Genetic basis of clinical variants of chemotherapy toxicity in children with acute lymphoblastic leukemia (literature review)

Background. Treatment results of acute lymphoblastic leukemia in children on protocol, developed by one of the leading research study group BFM (Berlin-Frankfurt-Munster) are impressive - longstanding overall survival rate comprise 93.4 %. The basis of success is a differential approach based on prognostic factors. In some local issues BFM protocols receive criticism because of high toxicity, but trying to find results of complex protocol toxicity assessment by modern scales in local literature, it was absent.Aim. To study a toxicity of acute lymphoblastic leukemia treatment by ALL IC-BFM 2002 protocol.Materials and methods. 119 patients with primary diagnosed acute lymphoblastic leukemia were enrolled the study. All the patients were treated by ALL IC-BFM 2002 protocol. Toxicity assessment was performed by the scale of National Cancer Institute (NCI) USA, 2nd version.Results. The most often variants of toxicity during treatment according to the ALL IC-BFM 2002 protocol were myelo-suppression, infections and hepatotoxicity of I-IV degrees of severity. Clinically significant toxicity (grade IV) was myelosuppression and necessity for transfusions in 76.8-100 % (depending on prognostic risk group and as such protocol arm). Nephro- and hepatotoxicity described on high-dosed methotrexate (2000 mg/m2 or 5000 mg/m2) were I-II grade in 89.5 % patients. Stomatitis grade I-II was in 93.7 % patients of standard and intermediate risk groups, but in the most (90 %) patients from high risk group it was higher - grade III-IV. Mortality on protocol ALL IC-BFM 2002 caused by infection complications was 1.6 %. It should be noted, that supportive care, prescribed in ALL IC-BFM 2002 protocol help to prevent and correct severe toxicity effectively.Conclusion. The toxicity profile of ALL IC-BFM 2002 protocol, analyzed by frequency of toxicity grade III-IV with whole supportive care approaches, is acceptable. The noted variants of toxicity were fully resolved without irreversible consequences for the patients.

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Toxicity assessment of acute lymphoblastic leukemia treatment protocol ALL IC-BFM 2002

Валиев

Шервашидзе

Belysheva

2022

Onkogematologiâ

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New drug formulations of colony-stimulating factors in oncohematology

et al. 2023

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применение колониестимулирующих факторов стало самостоятельным направлением в комплексной сопроводительной терапии опухолевых заболеваний системы крови. Благодаря использованию гранулоцитарного колониестимулирующего фактора (Г-КСФ) стало возможным сократить период нейтропении, обеспечить оптимальный тайминг терапии, уменьшить частоту инфекционных осложнений. Разработка и активное использование новой формы Г-КСФ -пэгфилграстима -достоверно не уменьшили длительность нейтропении, но позволили уменьшить кратность введения препарата, время пребывания больного в стационаре и снизить вероятность «неэффективной» мобилизации гемопоэтических стволовых клеток. В настоящей статье приведены результаты современных исследований по преимуществам пегилированной формы Г-КСФ по сравнению с Г-КСФ, представлен алгоритм действий врача при оценке риска фебрильной нейтропении, освещены вопросы назначения препаратов Г-КСФ при лечении опухолевых заболеваний системы крови.

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Vincristine polyneuropathy in children with acute lymphoblastic leukemia: the association with the hereditary rs924607 polymorphism in the <i>CEP72</i> gene

Koryakina,

Kovtun,

Tsaur

et al. 2023

Almanac of Clinical Medicine

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Background: Vincristine polyneuropathy is a major neurotoxic complication of treatment for acute lymphoblastic leukemia in children. A close relationship between genetic variants in candidate genes associated with the vincristine neurotoxicity in various ethnic groups has been proposed. Therefore, identification of the genetic risk factors underlying the predisposition to vincristine polyneuropathy could allow the development of effective tools for preventive diagnostics aimed at identifying a high-risk group among patients treated with vincristine for a personalized approach to their chemotherapy. Aim: To study an association between the rs924607 polymorphism of the CEP72 gene and vincristine polyneuropathy in children with acute lymphoblastic leukemia. Materials and methods: This single center cohort study enrolled 199 children aged 3 to 17 years with newly diagnosed acute lymphoblastic leukemia, who received ALL-MB 2015 chemotherapy regimen. All patients were genotyped for the single nucleotide variant rs924607 in the CEP72 gene by real-time polymerase chain reaction and subsequent allelic discrimination. A comparative analysis of the incidence and clinical signs of vincristine polyneuropathy depending on the carrier of the genetic polymorphism was performed. Results: The incidence of vincristine polyneuropathy in the study pediatric group was 81.0% (n = 161); mostly these were patients with NCI-STCAE grade 2 severity. The rs924607 single nucleotide variant in the CEP72 gene was significantly associated with the neurotoxic complication, with 19.1% (n = 38) of the patients were homozygous for the minor allele (rs924607 genotype TT) and 46.2% (n = 92) had the ST genotype. Among the carriers of at least one rs924607 risk allele (T), the odds ratio for vincristine polyneuropathy was 2.91 (95% confidence interval 1.415.99, p = 0.004). No significant association between the genetic variant assessed and clinical signs of vincristine-induced polyneuropathy was found. Conclusion: The single nucleotide rs924607 polymorphism of the CEP72 gen can be a putative pharmacogenetic marker for vincristine polyneuropathy.

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Genetic basis of clinical variants of chemotherapy toxicity in children with acute lymphoblastic leukemia (literature review)

Cited by 4 publications

References 77 publications

Toxicity assessment of acute lymphoblastic leukemia treatment protocol ALL IC-BFM 2002

Toxicity assessment of acute lymphoblastic leukemia treatment protocol ALL IC-BFM 2002

New drug formulations of colony-stimulating factors in oncohematology

Vincristine polyneuropathy in children with acute lymphoblastic leukemia: the association with the hereditary rs924607 polymorphism in the <i>CEP72</i> gene

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