Tyrosine kinase inhibitors as initial therapy for patients with chronic myeloid Leukemia in accelerated phase

Maro Ohanian, Hagop M. Kantarjian, Alfonso Quintas-Cardama, Elias Jabbour, Lynne Abruzzo, Srdan Verstovsek, Gautam Borthakur, Farhad Ravandi, Guillermo Garcia-Manero, Richard Champlin, Sherry Pierce, Mona Lisa Alattar, Long Xuan Trinh, Raja Luthra, Alessandra Ferrajoli, Tapan Kadia, Susan O'brien, Jorge E. Cortes

Research output: Contribution to journalArticle

Abstract

Background Accelerated phase CML most frequently represents a progression state in CML. However, some patients present with AP features at the time of diagnosis. There is limited information on the outcome of these patients who received TKIs as initial therapy. Patients and Methods We analyzed the outcome of 51 consecutive patients with CML who presented with features of AP at the time of diagnosis, including blasts ≥ 15% (n = 6), basophils ≥ 20% (n = 22), platelets < 100 × 109/L (n = 3), cytogenetic clonal evolution (n = 17), or more than 1 feature (n = 3). Patients received initial therapy with imatinib (n = 30), dasatinib (n = 5), or nilotinib (n = 16). Results The rate of complete cytogenetic response for patients treated with imatinib was 80%, and with dasatinib or nilotinib was 90%. Major molecular response (MMR) (Breakpoint Cluster Region (BCR)-Abelson (ABL)/ABL ≤ 0.1%, International Scale [IS]) was achieved in 69% of patients including complete molecular response (BCR-ABL/ABL ≤ 0.0032% IS) in 49%. MMR rates for patients treated with imatinib were 63%, and with 2GTKIs, 76%. Overall survival at 36 months was 87% with imatinib and 95% with 2GTKIs. Conclusion TKIs should be considered standard initial therapy for patients with AP at the time of diagnosis.

Original languageEnglish (US)
Pages (from-to)155-162.E1
JournalClinical Lymphoma, Myeloma and Leukemia
Volume14
Issue number2
DOIs
StatePublished - Apr 2014
Externally publishedYes

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Leukemia, Myeloid, Accelerated Phase
Protein-Tyrosine Kinases
Therapeutics
Cytogenetics
Clonal Evolution
Basophils

Keywords

  • Accelerated phase CML (CML-AP)
  • Complete cytogenetic response (CCyR)
  • Major molecular response (MMR)
  • Second generation TKI (2GTKIs)
  • Tyrosine kinase inhibitors (TKI)

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

Cite this

Tyrosine kinase inhibitors as initial therapy for patients with chronic myeloid Leukemia in accelerated phase. / Ohanian, Maro; Kantarjian, Hagop M.; Quintas-Cardama, Alfonso; Jabbour, Elias; Abruzzo, Lynne; Verstovsek, Srdan; Borthakur, Gautam; Ravandi, Farhad; Garcia-Manero, Guillermo; Champlin, Richard; Pierce, Sherry; Alattar, Mona Lisa; Trinh, Long Xuan; Luthra, Raja; Ferrajoli, Alessandra; Kadia, Tapan; O'brien, Susan; Cortes, Jorge E.

In: Clinical Lymphoma, Myeloma and Leukemia, Vol. 14, No. 2, 04.2014, p. 155-162.E1.

Research output: Contribution to journalArticle

Ohanian, M, Kantarjian, HM, Quintas-Cardama, A, Jabbour, E, Abruzzo, L, Verstovsek, S, Borthakur, G, Ravandi, F, Garcia-Manero, G, Champlin, R, Pierce, S, Alattar, ML, Trinh, LX, Luthra, R, Ferrajoli, A, Kadia, T, O'brien, S & Cortes, JE 2014, 'Tyrosine kinase inhibitors as initial therapy for patients with chronic myeloid Leukemia in accelerated phase', Clinical Lymphoma, Myeloma and Leukemia, vol. 14, no. 2, pp. 155-162.E1. https://doi.org/10.1016/j.clml.2013.08.008
Ohanian, Maro ; Kantarjian, Hagop M. ; Quintas-Cardama, Alfonso ; Jabbour, Elias ; Abruzzo, Lynne ; Verstovsek, Srdan ; Borthakur, Gautam ; Ravandi, Farhad ; Garcia-Manero, Guillermo ; Champlin, Richard ; Pierce, Sherry ; Alattar, Mona Lisa ; Trinh, Long Xuan ; Luthra, Raja ; Ferrajoli, Alessandra ; Kadia, Tapan ; O'brien, Susan ; Cortes, Jorge E. / Tyrosine kinase inhibitors as initial therapy for patients with chronic myeloid Leukemia in accelerated phase. In: Clinical Lymphoma, Myeloma and Leukemia. 2014 ; Vol. 14, No. 2. pp. 155-162.E1.
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abstract = "Background Accelerated phase CML most frequently represents a progression state in CML. However, some patients present with AP features at the time of diagnosis. There is limited information on the outcome of these patients who received TKIs as initial therapy. Patients and Methods We analyzed the outcome of 51 consecutive patients with CML who presented with features of AP at the time of diagnosis, including blasts ≥ 15{\%} (n = 6), basophils ≥ 20{\%} (n = 22), platelets < 100 × 109/L (n = 3), cytogenetic clonal evolution (n = 17), or more than 1 feature (n = 3). Patients received initial therapy with imatinib (n = 30), dasatinib (n = 5), or nilotinib (n = 16). Results The rate of complete cytogenetic response for patients treated with imatinib was 80{\%}, and with dasatinib or nilotinib was 90{\%}. Major molecular response (MMR) (Breakpoint Cluster Region (BCR)-Abelson (ABL)/ABL ≤ 0.1{\%}, International Scale [IS]) was achieved in 69{\%} of patients including complete molecular response (BCR-ABL/ABL ≤ 0.0032{\%} IS) in 49{\%}. MMR rates for patients treated with imatinib were 63{\%}, and with 2GTKIs, 76{\%}. Overall survival at 36 months was 87{\%} with imatinib and 95{\%} with 2GTKIs. Conclusion TKIs should be considered standard initial therapy for patients with AP at the time of diagnosis.",
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T1 - Tyrosine kinase inhibitors as initial therapy for patients with chronic myeloid Leukemia in accelerated phase

