We investigated the safety and early disease control data for i.v. busulfan (Bu) in
combination with clofarabine (Clo) in patients with acute lymphoblastic leukemia undergoing
allogeneic hematopoietic stem cell transplantation (SCT). Fifty-one patients (median
age, 36 years; range, 20-64 years) received a matched sibling (n = 24), syngeneic
(n = 2), or matched unrelated donor transplant (n = 25) for acute lymphoblastic leukemia
in first complete remission (n = 30), second complete remission (n = 13), or active
disease (n = 8). More than one-half of the patients had a high-risk cytogenetic profile,
as defined by the presence of t(9;22) (n = 17), t(4;11) (n = 3), or complex cytogenetics
(n = 7). Clo 40 mg/m(2) was given once daily, with each dose followed by pharmacokinetically
dosed Bu infused over 3 hours daily for 4 days, followed by hematopoietic SCT 2 days
later. The Bu dose was based on drug clearance, as determined by the patient's response
to a 32-mg/m(2) Bu test dose given 48 hours before the high-dose regimen. The target
daily area under the receiver-operating characteristic curve was 5500 μM/min for patients
age <60 years and 4000 μM/min for those age ≥60 years. The regimen was well tolerated,
with a 100-day nonrelapse mortality rate of 6%. With a median follow-up of 14 months
among surviving patients (range, 6-28 months), the 1-year overall survival, disease-free
survival, and nonrelapse mortality rates were 67% (95% confidence interval [CI], 55%-83%),
54% (95% CI, 41%-71%), and 32% (95% CI, 16%-45%), respectively. For patients undergoing
SCT in first remission, these respective rates were 74%, 64%, and 25%. Our data indicate
that the combination of Clo and Bu provides effective disease control while maintaining
a favorable safety profile.