Russian Journal of OncologyRussian Journal of OncologyРоссийский онкологический журнал1028-99842412-9119Eco-Vector4017510.17816/onco40175ArticlesСтатьиResearch ArticleThe role of target therapy for mixed phenotype acute leukemiaРоль таргетной терапии при острых лейкозах со смешанным фенотипомAntipovaA. SАнтиповаА. СBaranovaOl’ga Yu.БарановаОльга Юрьевна

MD, PhD

канд. мед. наук, ст. науч. сотр. отд-ния химиотерапии гемобластозов

baranova-crc@mail.ruFrenkelM. AФренкельМ. АTupitsynN. NТупицынН. НN.N. Blokhin Russian Cancer Research CenterФГБНУ «Российский онкологический научный центр им. Н.Н. Блохина»15062015203VOL 20, NO3 (2015)ТОМ 20, №3 (2015)323822072020Copyright ©; 2015, Eco-VectorCopyright ©; 2015, ООО "Эко-Вектор"2015Eco-VectorООО "Эко-Вектор"https://rjonco.com/1028-9984/article/view/40175

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.

Цель исследования - изучение клинико-лабораторных, цитогенетических, молекулярных особенностей и прогноза при острых лейкозах со смешанным фенотипом (СФОЛ), а также роли ингибиторов тирозинкиназ (ИТК) в лечении Ph-позитивного варианта СФОЛ (Ph+СФОЛ). Материал и методы. Среди 208 больных, обследованных в ФГБНУ «РОНЦим. Н.Н. Блохина» с 2000 по 2014 г., редкий диагноз СФОЛ установлен у 5 (2,4%) пациентов. В целом группу составили 13 больных, в нее вошли 5 пациентов ФГБНУ «РОНЦ им. Н.Н. Блохина» и 8, наблюдавшихся в четырех других гематологических стационарах Москвы. Диагноз устанавливался в соответствии с критериями классификации ВОЗ 2008 г. Результаты. В группе анализируемых больных отмечены высокая частота достижения полной ремиссии (83,3%), низкая ранняя летальность (8,3%). Вместе с тем отдаленные результаты терапии были неудовлетворительными. Показатели 3-летней общей выживаемости (ОВ) составили 18,2% при медиане 14 мес, 3-летней безрецидивной выживаемости (БРВ) - 12,8% при медиане 16 мес. В группе больных Ph+СФОЛ использование иматиниба в комбинации с программами полихимиотерапии острого лимфобластного лейкоза (ОЛЛ) ассоциировалось с высокой непосредственной эффективностью и лучшей выживаемостью. Полные ремиссии достигнуты у всех больных Ph+СФОЛ. Показатель 3-летней ОВ в группе Ph+СФОЛ составил 61% (медиана 36 мес), показатель БРВ оказался низким. Заключение. Первичная диагностика острых лейкозов должна быть комплексной и обязательно включать иммунофенотипирование, цитогенетическое и молекулярно-биологическое исследование. При Ph-позитивном варианте СФОЛ обязательный компонент терапии - ИТК 1-го или 2-го поколения. Представляется более перспективным использование комбинации ИТК с режимами лечения ОЛЛ со сниженной интенсивностью. Проблема терапии пациентов с Ph-негативными СФОЛ остается нерешенной. Требуется проведение дальнейших исследований по изучению цитогенетического и молекулярно-биологического профиля этой категории острых лейкозов с целью разработки оптимальных режимов терапии.

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