Pub Date : 2022-07-20DOI: 10.17650/1818-8346-2022-17-3-108-113
R. Mustafin
Antitumor drug treatment of hemoblastoses always takes into account the patient comorbidity. Due to the frequent cardiovascular pathology and atherosclerosis, patients have to take statins along with antitumor treatment. Experimental studies have shown that statins inhibit the cholesterol synthesis (necessary for the vital activity of malignant cells), isoprenylation of the RAS and RHO oncogenes, and the proliferation of leukemic cells. In addition, the potentiation of antitumor drugs effect by statins, sensitization of leukemia and lymphomas cells to their effects were noted. when conducting a meta-analysis, it was found that mortality among patients with hematological malignancies taking statins is lower compared with the group of patients not receiving statins. This fact is probably explained not only by the improvement in cholesterol metabolism, but also by indirect antitumor effects of this group of drugs.
{"title":"Disputable questions of statins antitumor effects in hemoblastoses","authors":"R. Mustafin","doi":"10.17650/1818-8346-2022-17-3-108-113","DOIUrl":"https://doi.org/10.17650/1818-8346-2022-17-3-108-113","url":null,"abstract":"Antitumor drug treatment of hemoblastoses always takes into account the patient comorbidity. Due to the frequent cardiovascular pathology and atherosclerosis, patients have to take statins along with antitumor treatment. Experimental studies have shown that statins inhibit the cholesterol synthesis (necessary for the vital activity of malignant cells), isoprenylation of the RAS and RHO oncogenes, and the proliferation of leukemic cells. In addition, the potentiation of antitumor drugs effect by statins, sensitization of leukemia and lymphomas cells to their effects were noted. when conducting a meta-analysis, it was found that mortality among patients with hematological malignancies taking statins is lower compared with the group of patients not receiving statins. This fact is probably explained not only by the improvement in cholesterol metabolism, but also by indirect antitumor effects of this group of drugs.","PeriodicalId":36905,"journal":{"name":"Klinicheskaya Onkogematologiya/Clinical Oncohematology","volume":"70 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74562755","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 : 2022-07-20DOI: 10.17650/1818-8346-2022-17-3-98-107
E. Kotova, O. Gavrilina, I. Yakutik, A. Sudarikov, Y. Chabaeva, S. Kulikov, S. G. Beksaev, V. Troitskaya, G. Isinova, A. Sokolov, Z. Fidarova, I. Lukyanova, A. Abramova, V. Dvirnyk, I. Galtseva, T. Obukhova, E. Parovichnikova
Background. 6-mercaptopurine (6-MP) is a drug that is included in the treatment protocols for children and adults with acute lymphoblastic leukemias/lymphomas (ALL/LBL). It is known that individual differences in 6-MP tolerance can be explained by the TPMT and NUDT15 polymorphisms.Aim. To determine 6-MP toxicity profile in adult patients with Ph-negative ALL/LBL treated by ALL-2016 protocol, depending on the TPMT and NUDT15 polymorphisms.Materials and methods. The study included 54 adult patients with Ph-negative ALL/LBL (40 male and 14 female). The median age was 31 (18-51) years. T-ALL/LBL was diagnosed in 29 patients, B-ALL/LBL - in 22, acute leukemia with a mixed immunophenotype - in 3. All patients received treatment according to the multicenter study ALL-2016 (ClinicalTrials.gov, NCT03462095). polymorphisms in NUDT15 (*2, *3) and TPMT (*2, *3A, *3B, *3C) genes were detected using the allele-specific real-time polymerase chain reaction. Genomic DNA was extracted from patients peripheral blood samples. On the induction and consolidation therapy by the protocol, the received and proper 6-MP doses were calculated for all the patients. Drug toxicity was evaluated based on clinical and laboratory data.Results. TPMT and NUDT15 polymorphisms were detected in 11 (20 %) patients, more often in B-ALL - 7 (32 %) of 22 (p <0.05). A lower dose of 6-MP was received by patients with TPMT, NUDT15 polymorphisms only at consolidation IV (p = 0.01). we didn't find a correlation between the 6-MP toxicity and the polymorphisms in our patients (p >0.05).Conclusion. There were no differences in the received dose of 6-MP and the incidence of toxicity in adult patients between Ph-negative ALL/LBL with or without TPMT and NUDT15 polymorphisms treated according to ALL-2016 protocol (p >0.05). further studies including evaluation of 6-MP metabolites concentrations are required for a more complete understanding of the metabolism of this drug.
