in partially matched or mismatched URD-recipient pairs compared with either sibling or well-matched URD-recipient pairs. Acute and chronic graft-versus-host disease (aGVHD, cGVHD) are significantly more frequent with all levels of recategorized URD HLA matching. Importantly, overall survival (OS) and leukemia-free survival (LFS) remain significantly worse after URD-HCT at any matching level. No augmented GVL effect accompanied URD HLA mismatch. Compared with sibling donor transplants, we observed only marginally increased (not statistically significant) risks of relapse in well-matched, partially matched, and mismatched URD-HCT. These data confirm the applicability of revised HLA-matching scheme in analyzing retrospective data sets when fully informative, allele-level typing is unavailable. In this analysis, greater histoincompatibility can augment GVHD, but does not improve protection against relapse; thus the best donor remains the most closely matched donor.

Original language	English (US)
Pages (from-to)	1475-1478
Number of pages	4
Journal	Biology of Blood and Marrow Transplantation
Volume	15
Issue number	11
DOIs	https://doi.org/10.1016/j.bbmt.2009.06.016
State	Published - Nov 2009

Bibliographical note

Funding Information:
Financial disclosure: The CIBMTR is supported by Public Health Service Grant/Cooperative Agreement U24-CA76518 from the National Cancer Institute (NCI), the National Heart, Lung and Blood Institute (NHLBI), and the National Institute of Allergy and Infectious Diseases; Grant/Cooperative Agreement 5U01H L069294 from the NHLBI and NCI; Contract HHSH234200637015C from the Health Resources and Services Administration; Grants N00014-06-1-0704 and N00014-08-1-0058 from the Office of Naval Research; and grants from AABB, Aetna, American Society for Blood and Marrow Transplantation Amgen Inc, an anonymous donation to the Medical College of Wisconsin, Association of Medical Microbiology and Infectious Disease Canada Astellas Pharma US Inc, Baxter International Inc, Bayer HealthCare Pharmaceuticals, BloodCenter of Wisconsin, Blue Cross and Blue Shield Association, Bone Marrow Foundation, Canadian Blood and Marrow Transplant Group, Celgene Corp, CellGenix GmbH, Centers for Disease Control and Prevention, ClinImmune Labs, CTI Clinical Trial and Consulting Services, Cubist Pharmaceuticals, Cylex Inc, CytoTherm, DOR BioPharma Inc, Dynal Biotech (an Invitrogen Company), Enzon Pharmaceuticals Inc, European Group for Blood and Marrow Transplantation, Gambro BCT Inc, Gamida Cell Ltd, Genzyme Corp, Histogenetics Inc, HKS Medical Information Systems, Hospira Inc, Infectious Diseases Society of America, Kiadis Pharma, Kirin Brewery Co Ltd, Merck & Company, Medical College of Wisconsin, MGI Pharma Inc, Michigan Community Blood Centers, Millennium Pharmaceuticals Inc, Miller Pharmacal Group, Milliman USA Inc, Miltenyi Biotec Inc, National Marrow Donor Program, Nature Publishing Group, New York Blood Center, Novartis Oncology, Oncology Nursing Society, Osiris Therapeutics Inc, Otsuka Pharmaceutical Development & Commercialization Inc, Pall Life Sciences, PDL BioPharma Inc, Pfizer Inc, Pharmion Corp, Saladax Biomedical Inc, Schering Plough Corp, Society for Healthcare Epidemiology of America, StemCyte Inc, StemSoft Software Inc, Sysmex, Teva Pharmaceutical Industries, The Marrow Foundation, THERAKOS Inc, Vidacare Corp, Vion Pharmaceuticals Inc, ViraCor Laboratories, ViroPharma Inc, and Wellpoint Inc. The views expressed in this article do not reflect the official policy or position of the National Institute of Health, Department of the Navy, Department of Defense, or any other agency of the US Government. This project has also been supported by funding from the National Marrow Donor Program (NMDP) and the Department of the Navy, Office of Naval Research Grant N00014-05-1-0859 to the NMDP. Any opinions, findings, and conclusions or recommendations expressed in this article are those of the authors and do not necessarily reflect the views of the Office of Naval Research or the NMDP.

