المؤلفون: Raffaele Palmieri, Ilaria Del Principe, Luca Maurillo, Adriano Venditti, Francesco Buccisano

المصدر: Mediterranean Journal of Hematology and Infectious Diseases, Vol 15, Iss 1 (2023)

مصطلحات موضوعية: t-aml, T-mn, Clinical evaluation, Diseases of the blood and blood-forming organs, RC633-647.5

الوصف: Therapy-related myeloid neoplasms (t-MNs) encompass a specific sub-group of myeloid malignancies arising after exposure to radio/cytotoxic agents for the treatment of unrelated diseases. Such malignancies present unique features, including advanced age, high comorbidities burden, and unfavorable genetic profiles. All these features justify the need for a specific diagnostic work-up and dedicated treatment algorithms. However, as new classification systems recognize the unique clinical characteristics exhibited by t-MNs patients, how to assess fitness status in this clinical setting is largely unexplored. Optimizing fitness assessment would be crucial in the management of t-MNs patients, considering that factors usually contributing to a worse or better outcome (like age, comorbidities, and treatment history) are patient-specific. In the absence of specific tools for fitness assessment in this peculiar category of AML, the aim of this review is to describe all those factors related to patient, treatment and disease that allow planning treatments with an optimal risk/benefit ratio.

وصف الملف: electronic resource

العلاقة: http://www.mjhid.org/index.php/mjhid/article/view/5428Test; https://doaj.org/toc/2035-3006Test

الوصول الحر: https://doaj.org/article/95bfb52bd6f44e50ac28dbd25e6b9ba5Test

المؤلفون: Palmieri, Raffaele, Del Principe, Ilaria, Maurillo, Luca, Venditti, Adriano, Buccisano, Francesco

المساهمون: Palmieri, R, Del Principe, I, Maurillo, L, Venditti, A, Buccisano, F

مصطلحات موضوعية: T-AML, T-MN, Clinical evaluation, Settore MED/15

الوصف: Therapy-related myeloid neoplasms (t-MNs) encompass a specific sub-group of myeloid malignancies arising after exposure to radio/cytotoxic agents for the treatment of unrelated diseases. Such malignancies present unique features, including advanced age, high comorbidities burden, and unfavorable genetic profiles. All these features justify the need for a specific diagnostic work-up and dedicated treatment algorithms. However, as new classification systems recognize the unique clinical characteristics exhibited by t-MN patients, how to assess fitness status in this clinical setting is largely unexplored. Optimizing fitness assessment would be crucial in the management of t-MN patients, considering that factors usually contributing to a worse or better outcome (like age, comorbidities, and treatment history) are patient-specific.In the absence of specific tools for fitness assessment in this peculiar category of AML, the aim of this review is to describe all those factors related to patient, treatment, and disease that allow planning treatments with an optimal risk/benefit ratio.

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/37705524; info:eu-repo/semantics/altIdentifier/wos/WOS:001144634400001; volume:15; firstpage:1; lastpage:7; numberofpages:7; journal:MEDITERRANEAN JOURNAL OF HEMATOLOGY AND INFECTIOUS DISEASES; https://hdl.handle.net/2108/336623Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85170835504; http://dx.doi.org/10.4084/MJHID.2023.051Test

الإتاحة: https://doi.org/10.4084/MJHID.2023.051Test
https://hdl.handle.net/2108/336623Test

المؤلفون: Nikolai A. Lomov, Vladimir S. Viushkov, Sergey V. Ulianov, Alexey A. Gavrilov, Daniil A. Alexeyevsky, Artem V. Artemov, Sergey V. Razin, Mikhail A. Rubtsov

المصدر: International Journal of Molecular Sciences; Volume 23; Issue 17; Pages: 9824

مصطلحات موضوعية: therapy-related AML, t-AML, chromosomal translocation, topoisomerase inhibitors, etoposide, topoisomerase inhibitor-related leukemia, AML1, RUNX1, MLL, KMT2A