{"title":"Polymorphisms of the TPMT, NUDT15 genes and 6-mercaptopurine toxicity profile in adult patients with Ph-negative acute lymphoblastic leukemia/lymphomas on the ALL-2016 protocol","authors":"E. Kotova, O. Gavrilina, I. Yakutik, A. Sudarikov, Y. Chabaeva, S. Kulikov, S. G. Beksaev, V. Troitskaya, G. Isinova, A. Sokolov, Z. Fidarova, I. Lukyanova, A. Abramova, V. Dvirnyk, I. Galtseva, T. Obukhova, E. Parovichnikova","doi":"10.17650/1818-8346-2022-17-3-98-107","DOIUrl":"https://doi.org/10.17650/1818-8346-2022-17-3-98-107","url":null,"abstract":"Background. 6-mercaptopurine (6-MP) is a drug that is included in the treatment protocols for children and adults with acute lymphoblastic leukemias/lymphomas (ALL/LBL). It is known that individual differences in 6-MP tolerance can be explained by the TPMT and NUDT15 polymorphisms.Aim. To determine 6-MP toxicity profile in adult patients with Ph-negative ALL/LBL treated by ALL-2016 protocol, depending on the TPMT and NUDT15 polymorphisms.Materials and methods. The study included 54 adult patients with Ph-negative ALL/LBL (40 male and 14 female). The median age was 31 (18-51) years. T-ALL/LBL was diagnosed in 29 patients, B-ALL/LBL - in 22, acute leukemia with a mixed immunophenotype - in 3. All patients received treatment according to the multicenter study ALL-2016 (ClinicalTrials.gov, NCT03462095). polymorphisms in NUDT15 (*2, *3) and TPMT (*2, *3A, *3B, *3C) genes were detected using the allele-specific real-time polymerase chain reaction. Genomic DNA was extracted from patients peripheral blood samples. On the induction and consolidation therapy by the protocol, the received and proper 6-MP doses were calculated for all the patients. Drug toxicity was evaluated based on clinical and laboratory data.Results. TPMT and NUDT15 polymorphisms were detected in 11 (20 %) patients, more often in B-ALL - 7 (32 %) of 22 (p <0.05). A lower dose of 6-MP was received by patients with TPMT, NUDT15 polymorphisms only at consolidation IV (p = 0.01). we didn't find a correlation between the 6-MP toxicity and the polymorphisms in our patients (p >0.05).Conclusion. There were no differences in the received dose of 6-MP and the incidence of toxicity in adult patients between Ph-negative ALL/LBL with or without TPMT and NUDT15 polymorphisms treated according to ALL-2016 protocol (p >0.05). further studies including evaluation of 6-MP metabolites concentrations are required for a more complete understanding of the metabolism of this drug.","PeriodicalId":36905,"journal":{"name":"Klinicheskaya Onkogematologiya/Clinical Oncohematology","volume":"76 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80539051","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 : 2022-07-20DOI: 10.17650/1818-8346-2022-17-3-89-97
V. Potapenko, M. M. Antonov, N. V. Vinogradova, E. V. Doguzhieva, V. E. Karev, E. Karamurzin, G. V. Kachenya, A. Klimovich, S. Kozlov, Y. Krivolapov, S. Lapin, M. Pervakova, N. Potikhonova, I. Fedunyak, N. Medvedeva
Secondary hemophagocytic syndrome (sHLH) is a hyperinflammatory reaction which manifests with fever, cytopenia and organ damage. possible causes of sHLH include leishmaniasis. The article describes a clinical case of sHLH in patient with visceral leishmaniasis. A female 30 years old developed hectic daily fever up to 40 °C, pancytopenia, cytolytic syndrome, hyperferritin- and hypertriglyceridemia, immunoglobulin G to capsid antigens of the Epstein-Barr virus, enlarged liver and spleen a one and a half month after returning from Spain. based on the HLH-2004 and H-Score criteria, a sHLH was diagnosed, presumably associated with the Epstein-Barr virus. Immunosuppressive treatment with dexamethasone, cyclosporin-A and etoposide was started under the HLH-2004 program. Apyrexia, reduction of splenomegaly and resolution of cytolysis were achieved. The fever resumed 20 days after the start of chemotherapy, the spleen enlarged again, and therefore a diagnostic splenectomy was performed. Morphological analysis of the removed spleen revealed leishmania. After amphotericin-B therapy, the patient recovered. Chemotherapy of sHLH led to a temporary improvement for a period sufficient to verify the diagnosis and conducting of successful treatment.
