Pub Date : 2023-01-01DOI: 10.21320/2500-2139-2023-16-1-54-68
А. Г. Туркина, А. В. Кохно, Н. Н. Цыба, М. А. Гурьянова, Е. И. Сбитякова, А. В. Быкова, И. С. Немченко, Ю. Ю. Власова, Т. В. Читанава, А. Н. Петрова, О. А. Шухов, Е. Ю. Челышева, Е. В. Морозова, Е. Г. Ломаиа, Елена Андреевна Кузьмина, Е. Н. Паровичникова
Aim. To assess the efficacy and tolerability of asciminib in chronic myeloid leukemia (CML) patients after failure of ≥ 2 lines of tyrosine kinase inhibitors (TKIs) therapy under the МАР (Managed Access Program, NCT04360005) in Russia. Materials & Methods. The study enrolled 68 patients with Ph-positive CML chronic phase (CF), over 18 years of age, after failure of ≥ 2 lines of TKI therapy. The analysis was conducted on data from 50 patients who were followed-up for at least 3 months and did not undergo allo-HSCT. Dosing regimens were prescribed depending on T315I mutation. Asciminib 200 mg per os was administered twice a day to 20 patients with this mutation, and asciminib 40 mg per os was administered twice a day to 30 patients without this mutation. By the time of admission into the MAP, there were 42 (82 %) CF CML patients as well as 8 patients with second CF after accelerated phase (AF, n = 7) and myeloid blast crisis (BC, n = 1). None of them could be treated with any therapeutic alternative. 92 % of patients had received ≥ 3 lines of prior TKI therapy. Overall survival (OS) and discontinuation-free survival were estimated by the Kaplan-Meier method. A cumulative incidence function (CIF) was used to calculate the probability of achieving response. Multivariate analysis was based on Cox regression model. Results. The median asciminib treatment duration was 11 months (range 4–30 months). The probable 2-year OS was 96 %. After 12 and 24 months, discontinuation-free survival was 92 % and 70 %, respectively. On asciminib therapy, complete cytogenetic (CCyR/МR2), major molecular (MMR), and deep molecular (MR4) responses were achieved in 17 (42 %), 14 (30 %), and 9 (19 %) patients who had not responded to prior treatment at the point of enrollment. After completing the 12- and 24-month therapy, the probability of CCyR/МR2 achievement was 44 % and 62 %, that of MMR achievement was 32 % and 40 %, and that of MR4 achievement was 26 % and 37 %, respectively. The patients treated with different doses did not significantly differ in achieving either CCyR/МR2 or MMR. By multivariate analysis, the independently significant factor impacting the probability of achieving MMR on asciminib treatment was the best MR (BCR::ABL1 < 1 % vs. 1–10 % vs. ≥ 10 %) after prior TKI therapy (hazard ratio 7.5873; p = 0.0072). In 22 (44 %) patients, adverse events (AEs) of all grades were observed, and 8 (16 %) patients showed AEs grade 3/4 (predominantly thrombocythemia and neutropenia). None of the patients discontinued asciminib treatment due to AEs. Conclusion. Asciminib demonstrated highly promising efficacy in previously TKI-treated patients with T315I mutation (200 mg BID) and without it (40 mg BID). Asciminib can be regarded as therapeutic option after failure of other TKIs. Different doses of asciminib were equally well tolerated, which makes it applicable for patients with intolerance to other TKIs and also provides ground for considering dose increases in non-
的目标。在俄罗斯МАР (Managed Access Program, NCT04360005)下，评估阿西米尼治疗≥2系酪氨酸激酶抑制剂(TKIs)治疗失败后慢性髓性白血病(CML)患者的疗效和耐受性。材料,方法。该研究纳入了68例ph阳性CML慢性期(CF)患者，年龄超过18岁，TKI治疗失败≥2线。该分析是对50例患者的数据进行的，这些患者随访至少3个月，未接受同种异体造血干细胞移植。根据T315I突变情况制定给药方案。20例有这种突变的患者每天给予阿西米尼200毫克，30例无这种突变的患者每天给予阿西米尼40毫克。到MAP入院时，有42例(82%)CF CML患者以及8例加速期(AF, n = 7)和髓细胞危象(BC, n = 1)后的第二次CF患者，均无法接受任何治疗。92%的患者既往接受过≥3线TKI治疗。总生存期(OS)和无停药生存期采用Kaplan-Meier法估计。累积关联函数(CIF)用于计算达到响应的概率。多因素分析采用Cox回归模型。结果。阿西米尼治疗的中位持续时间为11个月(范围4-30个月)。2年生存率为96%。12个月和24个月后，无停药生存率分别为92%和70%。在阿西米尼治疗中，17例(42%)、14例(30%)和9例(19%)在入组时对先前治疗无反应的患者中实现了完全细胞遗传学(CCyR/МR2)、主要分子(MMR)和深分子(MR4)应答。完成12个月和24个月的治疗后，CCyR/МR2达到的概率分别为44%和62%，MMR达到的概率分别为32%和40%，MR4达到的概率分别为26%和37%。接受不同剂量治疗的患者在达到CCyR/МR2或MMR方面没有显著差异。通过多因素分析，影响阿西米尼治疗后MMR实现概率的独立显著因素是最佳MR (BCR::ABL1 <1% vs. 1 - 10% vs.≥10%)(风险比7.5873;P = 0.0072)。在22例(44%)患者中，观察到所有级别的不良事件(ae)， 8例(16%)患者出现3/4级不良事件(主要是血小板减少症和中性粒细胞减少症)。没有患者因不良反应而停止阿西米尼治疗。结论。阿西米尼在先前接受tki治疗的T315I突变(200 mg BID)和非T315I突变(40 mg BID)患者中显示出非常有希望的疗效。阿西米尼可作为其他TKIs失败后的治疗选择。不同剂量的阿西米尼的耐受性同样良好，这使得它适用于对其他TKIs不耐受的患者，也为考虑对无反应者增加剂量提供了依据。阿西米尼在早期治疗阶段(一线或二线)的疗效研究以及与atp结合TKIs联合治疗对TKI治疗反应不足的CML患者的疗效研究也有良好的前景。
