The role of high-dose methotrexate in T-cell acute lymphoblastic leukemia treatment: multicenter study results of ALL IC-BFM 2002 protocol

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Abstract

Backround. A progress in Tcell acute lymphoblastic leukemia (TALL) treatment has been achieved in recent years by use a combination of riskadopted chemoradiation therapy, based on highdose (5000 mg/m2) methotrexate. A prerequisite for successful therapy is carefully follow supportive care principles and recommendations, which include blood serum methotrexate concentration monitoring, leucovorin rescue and alkaline solutions use for the best methotrexate elimination and decrease its toxic effects.

Aim. To assess the effectiveness of ALL ICFM 2002 protocol based on highdose methotrexate for Tcell acute lymphoblastic leukemia.

Materials and methods. From 2003 to 2023 in retroprospective study 67 patients with primary diagnosed TALL were enrolled. Median age was 7.4 years (from 0 to 18 years). All the patients were treated according to riskadopted ALL ICFM 2002 protocol. The therapy efficacy was assessed by overall (OS), eventfree (EFS) and relapsefree survival analysis. The survival rates were calculated with statistic program SSS 21.0 by Kaplan–Meier method.

Results. The use of highdose methotrexate for TALL treatment in ALL ICFM 2002 protocol secure high survival rates: 10‑year OS was 82.5 ± 3 %, EFS – 79.3 ± 3 %. Analyzing OS and EFS depending on prognostic risk group we found that standard risk patients had OS and EFS 85.4 ± 6.9 and 78.4 ± 8 %, intermediate – 85.6 ± 6.7 and 82 ± 7.3 % and highrisk – 34.6 ± 18.3 and 20.8 ± 17.1 % respectively (р >0.05).

Conclusion. ALL ICFM 2002 protocol for TALL includes highdose (5000 mg/m2) methotrexate is an effective for standard and intermediate risk patients, but for TALL patients with unfavorable prognostic factors it is necessary a therapy modification by additional cytotoxic and targeted options (nelarabine and daratumumab) inclusion and widening the indications for allogeneic stem cell transplantation.

About the authors

T. T. Valiev

L.A. Durnov Research Institute of Pediatric Oncology and Hematology, N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia

Author for correspondence.
Email: timurvaliev@mail.ru
ORCID iD: 0000-0002-1469-2365

 24 Kashirskoe Shosse, Moscow 115522

Russian Federation

M. A. Shervashidze

L.A. Durnov Research Institute of Pediatric Oncology and Hematology, N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia

ORCID iD: 0000-0002-8350-4153

 24 Kashirskoe Shosse, Moscow 115522

Russian Federation

I. V. Osipova

Republican Children’s Clinical Hospital, Ministry of Health of the Republic of Tatarstan

ORCID iD: 0000-0001-9998-5409

140 Orenburgskiy Trakt, Kazan 420138

Russian Federation

T. I. Burlutskaya

Regional Children’s Clinical Hospital

ORCID iD: 0000-0003-4043-0366

44 Gubkina St., Belgorod 308036

Russian Federation

G. A. Aleskerova

National Center for Oncology, Ministry of Health of the Republic of Azerbaijan

ORCID iD: 0000-0002-0506-9491

79b G. Zardabi Prospekt, Baku AZ1011

Azerbaijan

S. N. Yuldasheva

V.K. Gusak Institute of Emergency and Reconstructive Surgery, Ministry of Health of Russia

ORCID iD: 0000-0003-2614-2560

47 Prospekt Leninskiy, Donetsk 283045, Donetsk People’s Republic

Russian Federation

S. L. Sabantsev

L.I. Sokolova Ioshkar-Ola Municipal Children’s Hospital

ORCID iD: 0009-0002-0269-8011

104 Volkova St., Ioshkar-Ola 424004

Russian Federation

O. V. Paina

Raisa Gorbacheva Memorial Research Institute for Pediatric Oncology, Hematology and Transplantation, I.P. Pavlov First
Saint Petersburg State Medical University, Ministry of Health of Russia

ORCID iD: 0000-0001-7263-4326

6–8 L’va Tolstogo St., Saint Petersburg 197022

Russian Federation

N. A. Batmanova

L.A. Durnov Research Institute of Pediatric Oncology and Hematology, N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia

ORCID iD: 0000-0002-5728-2243

 24 Kashirskoe Shosse, Moscow 115522

Russian Federation

L. S. Zubarovskaya

Raisa Gorbacheva Memorial Research Institute for Pediatric Oncology, Hematology and Transplantation, I.P. Pavlov First
Saint Petersburg State Medical University, Ministry of Health of Russia

ORCID iD: 0000-0003-2594-7703

6–8 L’va Tolstogo St., Saint Petersburg 197022

Russian Federation

K. I. Kirgizov

L.A. Durnov Research Institute of Pediatric Oncology and Hematology, N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia

ORCID iD: 0000-0002-2945-284X

 24 Kashirskoe Shosse, Moscow 115522

Russian Federation

S. R. Varfolomeeva

L.A. Durnov Research Institute of Pediatric Oncology and Hematology, N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia

ORCID iD: 0000-0001-6131-1783

 24 Kashirskoe Shosse, Moscow 115522

Russian Federation

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