title: Nonmyeloablative bone marrow transplantation: Infectious complications in 65 recipients of HLA-identical and mismatched transplants.
abstract: Infections are a common complication of allogeneic bone marrow transplantation and the leading cause of transplantation-related mortality. It had been hypothesized that transplantation following nonmyeloablative preparative regimens would result in fewer infections by causing less mucosal injury, less graft-versus-host disease, and allowing earlier immune reconstitution. We have retrospectively reviewed the infectious complications of 65 consecutive patients with advanced hematologic malignancies who underwent bone marrow transplantation using a novel preparative regimen consisting of cyclophosphamide, thymic irradiation, and in vivo T-cell depletion. Cytomegalovirus (CMV) infection occurred in 52% of cases in which the donor or recipient had evidence of prior CMV exposure. Using a strategy of preemptive therapy and secondary prophylaxis with ganciclovir, no CMV disease occurred. Infections with gram-positive bacteria predominated over the first 100 days after bone marrow transplantation. Thereafter, the relative proportion of gram-negative infections increased without a significant increase in episodes of neutropenia. The rate of bacterial infections was not influenced by relapse of the underlying malignancy. Seven patients developed infections with Aspergillus species, which was the most common infectious cause of death in these patients. Infections with viruses other than CMV (n=10) and with protozoan organisms (n=2) also occurred. The use of HLA-mismatched donors, the occurrence of grade II-IV acute graft-versus-host disease, and treatment with corticosteroids did not influence the risk of CMV or bacterial or fungal infections in patients who underwent transplantation following this preparative regimen. Overall, the incidence and spectrum of infections in this series was similar to the reported incidence of infections following conventional myeloablative allogeneic stem cell transplantation. We conclude that a quantitative T-cell deficiency in these extensively T-cell depleted patients may be a risk factor for infection, even in the absence of graft-versus-host disease.
authors.affiliation: Allogeneic Bone Marrow Transplant Program, Princess Margaret Hospital/University Health Network, University of Toronto, 610 University Avenue, Toronto, Ontario, Canada M5G 2M9. andrew.daly@uhn.on.ca
authors.forename: Andrew
authors.initials: A
authors.lastname: Daly
authors.forename: Steven
authors.initials: S
authors.lastname: McAfee
authors.forename: Bimal
authors.initials: B
authors.lastname: Dey
authors.forename: Christine
authors.initials: C
authors.lastname: Colby
authors.forename: Leah
authors.initials: L
authors.lastname: Schulte
authors.forename: Beow
authors.initials: B
authors.lastname: Yeap
authors.forename: Robert
authors.initials: R
authors.lastname: Sackstein
authors.forename: Nancy J
authors.initials: NJ
authors.lastname: Tarbell
authors.forename: David
authors.initials: D
authors.lastname: Sachs
authors.forename: Megan
authors.initials: M
authors.lastname: Sykes
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Spitzer
mesh_terms: D000293:Adolescent; D000328:Adult; D001228:Aspergillosis / Q000209:etiology / Q000401:mortality; D016026:Bone Marrow Transplantation / Q000276:immunology*; D015331:Cohort Studies; D003520:Cyclophosphamide; D004198:Disease Susceptibility; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology; D016905:Gram-Negative Bacterial Infections / Q000209:etiology / Q000401:mortality; D006680:HLA Antigens / Q000276:immunology; D019337:Hematologic Neoplasms / Q000276:immunology / Q000628:therapy; D006648:Histocompatibility; D006801:Humans; D007239:Infections / Q000453:epidemiology / Q000209:etiology*; D017708:Leukocyte Transfusion; D008212:Lymphocyte Depletion; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000209:etiology; D011528:Protozoan Infections / Q000453:epidemiology / Q000209:etiology; D012189:Retrospective Studies; D013601:T-Lymphocytes; D013950:Thymus Gland / Q000528:radiation effects; D019172:Transplantation Conditioning / Q000009:adverse effects*; D014777:Virus Diseases / Q000453:epidemiology / Q000209:etiology
chemical_list: D006680:HLA Antigens; D003520:Cyclophosphamide