title: Incidence of Viral and fungal infections following busulfan-based reduced-intensity versus myeloablative conditioning in pediatric allogeneic stem cell transplantation recipients.
abstract: Reductions in the duration and nadir of neutropenia have translated into a significant decrease in bacteremia in adult recipients of allogeneic stem cell transplantation (allo-SCT) with reduced-intensity conditioning (RIC) during the first 30 days after transplantation. It remains to be determined whether RIC allo-SCT also will result in a decrease in systemic viral infections (SVIs) and invasive fungal infections (IFIs), which are more dependent on alterations in cellular immunity. We compared the incidence of SVIs and IFIs in children receiving busulfan-based RIC allo-SCT and in children receiving myeloablative conditioning (MAC) allo-SCT for various malignant and nonmalignant diseases. Allo-SCT recipients at risk for cytomegalovirus (CMV) received ganciclovir/foscarnet, and most of the patients received antifungal prophylaxis with liposomal amphotericin B until day +100. Eighty-six patients (median age, 7.5 years; 70% with malignant disease, 30% with nonmalignant disease; 80% average risk, 20% poor risk) were evaluated. The probability of developing grade II-IV acute graft-versus-host disease (aGVHD) was 29.1% (95% confidence interval [CI]=16.7%-41.6%) in RIC allo-SCT versus 40.3% (95% CI=23.9%-56.6%) in MAC allo-SCT (P=.23), and that of chronic GVHD (cGVHD) was 28.9% (95% CI=14.7%-43.0%) in RIC allo-SCT versus 28.4% (95% CI=10.5%-46.3%) in MAC allo-SCT (P=.73). The overall probability of developing an SVI was 58%, and that of developing an IFI was 15%. These probabilities did not differ significantly by conditioning intensity. In a multivariate Cox regression model, the following were identified as independent risk factors for invasive fungal infection: older age (hazard ratio [HR]=1.3; 95% CI=1.1-1.6; P=< .01), poor risk status (HR=6.5; 95% CI =1.1-37.4; P=.03), and CMV-positive recipient (high vs low CMV risk group, HR=26.7; 95% CI=3.4-210.8; P=< .01). Overall infection-related mortality was only 1.1% (1/86) for SVIs and 2.3% (2/86) for IFIs. Our data indicate that RIC allo-SCT does not carry a lower risk of SVIs and IFIs than MAC allo-SCT in pediatric recipients.
authors.affiliation: Department of Pediatrics, Morgan Stanley Children's Hospital of New York-Presbyterian, Columbia University, New York, New York 10032, USA.
authors.forename: Prakash
authors.initials: P
authors.lastname: Satwani
authors.forename: Leah
authors.initials: L
authors.lastname: Baldinger
authors.forename: Jason
authors.initials: J
authors.lastname: Freedman
authors.forename: Judith S
authors.initials: JS
authors.lastname: Jacobson
authors.forename: Jon
authors.initials: J
authors.lastname: Guerra
authors.forename: Carmella
authors.initials: C
authors.lastname: van de Ven
authors.forename: Erin
authors.initials: E
authors.lastname: Morris
authors.forename: James
authors.initials: J
authors.lastname: Garvin
authors.forename: Diane
authors.initials: D
authors.lastname: George
authors.forename: M Brigid
authors.initials: MB
authors.lastname: Bradley
authors.forename: Monica
authors.initials: M
authors.lastname: Bhatia
authors.forename: Bradford
authors.initials: B
authors.lastname: Tallamy
authors.forename: Joseph
authors.initials: J
authors.lastname: Schwartz
authors.forename: Zhezhen
authors.initials: Z
authors.lastname: Jin
authors.forename: Mitchell S
authors.initials: MS
authors.lastname: Cairo
mesh_terms: D002066:Busulfan / Q000008:administration & dosage / Q000009:adverse effects*; D002648:Child; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D015994:Incidence; D053208:Kaplan-Meier Estimate; D008297:Male; D015999:Multivariate Analysis; D009181:Mycoses / Q000209:etiology* / Q000276:immunology; D012307:Risk Factors; D015996:Survival Rate; D019172:Transplantation Conditioning / Q000009:adverse effects* / Q000379:methods; D014777:Virus Diseases / Q000209:etiology* / Q000276:immunology
chemical_list: D002066:Busulfan