HLA DR15 Antigen Status Does Not Impact Graft-versus-Host Disease or Survival in HLA-Matched Sibling Transplantation for Hematologic Malignancies

Minoo Battiwalla; Kristin Ellis; Peigang Li; Steven Z. Pavletic; Gorgun Akpek; Peiman Hematti; Thomas R. Klumpp; Richard T. Maziarz; Bipin N. Savani; Mahmoud D. Aljurf; Mitchell S. Cairo; William R. Drobyski; Biju George; Theresa Hahn; Nandita Khera; Mark R. Litzow; Alison W. Loren; Wael Saber; Mukta Arora; Alvaro Urbano-Ispizua; Corey Cutler; Mary E D Flowers; Stephen R. Spellman

doi:10.1016/j.bbmt.2012.02.011

HLA DR15 Antigen Status Does Not Impact Graft-versus-Host Disease or Survival in HLA-Matched Sibling Transplantation for Hematologic Malignancies

Minoo Battiwalla, Kristin Ellis, Peigang Li, Steven Z. Pavletic, Gorgun Akpek, Peiman Hematti, Thomas R. Klumpp, Richard T. Maziarz, Bipin N. Savani, Mahmoud D. Aljurf, Mitchell S. Cairo, William R. Drobyski, Biju George, Theresa Hahn, Nandita Khera, Mark R. Litzow, Alison W. Loren, Wael Saber, Mukta Arora, Alvaro Urbano-IspizuaCorey Cutler, Mary E D Flowers, Stephen R. Spellman

Medicine - Hematology, Oncology, Transplant

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

10 Scopus citations

Abstract

The HLA class II DRB1 antigen DR15 is an important prognostic marker in immune-mediated marrow failure states. DR15 has also been associated with favorable outcomes (reduced acute graft-versus-host disease [aGVHD] and relapse) after allogeneic hematopoietic cell transplant. To elucidate the impact of DR15 on transplantation outcomes, we conducted a retrospective study of 2891 recipients of first allogeneic stem cell transplant from HLA-matched sibling donors for the treatment of acute leukemia, chronic myeloid leukemia, or myelodysplastic syndrome (MDS) between 1990 and 2007. All patients received conventional myeloablative conditioning, T-replete grafts, and cyclosporine plus methotrexate-based GVHD prophylaxis. DNA-based HLA typing allowed categorization of 732 patients (25.3%) as positive and 2159 patients (74.7%) as negative for DRB1*15:01 or *15:02 (DR15). There were no significant differences in baseline characteristics between the HLA DR15 positive and negative groups. In univariate analysis, HLA-DR15 status had no impact on neutrophil engraftment, aGVHD, chronic GVHD (cGVHD), treatment-related mortality, relapse, disease-free survival, or overall survival (OS). In multivariate analysis, DR15 status showed no significant difference in aGVHD, cGVHD, OS, or relapse. In conclusion, DR15 status had no impact on major HLA-matched sibling donor hematopoietic cell transplant outcomes in this large and homogenous cohort of patients with leukemia and MDS.

Original language	English (US)
Pages (from-to)	1302-1308
Number of pages	7
Journal	Biology of Blood and Marrow Transplantation
Volume	18
Issue number	8
DOIs	https://doi.org/10.1016/j.bbmt.2012.02.011
State	Published - Aug 2012

Bibliographical note

Funding Information:
Financial disclosure: This work was supported by the National Institute of Health (NIH) intramural research programs of the NHLBI and NCI. 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 (NIAID) ; a Grant/Cooperative Agreement 5U01HL069294 from NHLBI and NCI ; a contract HHSH234200637015C with Health Resources and Services Administration (HRSA/DHHS); two grants N00014-10-1-0204 and N00014-1-1-0339 from the Office of Naval Research ; and grants from Allos, Inc.; Amgen, Inc.; Angioblast; anonymous donation to the Medical College of Wisconsin; Ariad; Be the Match Foundation; Blue Cross and Blue Shield Association; Buchanan Family Foundation; CaridianBCT; Celgene Corporation; CellGenix, GmbH; Children's Leukemia Research Association; Fresenius-Biotech North America, Inc.; Gamida Cell Teva Joint Venture Ltd.; Genentech, Inc.; Genzyme Corporation; GlaxoSmithKline; Kiadis Pharma; The Leukemia & Lymphoma Society; The Medical College of Wisconsin; Millennium Pharmaceuticals, Inc.; Milliman USA, Inc.; Miltenyi Biotec, Inc.; National Marrow Donor Program; OptumHealth Care Solutions, Inc.; Otsuka America Pharmaceutical, Inc.; Seattle Genetics; Sigma-Tau Pharmaceuticals; Soligenix, Inc.; Swedish Orphan Biovitrum; THERAKOS, Inc.; and Wellpoint, Inc.