{"title":"Асциминиб у больных хроническим миелолейкозом, не имеющих альтернативных методов лечения: результаты исследования в рамках программы расширенного доступа МАР (Managed Access Program, NCT04360005) в России","authors":"А. Г. Туркина, А. В. Кохно, Н. Н. Цыба, М. А. Гурьянова, Е. И. Сбитякова, А. В. Быкова, И. С. Немченко, Ю. Ю. Власова, Т. В. Читанава, А. Н. Петрова, О. А. Шухов, Е. Ю. Челышева, Е. В. Морозова, Е. Г. Ломаиа, Елена Андреевна Кузьмина, Е. Н. Паровичникова","doi":"10.21320/2500-2139-2023-16-1-54-68","DOIUrl":"https://doi.org/10.21320/2500-2139-2023-16-1-54-68","url":null,"abstract":"Aim. To assess the efficacy and tolerability of asciminib in chronic myeloid leukemia (CML) patients after failure of ≥ 2 lines of tyrosine kinase inhibitors (TKIs) therapy under the МАР (Managed Access Program, NCT04360005) in Russia. Materials & Methods. The study enrolled 68 patients with Ph-positive CML chronic phase (CF), over 18 years of age, after failure of ≥ 2 lines of TKI therapy. The analysis was conducted on data from 50 patients who were followed-up for at least 3 months and did not undergo allo-HSCT. Dosing regimens were prescribed depending on T315I mutation. Asciminib 200 mg per os was administered twice a day to 20 patients with this mutation, and asciminib 40 mg per os was administered twice a day to 30 patients without this mutation. By the time of admission into the MAP, there were 42 (82 %) CF CML patients as well as 8 patients with second CF after accelerated phase (AF, n = 7) and myeloid blast crisis (BC, n = 1). None of them could be treated with any therapeutic alternative. 92 % of patients had received ≥ 3 lines of prior TKI therapy. Overall survival (OS) and discontinuation-free survival were estimated by the Kaplan-Meier method. A cumulative incidence function (CIF) was used to calculate the probability of achieving response. Multivariate analysis was based on Cox regression model. Results. The median asciminib treatment duration was 11 months (range 4–30 months). The probable 2-year OS was 96 %. After 12 and 24 months, discontinuation-free survival was 92 % and 70 %, respectively. On asciminib therapy, complete cytogenetic (CCyR/МR2), major molecular (MMR), and deep molecular (MR4) responses were achieved in 17 (42 %), 14 (30 %), and 9 (19 %) patients who had not responded to prior treatment at the point of enrollment. After completing the 12- and 24-month therapy, the probability of CCyR/МR2 achievement was 44 % and 62 %, that of MMR achievement was 32 % and 40 %, and that of MR4 achievement was 26 % and 37 %, respectively. The patients treated with different doses did not significantly differ in achieving either CCyR/МR2 or MMR. By multivariate analysis, the independently significant factor impacting the probability of achieving MMR on asciminib treatment was the best MR (BCR::ABL1 < 1 % vs. 1–10 % vs. ≥ 10 %) after prior TKI therapy (hazard ratio 7.5873; p = 0.0072). In 22 (44 %) patients, adverse events (AEs) of all grades were observed, and 8 (16 %) patients showed AEs grade 3/4 (predominantly thrombocythemia and neutropenia). None of the patients discontinued asciminib treatment due to AEs. Conclusion. Asciminib demonstrated highly promising efficacy in previously TKI-treated patients with T315I mutation (200 mg BID) and without it (40 mg BID). Asciminib can be regarded as therapeutic option after failure of other TKIs. Different doses of asciminib were equally well tolerated, which makes it applicable for patients with intolerance to other TKIs and also provides ground for considering dose increases in non-","PeriodicalId":36905,"journal":{"name":"Klinicheskaya Onkogematologiya/Clinical Oncohematology","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136052417","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-11-07DOI: 10.17650/1818-8346-2022-17-4-166-176
A. Vasileva, O. Aleshina, B. Biderman, A. Sudarikov
T-cell acute lymphoblastic leukemia/lymphoma (T-ALL) is an aggressive hematological disease. Modern polychemotherapy protocols allow achieving a 5-year overall survival of 60–90 % in different age groups, however, relapses and refractory forms of T-ALL remain incurable. Over the past decades, the pathogenesis of this variant of leukemia has been studied in many trials, and it has been found that various signaling pathways are involved in the multi-step process of leukemogenesis. This opens the way for targeted therapy.In this review, we provide an update on the pathogenesis of T-ALL, opportunities for introducing targeted therapies, and issues that remain to be addressed.
