nodgoРоссийский журнал детской гематологии и онкологии (РЖДГиО)Russian Journal of Pediatric Hematology and Oncology2311-12672413-5496LTD “Graphica”10.21682/2311-1267-2025-12-2-107-112nodgo-1156Research ArticleКЛИНИЧЕСКИЕ НАБЛЮДЕНИЯCLINICAL CASESПерсонализированная консолидирующая терапия венетоклаксом при вторичном остром миелоидном лейкозе у пациента после нейробластомы: успешный клинический случайPersonalized consolidation therapy with venetoclax for secondary acute myeloblastic leukemia in a patient after neuroblastoma: a successful clinical casehttps://orcid.org/0000-0002-6129-2647АнтошинМ. М.AntoshinM. M.

Михаил Михайлович Антошин - врач-гематолог, и.о. заведующего отделением гематологии и химиотерапии № 1 РДКБ – филиала РНИМУ им. Н.И. Пирогова.

119571, Москва, Ленинский просп., 117

Hematologist, Acting Head of the Hematology and Chemotherapy Department No. 1 of the Russian Children’s Clinical Hospital – Branch of the N.I. Pirogov Russian National Research Medical University, Ministry of Health of Russia.

117 Leninskiy Prosp., Moscow, 117997

antoshin_m_m@rdkb.ruhttps://orcid.org/0000-0002-3260-3338КарташоваВ. В.KartashovaV. V.

врач-детский онколог отделения гематологии и химиотерапии № 1 РДКБ – филиала РНИМУ им. Н.И. Пирогова.

119571, Москва, Ленинский просп., 117

Pediatric Oncologist Hematology and Chemotherapy Department No. 1 of the Russian Children’s Clinical Hospital – Branch of the N.I. Pirogov Russian National Research Medical University, Ministry of Health of Russia.

117 Leninskiy Prosp., Moscow, 117997

kartashovavalerija@mail.ruhttps://orcid.org/0000-0003-4431-1444СкоробогатоваЕ. В.SkorobogatovaE. V.

д.м.н., врач-анестезиолог-реаниматолог, заведующая отделением трансплантации костного мозга РДКБ – филиала РНИМУ им. Н.И. Пирогова.

119571, Москва, Ленинский просп., 117

Dr. of Sci. (Med.), Anesthesiologist-Reanimatologist, Head of Bone Marrow Transplantation Department at Russian Children’s Clinical Hospital – Branch of the N.I. Pirogov Russian National Research Medical University, Ministry of Health of Russia.

117 Leninskiy Prosp., Moscow, 117997

skorobog.e@mail.ruРДКБ – филиал ФГАОУ ВО РНИМУ им. Н.И. Пирогова Минздрава РоссииРоссияRussian Children’s Clinical Hospital – Branch of the N.I. Pirogov Russian National Research Medical University, Ministry of Health of RussiaRussian Federation202501082025122107112Copyright © Антошин М.М., Карташова В.В., Скоробогатова Е.В., 20252025Антошин М.М., Карташова В.В., Скоробогатова Е.В.Antoshin M.M., Kartashova V.V., Skorobogatova E.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://journal.nodgo.org/jour/article/view/1156

Нейробластома (НБ) представляет собой новообразование эмбрионального генеза, возникающее из недифференцированных нейроэктодермальных клеток нервного гребня, которое нередко характеризуется высокоагрессивным злокачественным течением. Вторичный острый миелоидный лейкоз (ОМЛ) после НБ – редкое и тяжелое осложнение терапии, характеризующееся химиорезистентностью и неблагоприятным прогнозом.

В статье представлен клинический случай успешного применения персонализированной консолидирующей терапии венетоклаксом в комбинации с 5-азацитидином у пациента с ОМЛ после лечения НБ. Несмотря на первично-рефрактерное течение ОМЛ и безуспешность стандартных схем терапии, применение аллогенной трансплантации гемопоэтических стволовых клеток от гаплоидентичного донора в сочетании с консолидирующей терапией, проведенной в посттрансплантационном периоде, позволило достичь стойкой ремиссии по двум онкологическим заболеваниям.

