Prognostic factors and survival outcomes in patients with chronic myeloid leukemia in blast phase in the tyrosine kinase inhibitor era: Cohort study of 477 patients

Preetesh Jain, Hagop M. Kantarjian, Ahmad Ghorab, Koji Sasaki, Elias J. Jabbour, Graciela Nogueras Gonzalez, Rashmi Kanagal-Shamanna, Ghayas C. Issa, Guillermo Garcia-Manero, K. C. Devendra, Sara Dellasala, Sherry Pierce, Marina Konopleva, William G. Wierda, Srdan Verstovsek, Naval G. Daver, Tapan M. Kadia, Gautam Borthakur, Susan O'Brien, Zeev EstrovFarhad Ravandi, Jorge E. Cortes

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)4391-4402
Number of pages12
JournalCancer
Volume123
Issue number22
DOIs
StatePublished - Nov 15 2017
Externally publishedYes

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Blast Crisis
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Protein-Tyrosine Kinases
Cohort Studies
Survival
Stem Cell Transplantation
Therapeutics
Chromosomes, Human, Pair 15
Drug Therapy
Platelet Count
L-Lactate Dehydrogenase
Proportional Hazards Models
Cytogenetics
Chromosome Aberrations
Phosphotransferases
Multivariate Analysis
Regression Analysis

Keywords

  • blast phase (BP)
  • bosutinib
  • chronic myeloid leukemia (CML)
  • dasatinib
  • imatinib
  • nilotinib
  • ponatinib
  • tyrosine kinase inhibitors (TKI)

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Prognostic factors and survival outcomes in patients with chronic myeloid leukemia in blast phase in the tyrosine kinase inhibitor era : Cohort study of 477 patients. / Jain, Preetesh; Kantarjian, Hagop M.; Ghorab, Ahmad; Sasaki, Koji; Jabbour, Elias J.; Nogueras Gonzalez, Graciela; Kanagal-Shamanna, Rashmi; Issa, Ghayas C.; Garcia-Manero, Guillermo; Devendra, K. C.; Dellasala, Sara; Pierce, Sherry; Konopleva, Marina; Wierda, William G.; Verstovsek, Srdan; Daver, Naval G.; Kadia, Tapan M.; Borthakur, Gautam; O'Brien, Susan; Estrov, Zeev; Ravandi, Farhad; Cortes, Jorge E.

In: Cancer, Vol. 123, No. 22, 15.11.2017, p. 4391-4402.

Research output: Contribution to journalArticle

Jain, P, Kantarjian, HM, Ghorab, A, Sasaki, K, Jabbour, EJ, Nogueras Gonzalez, G, Kanagal-Shamanna, R, Issa, GC, Garcia-Manero, G, Devendra, KC, Dellasala, S, Pierce, S, Konopleva, M, Wierda, WG, Verstovsek, S, Daver, NG, Kadia, TM, Borthakur, G, O'Brien, S, Estrov, Z, Ravandi, F & Cortes, JE 2017, 'Prognostic factors and survival outcomes in patients with chronic myeloid leukemia in blast phase in the tyrosine kinase inhibitor era: Cohort study of 477 patients', Cancer, vol. 123, no. 22, pp. 4391-4402. https://doi.org/10.1002/cncr.30864
Jain, Preetesh ; Kantarjian, Hagop M. ; Ghorab, Ahmad ; Sasaki, Koji ; Jabbour, Elias J. ; Nogueras Gonzalez, Graciela ; Kanagal-Shamanna, Rashmi ; Issa, Ghayas C. ; Garcia-Manero, Guillermo ; Devendra, K. C. ; Dellasala, Sara ; Pierce, Sherry ; Konopleva, Marina ; Wierda, William G. ; Verstovsek, Srdan ; Daver, Naval G. ; Kadia, Tapan M. ; Borthakur, Gautam ; O'Brien, Susan ; Estrov, Zeev ; Ravandi, Farhad ; Cortes, Jorge E. / Prognostic factors and survival outcomes in patients with chronic myeloid leukemia in blast phase in the tyrosine kinase inhibitor era : Cohort study of 477 patients. In: Cancer. 2017 ; Vol. 123, No. 22. pp. 4391-4402.
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title = "Prognostic factors and survival outcomes in patients with chronic myeloid leukemia in blast phase in the tyrosine kinase inhibitor era: Cohort study of 477 patients",
abstract = "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.",
keywords = "blast phase (BP), bosutinib, chronic myeloid leukemia (CML), dasatinib, imatinib, nilotinib, ponatinib, tyrosine kinase inhibitors (TKI)",
author = "Preetesh Jain and Kantarjian, {Hagop M.} and Ahmad Ghorab and Koji Sasaki and Jabbour, {Elias J.} and {Nogueras Gonzalez}, Graciela and Rashmi Kanagal-Shamanna and Issa, {Ghayas C.} and Guillermo Garcia-Manero and Devendra, {K. C.} and Sara Dellasala and Sherry Pierce and Marina Konopleva and Wierda, {William G.} and Srdan Verstovsek and Daver, {Naval G.} and Kadia, {Tapan M.} and Gautam Borthakur and Susan O'Brien and Zeev Estrov and Farhad Ravandi and Cortes, {Jorge E.}",
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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.

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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