TY - JOUR
T1 - The clinical impact of time to response in de novo accelerated-phase chronic myeloid leukemia
AU - Ohanian, Maro
AU - Kantarjian, Hagop M.
AU - Shoukier, Mahran
AU - Dellasala, Sara
AU - Musaelyan, Arine
AU - Nogueras Gonzalez, Graciela M.
AU - Jabbour, Elias
AU - Abruzzo, Lynne
AU - Verstovsek, Srdan
AU - Borthakur, Gautam
AU - Ravandi, Farhad
AU - Garcia-Manero, Guillermo
AU - Tamamyan, Gevorg
AU - Champlin, Richard
AU - Pierce, Sherry
AU - Ferrajoli, Alessandra
AU - Kadia, Tapan
AU - Cortes, Jorge E.
N1 - Publisher Copyright:
© 2020 Wiley Periodicals LLC
PY - 2020/10/1
Y1 - 2020/10/1
N2 - 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.
AB - 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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U2 - 10.1002/ajh.25907
DO - 10.1002/ajh.25907
M3 - Article
C2 - 32557828
AN - SCOPUS:85088403099
SN - 0361-8609
VL - 95
SP - 1127
EP - 1134
JO - American Journal of Hematology
JF - American Journal of Hematology
IS - 10
ER -