{"title":"Molecular genetic abnormalities in patients with T-cell acute lymphoblastic leukemia: a literature review","authors":"A. Vasileva, O. Aleshina, B. Biderman, A. Sudarikov","doi":"10.17650/1818-8346-2022-17-4-166-176","DOIUrl":"https://doi.org/10.17650/1818-8346-2022-17-4-166-176","url":null,"abstract":"T-cell acute lymphoblastic leukemia/lymphoma (T-ALL) is an aggressive hematological disease. Modern polychemotherapy protocols allow achieving a 5-year overall survival of 60–90 % in different age groups, however, relapses and refractory forms of T-ALL remain incurable. Over the past decades, the pathogenesis of this variant of leukemia has been studied in many trials, and it has been found that various signaling pathways are involved in the multi-step process of leukemogenesis. This opens the way for targeted therapy.In this review, we provide an update on the pathogenesis of T-ALL, opportunities for introducing targeted therapies, and issues that remain to be addressed.","PeriodicalId":36905,"journal":{"name":"Klinicheskaya Onkogematologiya/Clinical Oncohematology","volume":"33 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83646869","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-11-07DOI: 10.17650/1818-8346-2022-17-4-196-204
A. Kasimova, A. Kolbin, M. Proskurin, Y. Balykina
Background. Chronic lymphocytic leukemia (CLL) is a b-cell tumor of small b-lymphocytes. In CLL, significant lymphocytosis (5000 monoclonal b-lymphocytes) is observed in the blood, there are no morphological signs of bone marrow involvement. The 2020 Russian Clinical Guidelines “Chronic lymphocytic leukemia/Small lymphocyte lymphoma” approved several main chemotherapy regimens for the treatment of CLL patients.Aim. To perform a pharmacoeconomic analysis of the feasibility of fixed therapy regimens based on venetoclax in comparison with other targeted drugs registered in Russia, from the class of bruton kinase inhibitors, used until CLL progression or unacceptable toxicity.Materials and methods. A list of direct costs in the health care system was compiled. To assess the change in the cost structure and budget impact analyze, 4 mathematical models were constructed from a health care system perspective. Model 1 analyzed the direct costs of the health care system over 5 years, without taking into account the addition of new patients to the model. At the beginning of the modeling, the patients were equally divided between the strategies; later, there was a natural withdrawal of patients from the cycle. Models 2–4 analyze the economic impact of increasing the proportion of venetoclax-based fixed regimens.Results. with venetoclax + rituximab and venetoclax + obinutuzumab combinations used in 65 % of new patients, a cost reduction of 6.97 % would be observed in 2nd year of the budget impact analysis. In the case of an increase in the use of venetoclax in combination with rituximab or obinutuzumab to 80 % for new patients in the 5th year of the budget impact analysis, direct costs will decrease by 31.17 %, to 9,077,299,932 rubles.Conclusion. Increasing the proportion of fixed-dose venetoclax-based combinations compared to regimens prior to CLL progression or unacceptable toxicity in all models demonstrates cost-effectiveness.
{"title":"Pharmacoeconomic analysis of fixed-duration targeted therapy regimens for chronic lymphocytic leukemia compared with therapy used until progression or intolerable toxicity","authors":"A. Kasimova, A. Kolbin, M. Proskurin, Y. Balykina","doi":"10.17650/1818-8346-2022-17-4-196-204","DOIUrl":"https://doi.org/10.17650/1818-8346-2022-17-4-196-204","url":null,"abstract":"Background. Chronic lymphocytic leukemia (CLL) is a b-cell tumor of small b-lymphocytes. In CLL, significant lymphocytosis (5000 monoclonal b-lymphocytes) is observed in the blood, there are no morphological signs of bone marrow involvement. The 2020 Russian Clinical Guidelines “Chronic lymphocytic leukemia/Small lymphocyte lymphoma” approved several main chemotherapy regimens for the treatment of CLL patients.Aim. To perform a pharmacoeconomic analysis of the feasibility of fixed therapy regimens based on venetoclax in comparison with other targeted drugs registered in Russia, from the class of bruton kinase inhibitors, used until CLL progression or unacceptable toxicity.Materials and methods. A list of direct costs in the health care system was compiled. To assess the change in the cost structure and budget impact analyze, 4 mathematical models were constructed from a health care system perspective. Model 1 analyzed the direct costs of the health care system over 5 years, without taking into account the addition of new patients to the model. At the beginning of the modeling, the patients were equally divided between the strategies; later, there was a natural withdrawal of patients from the cycle. Models 2–4 analyze the economic impact of increasing the proportion of venetoclax-based fixed regimens.Results. with venetoclax + rituximab and venetoclax + obinutuzumab combinations used in 65 % of new patients, a cost reduction of 6.97 % would be observed in 2nd year of the budget impact analysis. In the case of an increase in the use of venetoclax in combination with rituximab or obinutuzumab to 80 % for new patients in the 5th year of the budget impact analysis, direct costs will decrease by 31.17 %, to 9,077,299,932 rubles.Conclusion. Increasing the proportion of fixed-dose venetoclax-based combinations compared to regimens prior to CLL progression or unacceptable toxicity in all models demonstrates cost-effectiveness.","PeriodicalId":36905,"journal":{"name":"Klinicheskaya Onkogematologiya/Clinical Oncohematology","volume":"36 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82258576","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-11-07DOI: 10.17650/1818-8346-2022-17-4-185-195