Keywords

DR15
GVHD
Graft-versus-lymphoma
Hematopoietic stem cell transplantation (HSCT)
Survival

UN SDGs

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

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10.1016/j.bbmt.2012.02.011

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Battiwalla, M., Ellis, K., Li, P., Pavletic, S. Z., Akpek, G., Hematti, P., Klumpp, T. R., Maziarz, R. T., Savani, B. N., Aljurf, M. D., Cairo, M. S., Drobyski, W. R., George, B., Hahn, T., Khera, N., Litzow, M. R., Loren, A. W., Saber, W., Arora, M., ... Spellman, S. R. (2012). HLA DR15 Antigen Status Does Not Impact Graft-versus-Host Disease or Survival in HLA-Matched Sibling Transplantation for Hematologic Malignancies. Biology of Blood and Marrow Transplantation, 18(8), 1302-1308. https://doi.org/10.1016/j.bbmt.2012.02.011

Battiwalla, M, Ellis, K, Li, P, Pavletic, SZ, Akpek, G, Hematti, P, Klumpp, TR, Maziarz, RT, Savani, BN, Aljurf, MD, Cairo, MS, Drobyski, WR, George, B, Hahn, T, Khera, N, Litzow, MR, Loren, AW, Saber, W, Arora, M, Urbano-Ispizua, A, Cutler, C, Flowers, MED & Spellman, SR 2012, 'HLA DR15 Antigen Status Does Not Impact Graft-versus-Host Disease or Survival in HLA-Matched Sibling Transplantation for Hematologic Malignancies', Biology of Blood and Marrow Transplantation, vol. 18, no. 8, pp. 1302-1308. https://doi.org/10.1016/j.bbmt.2012.02.011

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title = "HLA DR15 Antigen Status Does Not Impact Graft-versus-Host Disease or Survival in HLA-Matched Sibling Transplantation for Hematologic Malignancies",

abstract = "The HLA class II DRB1 antigen DR15 is an important prognostic marker in immune-mediated marrow failure states. DR15 has also been associated with favorable outcomes (reduced acute graft-versus-host disease [aGVHD] and relapse) after allogeneic hematopoietic cell transplant. To elucidate the impact of DR15 on transplantation outcomes, we conducted a retrospective study of 2891 recipients of first allogeneic stem cell transplant from HLA-matched sibling donors for the treatment of acute leukemia, chronic myeloid leukemia, or myelodysplastic syndrome (MDS) between 1990 and 2007. All patients received conventional myeloablative conditioning, T-replete grafts, and cyclosporine plus methotrexate-based GVHD prophylaxis. DNA-based HLA typing allowed categorization of 732 patients (25.3%) as positive and 2159 patients (74.7%) as negative for DRB1*15:01 or *15:02 (DR15). There were no significant differences in baseline characteristics between the HLA DR15 positive and negative groups. In univariate analysis, HLA-DR15 status had no impact on neutrophil engraftment, aGVHD, chronic GVHD (cGVHD), treatment-related mortality, relapse, disease-free survival, or overall survival (OS). In multivariate analysis, DR15 status showed no significant difference in aGVHD, cGVHD, OS, or relapse. In conclusion, DR15 status had no impact on major HLA-matched sibling donor hematopoietic cell transplant outcomes in this large and homogenous cohort of patients with leukemia and MDS.",

keywords = "DR15, GVHD, Graft-versus-lymphoma, Hematopoietic stem cell transplantation (HSCT), Survival",