{"title":"Hemophagocytic syndrome associated with leishmaniasis: case report","authors":"V. Potapenko, M. M. Antonov, N. V. Vinogradova, E. V. Doguzhieva, V. E. Karev, E. Karamurzin, G. V. Kachenya, A. Klimovich, S. Kozlov, Y. Krivolapov, S. Lapin, M. Pervakova, N. Potikhonova, I. Fedunyak, N. Medvedeva","doi":"10.17650/1818-8346-2022-17-3-89-97","DOIUrl":"https://doi.org/10.17650/1818-8346-2022-17-3-89-97","url":null,"abstract":"Secondary hemophagocytic syndrome (sHLH) is a hyperinflammatory reaction which manifests with fever, cytopenia and organ damage. possible causes of sHLH include leishmaniasis. The article describes a clinical case of sHLH in patient with visceral leishmaniasis. A female 30 years old developed hectic daily fever up to 40 °C, pancytopenia, cytolytic syndrome, hyperferritin- and hypertriglyceridemia, immunoglobulin G to capsid antigens of the Epstein-Barr virus, enlarged liver and spleen a one and a half month after returning from Spain. based on the HLH-2004 and H-Score criteria, a sHLH was diagnosed, presumably associated with the Epstein-Barr virus. Immunosuppressive treatment with dexamethasone, cyclosporin-A and etoposide was started under the HLH-2004 program. Apyrexia, reduction of splenomegaly and resolution of cytolysis were achieved. The fever resumed 20 days after the start of chemotherapy, the spleen enlarged again, and therefore a diagnostic splenectomy was performed. Morphological analysis of the removed spleen revealed leishmania. After amphotericin-B therapy, the patient recovered. Chemotherapy of sHLH led to a temporary improvement for a period sufficient to verify the diagnosis and conducting of successful treatment.","PeriodicalId":36905,"journal":{"name":"Klinicheskaya Onkogematologiya/Clinical Oncohematology","volume":"310 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76454405","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 : 2022-07-20DOI: 10.17650/1818-8346-2022-17-3-62-72
L. Golovkina, A. G. Stremoukhova, T. Pushkina, B. B. Khasigova, G. V. Atroshchenko, R. S. Kalandarov, L. Kuzmina, V. Vasilieva, E. Parovichnikova
Background. when transplantation of hematopoietic stem cells (HSC) is performing, it is necessary to take into account the incompatibility of the donor and recipient in terms of erythrocyte antigens in order to assess the possibility of immunological complications during HSC transfusion and/or graft engraftment (acute hemolysis, delayed hemolysis, etc.). The results of serological research methods do not always allow identifying the true group affiliation due to posttransfusion chimerism in patients and/or the presence of antigen allelic polymorphism.Aim. To establish the frequency of ABO-incompatible allo-HSC transplantations in the National Research Center for Hematology, to determine by molecular methods the group affiliation of patients with a weakened expression of antigens and/or after multiple blood transfusions before HSC transplantation, to clarify the blood type of HSC donors with a weakened expression of antigens.Materials and methods. The blood of 270 HSC donor-recipient couples was examined. The blood group of the ABO, Rhesus, MNS, Kell systems was determined in a plane agglutination test using the corresponding IgM class Tsoliclones and in gel cards. Genotyping was performed by polymerase chain reaction with primers to identify the genes of the ABO, Rhesus, Kell, and MNS systems.Results. In 2018-2020 270 HSC transplantations were performed at the National Research Center for Hematology. In 141 (52.22 %) couples, incompatibility of the donor and recipient according to the ABO system was revealed: major - 23.33 %, minor - 20 %; bidirectional - 8.89 %. problems in assessing of serological results were observed in 97 (36.3 %) patients: in 78 patients with post-transfusion chimerism and 19 patients with weakened antigen expression; in 15 (5.56 %) HSC donors: in 4 due to the lack of information about the blood group of cryopreserved cells, in 10 due to weakened antigen expression, in 1 to search for informative markers for monitoring HSC engraftment. The results of the study demonstrated that the percentage of agglutinated erythrocytes in post-transfusion chimerism cannot be a reliable criterion for establishing the true phenotype of a patient. In donors and patients with weakened expression of antigens, the presence of ABO*O1, -A1, -A2, -B1, RHD weak type 1, RHD weak type 2, RHD weak type 3, RHCE*Cw genes was confirmed. for the first time in Russia gene RHCE*01.38 was found.Conclusion. The prevalence of ABO-incompatible HSC transplants was noted. problems with serological determination of the blood group in a third of patients before HSC transplantation arose due to the presence of post-transfusion chimerism and weakened expression of antigens. Determining of the genotypes of HSC donors is necessary when the expression of antigens is weakened and cryopreserved cells are received. The percentage of agglutinated erythrocytes in post-transfusion chimerism cannot be a reliable criterion for establishing the true phenotype of a patient. Detec