N. Matinyan, T. Valiev, L. Martynov, V. Akimov, E. A. Kovaleva, Yuri V. Buidenok
Background. Acute tumor lysis syndrome (ATLS) complicates the treatment of highly aggressive leukemias and lymphomas in children and leads to death in 21.4 % of severe cases. ATLS is based on the death of tumor cells, so the volume of decay products exceeds the excretory capacity of the kidneys. The ATLS risk group includes patients with acute lymphoblastic leukemia accompanied by hyperleukocytosis (above 100 × 109/L) and non-Hodgkin’s lymphomas with a large tumor mass (stage III–Iv of the disease). The development of acute renal and then multiple organ failure require intensive monitoring of ATLS clinical and biochemical markers and the development of optimal patient management tactics jointly by an intensive care physician and a pediatric oncologist-hematologist.Aim. To summarize the literature and our own clinical experience in the diagnosis and treatment of ATLS in pediatric oncohematology.Materials and methods. The literature data on the diagnosis and treatment of ATLS in children with oncohematological diseases were analyzed. Summarized own clinical experience from January 2009 to January 2022.Results. Of 379 patients with acute lymphoblastic leukemia and non-Hodgkin’s lymphomas, who are at risk for developing ATLS, 350 (93.4 %) patients underwent conservative ATLS therapy, of which in 31 (8.8 %) cases, hemodiafiltration was required to eliminate tumor decay products. The average number of hemodiafiltration procedures is 3 (from 1 to 15). Nevertheless, despite the whole range of therapeutic measures, the addition of infectious and multiple organ complications caused death in 7 (22.6 %) of 31 patients. Most (5 out of 7) fatal cases occurred between 2009 and 2013, and the number of lethal cases because of ATLS from 2014 to 2022 years were only 2. In 24 (77.4 %) patients, the signs of ATLS were successfully managed, the patients continued antitumor treatment. when observing patients for 6 years (from 7 months to 13 years), there were no signs of disease relapse, as well as renal dysfunction.Conclusion. prevention and treatment of ATLS, including cytoreductive prephase, infusion therapy, allopurinol and rasburicase, and in case of ineffectiveness, hemodiafiltration is the basis of modern intensive therapy for hematological malignancies in children. Additional study of the pathogenetic mechanisms of ATLS development, identification of key targets of drug therapy, and a multidisciplinary approach in the treatment of an extremely unfavorable group of oncohematological patients with advanced stages of the tumor process are possible components for further increasing the effectiveness of ATLS therapy.
{"title":"Tumour lysis syndrome: modern aspects of the problem","authors":"N. Matinyan, T. Valiev, L. Martynov, V. Akimov, E. A. Kovaleva, Yuri V. Buidenok","doi":"10.17650/1818-8346-2022-17-4-185-195","DOIUrl":"https://doi.org/10.17650/1818-8346-2022-17-4-185-195","url":null,"abstract":"Background. Acute tumor lysis syndrome (ATLS) complicates the treatment of highly aggressive leukemias and lymphomas in children and leads to death in 21.4 % of severe cases. ATLS is based on the death of tumor cells, so the volume of decay products exceeds the excretory capacity of the kidneys. The ATLS risk group includes patients with acute lymphoblastic leukemia accompanied by hyperleukocytosis (above 100 × 109/L) and non-Hodgkin’s lymphomas with a large tumor mass (stage III–Iv of the disease). The development of acute renal and then multiple organ failure require intensive monitoring of ATLS clinical and biochemical markers and the development of optimal patient management tactics jointly by an intensive care physician and a pediatric oncologist-hematologist.Aim. To summarize the literature and our own clinical experience in the diagnosis and treatment of ATLS in pediatric oncohematology.Materials and methods. The literature data on the diagnosis and treatment of ATLS in children with oncohematological diseases were analyzed. Summarized own clinical experience from January 2009 to January 2022.Results. Of 379 patients with acute lymphoblastic leukemia and non-Hodgkin’s lymphomas, who are at risk for developing ATLS, 350 (93.4 %) patients underwent conservative ATLS therapy, of which in 31 (8.8 %) cases, hemodiafiltration was required to eliminate tumor decay products. The average number of hemodiafiltration procedures is 3 (from 1 to 15). Nevertheless, despite the whole range of therapeutic measures, the addition of infectious and multiple organ complications caused death in 7 (22.6 %) of 31 patients. Most (5 out of 7) fatal cases occurred between 2009 and 2013, and the number of lethal cases because of ATLS from 2014 to 2022 years were only 2. In 24 (77.4 %) patients, the signs of ATLS were successfully managed, the patients continued antitumor treatment. when observing patients for 6 years (from 7 months to 13 years), there were no signs of disease relapse, as well as renal dysfunction.Conclusion. prevention and treatment of ATLS, including cytoreductive prephase, infusion therapy, allopurinol and rasburicase, and in case of ineffectiveness, hemodiafiltration is the basis of modern intensive therapy for hematological malignancies in children. Additional study of the pathogenetic mechanisms of ATLS development, identification of key targets of drug therapy, and a multidisciplinary approach in the treatment of an extremely unfavorable group of oncohematological patients with advanced stages of the tumor process are possible components for further increasing the effectiveness of ATLS therapy.","PeriodicalId":36905,"journal":{"name":"Klinicheskaya Onkogematologiya/Clinical Oncohematology","volume":"3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78426953","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-11-07DOI: 10.17650/1818-8346-2022-17-4-138-157
L. Babicheva
.