جغرافية الموضوع: agris

الوصف: Topoisomerase inhibitors are widely used in cancer chemotherapy. However, one of the potential long-term adverse effects of such therapy is acute leukemia. A key feature of such therapy-induced acute myeloid leukemia (t-AML) is recurrent chromosomal translocations involving AML1 (RUNX1) or MLL (KMT2A) genes. The formation of chromosomal translocation depends on the spatial proximity of translocation partners and the mobility of the DNA ends. It is unclear which of these two factors might be decisive for recurrent t-AML translocations. Here, we used fluorescence in situ hybridization (FISH) and chromosome conformation capture followed by sequencing (4C-seq) to investigate double-strand DNA break formation and the mobility of broken ends upon etoposide treatment, as well as contacts between translocation partner genes. We detected the separation of the parts of the broken AML1 gene, as well as the increased mobility of these separated parts. 4C-seq analysis showed no evident contacts of AML1 and MLL with loci, implicated in recurrent t-AML translocations, either before or after etoposide treatment. We suggest that separation of the break ends and their increased non-targeted mobility—but not spatial predisposition of the rearrangement partners—plays a major role in the formation of these translocations.

وصف الملف: application/pdf

العلاقة: Molecular Genetics and Genomics; https://dx.doi.org/10.3390/ijms23179824Test

الإتاحة: https://doi.org/10.3390/ijms23179824Test

المؤلفون: Gross, Auguste Sophia

المساهمون: female, N.N.

مصطلحات موضوعية: therapy-related AML, t-AML, AML-pCT, Acute Myeloid Leukemia, prognosis, long-term survival, ddc:610

الوصف: Einleitung: Etwa 7% aller adulten Akuten Myeloischen Leukämien (AML) sind Folge einer vorangegangenen Chemo-/Strahlentherapie aufgrund einer Primärerkrankung (therapieassoziierte AML, t-AML). Patient*innen mit t-AML haben ein kürzeres Gesamtüberleben (OS) als mit de-novo AML. Unklar ist jedoch, inwieweit die schlechte Prognose von der t-AML per se getragen wird oder doch eher durch die oft damit einhergehenden ungünstigen patienten- und krankheitsspezifischen Eigenschaften. In dieser Arbeit werden deshalb Charakteristika von t-AML- denen von de-novo AML- Patient*innen gegenübergestellt. Ziel ist es, das OS bei t-AML unter Berücksichtigung prognostisch relevanter Subgruppen im Vergleich zur de-novo AML zu analysieren und den prognostischen Stellenwert der t-AML zu ermitteln. Ferner sollen weitere Faktoren identifiziert werden, die das OS bei t-AML beeinflussen. Methoden: Die Daten von 225 im Zeitraum von 1995-2018 erstdiagnostizierten t-AML- Patient*innen wurden retrospektiv erfasst. Die Referenzkohorte umfasst 908 de-novo AML. Vergleiche zweier Gruppen hinsichtlich Patientencharakteristika erfolgten mittels des Pearson-Chi-Quadrat-/Exakten Fisher-Tests und Mann-Whitney-U-Tests. Das OS wurde durch die Kaplan-Meier-Methode berechnet und Unterschiede durch den Logrank- Test ermittelt. Zur Identifikation unabhängiger Prognosefaktoren wurde ein Cox- Regressionsmodell etabliert. Einflussfaktoren auf die Nicht-Rezidiv- und Rezidiv- assoziierte Mortalität (NRM, RR) wurden anhand der cause-specific hazard Methode ermittelt. Ergebnisse: Das mediane OS der intensiv therapierten t-AML-Patient*innen betrug 13,7 Monate und war signifikant schlechter als bei de-novo AML (39,4 Monate; p<0,001). T- AML-Patient*innen waren signifikant älter, hatten häufiger eine ungünstige Genetik und mehr Komorbiditäten. In der Subgruppenanalyse bestand kein Unterschied im OS mehr, wenn sich t-AML- und de-novo AML-Patient*innen in Therapiemodalität, Genetik und/oder Alter glichen. Dies galt bei intensiver Therapie für die Risikogruppen APL ...