Keywords

Chronic myelogenous leukemia
Graft versus leukemia
Graft-versus-host disease
HLA matching
Unrelated donor allotransplantation

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.bbmt.2009.06.016

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Weisdorf, D. J., Nelson, G., Lee, S. J., Haagenson, M., Spellman, S., Antin, J. H., Bolwell, B., Cahn, J. Y., Cervantes, F., Copelan, E., Gale, R., Gratwohl, A., Khoury, H. J., McCarthy, P., Marks, D. I., Szer, J., Woolfrey, A., Cortes-Franco, J., Horowitz, M. M., & Arora, M. (2009). Sibling versus unrelated donor allogeneic hematopoietic cell transplantation for chronic myelogenous leukemia: Refined HLA matching reveals more graft-versus-host disease but not less relapse. Biology of Blood and Marrow Transplantation, 15(11), 1475-1478. https://doi.org/10.1016/j.bbmt.2009.06.016

Sibling versus unrelated donor allogeneic hematopoietic cell transplantation for chronic myelogenous leukemia: Refined HLA matching reveals more graft-versus-host disease but not less relapse. / Weisdorf, Daniel J.; Nelson, Gene; Lee, Stephanie J. et al.
In: Biology of Blood and Marrow Transplantation, Vol. 15, No. 11, 11.2009, p. 1475-1478.

Research output: Contribution to journal › Article › peer-review

Weisdorf, DJ, Nelson, G, Lee, SJ, Haagenson, M, Spellman, S, Antin, JH, Bolwell, B, Cahn, JY, Cervantes, F, Copelan, E, Gale, R, Gratwohl, A, Khoury, HJ, McCarthy, P, Marks, DI, Szer, J, Woolfrey, A, Cortes-Franco, J, Horowitz, MM & Arora, M 2009, 'Sibling versus unrelated donor allogeneic hematopoietic cell transplantation for chronic myelogenous leukemia: Refined HLA matching reveals more graft-versus-host disease but not less relapse', Biology of Blood and Marrow Transplantation, vol. 15, no. 11, pp. 1475-1478. https://doi.org/10.1016/j.bbmt.2009.06.016

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abstract = "Unrelated donor (URD) hematopoietic cell transplantation (HCT) can eradicate chronicmyelogenous leukemia (CML). It has been postulated that greater donor-recipient histoincompatibility can augment the graft-versus-leukemia (GVL) effect. We previously reported similar, but not equivalent, outcomes of URD versus sibling donor HCT for CML using an older, less precise classification of HLA matching. Here, we used our recently refined HLA-matching classification, which is suitable for interpretation when complete allele-level typing is unavailable, to reanalyze outcomes of previous HCT for CML. We found that using our new matching criteria identifies substantially more frequent mismatching than older, less precise {"}6 of 6 antigen-matched{"} URD-HCT. Under the new criteria, only 37% of those previously deemed {"}HLA- matched{"} were HLA well matched, and 44% were partially matched. Using our refined matching criteria confirms the greater risk of graft failure in partially matched or mismatched URD-recipient pairs compared with either sibling or well-matched URD-recipient pairs. Acute and chronic graft-versus-host disease (aGVHD, cGVHD) are significantly more frequent with all levels of recategorized URD HLA matching. Importantly, overall survival (OS) and leukemia-free survival (LFS) remain significantly worse after URD-HCT at any matching level. No augmented GVL effect accompanied URD HLA mismatch. Compared with sibling donor transplants, we observed only marginally increased (not statistically significant) risks of relapse in well-matched, partially matched, and mismatched URD-HCT. These data confirm the applicability of revised HLA-matching scheme in analyzing retrospective data sets when fully informative, allele-level typing is unavailable. In this analysis, greater histoincompatibility can augment GVHD, but does not improve protection against relapse; thus the best donor remains the most closely matched donor.",

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author = "Weisdorf, {Daniel J.} and Gene Nelson and Lee, {Stephanie J.} and Michael Haagenson and Stephen Spellman and Antin, {Joseph H.} and Brian Bolwell and Cahn, {Jean Yves} and Francisco Cervantes and Edward Copelan and Robert Gale and Alois Gratwohl and Khoury, {H. Jean} and Philip McCarthy and Marks, {David I.} and Jeff Szer and Ann Woolfrey and Jorge Cortes-Franco and Horowitz, {Mary M.} and Mukta Arora",