{"title":"Molecular methods in identifying the true grouping of erythrocytes in patients with blood system diseases before transplantation of hematopoietic stem cells and their donors","authors":"L. Golovkina, A. G. Stremoukhova, T. Pushkina, B. B. Khasigova, G. V. Atroshchenko, R. S. Kalandarov, L. Kuzmina, V. Vasilieva, E. Parovichnikova","doi":"10.17650/1818-8346-2022-17-3-62-72","DOIUrl":"https://doi.org/10.17650/1818-8346-2022-17-3-62-72","url":null,"abstract":"Background. when transplantation of hematopoietic stem cells (HSC) is performing, it is necessary to take into account the incompatibility of the donor and recipient in terms of erythrocyte antigens in order to assess the possibility of immunological complications during HSC transfusion and/or graft engraftment (acute hemolysis, delayed hemolysis, etc.). The results of serological research methods do not always allow identifying the true group affiliation due to posttransfusion chimerism in patients and/or the presence of antigen allelic polymorphism.Aim. To establish the frequency of ABO-incompatible allo-HSC transplantations in the National Research Center for Hematology, to determine by molecular methods the group affiliation of patients with a weakened expression of antigens and/or after multiple blood transfusions before HSC transplantation, to clarify the blood type of HSC donors with a weakened expression of antigens.Materials and methods. The blood of 270 HSC donor-recipient couples was examined. The blood group of the ABO, Rhesus, MNS, Kell systems was determined in a plane agglutination test using the corresponding IgM class Tsoliclones and in gel cards. Genotyping was performed by polymerase chain reaction with primers to identify the genes of the ABO, Rhesus, Kell, and MNS systems.Results. In 2018-2020 270 HSC transplantations were performed at the National Research Center for Hematology. In 141 (52.22 %) couples, incompatibility of the donor and recipient according to the ABO system was revealed: major - 23.33 %, minor - 20 %; bidirectional - 8.89 %. problems in assessing of serological results were observed in 97 (36.3 %) patients: in 78 patients with post-transfusion chimerism and 19 patients with weakened antigen expression; in 15 (5.56 %) HSC donors: in 4 due to the lack of information about the blood group of cryopreserved cells, in 10 due to weakened antigen expression, in 1 to search for informative markers for monitoring HSC engraftment. The results of the study demonstrated that the percentage of agglutinated erythrocytes in post-transfusion chimerism cannot be a reliable criterion for establishing the true phenotype of a patient. In donors and patients with weakened expression of antigens, the presence of ABO*O1, -A1, -A2, -B1, RHD weak type 1, RHD weak type 2, RHD weak type 3, RHCE*Cw genes was confirmed. for the first time in Russia gene RHCE*01.38 was found.Conclusion. The prevalence of ABO-incompatible HSC transplants was noted. problems with serological determination of the blood group in a third of patients before HSC transplantation arose due to the presence of post-transfusion chimerism and weakened expression of antigens. Determining of the genotypes of HSC donors is necessary when the expression of antigens is weakened and cryopreserved cells are received. The percentage of agglutinated erythrocytes in post-transfusion chimerism cannot be a reliable criterion for establishing the true phenotype of a patient. Detec","PeriodicalId":36905,"journal":{"name":"Klinicheskaya Onkogematologiya/Clinical Oncohematology","volume":"85 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74320685","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 : 2022-07-20DOI: 10.17650/1818-8346-2022-17-3-48-61
V. Potapenko, E. Baumert, A. A. Bobrova, R. V. Vashchenkov, N. Dorofeeva, K. Kaplanov, E. Karyagina, A. Levanov, A. Luchinin, S. Moiseev, A. V. Novitskiĭ, A. Nizamutdinova, О. V. Pirogova, S. Povzun, М. V. Platonov, V. Porunova, D. Ptashnikov, V. V. Ryabchikova, S. Y. Simeniv, I. Skorokhod, Е. А. Ukrainchenko, D. Chaginskaya, T. Shelekhova, M. Shirokova, A. A. Shutylev, N. Medvedeva
Background. The treatment options for patients with multiple myeloma who refractory to previous bortezomib and lenalidomide therapy are limited. Pomalidomide is ап immunomodulatory agent that was registered for the treatment of patients with double refractory multiple myeloma.Aim. To evaluate efficacy, safety and optimal course of the therapy with pomalidomide in routine practice in patients with double refractory multiple myeloma.Materials and methods. Overall, 71 patients with double refractory multiple myeloma were included in the retrospective analysis. There were 36 males and 35 females. The median age was 61 years (range 35-79). According to Durie-Salmon staging system, there were 53 (79.1 %) patients in stage III, 13 (19.4 %) - stage II, and 1 (1.5 %) - stage I.The stage was unknown in 4 patients. Kidney impairment at the onset was in 10 (15 %) patients, the normal function was in 57 (85 %) patients and 4 patients had no data. Most patients (n = 68, 95.8 %) received pomalidomide in one therapy line, in 3 (4.2 %) patients - drug was given in two lines, totally 74 episodes of use. Median number of drugs prescribed prior to pomalidomide were 4 (2-9) drugs, including target ones - 2 (2-5). In the first remission 31 (43.6 %) patients received high-dose therapy with autologous stem cell transplantation. pomalidomide was administered in combination with low doses of dexamethasone (PomDex, n = 44; 59.4 %) and as a part of triple regimens (n = 30; 40.6 %). previously exposed (n = 22; 73.3 %) and new drugs (n = 8; 26.7 %) were used in the combination treatment. In 44 (61.9 %) patients pomalidomide was administered more than 3 years after the onset of the disease, median 63.5 (37-184) months. In 27 (38.1 %) patients it was given within less than 3 years after the onset, median 21 (6-36) months. The primary endpoint was progression-free survival. Secondary endpoints - pomalidomide tolerability, response rate and optimal third drug in the triple regimen. The dependence of progression-free survival, frequency of response and adverse events from the pretreatment, the choice of the third drug, gender, age, immunochemical variant, stage according to the International Staging System and to Durie-Salmon classification was studied.Results. The median time from the diagnosis to the start of pomalidomide therapy was 44.5 (6-184) months. The median of cycles with pomalidomide was 3 (1-30). The response was achieved in 52 (70 %) patients. The median progression-free survival was 4 (1-30) months, overall survival - 6 (0.5-42) months. Adverse effects were noted in 34 (46.5 %) patients. The most frequent adverse events were neutropenia grade III-IV (n = 14; 41.3 %), infection (n = 7; 20.7 %) and fatigue with limitation of daily activity (n = 6; 20.6 %). The rate of adverse events was higher in patients with triplets than doublets regimens of therapy: 43.3 % (n = 13) and 27.2 % (n = 12) respectively (p = 0.008). There were no statistically significant differences in