．
{"title":"Review of the 1st Conference “Diagnosis and treatment of oncological and hematological diseases in HIV infection. Confident in the present – without fear in the future”","authors":"L. Babicheva","doi":"10.17650/1818-8346-2022-17-4-138-157","DOIUrl":"https://doi.org/10.17650/1818-8346-2022-17-4-138-157","url":null,"abstract":"<jats:p>.</jats:p>","PeriodicalId":36905,"journal":{"name":"Klinicheskaya Onkogematologiya/Clinical Oncohematology","volume":"194 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72773661","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-11-07DOI: 10.17650/1818-8346-2022-17-4-126-137
Y. Dinikina, A. Mikhailov, M. A. Rusina, A. Smirnova, N. A. Vorob’ov, N. Kataev, A. Kubasov
Background. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective treatment method of refractory and recurrent forms of acute leukemia in children, while the question of choosing a conditioning regimen in order to achieve the best treatment results remains debatable. Conditioning based on total body irradiation (TbI) was confirmed to be most effective in some trials, but there are still issues of overcoming early and late toxicity, as well as difficulties in planning and routing patients.Aim. To share the experience of interdisciplinary patient management during the conditioning period with TbI inclusion in Saint petersburg, to evaluate the feasibility, toxicity and effectiveness of the method.Materials and methods. patients undergoing allo-HSCT for high risk acute lymphoblastic leukemia conditioned either with TbI (n = 12) or chemotherapy (n = 10) were included. Medical data were retrospectively analyzed with an assessment of the following transplant outcomes: HSCT-associated toxicity, the frequency and severity of infectious complications, graft versus host disease, as well as overall and event-free survival rates. we have evaluated radiotherapy plans in order to assess the compliance of radiation exposure with acceptable values for critical organs.Results. All patients with acute lymphoblastic leukemia in both groups received appropriate myeloablative conditioning. According to the study results, despite the lack of significance, we obtained differences in HSCT-associated mortality (8.3 and 30 %; p = 0.151), 2-years overall and event-free survival (66 ± 13.6 and 36 ± 16.1 %; p = 0.122) in group with TbI and HdCT respectively. It should be noted that there was a trend towards a decrease of toxic reactions frequency in case of TbI-containing regimens; however we didn’t reveal any significant differences in the number of infectious complications during post-transplant period. The median follow-up was 24.2 months and there were no signs of delayed toxicity.Conclusion. TbI-based conditioning was well tolerated with a low incidence of early and delayed toxicity, better overall and event-free survival. based on feasibility of TbI in Saint petersburg hospitals it is possible to recommend the method in routine practice, taking into account clinical indications.
