Risk factors for acute graft-versus-host disease after human leukocyte antigen-identical sibling transplants for adults with leukemia

Theresa Hahn, Philip L. McCarthy, Mei Jie Zhang, Dan Wang, Mukta Arora, Haydar Frangoul, Robert Peter Gale, Gregory A. Hale, John Horan, Luis Isola, Richard T. Maziarz, Jon J. Van Rood, Vikas Gupta, Joerg Halter, Vijay Reddy, Pierre Tiberghien, Mark R Litzow, Claudio Anasetti, Stephen Pavletic, Olle Ringdén

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Abstract

Purpose: Acute graft-versus-host disease (GVHD) causes substantial morbidity and mortality after human leukocyte antigen (HLA)-identical sibling transplants. No large registry studies of acute GVHD risk factors have been reported in two decades. Risk factors may have changed in this interval as transplant-related techniques have evolved. Patients and Methods: Acute GVHD risk factors were analyzed in 1,960 adults after HLA-identical sibling myeloablative transplant for acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), or chronic myeloid leukemia (CML) reported by 226 centers worldwide to the Center for International Blood and Marrow Transplant Research from 1995 to 2002. Outcome was measured as time from transplant to onset of grade 2 to 4 acute GVHD, with death without acute GVHD as a competing risk. Results: Cumulative incidence of grade 2 to 4 acute GVHD was 35% (95% CI, 33% to 37%). In multivariable analyses, factors significantly associated with grade 2 to 4 acute GVHD were cyclophosphamide + total-body irradiation versus busulfan + cyclophosphamide (relative risk [RR] = 1.4; P < .0001), blood cell versus bone marrow grafts in patients age 18 to 39 years (RR = 1.43; P = .0023), recipient age 40 and older versus age 18 to 39 years receiving bone marrow grafts (RR = 1.44; P = .0005), CML versus AML/ALL (RR = 1.35; P = .0003), white/Black versus Asian/Hispanic race (RR = 1.54; P = .0003), Karnofsky performance score less than 90 versus 90 to 100 (RR = 1.27; P = .014), and recipient/donor cytomegalovirus-seronegative versus either positive (RR = 1.20; P = .04). Stratification by disease showed the same significant predictors of grade 2 to 4 acute GVHD for CML; however, KPS and cytomegalovirus serostatus were not significant predictors for AML/ALL. Conclusion: This analysis confirmed several previously reported risk factors for grade 2 to 4 acute GVHD. However, several new factors were identified whereas others are no longer significant. These new data may facilitate individualized risk estimates and raise several interesting biologic questions.

Original languageEnglish (US)
Pages (from-to)5728-5734
Number of pages7
JournalJournal of Clinical Oncology
Volume26
Issue number35
DOIs
StatePublished - Dec 10 2008

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Graft vs Host Disease
HLA Antigens
Siblings
Leukemia
Transplants
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Acute Myeloid Leukemia
Bone Marrow
Cytomegalovirus
Cyclophosphamide
Busulfan
Whole-Body Irradiation
Hispanic Americans
Statistical Factor Analysis
Registries
Blood Cells
Tissue Donors
Morbidity
Mortality

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Risk factors for acute graft-versus-host disease after human leukocyte antigen-identical sibling transplants for adults with leukemia. / Hahn, Theresa; McCarthy, Philip L.; Zhang, Mei Jie; Wang, Dan; Arora, Mukta; Frangoul, Haydar; Gale, Robert Peter; Hale, Gregory A.; Horan, John; Isola, Luis; Maziarz, Richard T.; Van Rood, Jon J.; Gupta, Vikas; Halter, Joerg; Reddy, Vijay; Tiberghien, Pierre; Litzow, Mark R; Anasetti, Claudio; Pavletic, Stephen; Ringdén, Olle.

In: Journal of Clinical Oncology, Vol. 26, No. 35, 10.12.2008, p. 5728-5734.

