Abstract:Therapy-related myeloid neoplasms are neoplastic processes arising as a result of chemotherapy, radiation therapy, or a combination of these modalities given for a primary condition. The disease biology varies based on the etiology and treatment modalities patients receive for their primary condition. Topoisomerase Ⅱ inhibitor therapy results in balanced translocations. Alkylating agents, characteristically, give rise to more complex karyotypes and mutations in p53. Other etiologies include radiation therapy, … Show more
“…Patients #9 and #11 were AZA responders (respectively, mCR and SD with HI), whereas patients #14, #15, and #19 were in progression. Median number of AZA cycles was 5 (range, [3][4][5][6][7][8], and median OS was 14 months (range, [3][4][5][6][7][8][9][10][11][12][13][14][15]. In patients #9, #14, and #15, we failed to detect any change of mutated clone VAF under AZA treatment.…”
Section: Correlation Between Aza Response and Putative Function Of mentioning
confidence: 77%
“…2,5 T-MN are frequently associated with recurrent chromosomal aberrations based on specific therapy with alkylating agents commonly leading to abnormalities of chromosome 5/7 (often in the setting of complex cytogenetics), while topoisomerase II inhibitors being associated with balanced rearrangements including 11q23 2,7,8 risk to develop t-MN is correlated with type, dose, and duration of treatment but also environment, age, and comorbidities of patient. 2,5 Additionally, recent studies strongly support that the presence of clonal hematopoiesis of indeterminate potential (CHIP) is significantly associated with the risk of developing a subsequent t-MN. 9,10 These studies suggest that pre-existing clones may be selected following cytotoxic chemotherapy.…”
mentioning
confidence: 99%
“…Outcomes of t-MN are poor, with lower response rate and overall survival estimated around 10% at 5 years. 5 Azacitidine (AZA), a hypomethylating agent, is the standard treatment for AML, and MDS patients were not eligible for intensive chemotherapy. 11,12 Response rates for AZA treatment of t-MN are similar to de novo MDS but were associated with shorter survival.…”
Introduction
Therapy‐related myelodysplastic syndrome and acute myeloid leukemia (t‐MDS/AML) are defined as complications of previous cytotoxic therapy. Azacitidine (AZA), a hypomethylating agent, has showed activity in t‐MDS/AML.
Objectives
We evaluated the clonal dynamics of AZA‐treated t‐MDS/AML.
Methods
We collected bone marrow samples, at diagnosis and during treatment, from AZA‐treated t‐MDS/AML patients. NGS on 19 myeloid genes was performed, and candidate mutations with a variant allele frequency >5% were selected.
Results
Seven t‐AML and 12 t‐MDS were included with median age of 71 (56‐82) years old, median number of AZA cycles of 6 (1‐15), and median overall survival (OS) of 14 (3‐29) months. We observed correlation between AZA response and clonal selection. Decrease of TP53‐mutated clone was correlated with response to AZA, confirming AZA efficacy in this subgroup. In some patients, emergence of mutations was correlated with progression or relapse without impact on OS. Clones with mutations in genes for DNA methylation regulation frequently occurred with other mutations and remained stable during AZA treatment, independent of AZA response.
Conclusion
We confirmed that the molecular complexity of t‐MNs and that the follow‐up of clonal selection during AZA treatment could be useful to define treatment combination.
“…Patients #9 and #11 were AZA responders (respectively, mCR and SD with HI), whereas patients #14, #15, and #19 were in progression. Median number of AZA cycles was 5 (range, [3][4][5][6][7][8], and median OS was 14 months (range, [3][4][5][6][7][8][9][10][11][12][13][14][15]. In patients #9, #14, and #15, we failed to detect any change of mutated clone VAF under AZA treatment.…”
Section: Correlation Between Aza Response and Putative Function Of mentioning
confidence: 77%
“…2,5 T-MN are frequently associated with recurrent chromosomal aberrations based on specific therapy with alkylating agents commonly leading to abnormalities of chromosome 5/7 (often in the setting of complex cytogenetics), while topoisomerase II inhibitors being associated with balanced rearrangements including 11q23 2,7,8 risk to develop t-MN is correlated with type, dose, and duration of treatment but also environment, age, and comorbidities of patient. 2,5 Additionally, recent studies strongly support that the presence of clonal hematopoiesis of indeterminate potential (CHIP) is significantly associated with the risk of developing a subsequent t-MN. 9,10 These studies suggest that pre-existing clones may be selected following cytotoxic chemotherapy.…”
mentioning
confidence: 99%
“…Outcomes of t-MN are poor, with lower response rate and overall survival estimated around 10% at 5 years. 5 Azacitidine (AZA), a hypomethylating agent, is the standard treatment for AML, and MDS patients were not eligible for intensive chemotherapy. 11,12 Response rates for AZA treatment of t-MN are similar to de novo MDS but were associated with shorter survival.…”
Introduction
Therapy‐related myelodysplastic syndrome and acute myeloid leukemia (t‐MDS/AML) are defined as complications of previous cytotoxic therapy. Azacitidine (AZA), a hypomethylating agent, has showed activity in t‐MDS/AML.