В статье также обсуждаются сложности лечения вторичного ОМЛ, включая химиорезистентность и высокий риск рецидива. Консолидирующая терапия на основе венетоклакса и гипометилирующих агентов является перспективным подходом для улучшения результатов лечения пациентов с вторичным ОМЛ после НБ, демонстрируя возможность достижения длительной ремиссии и удовлетворительный профиль безопасности.

Neuroblastoma (NB) is a malignant embryonic tumor arising from undifferentiated neuroectodermal cells of the neural crest, often exhibiting highly aggressive behavior. Secondary acute myeloid leukemia (AML) following NB is a rare and complex therapy-related complication characterized by chemoresistance and a poor prognosis.

This article presents a clinical case of successful personalized consolidation therapy with venetoclax in combination with 5-azacytidine in a patient with AML after NB treatment. Despite the primary refractory course of AML and the failure of standard therapeutic regimens, the use of allogeneic hematopoietic stem cell transplantation from a haploidentical donor, combined with consolidation therapy in the post-transplant period, enabled the achievement of sustained remission of both malignancies.

The article also discusses the challenges of treating secondary AML, including chemoresistance and the high risk of relapse. Consolidation therapy based on venetoclax and hypomethylating agents represents a promising approach to improving outcomes in patients with secondary AML after NB, offering the potential for long-term remission with a favorable safety profile.