Research output: Contribution to journalArticle

Hahn, T, McCarthy, PL, Zhang, MJ, Wang, D, Arora, M, Frangoul, H, Gale, RP, Hale, GA, Horan, J, Isola, L, Maziarz, RT, Van Rood, JJ, Gupta, V, Halter, J, Reddy, V, Tiberghien, P, Litzow, MR, Anasetti, C, Pavletic, S & Ringdén, O 2008, 'Risk factors for acute graft-versus-host disease after human leukocyte antigen-identical sibling transplants for adults with leukemia', Journal of Clinical Oncology, vol. 26, no. 35, pp. 5728-5734. https://doi.org/10.1200/JCO.2008.17.6545
Hahn, Theresa ; McCarthy, Philip L. ; Zhang, Mei Jie ; Wang, Dan ; Arora, Mukta ; Frangoul, Haydar ; Gale, Robert Peter ; Hale, Gregory A. ; Horan, John ; Isola, Luis ; Maziarz, Richard T. ; Van Rood, Jon J. ; Gupta, Vikas ; Halter, Joerg ; Reddy, Vijay ; Tiberghien, Pierre ; Litzow, Mark R ; Anasetti, Claudio ; Pavletic, Stephen ; Ringdén, Olle. / Risk factors for acute graft-versus-host disease after human leukocyte antigen-identical sibling transplants for adults with leukemia. In: Journal of Clinical Oncology. 2008 ; Vol. 26, No. 35. pp. 5728-5734.
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abstract = "Purpose: Acute graft-versus-host disease (GVHD) causes substantial morbidity and mortality after human leukocyte antigen (HLA)-identical sibling transplants. No large registry studies of acute GVHD risk factors have been reported in two decades. Risk factors may have changed in this interval as transplant-related techniques have evolved. Patients and Methods: Acute GVHD risk factors were analyzed in 1,960 adults after HLA-identical sibling myeloablative transplant for acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), or chronic myeloid leukemia (CML) reported by 226 centers worldwide to the Center for International Blood and Marrow Transplant Research from 1995 to 2002. Outcome was measured as time from transplant to onset of grade 2 to 4 acute GVHD, with death without acute GVHD as a competing risk. Results: Cumulative incidence of grade 2 to 4 acute GVHD was 35{\%} (95{\%} CI, 33{\%} to 37{\%}). In multivariable analyses, factors significantly associated with grade 2 to 4 acute GVHD were cyclophosphamide + total-body irradiation versus busulfan + cyclophosphamide (relative risk [RR] = 1.4; P < .0001), blood cell versus bone marrow grafts in patients age 18 to 39 years (RR = 1.43; P = .0023), recipient age 40 and older versus age 18 to 39 years receiving bone marrow grafts (RR = 1.44; P = .0005), CML versus AML/ALL (RR = 1.35; P = .0003), white/Black versus Asian/Hispanic race (RR = 1.54; P = .0003), Karnofsky performance score less than 90 versus 90 to 100 (RR = 1.27; P = .014), and recipient/donor cytomegalovirus-seronegative versus either positive (RR = 1.20; P = .04). Stratification by disease showed the same significant predictors of grade 2 to 4 acute GVHD for CML; however, KPS and cytomegalovirus serostatus were not significant predictors for AML/ALL. Conclusion: This analysis confirmed several previously reported risk factors for grade 2 to 4 acute GVHD. However, several new factors were identified whereas others are no longer significant. These new data may facilitate individualized risk estimates and raise several interesting biologic questions.",
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T1 - Risk factors for acute graft-versus-host disease after human leukocyte antigen-identical sibling transplants for adults with leukemia

AU - Hahn, Theresa

AU - McCarthy, Philip L.

AU - Zhang, Mei Jie

AU - Wang, Dan

AU - Arora, Mukta

AU - Frangoul, Haydar

AU - Gale, Robert Peter

AU - Hale, Gregory A.

AU - Horan, John

AU - Isola, Luis

AU - Maziarz, Richard T.

AU - Van Rood, Jon J.