author = "Minoo Battiwalla and Kristin Ellis and Peigang Li and Pavletic, {Steven Z.} and Gorgun Akpek and Peiman Hematti and Klumpp, {Thomas R.} and Maziarz, {Richard T.} and Savani, {Bipin N.} and Aljurf, {Mahmoud D.} and Cairo, {Mitchell S.} and Drobyski, {William R.} and Biju George and Theresa Hahn and Nandita Khera and Litzow, {Mark R.} and Loren, {Alison W.} and Wael Saber and Mukta Arora and Alvaro Urbano-Ispizua and Corey Cutler and Flowers, {Mary E D} and Spellman, {Stephen R.}",

note = "Funding Information: Financial disclosure: This work was supported by the National Institute of Health (NIH) intramural research programs of the NHLBI and NCI. 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 (NIAID) ; a Grant/Cooperative Agreement 5U01HL069294 from NHLBI and NCI ; a contract HHSH234200637015C with Health Resources and Services Administration (HRSA/DHHS); two grants N00014-10-1-0204 and N00014-1-1-0339 from the Office of Naval Research ; and grants from Allos, Inc.; Amgen, Inc.; Angioblast; anonymous donation to the Medical College of Wisconsin; Ariad; Be the Match Foundation; Blue Cross and Blue Shield Association; Buchanan Family Foundation; CaridianBCT; Celgene Corporation; CellGenix, GmbH; Children's Leukemia Research Association; Fresenius-Biotech North America, Inc.; Gamida Cell Teva Joint Venture Ltd.; Genentech, Inc.; Genzyme Corporation; GlaxoSmithKline; Kiadis Pharma; The Leukemia & Lymphoma Society; The Medical College of Wisconsin; Millennium Pharmaceuticals, Inc.; Milliman USA, Inc.; Miltenyi Biotec, Inc.; National Marrow Donor Program; OptumHealth Care Solutions, Inc.; Otsuka America Pharmaceutical, Inc.; Seattle Genetics; Sigma-Tau Pharmaceuticals; Soligenix, Inc.; Swedish Orphan Biovitrum; THERAKOS, Inc.; and Wellpoint, Inc. ",

year = "2012",

month = aug,

doi = "10.1016/j.bbmt.2012.02.011",

language = "English (US)",

volume = "18",

pages = "1302--1308",

journal = "Biology of Blood and Marrow Transplantation",

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TY - JOUR

T1 - HLA DR15 Antigen Status Does Not Impact Graft-versus-Host Disease or Survival in HLA-Matched Sibling Transplantation for Hematologic Malignancies

AU - Battiwalla, Minoo

AU - Ellis, Kristin

AU - Li, Peigang

AU - Pavletic, Steven Z.

AU - Akpek, Gorgun

AU - Hematti, Peiman

AU - Klumpp, Thomas R.

AU - Maziarz, Richard T.

AU - Savani, Bipin N.

AU - Aljurf, Mahmoud D.

AU - Cairo, Mitchell S.

AU - Drobyski, William R.

AU - George, Biju

AU - Hahn, Theresa

AU - Khera, Nandita

AU - Litzow, Mark R.

AU - Loren, Alison W.

AU - Saber, Wael

AU - Arora, Mukta

AU - Urbano-Ispizua, Alvaro

AU - Cutler, Corey

AU - Flowers, Mary E D

AU - Spellman, Stephen R.

N1 - Funding Information: Financial disclosure: This work was supported by the National Institute of Health (NIH) intramural research programs of the NHLBI and NCI. 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 (NIAID) ; a Grant/Cooperative Agreement 5U01HL069294 from NHLBI and NCI ; a contract HHSH234200637015C with Health Resources and Services Administration (HRSA/DHHS); two grants N00014-10-1-0204 and N00014-1-1-0339 from the Office of Naval Research ; and grants from Allos, Inc.; Amgen, Inc.; Angioblast; anonymous donation to the Medical College of Wisconsin; Ariad; Be the Match Foundation; Blue Cross and Blue Shield Association; Buchanan Family Foundation; CaridianBCT; Celgene Corporation; CellGenix, GmbH; Children's Leukemia Research Association; Fresenius-Biotech North America, Inc.; Gamida Cell Teva Joint Venture Ltd.; Genentech, Inc.; Genzyme Corporation; GlaxoSmithKline; Kiadis Pharma; The Leukemia & Lymphoma Society; The Medical College of Wisconsin; Millennium Pharmaceuticals, Inc.; Milliman USA, Inc.; Miltenyi Biotec, Inc.; National Marrow Donor Program; OptumHealth Care Solutions, Inc.; Otsuka America Pharmaceutical, Inc.; Seattle Genetics; Sigma-Tau Pharmaceuticals; Soligenix, Inc.; Swedish Orphan Biovitrum; THERAKOS, Inc.; and Wellpoint, Inc.