Objectives
We evaluated the clonal dynamics of AZA‐treated t‐MDS/AML.
Methods
We collected bone marrow samples, at diagnosis and during treatment, from AZA‐treated t‐MDS/AML patients. NGS on 19 myeloid genes was performed, and candidate mutations with a variant allele frequency >5% were selected.
Results
Seven t‐AML and 12 t‐MDS were included with median age of 71 (56‐82) years old, median number of AZA cycles of 6 (1‐15), and median overall survival (OS) of 14 (3‐29) months. We observed correlation between AZA response and clonal selection. Decrease of TP53‐mutated clone was correlated with response to AZA, confirming AZA efficacy in this subgroup. In some patients, emergence of mutations was correlated with progression or relapse without impact on OS. Clones with mutations in genes for DNA methylation regulation frequently occurred with other mutations and remained stable during AZA treatment, independent of AZA response.
Conclusion
We confirmed that the molecular complexity of t‐MNs and that the follow‐up of clonal selection during AZA treatment could be useful to define treatment combination.
“…The presence of blast cells on a complete blood count (CBC) is therefore very suspicious for leukemia. Blast cells are not typically found in the circulating blood of healthy individuals [17].…”
Leukemia is a gathering of malignancy began from bone marrow and will deliver impact on white platelet which will thus lead to anomaly. Presently t development of impact will continue by the undeveloped and juvenile WBC. Leukemia is an expansive term covering a range of infections. The focal point of enthusiasm for oncology leukemia vitamin C has the best technique by which it demonstrates the more noteworthy outcome. undeveloped cell takes amazingly elevated amounts of Ascorbic acid, which at that point allot their capacity and subdue the improvement of leukemia. Vitamin C levels manage HSC numbers and capacity. At the point when ascorbate levels are reduced, it can give the power to the deactivation of a catalyst called Tet2. The inactivation of TET2 is represented by change and insufficiency of vitamin-C may constrain Tet2 work in tissues in a way that builds the danger of leukemia. TET2 function is actually strengthen by ascorbate level. By encouraging DNA demethylation, tremendous-dose of ascorbate treatment can persuade stem cells to develop and the growth of cancerous stem cells will retarded by the tremendous dose of ascorbate level as investigated in mice. Tremendous dose of ascorbate might become a safe treatment for blood diseases caused by TET2-deficient leukemia stem cells, most likely in combination with other targeted therapies.
“…Частота ризику виникнення t MDS/t AML суттєво менша після алогенної ТКМ, ніж після проведення традиційної ХТ. Вважається, що післятрансплантаційні ВН зумовлені режимом інтенсивного хіміотерапев тичного кондиціонування [4,28,29,45,75]. Індивідуальна варіабельність ризику розвитку t MDS/t AML зумовлена генетичною схильні стю до генотоксичних впливів ПТ та хіміопре паратів [1,2,21,24,35,54,67,60,77].…”
Внимание! Подписаться на журнал «Современная педиатрия» Вы можете во всех отделениях связи УкраиныПодписной индекс 09850 НАЦИОНАЛЬНАЯ МЕДИЦИНСКАЯ АКАДЕМИЯ ПОСЛЕДИПЛОМНОГО ОБРАЗОВАНИЯ ИМЕНИ П.Л. ШУПИКА УКРАИНСКИЙ ИНСТИТУТ СТРАТЕГИЧЕСКИХ ИССЛЕДОВАНИЙ МЗ УКРАИНЫ БАХТИЯРОВА Д.О. Главный редактор Бережной В.В., доктор мед. наук, профессор кафедры педиатрии №2 НМАПО имени П.Л. Шупика Валиулис А. (Литва), Профессор, Генеральный директор клиники астмы, аллергии и хронических заболеваний легких, Генеральный директор EduCom (последипломное образование), Член Исполнительного комитета и казначей Европейской академии педиатрии (EAP / UEMS SP) Главный научный консультант Антипкин Ю.Г., академик НАМН Украины, директор ГУ «ИПАГ НАМН Украины» Заместители главного редактора Маменко М.Е., доктор мед. наук, профессор кафедры педиатрии №2 НМАПО имени П.Л. Шупика Волосовец А.П., чл. корр. НАМН Украины, доктор мед. наук, профессор, зав. кафедрой педиатрии №2 НМУ имени А.А. Богомольца
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