Intravenous Busulfan-Based Myeloablative Conditioning Regimens Prior to Hematopoietic Cell Transplantation for Hematologic Malignancies

Abstract

Busulfan (Bu)-containing regimens are commonly used in myeloablative regimens prior to allogeneic hematopoietic cell transplantation (HCT). Yet, there is considerable variability on how Bu is administered related to frequency (four times a day, Q6 or daily, Q24) and the combination with other chemotherapeutic agents (cyclophosphamide, Cy or fludarabine, Flu). A prospective cohort study of recipients of Bu-based conditioning according to contemporary practices was used to compare different approaches in using Bu (BuCy Q6 N=495; BuFlu Q24 N=331; BuCy Q24 N=96; BuFlu Q6 N=91) in patients with myeloid malignancies from 2009 to 2011. BuFlu Q24 recipients were more likely to be older and tended to have worse performance status and higher comorbid burden. The cumulative incidence of hepatic veno-occlusive disease (p=0.4), idiopathic pneumonia (p=0.5) and seizures (p=0.5) did not differ across groups. One-year HCT related mortality ranged from 12% to 16% (P=0.8), three-year relapse incidences ranged from 32% to 36% (p=0.8) and three-year overall survival ranged from 51% to 58% (p=0.2) across groups. This study demonstrates that the use of intravenous Bu Q6 or Q24 or accompanied by Cy or Flu have similar outcomes in the myeloablative setting for treatment of myeloid malignancies.

Safety and Efficacy of Once-Daily Intravenous Busulfan in Allogeneic Transplantation: A Matched-Pair Analysis

“…We considered 7 factors, including patient characteristics (age, sex, PS, and underlying diseases), and transplantation procedures (conditioning regimens, and donor-recipient relation), in the matching process, and all factors were well balanced between the 2 groups (Table 1). As in previous studies [9,10], there was no difference in OS, DFS, RR, or NRM between the 2 groups in the present study. The incidence of GVHD was also similar.…”

“…Their group showed similar estimated daily AUC, OS, and NRM. Recently, Pasquini et al [10] reported the results of a prospective cohort study based on data from the Center for International Blood and Marrow Transplant Research. In that study, 4 cohorts were compared, including ivBU1 combined with Flu or CY and ivBU4 combined with Flu or CY.…”

“…3 , D 1 3 X XToshiro KawakitaD 1 4 X X 4 , D 1 5 X XTetsuo MaedaD 1 6 X X 5 , D 1 7 X XTakanobu MorishitaD 1 8 X X 6 , D 1 9 X XRitsuro SuzukiD 2 0 X X 7 , D 2 1 X XTakahiro FukudaD 2 2 X X 8 , D 2 3 X XTatsuo IchinoheD 2 4 X X 9 , D 2 5 X XMio KurataD 2 6 X X 10 , D 2 7 X XYoshiko AtsutaD 2 8 X X 10 , D 2 9 X XYoshinobu KandaD 3 0 X X 1,2, * INTRODUCTION Intravenous administration of busulfan (ivBU) has been widely used in conditioning regimens for allogeneic hematopoietic stem cell transplantation (HSCT), especially in patients with myeloid malignancies, and its efficacy has been demonstrated in both prospective [1] and retrospective [2,3] studies. IvBU was originally administered 4 times daily (ivBU4) at .8 mg/kg over 2 hours according to the established method for the administration of oral busulfan [4,5], but ivBU4 requires frequent preparations and an inconvenient administration late at night.…”

“…To address these drawbacks, a once-daily infusion of ivBU (ivBU1) at 3.2 mg/kg over 3 hours seemed to be safe and convenient. After some pharmacokinetics studies of ivBU1 [6,7], a few studies compared ivBU1 and ivBU4 in various ways [8][9][10], and demonstrated that these 2 methods give similar clinical results.…”

The confused oncologic patient: a rational clinical approach

“…52 Seizure can manifest as encephalopathy resulting from either an electrolyte disturbance or from drug itself such as high dose busulphan. 53,54 Partial complex seizures may present only as confusion and can be prolonged from non-convulsive status epilepticus which is detectable only by EEG. Seizures may also occur with intrathecal administration of any drug including methotrexate, cytarabine, thiotepa, steroids, or rituximab.…”