Higher Risk of Cytomegalovirus and Aspergillus Infections in Recipients of T Cell-Depleted Unrelated Bone Marrow: Analysis of Infectious Complications in Patients Treated with T Cell Depletion Versus Immunosuppressive Therapy to Prevent Graft-versus-Host Disease

Jo Anne H van Burik; Shelly L. Carter; Alison G. Freifeld; Kevin P. High; Kamar T. Godder; Genovefa A. Papanicolaou; Adam M. Mendizabal; John E. Wagner; Saul Yanovich; Nancy A. Kernan

doi:10.1016/j.bbmt.2007.08.049

Higher Risk of Cytomegalovirus and Aspergillus Infections in Recipients of T Cell-Depleted Unrelated Bone Marrow: Analysis of Infectious Complications in Patients Treated with T Cell Depletion Versus Immunosuppressive Therapy to Prevent Graft-versus-Host Disease

Jo Anne H van Burik, Shelly L. Carter, Alison G. Freifeld, Kevin P. High, Kamar T. Godder, Genovefa A. Papanicolaou, Adam M. Mendizabal, John E. Wagner, Saul Yanovich, Nancy A. Kernan

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

125 Scopus citations

Abstract

Serious infections are a major obstacle limiting the usefulness of unrelated donor marrow transplantation. Graft-versus-host disease (GVHD) and its therapy are associated with a high risk of opportunistic infection. In this study, patients were randomized to receive 1 of 2 GVHD prophylaxis strategies, marrow T cell depletion, and cyclosporine (TCD) or methotrexate/cyclosporine (M/C) after transplantation. The patients underwent transplantation between March 1995 and October 2000 as part of a multicenter randomized trial. As a secondary analysis, we analyzed infections in this study cohort. Among the 404 patients who underwent transplantation, a total of 1598 infections were reported. The rates of serious and fatal infections did not differ between the TCD and M/C groups. Bacterial infections accounted for 1/3 of serious infections in each treatment arm. A significantly higher incidence of severe cytomegalovirus (CMV) and life-threatening or fatal aspergillus infections was observed in the patients receiving TCD (CMV, 28% vs 17% [P = .02]; aspergillosis, 16% vs 7% [P < .01]). The only independent risk factor for serious infection was the development of grade III-IV acute GVHD (aGVHD; hazard ratio = 1.41; 95% confidence interval = 1.03-1.91). Strategies to speed immune recovery, even in the absence of GVHD, are needed to overcome the risk of infection after unrelated donor transplantation.

Original language	English (US)
Pages (from-to)	1487-1498
Number of pages	12
Journal	Biology of Blood and Marrow Transplantation
Volume	13
Issue number	12
DOIs	https://doi.org/10.1016/j.bbmt.2007.08.049
State	Published - Dec 2007

