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The clinical impact of time to response in de novo accelerated‐phase chronic myeloid leukemia

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The clinical impact of time to response in de novo accelerated‐phase chronic myeloid leukemia

American Journal of Hematology

Fecha de publicación: 17 June 2020


Autores: 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 García ‐ Manero, Gevorg Tamamyan, Richard Champlin, Jerez Pierce, Alessandra Ferrajoli,Tapan Kadia, Jorge E. Cortes.

Background: 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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