{"title":"Pomalidomide in relapsed and refractory multiple myeloma: multicenter retrospective study","authors":"V. Potapenko, E. Baumert, A. A. Bobrova, R. V. Vashchenkov, N. Dorofeeva, K. Kaplanov, E. Karyagina, A. Levanov, A. Luchinin, S. Moiseev, A. V. Novitskiĭ, A. Nizamutdinova, О. V. Pirogova, S. Povzun, М. V. Platonov, V. Porunova, D. Ptashnikov, V. V. Ryabchikova, S. Y. Simeniv, I. Skorokhod, Е. А. Ukrainchenko, D. Chaginskaya, T. Shelekhova, M. Shirokova, A. A. Shutylev, N. Medvedeva","doi":"10.17650/1818-8346-2022-17-3-48-61","DOIUrl":"https://doi.org/10.17650/1818-8346-2022-17-3-48-61","url":null,"abstract":"Background. The treatment options for patients with multiple myeloma who refractory to previous bortezomib and lenalidomide therapy are limited. Pomalidomide is ап immunomodulatory agent that was registered for the treatment of patients with double refractory multiple myeloma.Aim. To evaluate efficacy, safety and optimal course of the therapy with pomalidomide in routine practice in patients with double refractory multiple myeloma.Materials and methods. Overall, 71 patients with double refractory multiple myeloma were included in the retrospective analysis. There were 36 males and 35 females. The median age was 61 years (range 35-79). According to Durie-Salmon staging system, there were 53 (79.1 %) patients in stage III, 13 (19.4 %) - stage II, and 1 (1.5 %) - stage I.The stage was unknown in 4 patients. Kidney impairment at the onset was in 10 (15 %) patients, the normal function was in 57 (85 %) patients and 4 patients had no data. Most patients (n = 68, 95.8 %) received pomalidomide in one therapy line, in 3 (4.2 %) patients - drug was given in two lines, totally 74 episodes of use. Median number of drugs prescribed prior to pomalidomide were 4 (2-9) drugs, including target ones - 2 (2-5). In the first remission 31 (43.6 %) patients received high-dose therapy with autologous stem cell transplantation. pomalidomide was administered in combination with low doses of dexamethasone (PomDex, n = 44; 59.4 %) and as a part of triple regimens (n = 30; 40.6 %). previously exposed (n = 22; 73.3 %) and new drugs (n = 8; 26.7 %) were used in the combination treatment. In 44 (61.9 %) patients pomalidomide was administered more than 3 years after the onset of the disease, median 63.5 (37-184) months. In 27 (38.1 %) patients it was given within less than 3 years after the onset, median 21 (6-36) months. The primary endpoint was progression-free survival. Secondary endpoints - pomalidomide tolerability, response rate and optimal third drug in the triple regimen. The dependence of progression-free survival, frequency of response and adverse events from the pretreatment, the choice of the third drug, gender, age, immunochemical variant, stage according to the International Staging System and to Durie-Salmon classification was studied.Results. The median time from the diagnosis to the start of pomalidomide therapy was 44.5 (6-184) months. The median of cycles with pomalidomide was 3 (1-30). The response was achieved in 52 (70 %) patients. The median progression-free survival was 4 (1-30) months, overall survival - 6 (0.5-42) months. Adverse effects were noted in 34 (46.5 %) patients. The most frequent adverse events were neutropenia grade III-IV (n = 14; 41.3 %), infection (n = 7; 20.7 %) and fatigue with limitation of daily activity (n = 6; 20.6 %). The rate of adverse events was higher in patients with triplets than doublets regimens of therapy: 43.3 % (n = 13) and 27.2 % (n = 12) respectively (p = 0.008). There were no statistically significant differences in ","PeriodicalId":36905,"journal":{"name":"Klinicheskaya Onkogematologiya/Clinical Oncohematology","volume":"358 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77327951","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 : 2022-07-20DOI: 10.17650/1818-8346-2022-17-3-73-82
K. I. Utesheva, E. Belyaeva, T. Valiev, A. Odzharova
Primary immunodeficiencies (PID) are genetically determined irreversible disorders of structure and/or functions of the immune system's cellular and humoral components, accompanied by frequent infectious diseases and contributing to the development of malignant neoplasms. Lymphomas are the most frequent oncological disease in PID patients: non-Hodgkin's lymphomas occur in 60 % of malignant neoplasms cases, Hodgkin lymphoma - in 20 %, leukemias - in 10 %, solid tumors - in 10 %. The risk of malignant lymphoproliferative diseases in PID patients amounts to 4-25 %, with the overall incidence of cancer 100-200 times higher than in immunocompetent population. Results of malignant neoplasms treatment in children with PID remain unsatisfactory due to the high rate of relapsed, refractory disease and anticancer therapy complications.This paper presents a clinical case of Hodgkin lymphoma with atypical localization in a female PID patient. peculiarities of this case are eye socket soft tissue involvement, slow response to therapy, and a high rate of infectious complications.