{"title":"First experience of total body irradiation in conditioning regimes for allogenic hematopoietic stem cells transplantation in children with acute lymphoblastic leukemia in Saint Petersburg","authors":"Y. Dinikina, A. Mikhailov, M. A. Rusina, A. Smirnova, N. A. Vorob’ov, N. Kataev, A. Kubasov","doi":"10.17650/1818-8346-2022-17-4-126-137","DOIUrl":"https://doi.org/10.17650/1818-8346-2022-17-4-126-137","url":null,"abstract":"Background. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective treatment method of refractory and recurrent forms of acute leukemia in children, while the question of choosing a conditioning regimen in order to achieve the best treatment results remains debatable. Conditioning based on total body irradiation (TbI) was confirmed to be most effective in some trials, but there are still issues of overcoming early and late toxicity, as well as difficulties in planning and routing patients.Aim. To share the experience of interdisciplinary patient management during the conditioning period with TbI inclusion in Saint petersburg, to evaluate the feasibility, toxicity and effectiveness of the method.Materials and methods. patients undergoing allo-HSCT for high risk acute lymphoblastic leukemia conditioned either with TbI (n = 12) or chemotherapy (n = 10) were included. Medical data were retrospectively analyzed with an assessment of the following transplant outcomes: HSCT-associated toxicity, the frequency and severity of infectious complications, graft versus host disease, as well as overall and event-free survival rates. we have evaluated radiotherapy plans in order to assess the compliance of radiation exposure with acceptable values for critical organs.Results. All patients with acute lymphoblastic leukemia in both groups received appropriate myeloablative conditioning. According to the study results, despite the lack of significance, we obtained differences in HSCT-associated mortality (8.3 and 30 %; p = 0.151), 2-years overall and event-free survival (66 ± 13.6 and 36 ± 16.1 %; p = 0.122) in group with TbI and HdCT respectively. It should be noted that there was a trend towards a decrease of toxic reactions frequency in case of TbI-containing regimens; however we didn’t reveal any significant differences in the number of infectious complications during post-transplant period. The median follow-up was 24.2 months and there were no signs of delayed toxicity.Conclusion. TbI-based conditioning was well tolerated with a low incidence of early and delayed toxicity, better overall and event-free survival. based on feasibility of TbI in Saint petersburg hospitals it is possible to recommend the method in routine practice, taking into account clinical indications.","PeriodicalId":36905,"journal":{"name":"Klinicheskaya Onkogematologiya/Clinical Oncohematology","volume":"62 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85637138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-11-07DOI: 10.17650/1818-8346-2022-17-4-177-184
N. Shen, A. S. Minin, E. Y. Gaydym, T. Ksenzova
Background. Nutritional deficiency in malignant hematological diseases is a common condition that contributes to a decrease in functionality, tolerability of anticancer treatment and patient quality of life, and an increase in mortality rates. Often, malnutrition develops even before the start of anticancer treatment or during therapy and often remains unrecognized up to pronounced stages. despite the obvious importance of assessing and correcting the nutritional status in patients with hematological malignancies, this problem remains poorly understood.Aim. To evaluate the effect of nutritional support on the tolerability and results of treatment in patients with hemoblastoses.Materials and methods. The study included 40 patients with newly diagnosed hemoblastoses with nutritional deficiency or at risk of its development, who received program chemotherapy. patients were randomized into 2 comparable groups: in the main group (n = 20) patients received 2–3 bottles of Nutridrink compact protein mixture per day for 30 days, in the control group (n = 20) they ate at their own discretion without the use of additional enteral nutrition.Results. Comparative results of laboratory monitoring showed a significant increase in albumin levels in the main group compared with the control group (p <0.01). In the main group, less severe gastrointestinal toxicity of systemic anticancer therapy was observed: a tendency to a lower incidence of diarrhea and mucositis, a statistically significant reduction in the frequency of constipation, and a significant 2.8-fold decrease in the frequency of taste changes (25 % versus 70 %). Assessment of hematological toxicity showed that pancytopenia persisted in the control group (decrease in leukocytes, erythrocytes, hemoglobin, hematocrit and platelets levels), which was absent in the main group; leukocytes, hemoglobin, hematocrit, platelets and eosinophils were statistically significantly lower compared to the main group.Conclusion. The use of the Nutridrink compact protein mixture within 30 days from the start of treatment in patients with newly diagnosed hemablastoses contributed to an increase in albumin level, and reduced the incidence of gastrointestinal and hematological toxicity during systemic antitumor therapy.
{"title":"Influence of nutritional support on tolerability and results of treatment in patients with newly diagnosed hemoblastoses received program chemotherapy","authors":"N. Shen, A. S. Minin, E. Y. Gaydym, T. Ksenzova","doi":"10.17650/1818-8346-2022-17-4-177-184","DOIUrl":"https://doi.org/10.17650/1818-8346-2022-17-4-177-184","url":null,"abstract":"Background. Nutritional deficiency in malignant hematological diseases is a common condition that contributes to a decrease in functionality, tolerability of anticancer treatment and patient quality of life, and an increase in mortality rates. Often, malnutrition develops even before the start of anticancer treatment or during therapy and often remains unrecognized up to pronounced stages. despite the obvious importance of assessing and correcting the nutritional status in patients with hematological malignancies, this problem remains poorly understood.Aim. To evaluate the effect of nutritional support on the tolerability and results of treatment in patients with hemoblastoses.Materials and methods. The study included 40 patients with newly diagnosed hemoblastoses with nutritional deficiency or at risk of its