Cardiac risks of imatinib in chronic myelogenous leukemia (CML) patients who receive allogeneic hematopoietic cell transplantation (Allo-HCT). J Clin Oncol 2008 May 20;26(15_suppl):7039
Date
05/20/2008Pubmed ID
27949600Abstract
: 7039 Background: Since the introduction of imatinib, the role of an allo-HCT in patients with CML has been essentially reserved for patients with advanced disease or resistance to tyrosine kinase inhibitors. Although the side effect profile of imatinib appears tolerable, there have been recent concerns regarding long term use and cardiac toxicity. Whether cardiac related toxicities of imatinib are increased with the addition of myeloablative transplantation is currently unknown.
METHODS: We evaluated the outcome of sixty-two patients with CML who received an allo-HCT at the University of Minnesota between 1999 and 2006. The median age at HCT was 38.3 (range; 6.9-56.9) years. All patients were conditioned with cyclophosphamide (120 mg/kg) and total body irradiation (1320 cGy). GVHD prophylaxis included CSA-based regimens. Disease status at time of HCT included thirty-seven patients in first chronic phase, nineteen in either a second chronic phase or an accelerated phase and six patients in a second accelerated phase. Of the 62 patients, 27 received imatinib therapy pre-or-post-HCT and 35 patients, either never received imatinib (n=32) or received it at the time of relapse (n=3). The mean time to HCT was significantly shorter for the non-imatinib group (248 vs.587 days; Wilcoxon rank-sum test: p=0.01).
RESULTS: The median time to follow-up is 1.96 years (range 0.04-7.30). In multiple regression analysis, disease status at time of HCT had a significant impact on overall survival (OS) and relapse-free survival (RFS) providing 2-year OS and RFS rates of 66% (CI: 0.45, 0.81) and 53% (CI: 0.32, 0.71) for the imatinib group and 57% (95%CI: 0.39, 0.72) and 49% (95%CI: 0.31, 0.64) for the non-imatinib group (Log-rank: p=0.09, 0.09, respectively). Relapse rates (RR) at 2 years were 24% and 14% for the imatinib group and non-imatinib group respectively (Grey-test: p=0.26). Transplant related mortality at 2-years was similar between groups. The incidence of cardiac toxicity at 1-year was 26% and 31% for the imatinib and non-imatinib groups respectively (Grey-test: p=0.49).
CONCLUSIONS: Patients that were treated with imatinib in the pre-or-post-HCT setting had no obvious increased risk of cardiac toxicity and a trend toward improved OS/RFS. No significant financial relationships to disclose.