Phase I/II Trial of Dose-Escalated Busulfan Delivered by Prolonged Continuous Infusion in Allogeneic Transplant Patients

Thomas C. Shea, Christine Walko, Yunro Chung, Anastasia Ivanova, Julia Sheets, Kamakshi Rao, Don Gabriel, Terry Comeau, William Wood, James Coghill, Paul Armistead, Stefanie Sarantopoulos, Jonathan Serody

Research output: Contribution to journalArticlepeer-review

5 Scopus citations


Intensive chemotherapy or chemotherapy plus irradiation and allogeneic stem cell transplantation can be curative for patients with hematologic diseases. Reduced-intensity transplants can also achieve cure and result in less treatment-related mortality but higher relapse rates. Thus, optimizing the conditioning regimens used in allogeneic transplantation remains an important goal. We conducted a phase I/II trial to determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of a continuous infusion of busulfan over 90 hours in conjunction with fludarabine followed by allogeneic related or unrelated donor transplant. Fifty-four patients with advanced hematologic malignancies were enrolled on this study. The MTD was identified as a 24-hour area under the curve (AUC) of approximately 7095 μM/min, which represents a 43% increase over the standard total daily AUC dose of 4800 μM/min given by intermittent schedules. DLTs at doses over 8000 μM/min were identified by a desquamative skin rash and mucositis. No dose-related increase in hepatic, pulmonary, or other organ toxicities were seen, whereas efficacy appeared to be improved at higher dose levels. Continuous-infusion busulfan with intermittent fludarabine provides an alternative treatment strategy that is generally well tolerated and permits an increase in total busulfan dose with encouraging efficacy. (NCI study no. NCT00448357.).

Original languageEnglish (US)
Pages (from-to)2129-2135
Number of pages7
JournalBiology of Blood and Marrow Transplantation
Issue number12
StatePublished - Dec 2015
Externally publishedYes


  • Allogeneic
  • Busulfan
  • Dose escalation
  • Pharmacokinetics

ASJC Scopus subject areas

  • Hematology
  • Transplantation


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