Abstract

Abstract 2347

The role of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the imatinib era in patients with chronic myelogenous leukemia (CML) in accelerated phase (AP) has not been evaluated due to few comparison study published. A prospective study was designed to compare the outcome of imatinib versus allo-HSCT for AP CML according to the World Health Organization (WHO) 2001 classification in our center (Registration Number: ChiCTR-TNC-10000955). In imatinib group, imatinib were given at an initial dose of 400 mg or 600 mg daily. In allo-HSCT group, the recommended treatment prior to transplantation was a short-term imatinib therapy less than 3 months. From April 2001 to September 2008, 132 patients were enrolled, 87 in imatinib group and 45 in allo-HSCT group, respectively, according to their intention. In allo-HSCT group, 19 patients performed transplant from a HLA-matched sibling donor, 23 from a HLA-mismatched sibling/haploidentical donor, and 3 from a HLA-mismatched unrelated donor. The end time of evaluation was April 2010. After a median follow-up of 45 months (range, 7–108 months) for 53 living patients on imatinib and 65 months (range, 18–108 months) for 38 living patients post allo-HSCT, imatinib was inferior to allo-HSCT in outcome, with the estimated 6-year event-free survival (EFS), overall survival (OS) and progression-free survival (PFS) rates of 39.2% vs 71.7% (P=0.035), 51.4% vs 83.3% (P=0.023), and 48.3% vs 95.2% (P=0.000), respectively. A multivariate analysis of the total population of 132 patients adding pretreatment characteristics and therapy (imatinib versus allo-HSCT) indicated that longer CML disease duration, pretreatment anemia and higher percentage of peripheral blasts were independent adverse prognostic factors for OS and PFS in common, imatinib therapy was only associated with shorter PFS. In order to analyze whether therapy play an important role in survival differences among patients with or without common pretreatment poor prognostic factors for OS and PFS, we categorized the entire cohort into low-risk (neither factor, n=40), intermediate-risk (either factor, n=59) or poor-risk (at least two factors, n=33). Therapy had no influence on the outcome in low-risk patients, with the estimated 6-year EFS, OS and PFS rates of 80.9% vs 80.7% (P=0.898), 100% vs 81.2% (P=0.114), and 85.2% vs 95.2% (P=0.365), in imatinib group vs allo-HSCT group, respectively. EFS and OS showed no difference by therapy in intermediate-risk patients, with the estimated 6-year EFS and OS rates of 47.1% vs 61.9% (P=0.788), and 61.3% vs 81.3% (P=0.773), in imatinib group vs allo-HSCT group, respectively. However more patients developed a relapse in advanced phase with imatinib compared to those with allo-HSCT, the estimated 6-year PFS rates were 55.7% vs 92.9% (P=0.047), respectively. The superiority of allo-HSCT was extremely significant in poor-risk patients, with the estimated 5-year EFS, OS and PFS rates of 9.3% vs 66.7% (P=0.034), 17.7% vs 100% (P=0.008) and 18.8% vs 100% (P=0.006), in imatinib group vs allo-HSCT group, respectively. We conclude that allo-HSCT is the first-line option for all patients with CML in AP; it is superior to imatinib with evident survival advantage for poor/intermediate-risk patients. However, the outcome of imatinib and allo-HSCT were equally good in low-risk patients with CML in AP. For such patients, it may also be advised that imatinib remains the primary option by carefully monitoring of MRD, and allo-HSCT may be considered if there is evidence of imatinib resistance.

Disclosures:

No relevant conflicts of interest to declare.

Author notes

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Asterisk with author names denotes non-ASH members.