Bibliographical note

Funding Information:
This work was supported by grants from the National Heart, Lung and Blood Institute (NHLBI): N01-HB-47095 (J.H.vB., J.E.W.), N01-HB-47097 (A.G.F., K.P.H., K.T.G., S.Y.), N01-HB-47094 (S.L.C., A.M.M.), and N01-HB-47098 (N.A.K., G.A.P.). We thank the patients who willingly entered this large clinical trial; the physicians, nurses, and other support staff who cared for the patients during the transplantation procedures; and the clinical investigation team at each participating institution who provided data collection and follow-up. We also thank the NHLBI for supporting this trial and Janet Hegland for her assistance with onsite auditing. The NHLBI was the sole funding source for the trial. In addition to the authors, the following transplantation centers, study physicians, and experts contributed to this study: University of Minnesota (n = 103; Daniel J. Weisdorf, MD), Memorial Sloan-Kettering Cancer Center (n = 70; Richard O'Reilly, MD and Esperanza Papadopoulos, MD), Medical College of Virginia (n = 53), Wake Forest University-Baptist (n = 36; David Hurd, MD), University of Nebraska (n = 34; Stephen Pavletic, MD and Michael Bishop, MD), University of Utah (n = 33; Finn Bo Petersen, MD and Patrick Beatty, MD), Stanford University (n = 25; Robert Negrin, MD), University of Iowa (n = 19; Robert Gingrich, MD), University of South Carolina (n = 13; Jean Henslee-Downey, MD), Ohio State University (n = 6; Edward Copelan, MD), Duke University (n = 6; Joanne Kurtzberg, MD), University of Kentucky (n = 5; John S. Thompson, MD and Gordon Phillips, MD), Medical College of Wisconsin (n = 4; James Casper, MD and Neal Flomenberg, MD), Western Pennsylvania Hospital (n = 2; Richard Shattuck, MD), University of Pittsburgh (n = 1; Albert Donnenberg, PhD), the EMMES Corporation (Donald Stablein, PhD and Elizabeth Wagner, MPH), NHLBI (LeeAnn Jensen, PhD, Nancy Geller, PhD, and Paul McCurdy, MD). J.H.vB. performed the research, analyzed the data, and wrote the manuscript; S.L.C. designed and performed the research, analyzed the data, and wrote the manuscript; A.G.F. performed the research, analyzed data, and wrote the manuscript; K.P.H. performed the research, analyzed the data, and wrote the manuscript; K.T.G. performed the research, analyzed the data, and wrote the manuscript; G.A.P. performed the research, analyzed the data, and wrote the manuscript; A.M.M. performed the research, analyzed the data, and wrote the manuscript; J.E.W. designed and performed the research, analyzed the data, and wrote the manuscript; S.Y. performed the research, analyzed the data, and wrote the manuscript; and N.A.K. designed and performed the research, analyzed the data, and wrote the manuscript.

Keywords

Aspergillosis
Cytomegalovirus
Hematopoietic stem cell transplantation
T cell depletion

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van Burik, J. A. H., Carter, S. L., Freifeld, A. G., High, K. P., Godder, K. T., Papanicolaou, G. A., Mendizabal, A. M., Wagner, J. E., Yanovich, S., & Kernan, N. A. (2007). Higher Risk of Cytomegalovirus and Aspergillus Infections in Recipients of T Cell-Depleted Unrelated Bone Marrow: Analysis of Infectious Complications in Patients Treated with T Cell Depletion Versus Immunosuppressive Therapy to Prevent Graft-versus-Host Disease. Biology of Blood and Marrow Transplantation, 13(12), 1487-1498. https://doi.org/10.1016/j.bbmt.2007.08.049

Higher Risk of Cytomegalovirus and Aspergillus Infections in Recipients of T Cell-Depleted Unrelated Bone Marrow: Analysis of Infectious Complications in Patients Treated with T Cell Depletion Versus Immunosuppressive Therapy to Prevent Graft-versus-Host Disease. / van Burik, Jo Anne H; Carter, Shelly L.; Freifeld, Alison G. et al.
In: Biology of Blood and Marrow Transplantation, Vol. 13, No. 12, 12.2007, p. 1487-1498.

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

van Burik, JAH, Carter, SL, Freifeld, AG, High, KP, Godder, KT, Papanicolaou, GA, Mendizabal, AM, Wagner, JE, Yanovich, S & Kernan, NA 2007, 'Higher Risk of Cytomegalovirus and Aspergillus Infections in Recipients of T Cell-Depleted Unrelated Bone Marrow: Analysis of Infectious Complications in Patients Treated with T Cell Depletion Versus Immunosuppressive Therapy to Prevent Graft-versus-Host Disease', Biology of Blood and Marrow Transplantation, vol. 13, no. 12, pp. 1487-1498. https://doi.org/10.1016/j.bbmt.2007.08.049

van Burik JAH, Carter SL, Freifeld AG, High KP, Godder KT, Papanicolaou GA et al. Higher Risk of Cytomegalovirus and Aspergillus Infections in Recipients of T Cell-Depleted Unrelated Bone Marrow: Analysis of Infectious Complications in Patients Treated with T Cell Depletion Versus Immunosuppressive Therapy to Prevent Graft-versus-Host Disease. Biology of Blood and Marrow Transplantation. 2007 Dec;13(12):1487-1498. doi: 10.1016/j.bbmt.2007.08.049

van Burik, Jo Anne H ; Carter, Shelly L. ; Freifeld, Alison G. et al. / Higher Risk of Cytomegalovirus and Aspergillus Infections in Recipients of T Cell-Depleted Unrelated Bone Marrow : Analysis of Infectious Complications in Patients Treated with T Cell Depletion Versus Immunosuppressive Therapy to Prevent Graft-versus-Host Disease. In: Biology of Blood and Marrow Transplantation. 2007 ; Vol. 13, No. 12. pp. 1487-1498.