острый миелоидный лейкознейробластомавенетоклаксконсолидирующая терапиятрансплантация гемопоэтических стволовых клетокacute myeloblastic leukemianeuroblastomavenetoclaxconsolidation therapyhematopoietic stem cell transplantationИсследование проведено без спонсорской поддержкиThe study was performed without external fundingReferencesBerthold F., Spix C., Kaatsch P., Lampert F. Incidence, Survival, and Treatment of Localized and Metastatic Neuroblastoma in Germany 1979–2015. Paediatr Drugs. 2017;19(6):577–93. doi: 10.1007/s40272-017-0251-3.Berthold F., Spix C., Kaatsch P., Lampert F. Incidence, Survival, and Treatment of Localized and Metastatic Neuroblastoma in Germany 1979–2015. Paediatr Drugs. 2017;19(6):577–93. doi: 10.1007/s40272-017-0251-3.Zhang X. EVI1 Disruption Post Neuroblastoma Treatment: A Case Analysis of Treatment-Associated Acute Myeloid Leukemia in a Pediatric Patient. Case Rep Oncol. 2023;16(1):893–9. doi: 10.1159/000533571.Zhang X. EVI1 Disruption Post Neuroblastoma Treatment: A Case Analysis of Treatment-Associated Acute Myeloid Leukemia in a Pediatric Patient. Case Rep Oncol. 2023;16(1):893–9. doi: 10.1159/000533571.Kushner B.H., Cheung N.K., Kramer K., Heller G., Jhanwar S.C. Neuroblastoma and treatment-related myelodysplasia/leukemia: the Memorial Sloan–Kettering experience and a literature review. J Clin Oncol. 1998;16(12):3880–9. doi: 10.1200/JCO.1998.16.12.3880.Kushner B.H., Cheung N.K., Kramer K., Heller G., Jhanwar S.C. Neuroblastoma and treatment-related myelodysplasia/leukemia: the Memorial Sloan–Kettering experience and a literature review. J Clin Oncol. 1998;16(12):3880–9. doi: 10.1200/JCO.1998.16.12.3880.Vyas C., Jain S., Kapoor G. Therapy Related AML/MDS Following Treatment for Childhood Cancer: Experience from a Tertiary Care Centre in North India. Indian J Hematol Blood Transfus. 2018;34(1):78–82. doi: 10.1007/s12288-017-0840-x.Vyas C., Jain S., Kapoor G. Therapy Related AML/MDS Following Treatment for Childhood Cancer: Experience from a Tertiary Care Centre in North India. Indian J Hematol Blood Transfus. 2018;34(1):78–82. doi: 10.1007/s12288-017-0840-x.Spitzer B., Rutherford K.D., Gundem G., McGovern E.M., Millard N.E., Arango Ossa J.E., Cheung I.Y., Gao T., Levine M.F., Zhang Y., Medina-Martínez J.S., Feng Y., Ptashkin R.N., Bolton K.L., Farnoud N., Zhou Y., Patel M.A., Asimomitis G., Cobbs C.C., Mohibullah N., Huberman K.H., Arcilla M.E., Kushner B.H., Modak S., Kung A.L., Zehir A., Levine R.L., Armstrong S.A., Cheung N.K.V., Papaemmanuil E. Bone Marrow Surveillance of Pediatric Cancer Survivors Identifies Clones that Predict Therapy-Related Leukemia. Clin Cancer Res. 2022;28(8):1614–27. doi: 10.1158/1078-0432.CCR-21-2451.Spitzer B., Rutherford K.D., Gundem G., McGovern E.M., Millard N.E., Arango Ossa J.E., Cheung I.Y., Gao T., Levine M.F., Zhang Y., Medina-Martínez J.S., Feng Y., Ptashkin R.N., Bolton K.L., Farnoud N., Zhou Y., Patel M.A., Asimomitis G., Cobbs C.C., Mohibullah N., Huberman K.H., Arcilla M.E., Kushner B.H., Modak S., Kung A.L., Zehir A., Levine R.L., Armstrong S.A., Cheung N.K.V., Papaemmanuil E. Bone Marrow Surveillance of Pediatric Cancer Survivors Identifies Clones that Predict Therapy-Related Leukemia. Clin Cancer Res. 2022;28(8):1614–27. doi: 10.1158/1078-0432.CCR-21-2451.Farhi D.C., Odell C.A., Shurin S.B. Myelodysplastic syndrome and acute myeloid leukemia after treatment for solid tumors of childhood. Am J Clin Pathol. 1993;100(3):270–5. doi: 10.1093/ajcp/100.3.270.Farhi D.C., Odell C.A., Shurin S.B. Myelodysplastic syndrome and acute myeloid leukemia after treatment for solid tumors of childhood. Am J Clin Pathol. 1993;100(3):270–5. doi: 10.1093/ajcp/100.3.270.Whittle S.B., Punia J.N., López-Terrada D., Gaikwad A., Hampton O.A., Heczey A. Therapy-related Acute Leukemia With Mixed Phenotype and Novel t(1:6)(q25;p23) After Treatment for Highrisk Neuroblastoma. J Pediatr Hematol Oncol. 