PY - 2012/8

Y1 - 2012/8

N2 - The HLA class II DRB1 antigen DR15 is an important prognostic marker in immune-mediated marrow failure states. DR15 has also been associated with favorable outcomes (reduced acute graft-versus-host disease [aGVHD] and relapse) after allogeneic hematopoietic cell transplant. To elucidate the impact of DR15 on transplantation outcomes, we conducted a retrospective study of 2891 recipients of first allogeneic stem cell transplant from HLA-matched sibling donors for the treatment of acute leukemia, chronic myeloid leukemia, or myelodysplastic syndrome (MDS) between 1990 and 2007. All patients received conventional myeloablative conditioning, T-replete grafts, and cyclosporine plus methotrexate-based GVHD prophylaxis. DNA-based HLA typing allowed categorization of 732 patients (25.3%) as positive and 2159 patients (74.7%) as negative for DRB1*15:01 or *15:02 (DR15). There were no significant differences in baseline characteristics between the HLA DR15 positive and negative groups. In univariate analysis, HLA-DR15 status had no impact on neutrophil engraftment, aGVHD, chronic GVHD (cGVHD), treatment-related mortality, relapse, disease-free survival, or overall survival (OS). In multivariate analysis, DR15 status showed no significant difference in aGVHD, cGVHD, OS, or relapse. In conclusion, DR15 status had no impact on major HLA-matched sibling donor hematopoietic cell transplant outcomes in this large and homogenous cohort of patients with leukemia and MDS.

AB - The HLA class II DRB1 antigen DR15 is an important prognostic marker in immune-mediated marrow failure states. DR15 has also been associated with favorable outcomes (reduced acute graft-versus-host disease [aGVHD] and relapse) after allogeneic hematopoietic cell transplant. To elucidate the impact of DR15 on transplantation outcomes, we conducted a retrospective study of 2891 recipients of first allogeneic stem cell transplant from HLA-matched sibling donors for the treatment of acute leukemia, chronic myeloid leukemia, or myelodysplastic syndrome (MDS) between 1990 and 2007. All patients received conventional myeloablative conditioning, T-replete grafts, and cyclosporine plus methotrexate-based GVHD prophylaxis. DNA-based HLA typing allowed categorization of 732 patients (25.3%) as positive and 2159 patients (74.7%) as negative for DRB1*15:01 or *15:02 (DR15). There were no significant differences in baseline characteristics between the HLA DR15 positive and negative groups. In univariate analysis, HLA-DR15 status had no impact on neutrophil engraftment, aGVHD, chronic GVHD (cGVHD), treatment-related mortality, relapse, disease-free survival, or overall survival (OS). In multivariate analysis, DR15 status showed no significant difference in aGVHD, cGVHD, OS, or relapse. In conclusion, DR15 status had no impact on major HLA-matched sibling donor hematopoietic cell transplant outcomes in this large and homogenous cohort of patients with leukemia and MDS.

KW - DR15

KW - GVHD

KW - Graft-versus-lymphoma

KW - Hematopoietic stem cell transplantation (HSCT)

KW - Survival

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SN - 1083-8791

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JO - Biology of Blood and Marrow Transplantation

JF - Biology of Blood and Marrow Transplantation

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ER -

HLA DR15 Antigen Status Does Not Impact Graft-versus-Host Disease or Survival in HLA-Matched Sibling Transplantation for Hematologic Malignancies

Abstract

Bibliographical note

Keywords

UN SDGs

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