note = "Funding Information: Financial disclosure: The CIBMTR is supported by Public Health Service Grant/Cooperative Agreement U24-CA76518 from the National Cancer Institute (NCI), the National Heart, Lung and Blood Institute (NHLBI), and the National Institute of Allergy and Infectious Diseases; Grant/Cooperative Agreement 5U01H L069294 from the NHLBI and NCI; Contract HHSH234200637015C from the Health Resources and Services Administration; Grants N00014-06-1-0704 and N00014-08-1-0058 from the Office of Naval Research; and grants from AABB, Aetna, American Society for Blood and Marrow Transplantation Amgen Inc, an anonymous donation to the Medical College of Wisconsin, Association of Medical Microbiology and Infectious Disease Canada Astellas Pharma US Inc, Baxter International Inc, Bayer HealthCare Pharmaceuticals, BloodCenter of Wisconsin, Blue Cross and Blue Shield Association, Bone Marrow Foundation, Canadian Blood and Marrow Transplant Group, Celgene Corp, CellGenix GmbH, Centers for Disease Control and Prevention, ClinImmune Labs, CTI Clinical Trial and Consulting Services, Cubist Pharmaceuticals, Cylex Inc, CytoTherm, DOR BioPharma Inc, Dynal Biotech (an Invitrogen Company), Enzon Pharmaceuticals Inc, European Group for Blood and Marrow Transplantation, Gambro BCT Inc, Gamida Cell Ltd, Genzyme Corp, Histogenetics Inc, HKS Medical Information Systems, Hospira Inc, Infectious Diseases Society of America, Kiadis Pharma, Kirin Brewery Co Ltd, Merck & Company, Medical College of Wisconsin, MGI Pharma Inc, Michigan Community Blood Centers, Millennium Pharmaceuticals Inc, Miller Pharmacal Group, Milliman USA Inc, Miltenyi Biotec Inc, National Marrow Donor Program, Nature Publishing Group, New York Blood Center, Novartis Oncology, Oncology Nursing Society, Osiris Therapeutics Inc, Otsuka Pharmaceutical Development & Commercialization Inc, Pall Life Sciences, PDL BioPharma Inc, Pfizer Inc, Pharmion Corp, Saladax Biomedical Inc, Schering Plough Corp, Society for Healthcare Epidemiology of America, StemCyte Inc, StemSoft Software Inc, Sysmex, Teva Pharmaceutical Industries, The Marrow Foundation, THERAKOS Inc, Vidacare Corp, Vion Pharmaceuticals Inc, ViraCor Laboratories, ViroPharma Inc, and Wellpoint Inc. The views expressed in this article do not reflect the official policy or position of the National Institute of Health, Department of the Navy, Department of Defense, or any other agency of the US Government. This project has also been supported by funding from the National Marrow Donor Program (NMDP) and the Department of the Navy, Office of Naval Research Grant N00014-05-1-0859 to the NMDP. Any opinions, findings, and conclusions or recommendations expressed in this article are those of the authors and do not necessarily reflect the views of the Office of Naval Research or the NMDP.",

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language = "English (US)",

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T1 - Sibling versus unrelated donor allogeneic hematopoietic cell transplantation for chronic myelogenous leukemia

T2 - Refined HLA matching reveals more graft-versus-host disease but not less relapse

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AU - Nelson, Gene

AU - Lee, Stephanie J.

AU - Haagenson, Michael

AU - Spellman, Stephen

AU - Antin, Joseph H.

AU - Bolwell, Brian

AU - Cahn, Jean Yves

AU - Cervantes, Francisco

AU - Copelan, Edward

AU - Gale, Robert

AU - Gratwohl, Alois

AU - Khoury, H. Jean

AU - McCarthy, Philip

AU - Marks, David I.

AU - Szer, Jeff

AU - Woolfrey, Ann

AU - Cortes-Franco, Jorge

AU - Horowitz, Mary M.

AU - Arora, Mukta

N1 - Funding Information: Financial disclosure: The CIBMTR is supported by Public Health Service Grant/Cooperative Agreement U24-CA76518 from the National Cancer Institute (NCI), the National Heart, Lung and Blood Institute (NHLBI), and the National Institute of Allergy and Infectious Diseases; Grant/Cooperative Agreement 5U01H L069294 from the NHLBI and NCI; Contract HHSH234200637015C from the Health Resources and Services Administration; Grants N00014-06-1-0704 and N00014-08-1-0058 from the Office of Naval Research; and grants from AABB, Aetna, American Society for Blood and Marrow Transplantation Amgen Inc, an anonymous donation to the Medical College of Wisconsin, Association of Medical Microbiology and Infectious Disease Canada Astellas Pharma US Inc, Baxter International Inc, Bayer HealthCare Pharmaceuticals, BloodCenter of Wisconsin, Blue Cross and Blue Shield Association, Bone Marrow Foundation, Canadian Blood and Marrow Transplant Group, Celgene Corp, CellGenix GmbH, Centers for Disease Control and Prevention, ClinImmune Labs, CTI Clinical Trial and Consulting Services, Cubist Pharmaceuticals, Cylex Inc, CytoTherm, DOR BioPharma Inc, Dynal Biotech (an Invitrogen Company), Enzon Pharmaceuticals Inc, European Group for Blood and Marrow Transplantation, Gambro BCT Inc, Gamida Cell Ltd, Genzyme Corp, Histogenetics Inc, HKS Medical Information Systems, Hospira Inc, Infectious Diseases Society of America, Kiadis Pharma, Kirin Brewery Co Ltd, Merck & Company, Medical College of Wisconsin, MGI Pharma Inc, Michigan Community Blood Centers, Millennium Pharmaceuticals Inc, Miller Pharmacal Group, Milliman USA Inc, Miltenyi Biotec Inc, National Marrow Donor Program, Nature Publishing Group, New York Blood Center, Novartis Oncology, Oncology Nursing Society, Osiris Therapeutics Inc, Otsuka Pharmaceutical Development & Commercialization Inc, Pall Life Sciences, PDL BioPharma Inc, Pfizer Inc, Pharmion Corp, Saladax Biomedical Inc, Schering Plough Corp, Society for Healthcare Epidemiology of America, StemCyte Inc, StemSoft Software Inc, Sysmex, Teva Pharmaceutical Industries, The Marrow Foundation, THERAKOS Inc, Vidacare Corp, Vion Pharmaceuticals Inc, ViraCor Laboratories, ViroPharma Inc, and Wellpoint Inc. The views expressed in this article do not reflect the official policy or position of the National Institute of Health, Department of the Navy, Department of Defense, or any other agency of the US Government. This project has also been supported by funding from the National Marrow Donor Program (NMDP) and the Department of the Navy, Office of Naval Research Grant N00014-05-1-0859 to the NMDP. Any opinions, findings, and conclusions or recommendations expressed in this article are those of the authors and do not necessarily reflect the views of the Office of Naval Research or the NMDP.

