Sequential regimen of clofarabine, cytosine arabinoside and reduced-intensity conditioned transplantation for primary refractory acute myeloid leukemia.

Abstract

The prognosis of patients with acute myeloid leukemia in whom primary treatment fails remains very poor. In order to improve such patients' outcome, we conducted a phase 2, prospective, multicenter trial to test the feasibility of a new sequential regimen, combining a short course of intensive chemotherapy and a reduced intensity-conditioning regimen, before allogeneic stem-cell transplantation. Twenty-four patients (median age, 47 years) with acute myeloid leukemia in primary treatment failure were included. Cytogenetic risk was poor in 15 patients (62%) and intermediate in nine (38%). The sequential regimen consisted of clofarabine (30 mg/m2/day) and cytosine arabinoside (1 g/m2/day) for 5 days, followed, after a 3-day rest, by reduced-intensity conditioning and allogeneic stem-cell transplantation combining cyclophosphamide (60 mg/kg), intravenous busulfan (3.2 mg/kg/day) for 2 days and anti-thymocyte globulin (2.5 mg/kg/day) for 2 days. Patients in complete remission at day +120 received prophylactic donor lymphocyte infusion. Eighteen patients (75%) achieved complete remission. With a median follow-up of 24.6 months, the Kaplan-Meier estimate of overall survival was 54% (95% CI: 33-71) at 1 year and 38% (95% CI: 18-46) at 2 years. The Kaplan-Meier estimate of leukemia-free survival was 46% (95% CI: 26-64) at 1 year and 29% (95% CI: 13-48) at 2 years. The cumulative incidence of non-relapse mortality was 8% (95% CI: 1-24) at 1 year and 12% (95% CI: 3-19) at 2 years. Results from this phase 2 prospective multicenter trial endorsed the safety and efficacy of a clofarabine-based sequential reduced-toxicity conditioning regimen, which warrants further investigation. This study was registered at www.clinicaltrials.gov, identifier number: NCT01188174.

• Authors: Mohamad Mohty, Florent Malard, Didier Blaise, Noel Milpied, Gérard Socié, Anne Huynh, Oumédaly Reman, Ibrahim Yakoub-Agha, Sabine Furst, Thierry Guillaume, Resa Tabrizi, Stéphane Vigouroux, Pierre Peterlin, Jean El-Cheikh, Philippe Moreau, Myriam Labopin, Patrice Chevallier
• Journal: Haematologica (Haematologica) Vol. 102 Issue 1 Pg. 184-191 (01 2017) ISSN: 1592-8721 [Electronic] Italy
• PMID: 27561720 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study)
• Copyright: Copyright© Ferrata Storti Foundation.

Chemical References

• Adenine Nucleotides
• Arabinonucleosides
• Cytarabine
• Clofarabine

Topics

• Adenine Nucleotides (administration & dosage)
• Adult
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Arabinonucleosides (administration & dosage)
• Clofarabine
• Cytarabine (administration & dosage)
• Drug Resistance, Neoplasm
• Female
• Graft Survival
• Graft vs Host Disease (diagnosis, etiology, prevention & control)
• Hematopoietic Stem Cell Transplantation (adverse effects, methods)
• Humans
• Leukemia, Myeloid, Acute (diagnosis, mortality, therapy)
• Male
• Middle Aged
• Retreatment
• Survival Analysis
• Tissue Donors
• Transplantation Chimera
• Transplantation Conditioning (methods)
• Transplantation, Homologous
• Treatment Outcome
• Young Adult