وصف الملف: application/pdf

العلاقة: https://refubium.fu-berlin.de/handle/fub188/41761Test; http://dx.doi.org/10.17169/refubium-41481Test; urn:nbn:de:kobv:188-refubium-41761-6

الإتاحة: https://doi.org/10.17169/refubium-41481Test
https://refubium.fu-berlin.de/handle/fub188/41761Test
https://nbn-resolving.org/urn:nbn:de:kobv:188-refubium-41761-6Test

المؤلفون: Tegenaw Tiruneh, Bamlaku Enawgaw, Elias Shiferaw

المصدر: Oncology and Therapy, Vol 8, Iss 1, Pp 45-57 (2020)

مصطلحات موضوعية: Chemotherapy, Genetic pathway, Radiation therapy, t-AML, t-MDS, t-MN, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282

الوصف: Abstract Therapy-related myeloid neoplasms are a life-threatening and often fatal complication, associated with poor prognosis outcomes and with high-risk unfavorable cytogenetic abnormalities including complex karyotype. They occur after the treatment of primary malignancies using chemotherapy and/or radiation therapy. Such therapy is not specific to cancer cells, and also damages the deoxyribonucleic acid (DNA) of normal cells, resulting in unbalanced and balanced translocations. There are eight genetic pathways, whose details are summarized in this review, depending on the cytogenetic abnormalities induced. This abnormality is the major contributor to the development of therapy-related myeloid neoplasms. The etiology of these neoplasms depends on the complex interaction between the nature and dose of the cytotoxic agent, the environment, and the presence of subsequent inherited mutations. This review aims to elaborate upon recent knowledge regarding the etiology, pathogenesis, and genetic pathways of therapy-related myeloid neoplasms. A deeper understanding of their etiology would aid physicians in more careful monitoring of patients during or after cytotoxic therapy for hematological malignancy. Ultimately, this knowledge could influence initial treatment strategies, with the aim of reducing both the incidence and serious complications of neoplasms. Therefore, early detection of DNA lesions is vital. The authors recommend that primary malignancy be treated with targeted therapy.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2366-1070Test; https://doaj.org/toc/2366-1089Test

الوصول الحر: https://doaj.org/article/49f88fadd7ac4a69a8e192cf2b0a181fTest

المؤلفون: Dimitrova, Stela, Micheva, Ilina

المساهمون: не

المصدر: Известия на Съюза на учените – Варна. Серия „Медицина и екология”; Vol 26, No 2 (2021); 20-26 ; Journal of the Union of Scientists - Varna. Medicine and Ecology Series; Vol 26, No 2 (2021); 20-26 ; 2603-4565 ; 1310-6031

مصطلحات موضوعية: acute myeloid leukemia, t-AML, elderly patients

الوصف: Acute myeloid leukemia (AML) is a therapeutic challenge in elderly patients because of the biology of the leukemia and the poor functional status of the patient. Acute myeloid leukemia following previous treatment (t-AML) is defined as a separate subtype of AML, which is associated with the late effects of previous chemotherapy or radiotherapy. The therapeutic results of patients with t-AML are limited and optimal treatment in these patients is an even greater challenge.Our patient is a 68-year-old woman who was hospitalized due to isolated anemia. The patient was diagnosed with breast cancer in 1996 and ovarian cancer in 2014, which were in remission at the time of the present hospitalization. Diagnostic procedures revealed therapy-related myelodysplastic syndrome (t-MDS) with a complex karyotype. The patient was stratified as high risk according to the revised IPSS. The patient received the best supportive care. Two months later, she was re-hospitalized due to fever, progressive weakness and fatigue, stomach discomfort, loss of appetite. Laboratory tests showed pancytopenia with 25% of myeloblasts in peripheral blood. The reassessment of the disease revealed evolution to t-AML with MDS-associated changes. Treatment with a hypomethylating agent was initiated. Unfortunately, the patient died with the symptoms of sudden cardiac death.The therapeutic decision in elderly patients with t-AML is difficult and multifactorial. Combinations of already approved agents and new molecules will improve and diversify the therapeutic choices in elderly patients with high-risk AML.