AU - Gupta, Vikas

AU - Halter, Joerg

AU - Reddy, Vijay

AU - Tiberghien, Pierre

AU - Litzow, Mark R

AU - Anasetti, Claudio

AU - Pavletic, Stephen

AU - Ringdén, Olle

PY - 2008/12/10

Y1 - 2008/12/10

N2 - Purpose: Acute graft-versus-host disease (GVHD) causes substantial morbidity and mortality after human leukocyte antigen (HLA)-identical sibling transplants. No large registry studies of acute GVHD risk factors have been reported in two decades. Risk factors may have changed in this interval as transplant-related techniques have evolved. Patients and Methods: Acute GVHD risk factors were analyzed in 1,960 adults after HLA-identical sibling myeloablative transplant for acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), or chronic myeloid leukemia (CML) reported by 226 centers worldwide to the Center for International Blood and Marrow Transplant Research from 1995 to 2002. Outcome was measured as time from transplant to onset of grade 2 to 4 acute GVHD, with death without acute GVHD as a competing risk. Results: Cumulative incidence of grade 2 to 4 acute GVHD was 35% (95% CI, 33% to 37%). In multivariable analyses, factors significantly associated with grade 2 to 4 acute GVHD were cyclophosphamide + total-body irradiation versus busulfan + cyclophosphamide (relative risk [RR] = 1.4; P < .0001), blood cell versus bone marrow grafts in patients age 18 to 39 years (RR = 1.43; P = .0023), recipient age 40 and older versus age 18 to 39 years receiving bone marrow grafts (RR = 1.44; P = .0005), CML versus AML/ALL (RR = 1.35; P = .0003), white/Black versus Asian/Hispanic race (RR = 1.54; P = .0003), Karnofsky performance score less than 90 versus 90 to 100 (RR = 1.27; P = .014), and recipient/donor cytomegalovirus-seronegative versus either positive (RR = 1.20; P = .04). Stratification by disease showed the same significant predictors of grade 2 to 4 acute GVHD for CML; however, KPS and cytomegalovirus serostatus were not significant predictors for AML/ALL. Conclusion: This analysis confirmed several previously reported risk factors for grade 2 to 4 acute GVHD. However, several new factors were identified whereas others are no longer significant. These new data may facilitate individualized risk estimates and raise several interesting biologic questions.

AB - Purpose: Acute graft-versus-host disease (GVHD) causes substantial morbidity and mortality after human leukocyte antigen (HLA)-identical sibling transplants. No large registry studies of acute GVHD risk factors have been reported in two decades. Risk factors may have changed in this interval as transplant-related techniques have evolved. Patients and Methods: Acute GVHD risk factors were analyzed in 1,960 adults after HLA-identical sibling myeloablative transplant for acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), or chronic myeloid leukemia (CML) reported by 226 centers worldwide to the Center for International Blood and Marrow Transplant Research from 1995 to 2002. Outcome was measured as time from transplant to onset of grade 2 to 4 acute GVHD, with death without acute GVHD as a competing risk. Results: Cumulative incidence of grade 2 to 4 acute GVHD was 35% (95% CI, 33% to 37%). In multivariable analyses, factors significantly associated with grade 2 to 4 acute GVHD were cyclophosphamide + total-body irradiation versus busulfan + cyclophosphamide (relative risk [RR] = 1.4; P < .0001), blood cell versus bone marrow grafts in patients age 18 to 39 years (RR = 1.43; P = .0023), recipient age 40 and older versus age 18 to 39 years receiving bone marrow grafts (RR = 1.44; P = .0005), CML versus AML/ALL (RR = 1.35; P = .0003), white/Black versus Asian/Hispanic race (RR = 1.54; P = .0003), Karnofsky performance score less than 90 versus 90 to 100 (RR = 1.27; P = .014), and recipient/donor cytomegalovirus-seronegative versus either positive (RR = 1.20; P = .04). Stratification by disease showed the same significant predictors of grade 2 to 4 acute GVHD for CML; however, KPS and cytomegalovirus serostatus were not significant predictors for AML/ALL. Conclusion: This analysis confirmed several previously reported risk factors for grade 2 to 4 acute GVHD. However, several new factors were identified whereas others are no longer significant. These new data may facilitate individualized risk estimates and raise several interesting biologic questions.

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