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title = "Higher Risk of Cytomegalovirus and Aspergillus Infections in Recipients of T Cell-Depleted Unrelated Bone Marrow: Analysis of Infectious Complications in Patients Treated with T Cell Depletion Versus Immunosuppressive Therapy to Prevent Graft-versus-Host Disease",

abstract = "Serious infections are a major obstacle limiting the usefulness of unrelated donor marrow transplantation. Graft-versus-host disease (GVHD) and its therapy are associated with a high risk of opportunistic infection. In this study, patients were randomized to receive 1 of 2 GVHD prophylaxis strategies, marrow T cell depletion, and cyclosporine (TCD) or methotrexate/cyclosporine (M/C) after transplantation. The patients underwent transplantation between March 1995 and October 2000 as part of a multicenter randomized trial. As a secondary analysis, we analyzed infections in this study cohort. Among the 404 patients who underwent transplantation, a total of 1598 infections were reported. The rates of serious and fatal infections did not differ between the TCD and M/C groups. Bacterial infections accounted for 1/3 of serious infections in each treatment arm. A significantly higher incidence of severe cytomegalovirus (CMV) and life-threatening or fatal aspergillus infections was observed in the patients receiving TCD (CMV, 28% vs 17% [P = .02]; aspergillosis, 16% vs 7% [P < .01]). The only independent risk factor for serious infection was the development of grade III-IV acute GVHD (aGVHD; hazard ratio = 1.41; 95% confidence interval = 1.03-1.91). Strategies to speed immune recovery, even in the absence of GVHD, are needed to overcome the risk of infection after unrelated donor transplantation.",

keywords = "Aspergillosis, Cytomegalovirus, Hematopoietic stem cell transplantation, T cell depletion",

author = "{van Burik}, {Jo Anne H} and Carter, {Shelly L.} and Freifeld, {Alison G.} and High, {Kevin P.} and Godder, {Kamar T.} and Papanicolaou, {Genovefa A.} and Mendizabal, {Adam M.} and Wagner, {John E.} and Saul Yanovich and Kernan, {Nancy A.}",

note = "Funding Information: This work was supported by grants from the National Heart, Lung and Blood Institute (NHLBI): N01-HB-47095 (J.H.vB., J.E.W.), N01-HB-47097 (A.G.F., K.P.H., K.T.G., S.Y.), N01-HB-47094 (S.L.C., A.M.M.), and N01-HB-47098 (N.A.K., G.A.P.). We thank the patients who willingly entered this large clinical trial; the physicians, nurses, and other support staff who cared for the patients during the transplantation procedures; and the clinical investigation team at each participating institution who provided data collection and follow-up. We also thank the NHLBI for supporting this trial and Janet Hegland for her assistance with onsite auditing. The NHLBI was the sole funding source for the trial. In addition to the authors, the following transplantation centers, study physicians, and experts contributed to this study: University of Minnesota (n = 103; Daniel J. Weisdorf, MD), Memorial Sloan-Kettering Cancer Center (n = 70; Richard O'Reilly, MD and Esperanza Papadopoulos, MD), Medical College of Virginia (n = 53), Wake Forest University-Baptist (n = 36; David Hurd, MD), University of Nebraska (n = 34; Stephen Pavletic, MD and Michael Bishop, MD), University of Utah (n = 33; Finn Bo Petersen, MD and Patrick Beatty, MD), Stanford University (n = 25; Robert Negrin, MD), University of Iowa (n = 19; Robert Gingrich, MD), University of South Carolina (n = 13; Jean Henslee-Downey, MD), Ohio State University (n = 6; Edward Copelan, MD), Duke University (n = 6; Joanne Kurtzberg, MD), University of Kentucky (n = 5; John S. Thompson, MD and Gordon Phillips, MD), Medical College of Wisconsin (n = 4; James Casper, MD and Neal Flomenberg, MD), Western Pennsylvania Hospital (n = 2; Richard Shattuck, MD), University of Pittsburgh (n = 1; Albert Donnenberg, PhD), the EMMES Corporation (Donald Stablein, PhD and Elizabeth Wagner, MPH), NHLBI (LeeAnn Jensen, PhD, Nancy Geller, PhD, and Paul McCurdy, MD). J.H.vB. performed the research, analyzed the data, and wrote the manuscript; S.L.C. designed and performed the research, analyzed the data, and wrote the manuscript; A.G.F. performed the research, analyzed data, and wrote the manuscript; K.P.H. performed the research, analyzed the data, and wrote the manuscript; K.T.G. performed the research, analyzed the data, and wrote the manuscript; G.A.P. performed the research, analyzed the data, and wrote the manuscript; A.M.M. performed the research, analyzed the data, and wrote the manuscript; J.E.W. designed and performed the research, analyzed the data, and wrote the manuscript; S.Y. performed the research, analyzed the data, and wrote the manuscript; and N.A.K. designed and performed the research, analyzed the data, and wrote the manuscript.",