development, who received program chemotherapy. patients were randomized into 2 comparable groups: in the main group (n = 20) patients received 2–3 bottles of Nutridrink compact protein mixture per day for 30 days, in the control group (n = 20) they ate at their own discretion without the use of additional enteral nutrition.Results. Comparative results of laboratory monitoring showed a significant increase in albumin levels in the main group compared with the control group (p <0.01). In the main group, less severe gastrointestinal toxicity of systemic anticancer therapy was observed: a tendency to a lower incidence of diarrhea and mucositis, a statistically significant reduction in the frequency of constipation, and a significant 2.8-fold decrease in the frequency of taste changes (25 % versus 70 %). Assessment of hematological toxicity showed that pancytopenia persisted in the control group (decrease in leukocytes, erythrocytes, hemoglobin, hematocrit and platelets levels), which was absent in the main group; leukocytes, hemoglobin, hematocrit, platelets and eosinophils were statistically significantly lower compared to the main group.Conclusion. The use of the Nutridrink compact protein mixture within 30 days from the start of treatment in patients with newly diagnosed hemablastoses contributed to an increase in albumin level, and reduced the incidence of gastrointestinal and hematological toxicity during systemic antitumor therapy.","PeriodicalId":36905,"journal":{"name":"Klinicheskaya Onkogematologiya/Clinical Oncohematology","volume":"45 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90356510","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-11-07DOI: 10.17650/1818-8346-2022-17-4-158-165
V. Kasatkin, I. Borodina, A. Deviaterikova, S. Malykh, A. F. Karelin
Background. The increase in life expectancy of children who survived cancer leads to new tasks for doctors, psychologists and rehabilitation specialists to assessing the consequences of the experienced disease and its treatment. The most common disorders in children who have survived oncological diseases are behavioral disorders, a decrease in mood background, as well as chronic fatigue.Aim. To identify predictors of behavioral disorders in children who have survived central nervous system oncological diseases.Materials and methods. The study involved 52 children with central nervous system tumors aged 6 to 17 years. The median time after completion of therapy in this group of patients was 18 (3–117) months.Results. As a result of the study, it was shown that such treatment parameters as the degree of tumor malignancy and the radiation therapy volume are associated with behavioral disorders in children who have survived cancer. In such children, a reduced mood background was revealed, and the older the child, the higher the probability of a reduced mood background. A reduced mood background is also associated with the use of vincristine preparation. Children who have a residual tumor are more likely to complain of unpleasant sensations in the body. All children, despite the specifics of their treatment, complain of constant fatigue, which affects their daily activity.Conclusion. Thus, factors that are associated with behavioral disorders in children who have survived oncological diseases in the central nervous system were identified.
{"title":"Identification of behavioral disorders using the Achenbach questionnaire in children with tumors of the posterior cranial fossa after completion of special treatment (pilot research)","authors":"V. Kasatkin, I. Borodina, A. Deviaterikova, S. Malykh, A. F. Karelin","doi":"10.17650/1818-8346-2022-17-4-158-165","DOIUrl":"https://doi.org/10.17650/1818-8346-2022-17-4-158-165","url":null,"abstract":"Background. The increase in life expectancy of children who survived cancer leads to new tasks for doctors, psychologists and rehabilitation specialists to assessing the consequences of the experienced disease and its treatment. The most common disorders in children who have survived oncological diseases are behavioral disorders, a decrease in mood background, as well as chronic fatigue.Aim. To identify predictors of behavioral disorders in children who have survived central nervous system oncological diseases.Materials and methods. The study involved 52 children with central nervous system tumors aged 6 to 17 years. The median time after completion of therapy in this group of patients was 18 (3–117) months.Results. As a result of the study, it was shown that such treatment parameters as the degree of tumor malignancy and the radiation therapy volume are associated with behavioral disorders in children who have survived cancer. In such children, a reduced mood background was revealed, and the older the child, the higher the probability of a reduced mood background. A reduced mood background is also associated with the use of vincristine preparation. Children who have a residual tumor are more likely to complain of unpleasant sensations in the body. All children, despite the specifics of their treatment, complain of constant fatigue, which affects their daily activity.Conclusion. Thus, factors that are associated with behavioral disorders in children who have survived oncological diseases in the central nervous system were identified.","PeriodicalId":36905,"journal":{"name":"Klinicheskaya Onkogematologiya/Clinical Oncohematology","volume":"54 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81431074","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-11-06DOI: 10.17650/1818-8346-2022-17-4-106-117
E. Morozova, N. Tsvetkov, M. V. Barabanshchikova, K. Yurovskaya, I. Moiseev
{"title":"New perspectives in the treatment of patients with intermediate-2 and high-risk myelodysplastic syndrome","authors":"E. Morozova, N. Tsvetkov, M. V. Barabanshchikova, K. Yurovskaya, I. Moiseev","doi":"10.17650/1818-8346-2022-17-4-106-117","DOIUrl":"https://doi.org/10.17650/1818-8346-2022-17-4-106-117","url":null,"abstract":"","PeriodicalId":36905,"journal":{"name":"Klinicheskaya Onkogematologiya/Clinical Oncohematology","volume":"33 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79706047","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-11-06DOI: 10.17650/1818-8346-2022-17-4-94-105
O. Vinogradova, M. Pankrashkina, D. Shikhbabaeva, M. Chernikov, A. L. Neverova, V. Ivanova, E. Nikitin, E. Usikova, V. Ptushkin