{"title":"Hodgkin lymphoma in patient with primary immunodeficiency: clinical features and treatment approaches","authors":"K. I. Utesheva, E. Belyaeva, T. Valiev, A. Odzharova","doi":"10.17650/1818-8346-2022-17-3-73-82","DOIUrl":"https://doi.org/10.17650/1818-8346-2022-17-3-73-82","url":null,"abstract":"Primary immunodeficiencies (PID) are genetically determined irreversible disorders of structure and/or functions of the immune system's cellular and humoral components, accompanied by frequent infectious diseases and contributing to the development of malignant neoplasms. Lymphomas are the most frequent oncological disease in PID patients: non-Hodgkin's lymphomas occur in 60 % of malignant neoplasms cases, Hodgkin lymphoma - in 20 %, leukemias - in 10 %, solid tumors - in 10 %. The risk of malignant lymphoproliferative diseases in PID patients amounts to 4-25 %, with the overall incidence of cancer 100-200 times higher than in immunocompetent population. Results of malignant neoplasms treatment in children with PID remain unsatisfactory due to the high rate of relapsed, refractory disease and anticancer therapy complications.This paper presents a clinical case of Hodgkin lymphoma with atypical localization in a female PID patient. peculiarities of this case are eye socket soft tissue involvement, slow response to therapy, and a high rate of infectious complications.","PeriodicalId":36905,"journal":{"name":"Klinicheskaya Onkogematologiya/Clinical Oncohematology","volume":"77 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80013269","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 : 2022-07-20DOI: 10.17650/1818-8346-2022-17-3-137-159
T. Valiev, M. Shervashidze, T. Belysheva
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.
{"title":"Toxicity assessment of acute lymphoblastic leukemia treatment protocol ALL IC-BFM 2002","authors":"T. Valiev, M. Shervashidze, T. Belysheva","doi":"10.17650/1818-8346-2022-17-3-137-159","DOIUrl":"https://doi.org/10.17650/1818-8346-2022-17-3-137-159","url":null,"abstract":"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.","PeriodicalId":36905,"journal":{"name":"Klinicheskaya Onkogematologiya/Clinical Oncohematology","volume":"28 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79238041","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 : 2022-07-20DOI: 10.17650/1818-8346-2022-17-3-83-88
I. Rekhtina, L. Y. Kolosova, V. Khyshova, A. Kovrigina, L. Mendeleeva
Neutrophilic leukocytosis is not specific for multiple myeloma (MM) and is a reason for the exclusion of myeloproliferative neoplasm.A clinical case of MM patient with neutrophilic hyperleukocytosis (75 х 109/L), liver and spleen enlargement at the disease onset is presented. Examination did not reveal t(9;22), BCR/ABL gene and JAK2V617F mutation. To exclude the combination of MM with chronic neutrophilic leukemia, a study of the clinically significant part of the CSFR3R gene was performed. The absence of a CSFR3R gene mutation made it possible to exclude chronic neutrophilic leukemia and start MM treatment. After the 1st therapy course with bortezomib, cyclophosphamide and dexamethasone, blood counts returned to normal, liver and spleen size decreased. After 6 therapy courses, complete hematological remission was achieved. An attempt to mobilize peripheral blood stem cells with cyclophosphamide was unsuccessful. The effectiveness of antimyeloma therapy proved the correctness of the diagnosis and the chosen treatment tactics.Neutrophilic leukocytosis in MM is explained by the ability of plasma cells to synthesize granulocyte colony-stimulating factor in some cases. In the presence of a plasma cell tumor, the analysis of the CSFR3R gene may be of decisive importance in the differential diagnosis of reactive neutrophilic leukocytosis due to MM and the combination of MM with chronic neutrophilic leukemia.
