Clofarabine combined with busulfan provides excellent disease control in adult patients with acute lymphoblastic leukemia undergoing allogeneic hematopoietic stem cell transplantation.

Abstract

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.

• Authors: Partow Kebriaei, Roland Basset, C Ledesma, S Ciurea, S Parmar, E J Shpall, C Hosing, Issa Khouri, M Qazilbash, U Popat, A Alousi, Y Nieto, R B Jones, M de Lima, R E Champlin, Borje S Andersson
• Journal: Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation (Biol Blood Marrow Transplant) Vol. 18 Issue 12 Pg. 1819-26 (Dec 2012) ISSN: 1523-6536 [Electronic] United States
• PMID: 22750645 (Publication Type: Clinical Trial, Phase II, Journal Article)
• Copyright: Copyright © 2012 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Chemical References

• Adenine Nucleotides
• Arabinonucleosides
• Clofarabine
• Busulfan

Topics

• Adenine Nucleotides (administration & dosage, adverse effects)
• Adult
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Arabinonucleosides (administration & dosage, adverse effects)
• Busulfan (administration & dosage, adverse effects)
• Clofarabine
• Female
• Hematopoietic Stem Cell Transplantation (methods)
• Humans
• Male
• Middle Aged
• Precursor Cell Lymphoblastic Leukemia-Lymphoma (drug therapy, surgery)
• Prospective Studies
• Transplantation Conditioning (methods)
• Young Adult