TY - JOUR
T1 - Prognostic factors and survival outcomes in patients with chronic myeloid leukemia in blast phase in the tyrosine kinase inhibitor era
T2 - Cohort study of 477 patients
AU - Jain, Preetesh
AU - Kantarjian, Hagop M.
AU - Ghorab, Ahmad
AU - Sasaki, Koji
AU - Jabbour, Elias J.
AU - Nogueras Gonzalez, Graciela
AU - Kanagal-Shamanna, Rashmi
AU - Issa, Ghayas C.
AU - Garcia-Manero, Guillermo
AU - Devendra, K. C.
AU - Dellasala, Sara
AU - Pierce, Sherry
AU - Konopleva, Marina
AU - Wierda, William G.
AU - Verstovsek, Srdan
AU - Daver, Naval G.
AU - Kadia, Tapan M.
AU - Borthakur, Gautam
AU - O'Brien, Susan
AU - Estrov, Zeev
AU - Ravandi, Farhad
AU - Cortes, Jorge E.
N1 - Publisher Copyright:
© 2017 American Cancer Society
PY - 2017/11/15
Y1 - 2017/11/15
N2 - BACKGROUND: Outcomes in patients with chronic myeloid leukemia in blast phase (CML-BP) are historically dismal. Herein, the authors sought to analyze the characteristics, prognostic factors, and survival outcomes in patients with CML-BP in the tyrosine kinase inhibitor (TKI) era. METHODS: A total of 477 patients with CML-BP were treated with a TKI at some point during the course of their CML. Cox proportional hazard models identified characteristics that were predictive of survival. Overall survival and failure-free survival were assessed. Optimal cutoff points for specific parameters were identified using classification and regression tree (CART) analysis. RESULTS: The median age of the patients was 53 years (range, 16-84 years) and 64% were male. Approximately 80% of patients initially were diagnosed in the chronic phase of CML at a median of 41 months (range, 0.7-298 months) before transformation to CML-BP. De novo CML-BP occurred in 71 patients. Approximately 72% of patients received TKI therapy before CML-BP. The initial therapy for CML-BP included a TKI alone (35%), a TKI with chemotherapy (46%), and non-TKI therapies (19%). The median overall survival was 12 months and the median failure-free survival was 5 months. In multivariate analysis, myeloid immunophenotype, prior TKI, age ≥58 years, lactate dehydrogenase level ≥1227 IU/L, platelet count < 102 K/μL, no history of stem cell transplantation, transition to BP from chronic phase/accelerated phase, and the presence of chromosome 15 aberrations predicted for a significantly increased risk of death. Achievement of major hematologic response and/or complete cytogenetic response to first-line treatment was found to be predictive of better survival. The combination of a TKI with intensive chemotherapy followed by stem cell transplantation appeared to confer the best outcome. CONCLUSIONS: Patients with CML-BP continue to pose a therapeutic challenge, have dismal outcomes, and require newer treatment approaches. Cancer 2017;123:4391-402.
AB - BACKGROUND: Outcomes in patients with chronic myeloid leukemia in blast phase (CML-BP) are historically dismal. Herein, the authors sought to analyze the characteristics, prognostic factors, and survival outcomes in patients with CML-BP in the tyrosine kinase inhibitor (TKI) era. METHODS: A total of 477 patients with CML-BP were treated with a TKI at some point during the course of their CML. Cox proportional hazard models identified characteristics that were predictive of survival. Overall survival and failure-free survival were assessed. Optimal cutoff points for specific parameters were identified using classification and regression tree (CART) analysis. RESULTS: The median age of the patients was 53 years (range, 16-84 years) and 64% were male. Approximately 80% of patients initially were diagnosed in the chronic phase of CML at a median of 41 months (range, 0.7-298 months) before transformation to CML-BP. De novo CML-BP occurred in 71 patients. Approximately 72% of patients received TKI therapy before CML-BP. The initial therapy for CML-BP included a TKI alone (35%), a TKI with chemotherapy (46%), and non-TKI therapies (19%). The median overall survival was 12 months and the median failure-free survival was 5 months. In multivariate analysis, myeloid immunophenotype, prior TKI, age ≥58 years, lactate dehydrogenase level ≥1227 IU/L, platelet count < 102 K/μL, no history of stem cell transplantation, transition to BP from chronic phase/accelerated phase, and the presence of chromosome 15 aberrations predicted for a significantly increased risk of death. Achievement of major hematologic response and/or complete cytogenetic response to first-line treatment was found to be predictive of better survival. The combination of a TKI with intensive chemotherapy followed by stem cell transplantation appeared to confer the best outcome. CONCLUSIONS: Patients with CML-BP continue to pose a therapeutic challenge, have dismal outcomes, and require newer treatment approaches. Cancer 2017;123:4391-402.
KW - blast phase (BP)
KW - bosutinib
KW - chronic myeloid leukemia (CML)
KW - dasatinib
KW - imatinib
KW - nilotinib
KW - ponatinib
KW - tyrosine kinase inhibitors (TKI)
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U2 - 10.1002/cncr.30864
DO - 10.1002/cncr.30864
M3 - Article
C2 - 28743165
AN - SCOPUS:85026356485
SN - 0008-543X
VL - 123
SP - 4391
EP - 4402
JO - Cancer
JF - Cancer
IS - 22
ER -