{"title":"Neutrophilic hyperleukocytosis in the multiple myeloma onset","authors":"I. Rekhtina, L. Y. Kolosova, V. Khyshova, A. Kovrigina, L. Mendeleeva","doi":"10.17650/1818-8346-2022-17-3-83-88","DOIUrl":"https://doi.org/10.17650/1818-8346-2022-17-3-83-88","url":null,"abstract":"Neutrophilic leukocytosis is not specific for multiple myeloma (MM) and is a reason for the exclusion of myeloproliferative neoplasm.A clinical case of MM patient with neutrophilic hyperleukocytosis (75 х 109/L), liver and spleen enlargement at the disease onset is presented. Examination did not reveal t(9;22), BCR/ABL gene and JAK2V617F mutation. To exclude the combination of MM with chronic neutrophilic leukemia, a study of the clinically significant part of the CSFR3R gene was performed. The absence of a CSFR3R gene mutation made it possible to exclude chronic neutrophilic leukemia and start MM treatment. After the 1st therapy course with bortezomib, cyclophosphamide and dexamethasone, blood counts returned to normal, liver and spleen size decreased. After 6 therapy courses, complete hematological remission was achieved. An attempt to mobilize peripheral blood stem cells with cyclophosphamide was unsuccessful. The effectiveness of antimyeloma therapy proved the correctness of the diagnosis and the chosen treatment tactics.Neutrophilic leukocytosis in MM is explained by the ability of plasma cells to synthesize granulocyte colony-stimulating factor in some cases. In the presence of a plasma cell tumor, the analysis of the CSFR3R gene may be of decisive importance in the differential diagnosis of reactive neutrophilic leukocytosis due to MM and the combination of MM with chronic neutrophilic leukemia.","PeriodicalId":36905,"journal":{"name":"Klinicheskaya Onkogematologiya/Clinical Oncohematology","volume":"8 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74481395","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 : 2022-07-20DOI: 10.17650/1818-8346-2022-17-3-160-170
I. Dyakov, K. K. Bushkova
Aim. To evaluate the pharmacoeconomic feasibility of using polatuzumab vedotin in combination with bendamustine and rituximab for the treatment of adult transplantation-ineligible patients with relapsed/refractory diffuse large B-cell lymphoma.Materials and methods. Study design - retrospective analysis of literature data. Pharmacoeconomic research methods - clinical and economic analysis (incremental cost-effectiveness analysis, case-based approach) using sensitivity assessment. The sources of the drug efficacy data were publications on conducted clinical trials; on the drugs cost -the State register of maximum selling prices, data from the manufacturer's company.Results. Polatuzumab vedotin is the unique drug from the class of monoclonal antibody-antimitotic agent conjugates registered in Russia for the treatment of adult transplantation-ineligible patients with relapsed/refractory diffuse large B-cell lymphoma. for this reason a case-based approach was applied as part of the cost-effectiveness analysis. As a result of clinical and economic analysis, it was found that the cost of progression free life-year added when using polatuzumab vedotin in combination with bendamustine and rituximab in patients with relapsed/refractory diffuse large b-cell lymphoma by 50.7 %, or by 11.4 million rubles, lower than the cost of progression free life-year added when using brentuximab vedotin in patients with relapsed/refractory Hodgkin's lymphoma. The sensitivity assessment showed the stability of the obtained results to changes in the input parameters of treatment cost and efficacy in a wide range of values.Conclusion. Use of polatuzumab vedotin in combination with bendamustine and rituximab for the treatment of adult transplantation-ineligible patients with diffuse large B-cell non-Hodgkin's lymphoma is pharmacoeconomically justified and appropriate.
{"title":"Comparative clinical and economic assessment of polatuzumab vedotin therapy in combination with bendamustine and rituximab for adult transplantation-ineligible patients with relapsed/refractory diffuse large B-cell lymphoma","authors":"I. Dyakov, K. K. Bushkova","doi":"10.17650/1818-8346-2022-17-3-160-170","DOIUrl":"https://doi.org/10.17650/1818-8346-2022-17-3-160-170","url":null,"abstract":"Aim. To evaluate the pharmacoeconomic feasibility of using polatuzumab vedotin in combination with bendamustine and rituximab for the treatment of adult transplantation-ineligible patients with relapsed/refractory diffuse large B-cell lymphoma.Materials and methods. Study design - retrospective analysis of literature data. Pharmacoeconomic research methods - clinical and economic analysis (incremental cost-effectiveness analysis, case-based approach) using sensitivity assessment. The sources of the drug efficacy data were publications on conducted clinical trials; on the drugs cost -the State register of maximum selling prices, data from the manufacturer's company.Results. Polatuzumab vedotin is the unique drug from the class of monoclonal antibody-antimitotic agent conjugates registered in Russia for the treatment of adult transplantation-ineligible patients with relapsed/refractory diffuse large B-cell lymphoma. for this reason a case-based approach was applied as part of the cost-effectiveness analysis. As a result of clinical and economic analysis, it was found that the cost of progression free life-year added when using polatuzumab vedotin in combination with bendamustine and rituximab in patients with relapsed/refractory diffuse large b-cell lymphoma by 50.7 %, or by 11.4 million rubles, lower than the cost of progression free life-year added when using brentuximab vedotin in patients with relapsed/refractory Hodgkin's lymphoma. The sensitivity assessment showed the stability of the obtained results to changes in the input parameters of treatment cost and efficacy in a wide range of values.Conclusion. Use of polatuzumab vedotin in combination with bendamustine and rituximab for the treatment of adult transplantation-ineligible patients with diffuse large B-cell non-Hodgkin's lymphoma is pharmacoeconomically justified and appropriate. ","PeriodicalId":36905,"journal":{"name":"Klinicheskaya Onkogematologiya/Clinical Oncohematology","volume":"24 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77524452","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 : 2022-07-20DOI: 10.17650/1818-8346-2022-17-3-119-126