Background. For many years the primary aim of treatment strategy for ph-negative myeloproliferative neoplasms has been to restrain disease progression, with lasting relief and management of symptoms to improve patients’ quality of life. Generally, this did not lead to a significant increase in life expectancy with primary myelofibrosis and didn’t decrease the risk of fibrosis in patients with polycythemia vera and essential thrombocythemia. To date a new class of targeted drugs has been developed, it is JAK2 inhibitors with pathogenetic effects. The results of clinical trials showed the high efficacy of the first registered drug of this its kind – ruxolitinib – that includes a faster reduction in the symptoms of tumor intoxication and in symptoms associated with the development of splenomegaly and increase in the overall survival rates. It is known that the data obtained during clinical trials of medicines may differ from the results obtained in routine clinical practice. In actual practice drugs are used in a much wider heterogeneous population of patients, less limited first of all by age and comorbid characteristics. It is possible to analyze cohorts of patients including a larger number of clinical cases with a longer follow-up period. In this regard of great interest is the actual clinical experience of long-term use of ruxolitinib in patients whose set is limited only by clinical contraindications for prescribing the drug.Aim. To present our own actual experience of targeted therapy of myelofibrosis and compare the results obtained with the data of clinical trials.Materials and methods. Our analysis includes data from 141 patients (67 (47.5 %) men and 74 (52.5 %) women) in a chronic phase myelofibrosis. All patients received ruxolitinib. Of these, 109 (69 %) patients had primary myelofibrosis, 26 (16 %) – postpolycythemia myelofibrosis, 6 (4 %) – postessential thrombocythemia myelofibrosis. The median age at the start of therapy was 62 (18–84) years. The median disease duration before ruxolitinib was prescribed – 79 (1–401) months. According to the dIpSS (dynamic International prognostic Scoring System) criteria, 13 % of patients were assigned to the low risk group, 38 % – to the intermediate-1, 36 % – to the intermediate-2, 13 % – to the high risk group. Most patients (52 %) had grade 3 bone marrow fibrosis.Results. The median duration of treatment was 18 (range from 1 to 115) months. Symptoms of intoxication were relieved 74 (81 %) of 91 patients, the spleen size decreased in 81 % of patients (the spleen size returned to normal in 25 % of patients). The increase in the median hemoglobin level was 15 %. The proportion of patients requiring blood transfusion decreased by 4 times (from 39 to 9 %). Mean platelet levels normalized in most patients with baseline high and low platelet levels. A complete clinical and hematological response was achieved in 16 % (n = 23) of cases, a partial response – in 26 % (n = 37) of cases, clinical improvement
{"title":"Possibilities of targeted therapy for myelofibrosis: Moscow experience","authors":"O. Vinogradova, M. Pankrashkina, D. Shikhbabaeva, M. Chernikov, A. L. Neverova, V. Ivanova, E. Nikitin, E. Usikova, V. Ptushkin","doi":"10.17650/1818-8346-2022-17-4-94-105","DOIUrl":"https://doi.org/10.17650/1818-8346-2022-17-4-94-105","url":null,"abstract":"Background. For many years the primary aim of treatment strategy for ph-negative myeloproliferative neoplasms has been to restrain disease progression, with lasting relief and management of symptoms to improve patients’ quality of life. Generally, this did not lead to a significant increase in life expectancy with primary myelofibrosis and didn’t decrease the risk of fibrosis in patients with polycythemia vera and essential thrombocythemia. To date a new class of targeted drugs has been developed, it is JAK2 inhibitors with pathogenetic effects. The results of clinical trials showed the high efficacy of the first registered drug of this its kind – ruxolitinib – that includes a faster reduction in the symptoms of tumor intoxication and in symptoms associated with the development of splenomegaly and increase in the overall survival rates. It is known that the data obtained during clinical trials of medicines may differ from the results obtained in routine clinical practice. In actual practice drugs are used in a much wider heterogeneous population of patients, less limited first of all by age and comorbid characteristics. It is possible to analyze cohorts of patients including a larger number of clinical cases with a longer follow-up period. In this regard of great interest is the actual clinical experience of long-term use of ruxolitinib in patients whose set is limited only by clinical contraindications for prescribing the drug.Aim. To present our own actual experience of targeted therapy of myelofibrosis and compare the results obtained with the data of clinical trials.Materials and methods. Our analysis includes data from 141 patients (67 (47.5 %) men and 74 (52.5 %) women) in a chronic phase myelofibrosis. All patients received ruxolitinib. Of these, 109 (69 %) patients had primary myelofibrosis, 26 (16 %) – postpolycythemia myelofibrosis, 6 (4 %) – postessential thrombocythemia myelofibrosis. The median age at the start of therapy was 62 (18–84) years. The median disease duration before ruxolitinib was prescribed – 79 (1–401) months. According to the dIpSS (dynamic International prognostic Scoring System) criteria, 13 % of patients were assigned to the low risk group, 38 % – to the intermediate-1, 36 % – to the intermediate-2, 13 % – to the high risk group. Most patients (52 %) had grade 3 bone marrow fibrosis.Results. The median duration of treatment was 18 (range from 1 to 115) months. Symptoms of intoxication were relieved 74 (81 %) of 91 patients, the spleen size decreased in 81 % of patients (the spleen size returned to normal in 25 % of patients). The increase in the median hemoglobin level was 15 %. The proportion of patients requiring blood transfusion decreased by 4 times (from 39 to 9 %). Mean platelet levels normalized in most patients with baseline high and low platelet levels. A complete clinical and hematological response was achieved in 16 % (n = 23) of cases, a partial response – in 26 % (n = 37) of cases, clinical improvement","PeriodicalId":36905,"journal":{"name":"Klinicheskaya Onkogematologiya/Clinical Oncohematology","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87844319","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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