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. 2014 Apr;14(2):155-162.e1.
doi: 10.1016/j.clml.2013.08.008. Epub 2013 Dec 9.

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

Maro Ohanian  1 , Hagop M Kantarjian  1 , Alfonso Quintas-Cardama  1 , Elias Jabbour  1 , Lynne Abruzzo  1 , Srdan Verstovsek  1 , Gautam Borthakur  1 , Farhad Ravandi  1 , Guillermo Garcia-Manero  1 , Richard Champlin  1 , Sherry Pierce  1 , Mona Lisa Alattar  1 , Long Xuan Trinh  1 , Raja Luthra  1 , Alessandra Ferrajoli  1 , Tapan Kadia  1 , Susan O'Brien  1 , Jorge E Cortes  2
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Tyrosine kinase inhibitors as initial therapy for patients with chronic myeloid leukemia in accelerated phase

Maro Ohanian et al. Clin Lymphoma Myeloma Leuk. 2014 Apr.

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 × 10(9)/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.

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

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Figures

Figure 1
Figure 1. Long-term outcome of patients with CML AP according to initial therapy
(A) Overall Survival, (B) Event Free Survival, (C) Transformation Free Survival, and (D) Failure Free Survival.
Figure 2
Figure 2. Long-term outcome by cytogenetic response at 12 months of patients with CML AP treated with TKI as initial therapy
(A) Overall Survival, (B) Event Free Survival, (C) Transformation Free Survival, and (D) Failure Free Survival.
Figure 3
Figure 3. Long-term outcome of patients with CML CP or AP receiving TKI as initial therapy
(A) Overall Survival, (B) Event Free Survival, (C) Transformation Free Survival, (D) Failure Free Survival.
See this image and copyright information in PMC

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