Fludarabine and exposure-targeted busulfan compares favorably with busulfan/cyclophosphamide-based regimens in pediatric hematopoietic cell transplantation: Maintaining efficacy with less toxicity

I. H. Bartelink, E. M.L. van Reij, C. E. Gerhardt, E. M. van Maarseveen, A. de Wildt, B. Versluys, C. A. Lindemans, M. B. Bierings, Jaap Jan Boelens

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Busulfan (Bu) is used as a myeloablative agent in conditioning regimens before allogeneic hematopoietic cell transplantation (allo-HCT). In line with strategies explored in adults, patient outcomes may be optimized by replacing cyclophosphamide (Cy) with or without melphalan (Mel) with fludarabine (Flu). We compared outcomes in 2 consecutive cohorts of HCT recipients with a nonmalignant HCT indication, a myeloid malignancy, or a lymphoid malignancy with a contraindication for total body irradiation (TBI). Between 2009 and 2012, 64 children received Flu+Bu at a target dose of 80-95mg·h/L, and between 2005 and 2008, 50children received Bu targeted to 74-80mg·h/L+Cy. In the latter group, Mel was added for patients with myeloid malignancy (n=12). Possible confounding effects of calendar time were studied in 69 patients receiving a myeloablative dose of TBI between 2005 and 2012. Estimated 2-year survival and event-free survival were 82% and 78%, respectively, in the FluBu arm and 78% and 72%, respectively, in the BuCy (Mel) arm (P=not significant). Compared with the BuCy (Mel) arm, less toxicity was noted in the FluBu arm, with lower rates of acute (noninfectious) lung injury (16% versus 36%; P= .007), veno-occlusive disease (3% versus 28%; P= .003), chronic graft-versus-host disease (9% versus 26%; P= .047), adenovirus infection (3%versus 32%; P= .001), and human herpesvirus 6 infection reactivation (21% versus 44%; P= .005). Furthermore, the median duration of neutropenia was shorter in the FluBu arm (11days versus 22days; P<.001), and the patients in this arm required fewer transfusions. Our data indicate that Flu (160mg/m2) with targeted myeloablative Bu (90mg·h/L) is less toxic than and equally effective as BuCy (Mel) in patients with similar indications for allo-HCT.

Original languageEnglish
Pages (from-to)345-353
Number of pages9
JournalBiology of blood and marrow transplantation
Issue number3
Publication statusPublished - Mar 2014


  • Busulfan
  • Fludarabine
  • Hematopoietic cell transplantation
  • Pediatrics

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