The clinical impact of time to response in de novo accelerated-phase chronic myeloid leukemia |
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| Authors: | Maro Ohanian Hagop M. Kantarjian Mahran Shoukier Sara Dellasala Arine Musaelyan Graciela M. Nogueras Gonzalez Elias Jabbour Lynne Abruzzo Srdan Verstovsek Gautam Borthakur Farhad Ravandi Guillermo Garcia-Manero Gevorg Tamamyan Richard Champlin Sherry Pierce Alessandra Ferrajoli Tapan Kadia Jorge E. Cortes |
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| Affiliation: | 1. Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA;2. Department of Internal Medicine, RWJBH Healthcare System, Jersey City, New Jersey, USA;3. Department of Biostatistics, the University of Texas MD Anderson Cancer Center, Houston, Texas, USA;4. Department of Pathology, the Ohio State University Wexner Medical Center, Columbus, Ohio, USA;5. Pediatric Cancer and Blood Disorders Center of Armenia, Yerevan State Medical University, Yerevan, Armenia;6. Department of Stem Cell Transplantation and Cellular Therapy, the University of Texas MD Anderson Cancer Center, Houston, Texas, USA;7. Georgia Cancer Center, Augusta, Georgia, USA |
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| Abstract: | We aimed to describe the impact of time to response on the outcomes of 75 patients with accelerated-phase chronic myeloid leukemia (CML-AP) at diagnosis. Patients had at least 1 feature of AP: blasts ≥15% (n = 2), basophils ≥20% (n = 19), platelets <100 × 109/L (n = 7), cytogenetic clonal evolution (n = 34), or more than one factor (n = 13). Thirty-three patients received imatinib; 42 received a second-generation tyrosine kinase inhibitor (2GTKI) (19 dasatinib and 23 nilotinib). We used chi-square and Kaplan-Meier analyses to determine the impact of various degrees of molecular and cytogenetic response at early time points (3 and 6 months) on rates of overall cytogenetic and molecular response, overall survival (OS), event-free survival (EFS), transformation-free survival (TFS), and failure-free survival (FFS). After a median follow-up of 96 months (range: 18-224 months), the overall rate of complete cytogenetic response was 79%, of major molecular response, 71%, and of molecular reponse (MR)4.5, 59%. Patients who achieved a major cytogenetic response (MCyR) (n = 49) at 3 months had significantly better 3-year OS (94% vs 75%; P = .002), TFS (98% vs 73%; P < .001), EFS (93% vs 42%; P < .001), and FFS (83% vs 25%; P < .001) rates than patients who did not have MCyR at 3 months. Most (67%) who eventually achieved sustained MR4.5 had achieved MCyR at 3 months. In de novo CML-AP, early response at 3 and 6 months is a strong determinant of long-term outcome. |
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