وصف الملف: application/pdf

العلاقة: https://journals.mu-varna.bg/index.php/isuvsme/article/view/8112/7402Test; https://journals.mu-varna.bg/index.php/isuvsme/article/view/8112Test

الإتاحة: https://doi.org/10.14748/isuvsme.v26i1.8112Test
https://journals.mu-varna.bg/index.php/isuvsme/article/view/8112Test

المؤلفون: Ana Vega González de Viñaspre, Carlos De Miguel Sánchez, Diego Robles De Castro, Verónica Roldán Galiacho, Arantza Mendizabal Abad, José María Guinea De Castro

المصدر: Clinical Case Reports, Vol 9, Iss 1, Pp 572-573 (2021)

مصطلحات موضوعية: faggot cells, faggot neutrophils, therapy‐related acute myeloid leukemia (t‐AML) with inv(16), Medicine, Medicine (General), R5-920

الوصف: Faggot cells are an uncommon finding in nonacute promyelocytic leukemia, even rarer when observed in mature granulocytic cells. Inv(16) should be dismissed when pre‐eosinophilic granulation and faggot neutrophils are observed.

العلاقة: https://doi.org/10.1002/ccr3.3462Test; https://doaj.org/toc/2050-0904Test; https://doaj.org/article/4786eeb946a14a75909cc0a8544fade7Test

الإتاحة: https://doi.org/10.1002/ccr3.3462Test
https://doaj.org/article/4786eeb946a14a75909cc0a8544fade7Test

المؤلفون: Crisci S., Pota E., Iaccarino G., Postiglione I., Meo C., Mele S., De Filippi R., Pinto A.

المساهمون: Crisci, S., Pota, E., Iaccarino, G., Postiglione, I., Meo, C., Mele, S., De Filippi, R., Pinto, A.

مصطلحات موضوعية: Core binding factor runt domain alpha subunit 2, Ewing sarcoma family of tumor, Pediatric Ewing sarcoma, Runt-related transcription factor 1, t-AML, Child, Preschool, Human, Leukemia, Myeloid, Acute, Male, Neuroectodermal Tumors, Primitive, Thoracic Wall

العلاقة: info:eu-repo/semantics/altIdentifier/wos/WOS:000585113900004; volume:20; issue:10; firstpage:e660; lastpage:e666; journal:CLINICAL LYMPHOMA MYELOMA & LEUKEMIA; http://hdl.handle.net/11588/867250Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85091905139

الإتاحة: https://doi.org/10.1016/j.clml.2020.05.020Test
http://hdl.handle.net/11588/867250Test

المؤلفون: Aiqi Zhao, Mingzhe Zhao, Wenbin Qian, Aibin Liang, Ping Li, Hui Liu

مصطلحات موضوعية: Immunology, Applied Immunology (incl. Antibody Engineering, Xenotransplantation and T-cell Therapies), Autoimmunity, Cellular Immunology, Humoural Immunology and Immunochemistry, Immunogenetics (incl. Genetic Immunology), Innate Immunity, Transplantation Immunology, Tumour Immunology, Immunology not elsewhere classified, Genetic Immunology, Animal Immunology, Veterinary Immunology, chimeric antigen receptor T cells (CAR T), cellular immunotherapy, late effects, refractory/relapsed B-cell lymphoma, second cancer, therapy-related myelodysplastic syndrome (t-MDS), therapy-related acute myeloid leukemia (t-AML)

