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.
Bibliographical noteFunding 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.
- Hematopoietic stem cell transplantation
- T cell depletion