2017;39(8):e486–8. doi: 10.1097/MPH.0000000000000956.Whittle S.B., Punia J.N., López-Terrada D., Gaikwad A., Hampton O.A., Heczey A. Therapy-related Acute Leukemia With Mixed Phenotype and Novel t(1:6)(q25;p23) After Treatment for Highrisk Neuroblastoma. J Pediatr Hematol Oncol. 2017;39(8):e486–8. doi: 10.1097/MPH.0000000000000956.Fabozzi F., Carrozzo R., Lodi M., Di Giannatale A., Cipri S., Rosignoli C., Giovannoni I., Stracuzzi A., Rizza T., Montante C., Agolini E., Di Nottia M., Galaverna F., Del Baldo G., Del Bufalo F., Mastronuzzi A., De Ioris M.A. Case report: A safeguard in the sea of variants of uncertain significance: a case study on child with high risk neuroblastoma and acute myeloid leukemia. Front Oncol. 2024;13:1324013. doi: 10.3389/fonc.2023.1324013.Fabozzi F., Carrozzo R., Lodi M., Di Giannatale A., Cipri S., Rosignoli C., Giovannoni I., Stracuzzi A., Rizza T., Montante C., Agolini E., Di Nottia M., Galaverna F., Del Baldo G., Del Bufalo F., Mastronuzzi A., De Ioris M.A. Case report: A safeguard in the sea of variants of uncertain significance: a case study on child with high risk neuroblastoma and acute myeloid leukemia. Front Oncol. 2024;13:1324013. doi: 10.3389/fonc.2023.1324013.Kushner B.H., Kramer K., Modak S., Qin L.X., Yataghena K., Jhanwar S.C., Cheung N.K. Reduced risk of secondary leukemia with fewer cycles of dose-intensive induction chemotherapy in patients with neuroblastoma. Pediatr Blood Cancer. 2009;53(1):17–22. doi: 10.1002/pbc.21931.Kushner B.H., Kramer K., Modak S., Qin L.X., Yataghena K., Jhanwar S.C., Cheung N.K. Reduced risk of secondary leukemia with fewer cycles of dose-intensive induction chemotherapy in patients with neuroblastoma. Pediatr Blood Cancer. 2009;53(1):17–22. doi: 10.1002/pbc.21931.Michmerhuizen N.L., Klco J.M., Mullighan C.G. Mechanistic insights and potential therapeutic approaches for NUP98-rearranged hematologic malignancies. Blood. 2020;136(20):2275–89. doi: 10.1182/blood.2020007093.Michmerhuizen N.L., Klco J.M., Mullighan C.G. Mechanistic insights and potential therapeutic approaches for NUP98-rearranged hematologic malignancies. Blood. 2020;136(20):2275–89. doi: 10.1182/blood.2020007093.Fan S., Huo W.X., Yang Y., Shen M.Z., Mo X.D. Efficacy and safety of ruxolitinib in steroid-refractory graft-versus-host disease: A meta-analysis. Front Immunol. 2022;13:954268. doi: 10.3389/fimmu.2022.954268.Fan S., Huo W.X., Yang Y., Shen M.Z., Mo X.D. Efficacy and safety of ruxolitinib in steroid-refractory graft-versus-host disease: A meta-analysis. Front Immunol. 2022;13:954268. doi: 10.3389/fimmu.2022.954268.Creutzig U., Zimmermann M., Ritter J., Reinhardt D., Hermann J., Henze G., Jürgens H., Kabisch H., Reiter A., Riehm H., Gadner H., Schellong G. Treatment strategies and long-term results in paediatric patients treated in four consecutive AML-BFM trials. Leukemia. 2005;19(12):2030–42. doi: 10.1038/sj.leu.2403920.Creutzig U., Zimmermann M., Ritter J., Reinhardt D., Hermann J., Henze G., Jürgens H., Kabisch H., Reiter A., Riehm H., Gadner H., Schellong G. Treatment strategies and long-term results in paediatric patients treated in four consecutive AML-BFM trials. Leukemia. 2005;19(12):2030–42. doi: 10.1038/sj.leu.2403920.Senapati J., Kadia T.M., Ravandi F. Maintenance therapy in acute myeloid leukemia: advances and controversies. Haematologica. 2023;108(9):2289–304. doi: 10.3324/haematol.2022.281810.Senapati J., Kadia T.M., Ravandi F. Maintenance therapy in acute myeloid leukemia: advances and controversies. Haematologica. 2023;108(9):2289–304. doi: 10.3324/haematol.2022.281810.Sievers E.L., Lange B.J., Sondel P.M., Krailo M.D., Gan J., Tjoa T., Liu-Mares W., Feig S.A. Childrenʼs cancer group trials of interleukin-2 therapy to prevent relapse of acute myelogenous leukemia. Cancer J Sci Am. 2000;6 Suppl 1:S39–44. PMID: 10685657.Sievers E.L., Lange B.J., Sondel P.M., Krailo M.D., Gan J., Tjoa T., Liu-Mares W., Feig S.A. Childrenʼs cancer group trials of interleukin-2 therapy to prevent relapse of acute myelogenous leukemia. Cancer J Sci Am. 2000;6 Suppl 1:S39–44. PMID: 10685657.

The authors declare that there are no conflicts of interest present.