The role of target therapy for mixed phenotype acute leukemia


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Abstract

Aim was to study clinical and laboratory test results, cytogenetic and molecular characteristics and prognosis of mixed phenotype acute leukemia (MPAL) as well as the role of tyrosine-kinase inhibitors (TKIs) in treatment of Ph-positive MPAL (Ph+ MPAL). Material and methods. The rare MPAL diagnosis was determined in 5 (2.4%) out of 208 patients examined in N.N. Blokhin Russian Cancer Research Center (NNBRCRC) between 2000 and 2014. On the whole, the study group included 13 patients, 5 - from NNBRCRC and 8 - treated in four other hematological hospitals of Moscow. The diagnosis was established according to WHO classification, 2008. Results. High percentage of the complete remission (83.3%) and low early lethality (8.3%) was observed in the study group. However, the long-term therapy results were unsatisfactory. 3-year overall survival (OS) rate amounted 18.2% with the median of 14 months, and 3-year relapse free survival (RFS) was 12.8%, with the median of 16 months. Imatinib based treatment in combination with acute lymphoblastic leukemia (ALL) polychemotherapy of the patients with Ph+ MPAL associated with high immediate efficacy and better survival. Complete remission was achieved in all patients with Ph+ MPAL. 3-year OS of Ph+MPAL patients was 61% (median 36 months); RFS was low. Conclusion. Primary acute leukemia diagnostics should be complex and necessarily include immune phenotype evaluation, cytogenetic and molecular biological tests. 1-st or 2-ndgeneration TKIs should be included in Ph+MPAL treatment. TKIs may be more effectively combined with lower intensive ALL therapy regimens. The problem of Ph-negative MPAL patients ’ treatment remains unresolved. Further studies of cytogenetic and molecular biological profile of this acute leukemia type are necessary to develop optimal therapy regimens.

About the authors

A. S Antipova

N.N. Blokhin Russian Cancer Research Center

115478, Moscow, Russian Federation

Ol’ga Yu. Baranova

N.N. Blokhin Russian Cancer Research Center

Email: baranova-crc@mail.ru
MD, PhD 115478, Moscow, Russian Federation

M. A Frenkel

N.N. Blokhin Russian Cancer Research Center

115478, Moscow, Russian Federation

N. N Tupitsyn

N.N. Blokhin Russian Cancer Research Center

115478, Moscow, Russian Federation

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