The role of nelarabine in the treatment of T-cell acute lymphoblastic leukemia: literature review and own experience


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Abstract

Aim. The analysis of experience of nelarabine use in refractory/relapsed T-cell acute lymphoblastic leukemia (T-ALL) depending on the immunophenotype and the line of therapy. Materials and methods. All the patients with relapsed or refractory T-ALL aged from 0 to 18 years who received treatment with nelarabine as a part of the therapeutic element R6 were included in the study. For all patients a detailed immunological analysis of leukemia cells with discrimination of immunological variants TI, TII, TIII or TIV was performed. Patients administered with nelarabine as a first therapeutic element were referred to the first-line therapy group, other patients were referred to the second-line therapy group. Nelarabine was administered as intravenous infusion at a dose of 650 mg/m2, on days 1-5. Allogeneic hematopoietic stem cells transplantation (allo-HSCT) was considered for all patients. Results. From 2009 to 2017, 54 patients with refractory/relapsed T-ALL were treated with nelarabine. Five-year event-free survival (EFS) and overall survival (OS) was 28% for all patients, cumulative risk of relapse (CIR) was 27%. EFS was significantly higher in nelarabine first-line therapy group in comparison with second-line therapy group (34±8% vs 8±8%, p=0,05). In patients after allo-HSCT EFS, OS and CIR were 51±10%, 50±10% and 39,1±9,5% accordingly. The best results were achieved in patients with TI immunophenotype. No toxicity-related mortality as well as severe neurologic complications or discontinuation of therapy associated with use of nelarabine were reported. Conclusion. The use of nelarabine is an effective strategy for the treatment of relapsed and refractory T-ALL. The best treatment outcomes were obtained in patients with TI immunophenotype and in the first-line therapy group. Optimal dosage regimens can be established during controlled clinical trials.

About the authors

Y Y DYAKONOVA

Dmitry Rogachev National Research Center for Pediatric Hematology, Oncology, and Immunology

врач-гематолог отд-ния онкогематологии НМИЦ ДГОИ им. Д. Рогачева; http://orcid.org/0000-0002-8725-7532 Moscow, Russia

O I BYDANOV

Dmitry Rogachev National Research Center for Pediatric Hematology, Oncology, and Immunology; Republican Scientific and Practical Center for Pediatric Oncology, Hematology, and Immunology

н.с., специалист по биостатистике и базам данных республиканского научно-практического центра детской онкологии и гематологии Республики Беларусь; http://orcid. org/0000-0003-3232-2322 Minsk, Republic of Belarus

A M POPOV

Dmitry Rogachev National Research Center for Pediatric Hematology, Oncology, and Immunology

к.м.н., заведующий лабораторией иммунофенотипирования НМИЦ ДГОИ им. Д. Рогачева; http://orcid.org/0000-0002-0889-6986 Moscow, Russia

Y V OLSHANSKAYA

Dmitry Rogachev National Research Center for Pediatric Hematology, Oncology, and Immunology

к.м.н., зав. лабораторией молекулярной генетики НМИЦ ДГОИ им. Д. Рогачева; yuliaolshanskaya@gmail.com; http://orcid.org/0000-0002-2352-7716 Moscow, Russia

E G BOICHENKO

Children City Hospital №1

д.м.н., зав. отд-нием онкогематологии СПб ГБУЗ «Детская городская больница №1»; http://orcid. org/0000-0002-2731-4531 Saint-Petersburg, Russia

O V ALEYNIKOVA

Republican Scientific and Practical Center for Pediatric Oncology, Hematology, and Immunology

д.м.н., профессор, директор республиканского научно-практического центра детской онкологии и гематологии Республики Беларусь; http://orcid.org/0000-0003-0143-1921 Minsk, Republic of Belarus

M A MASCHAN

Dmitry Rogachev National Research Center for Pediatric Hematology, Oncology, and Immunology

д.м.н., зам. генерального директора, директор Высшей школы молекулярной и экспериментальной медицины НМИЦ ДГОИ им. Д. Рогачева; http://orcid. org/0000-0003-1735-0093 Moscow, Russia

L N SHELIKHOVA

Dmitry Rogachev National Research Center for Pediatric Hematology, Oncology, and Immunology

к.м.н., заведующая отделением трансплантации гемопоэтических стволовых клеток №1 НМИЦ ДГОИ им. Д. Рогачева; http://orcid.org/0000-0003-0520-5630 Moscow, Russia

D V LITVINOV

Dmitry Rogachev National Research Center for Pediatric Hematology, Oncology, and Immunology

к.м.н., зам. медицинского директора, главный врач НМИЦ ДГОИ им. Д. Рогачева; http://orcid.org/ 0000-0002-7461-0050 Moscow, Russia

L A KHACHATRYAN

Dmitry Rogachev National Research Center for Pediatric Hematology, Oncology, and Immunology

кандидат медицинских наук, зав. боксированным отделением гематологии/онкологии НМИЦ ДГОИ им. Д. Рогачева Moscow, Russia

N I PONOMAREVA

Russian Children Clinical Hospital

зав. отделением онкогематологии и химиотерапии РДКБ, г. Москва; http://orcid.org/0000-0003-4532-6613 Moscow, Russia

L G FECHINA

Regional Children Clinical Hospital №1

к.м.н., руководитель центра детской гематологии и онкологии областной детской больницы г. Екатеринбурга; http://orcid.org/0000-0002-1885-3912 Ekaterinburg, Russia

G A NOVICHKOVA

Dmitry Rogachev National Research Center for Pediatric Hematology, Oncology, and Immunology

д.м.н., заместитель генерального директора по научно-клинической работе, медицинский директор НМИЦ ДГОИ им. Д. Рогачева; http://orcid. org/0000-0002-2322-5734 Moscow, Russia

E D PASHANOV

Dmitry Rogachev National Research Center for Pediatric Hematology, Oncology, and Immunology

д.м.н., зав. отделом научного проектирования и контролируемых клинических исследований НМИЦ ДГОИ им. Д. Рогачева; http://orcid.org/0000-0003-0080-3367 Moscow, Russia

A I KARACHUNSKIY

Dmitry Rogachev National Research Center for Pediatric Hematology, Oncology, and Immunology

Email: aikarat@mail.ru
д.м.н., зам. генерального директора, директор Института онкологии, радиологии и ядерной медицины НМИЦ ДГОИ им. Д. Рогачева; http://orcid. org/0000-0002-9300-198X Moscow, Russia

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