AU - Ohanian, Maro

AU - Kantarjian, Hagop M.

AU - Quintas-Cardama, Alfonso

AU - Jabbour, Elias

AU - Abruzzo, Lynne

AU - Verstovsek, Srdan

AU - Borthakur, Gautam

AU - Ravandi, Farhad

AU - Garcia-Manero, Guillermo

AU - Champlin, Richard

AU - Pierce, Sherry

AU - Alattar, Mona Lisa

AU - Trinh, Long Xuan

AU - Luthra, Raja

AU - Ferrajoli, Alessandra

AU - Kadia, Tapan

AU - O'brien, Susan

AU - Cortes, Jorge E.

PY - 2014/4

Y1 - 2014/4

N2 - Background Accelerated phase CML most frequently represents a progression state in CML. However, some patients present with AP features at the time of diagnosis. There is limited information on the outcome of these patients who received TKIs as initial therapy. Patients and Methods We analyzed the outcome of 51 consecutive patients with CML who presented with features of AP at the time of diagnosis, including blasts ≥ 15% (n = 6), basophils ≥ 20% (n = 22), platelets < 100 × 109/L (n = 3), cytogenetic clonal evolution (n = 17), or more than 1 feature (n = 3). Patients received initial therapy with imatinib (n = 30), dasatinib (n = 5), or nilotinib (n = 16). Results The rate of complete cytogenetic response for patients treated with imatinib was 80%, and with dasatinib or nilotinib was 90%. Major molecular response (MMR) (Breakpoint Cluster Region (BCR)-Abelson (ABL)/ABL ≤ 0.1%, International Scale [IS]) was achieved in 69% of patients including complete molecular response (BCR-ABL/ABL ≤ 0.0032% IS) in 49%. MMR rates for patients treated with imatinib were 63%, and with 2GTKIs, 76%. Overall survival at 36 months was 87% with imatinib and 95% with 2GTKIs. Conclusion TKIs should be considered standard initial therapy for patients with AP at the time of diagnosis.

AB - Background Accelerated phase CML most frequently represents a progression state in CML. However, some patients present with AP features at the time of diagnosis. There is limited information on the outcome of these patients who received TKIs as initial therapy. Patients and Methods We analyzed the outcome of 51 consecutive patients with CML who presented with features of AP at the time of diagnosis, including blasts ≥ 15% (n = 6), basophils ≥ 20% (n = 22), platelets < 100 × 109/L (n = 3), cytogenetic clonal evolution (n = 17), or more than 1 feature (n = 3). Patients received initial therapy with imatinib (n = 30), dasatinib (n = 5), or nilotinib (n = 16). Results The rate of complete cytogenetic response for patients treated with imatinib was 80%, and with dasatinib or nilotinib was 90%. Major molecular response (MMR) (Breakpoint Cluster Region (BCR)-Abelson (ABL)/ABL ≤ 0.1%, International Scale [IS]) was achieved in 69% of patients including complete molecular response (BCR-ABL/ABL ≤ 0.0032% IS) in 49%. MMR rates for patients treated with imatinib were 63%, and with 2GTKIs, 76%. Overall survival at 36 months was 87% with imatinib and 95% with 2GTKIs. Conclusion TKIs should be considered standard initial therapy for patients with AP at the time of diagnosis.

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KW - Complete cytogenetic response (CCyR)

KW - Major molecular response (MMR)

KW - Second generation TKI (2GTKIs)

KW - Tyrosine kinase inhibitors (TKI)

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