year = "2007",

month = dec,

doi = "10.1016/j.bbmt.2007.08.049",

language = "English (US)",

volume = "13",

pages = "1487--1498",

journal = "Biology of Blood and Marrow Transplantation",

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TY - JOUR

T1 - Higher Risk of Cytomegalovirus and Aspergillus Infections in Recipients of T Cell-Depleted Unrelated Bone Marrow

T2 - Analysis of Infectious Complications in Patients Treated with T Cell Depletion Versus Immunosuppressive Therapy to Prevent Graft-versus-Host Disease

AU - van Burik, Jo Anne H

AU - Carter, Shelly L.

AU - Freifeld, Alison G.

AU - High, Kevin P.

AU - Godder, Kamar T.

AU - Papanicolaou, Genovefa A.

AU - Mendizabal, Adam M.

AU - Wagner, John E.

AU - Yanovich, Saul

AU - Kernan, Nancy A.

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AB - Serious infections are a major obstacle limiting the usefulness of unrelated donor marrow transplantation. Graft-versus-host disease (GVHD) and its therapy are associated with a high risk of opportunistic infection. In this study, patients were randomized to receive 1 of 2 GVHD prophylaxis strategies, marrow T cell depletion, and cyclosporine (TCD) or methotrexate/cyclosporine (M/C) after transplantation. The patients underwent transplantation between March 1995 and October 2000 as part of a multicenter randomized trial. As a secondary analysis, we analyzed infections in this study cohort. Among the 404 patients who underwent transplantation, a total of 1598 infections were reported. The rates of serious and fatal infections did not differ between the TCD and M/C groups. Bacterial infections accounted for 1/3 of serious infections in each treatment arm. A significantly higher incidence of severe cytomegalovirus (CMV) and life-threatening or fatal aspergillus infections was observed in the patients receiving TCD (CMV, 28% vs 17% [P = .02]; aspergillosis, 16% vs 7% [P < .01]). The only independent risk factor for serious infection was the development of grade III-IV acute GVHD (aGVHD; hazard ratio = 1.41; 95% confidence interval = 1.03-1.91). Strategies to speed immune recovery, even in the absence of GVHD, are needed to overcome the risk of infection after unrelated donor transplantation.

KW - Aspergillosis

KW - Cytomegalovirus

KW - Hematopoietic stem cell transplantation

KW - T cell depletion

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Higher Risk of Cytomegalovirus and Aspergillus Infections in Recipients of T Cell-Depleted Unrelated Bone Marrow: Analysis of Infectious Complications in Patients Treated with T Cell Depletion Versus Immunosuppressive Therapy to Prevent Graft-versus-Host Disease

Abstract

Bibliographical note

Keywords

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