G. Kuchma, U. A. Yakubova, L. Kozlova, S. A. Lebedenko, F. R. Sayfutdinov
Background. Oncohematological patients are more predispose to SARS-CoV-2 infection than healthy individuals and patients with malignant neoplasms, and also they have a worse prognosis, which is because of immune system disorders, both due to the underlying disease and as a result of immunosuppressive therapy. There is limited data regarding the impact of SARS-CoV-2 infection on the survival of patients with chronic myeloid leukemia (CML).Aim. To evaluate the course and outcome of COVID-19 in patients with CML in the Orenburg region during the SARS-CoV-2 pandemic.Materials and methods. All 166 patients with CML over 18 years of age were analyzed during the COVID-19 pandemic between february 2020 and December 2021. The source of information was data from the personalized register of patients with CML and the unified state health information system.Results. The proportion of SARS-CoV-2 infection among patients with CML was 36 %. The risk of infection was not affected by age, gender, work features, place of residence, phase or duration of the disease, and therapy. underwent COVID-19 patients were 1.6 times more likely to be overweight and 2 times more likely to have a second cancer. A significant increase in the number of outpatient visits to polyclinics and number of hospital admissions during the pandemic was revealed in the group of patients who had SARS-CoV-2 infection. underwent COVID-19 patients were over 60 years of age in 48.3 % of cases and had one or more comorbidities in 77.6 % cases. SARS-CoV-2-infected patients with CML had a favorable outcome: a mild course of infection in 75.9 % of cases and a low mortality rate - 6.8 % (4 of 58 patients) were observed. COVID-19 was recognized as the cause of death in only 2 patients with optimal molecular response and comorbidity. In two other patients who underwent COVID-19, the progression of CML to a blast crisis was recognized as the cause of death. There were no significant differences in mortality level in the group of patients who had SARS-CoV-2 infection and those who did not have COVID-19.Conclusion. patients with CML living in the Orenburg region have a low susceptibility to SARS-CoV-2 infection and a mild course of the disease. The mortality rate for CML patients infected with SARS-CoV-2 was 6.8 %. unfavorable factors in the overall survival of patients with CML infected with SARS-CoV-2 were high comorbidity and blast crisis. Reducing the number of outpatient visits during the pandemic and using remote medical consultations is likely to reduce the risk of SARS-CoV-2 infection.
{"title":"COVID-19 infection in patients with chronic myeloid leukemia in the Orenburg region during the SARS-CoV-2 pandemic","authors":"G. Kuchma, U. A. Yakubova, L. Kozlova, S. A. Lebedenko, F. R. Sayfutdinov","doi":"10.17650/1818-8346-2022-17-3-119-126","DOIUrl":"https://doi.org/10.17650/1818-8346-2022-17-3-119-126","url":null,"abstract":"Background. Oncohematological patients are more predispose to SARS-CoV-2 infection than healthy individuals and patients with malignant neoplasms, and also they have a worse prognosis, which is because of immune system disorders, both due to the underlying disease and as a result of immunosuppressive therapy. There is limited data regarding the impact of SARS-CoV-2 infection on the survival of patients with chronic myeloid leukemia (CML).Aim. To evaluate the course and outcome of COVID-19 in patients with CML in the Orenburg region during the SARS-CoV-2 pandemic.Materials and methods. All 166 patients with CML over 18 years of age were analyzed during the COVID-19 pandemic between february 2020 and December 2021. The source of information was data from the personalized register of patients with CML and the unified state health information system.Results. The proportion of SARS-CoV-2 infection among patients with CML was 36 %. The risk of infection was not affected by age, gender, work features, place of residence, phase or duration of the disease, and therapy. underwent COVID-19 patients were 1.6 times more likely to be overweight and 2 times more likely to have a second cancer. A significant increase in the number of outpatient visits to polyclinics and number of hospital admissions during the pandemic was revealed in the group of patients who had SARS-CoV-2 infection. underwent COVID-19 patients were over 60 years of age in 48.3 % of cases and had one or more comorbidities in 77.6 % cases. SARS-CoV-2-infected patients with CML had a favorable outcome: a mild course of infection in 75.9 % of cases and a low mortality rate - 6.8 % (4 of 58 patients) were observed. COVID-19 was recognized as the cause of death in only 2 patients with optimal molecular response and comorbidity. In two other patients who underwent COVID-19, the progression of CML to a blast crisis was recognized as the cause of death. There were no significant differences in mortality level in the group of patients who had SARS-CoV-2 infection and those who did not have COVID-19.Conclusion. patients with CML living in the Orenburg region have a low susceptibility to SARS-CoV-2 infection and a mild course of the disease. The mortality rate for CML patients infected with SARS-CoV-2 was 6.8 %. unfavorable factors in the overall survival of patients with CML infected with SARS-CoV-2 were high comorbidity and blast crisis. Reducing the number of outpatient visits during the pandemic and using remote medical consultations is likely to reduce the risk of SARS-CoV-2 infection.","PeriodicalId":36905,"journal":{"name":"Klinicheskaya Onkogematologiya/Clinical Oncohematology","volume":"46 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87500490","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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