الوصف: Background Several chimeric antigen receptor T cells (CAR T) targeting CD19 have induced profound and prolonged remission for refractory/relapsed (R/R) B-cell lymphoma. The risk of secondary malignancies, especially myeloid neoplasms, is of particular concern in the CAR T community, which still remains unclear. Methods Four patients with R/R B-cell lymphoma after CD19 CAR T therapy diagnosed with secondary myeloid neoplasms (SMN) from 2 hospitals in eastern China were presented, including 3 with myelodysplastic syndrome (MDS) and 1 with acute myeloid leukemia (AML). Using single-cell RNA sequencing (scRNA-seq), we compared the cellular components of bone marrow (BM) samples obtained from one of these MDS patients and a health donor. We also provided a review of recently published literature concerning SMN risk of CAR T therapy. Results Relevant demographic, clinical, laboratory, therapeutic and outcome data were collected and presented by chart review. In our case series, the male-female ratio was 3.0 and the median age at MDS onset was 61.25 years old (range, 50-78). Median number of previous systemic therapies was 4.5 (range, 4-5), including autologous hematopoietic stem cell transplantation (auto-HSCT) in one patient. BM assessments prior to CAR T therapy confirmed normal hematopoiesis without myeloid neoplasms. Moreover, for 3 patients with SMN in our series, cytogenetic analysis predicted a relatively adverse outcome. In our experience and in the literature, treatment choices for the patients with SMN included allogeneic hematopoietic stem cell transplantation (allo-HSCT), hypomethylating agent (HMA), period filgrastim, transfusions and other supportive care. Finally, treatment responses of lymphoma, together with SMN, directly correlated with the overall survival of this community. Of note, it appeared that pathogenesis of MDS wasn’t associated with the CAR T toxicities, since all 4 patients experienced a pretty mild CRS of grade 1-2. Additionally, scRNA-seq analysis described the transcriptional ...

العلاقة: https://figshare.com/articles/dataset/Table_1_Secondary_myeloid_neoplasms_after_CD19_CAR_T_therapy_in_patients_with_refractory_relapsed_B-cell_lymphoma_Case_series_and_review_of_literature_xlsx/21894969Test

الإتاحة: https://doi.org/10.3389/fimmu.2022.1063986.s001Test
https://figshare.com/articles/dataset/Table_1_Secondary_myeloid_neoplasms_after_CD19_CAR_T_therapy_in_patients_with_refractory_relapsed_B-cell_lymphoma_Case_series_and_review_of_literature_xlsx/21894969Test

المؤلفون: Juliusson, Gunnar, Lazarevic, Vladimir, Lehmann, Sören

المساهمون: Röllig, Christoph, Editor, Ossenkoppele, Gert J., Editor

المصدر: Acute Myeloid Leukemia StemTherapy: National Initiative on Stem Cells for Regenerative Therapy. :1-22

مصطلحات موضوعية: Benzene, Diagnosis, Exposure, Hereditary conditions, Incidence, Mutations, Prevalence, Secondary AML, Sex, Survival, t-AML, Medicin och hälsovetenskap, Klinisk medicin, Cancer och onkologi, Medical and Health Sciences, Clinical Medicine, Cancer and Oncology

الوصف: Acute myeloid leukemia (AML) is a grave disease with an incidence of 4 per 100,000 a year. It can present in all ages, but the median age is 70 years. One-third of such patients have secondary AML, that is, AML following chemoradiotherapy or a transformation from previous myelodysplastic syndrome (MDS) or myeloproliferative neoplasia. A combination of genetic, epigenetic, and environmental factors may be responsible for the development of most cases of AML. The pathogenesis of AML is characterized by the serial acquisition of somatic mutations and several genes are recurrently mutated in AML. Exposures to benzene, cigarette smoking, pesticides, embalming fluids, accidental or professional ionization radiation, therapeutic radiotherapy, and radioactive I-131 therapy can cause AML with or without a preceding MDS phase. Alkylating agents (e.g., melphalan, cyclophosphamide), topoisomerase-II inhibitors (e.g., etoposide, doxorubicin), and other drugs (e.g., azathioprine) are described to be associated with the development of therapy-related AML (t-AML). Furthermore, about 5–15% of adults and 4–13% of pediatric patients with MDS or AML carry germline pathogenic variants in cancer susceptibility genes. Individuals with clonal hematopoiesis (CHIP) progress to AML at a rate of about 1% per year. Higher age of onset, obesity, previous autoimmune disease, and antecedent MDS or MPN are associated with a risk for developing AML.

الوصول الحر: https://lup.lub.lu.se/record/717b7c46-5247-473a-b141-582f8bbe4c68Test
http://dx.doi.org/10.1007/978-3-030-72676-8_1Test