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N2 - Unrelated donor (URD) hematopoietic cell transplantation (HCT) can eradicate chronicmyelogenous leukemia (CML). It has been postulated that greater donor-recipient histoincompatibility can augment the graft-versus-leukemia (GVL) effect. We previously reported similar, but not equivalent, outcomes of URD versus sibling donor HCT for CML using an older, less precise classification of HLA matching. Here, we used our recently refined HLA-matching classification, which is suitable for interpretation when complete allele-level typing is unavailable, to reanalyze outcomes of previous HCT for CML. We found that using our new matching criteria identifies substantially more frequent mismatching than older, less precise "6 of 6 antigen-matched" URD-HCT. Under the new criteria, only 37% of those previously deemed "HLA- matched" were HLA well matched, and 44% were partially matched. Using our refined matching criteria confirms the greater risk of graft failure in partially matched or mismatched URD-recipient pairs compared with either sibling or well-matched URD-recipient pairs. Acute and chronic graft-versus-host disease (aGVHD, cGVHD) are significantly more frequent with all levels of recategorized URD HLA matching. Importantly, overall survival (OS) and leukemia-free survival (LFS) remain significantly worse after URD-HCT at any matching level. No augmented GVL effect accompanied URD HLA mismatch. Compared with sibling donor transplants, we observed only marginally increased (not statistically significant) risks of relapse in well-matched, partially matched, and mismatched URD-HCT. These data confirm the applicability of revised HLA-matching scheme in analyzing retrospective data sets when fully informative, allele-level typing is unavailable. In this analysis, greater histoincompatibility can augment GVHD, but does not improve protection against relapse; thus the best donor remains the most closely matched donor.

AB - Unrelated donor (URD) hematopoietic cell transplantation (HCT) can eradicate chronicmyelogenous leukemia (CML). It has been postulated that greater donor-recipient histoincompatibility can augment the graft-versus-leukemia (GVL) effect. We previously reported similar, but not equivalent, outcomes of URD versus sibling donor HCT for CML using an older, less precise classification of HLA matching. Here, we used our recently refined HLA-matching classification, which is suitable for interpretation when complete allele-level typing is unavailable, to reanalyze outcomes of previous HCT for CML. We found that using our new matching criteria identifies substantially more frequent mismatching than older, less precise "6 of 6 antigen-matched" URD-HCT. Under the new criteria, only 37% of those previously deemed "HLA- matched" were HLA well matched, and 44% were partially matched. Using our refined matching criteria confirms the greater risk of graft failure in partially matched or mismatched URD-recipient pairs compared with either sibling or well-matched URD-recipient pairs. Acute and chronic graft-versus-host disease (aGVHD, cGVHD) are significantly more frequent with all levels of recategorized URD HLA matching. Importantly, overall survival (OS) and leukemia-free survival (LFS) remain significantly worse after URD-HCT at any matching level. No augmented GVL effect accompanied URD HLA mismatch. Compared with sibling donor transplants, we observed only marginally increased (not statistically significant) risks of relapse in well-matched, partially matched, and mismatched URD-HCT. These data confirm the applicability of revised HLA-matching scheme in analyzing retrospective data sets when fully informative, allele-level typing is unavailable. In this analysis, greater histoincompatibility can augment GVHD, but does not improve protection against relapse; thus the best donor remains the most closely matched donor.

KW - Chronic myelogenous leukemia

KW - Graft versus leukemia

KW - Graft-versus-host disease

KW - HLA matching

KW - Unrelated donor allotransplantation

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Sibling versus unrelated donor allogeneic hematopoietic cell transplantation for chronic myelogenous leukemia: Refined HLA matching reveals more graft-versus-host disease but not less relapse

Abstract

Bibliographical note

Keywords

UN SDGs

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