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https://www.readbyqxmd.com/read/30271175/therapy-related-myeloid-neoplasms-clinical-perspectives
#1
REVIEW
Luana Fianchi, Marianna Criscuolo, Emiliano Fabiani, Giulia Falconi, Alessio Maria Edoardo Maraglino, Maria Teresa Voso, Livio Pagano
Therapy-related myeloid neoplasms (t-MNs) are a complication of cytotoxic treatment for primary tumors and autoimmune diseases. t-MNs result from a complex interaction between individual predisposition and exposition to toxic agents. Some different biological and clinical characteristics can be recognized according to the type of anticancer drug. Compared to de novo myeloid neoplasms, prognosis of t-MN is dismal. Age and karyotype are the most important prognostic factors for t-MN, which should be treated with frontline chemotherapy treatments that are appropriate for patients with myelodysplastic syndrome (MDS) and de novo acute myeloid leukemia (AML) with similar disease characteristics...
2018: OncoTargets and Therapy
https://www.readbyqxmd.com/read/30124476/age-related-clonal-hematopoiesis-implications-for-hematopoietic-stem-cell-transplantation
#2
Sagi Abelson, Jean C Y Wang
PURPOSE OF REVIEW: Over the past decade, advances in hematopoietic stem cell transplantation (HSCT) have enabled older individuals to undergo the procedure as well as to serve as donors. Recently, aging has been linked with the development of age-related clonal hematopoiesis (ARCH), defined as the gradual clonal expansion of hematopoietic stem and progenitor cells (HSPC) carrying recurrent disruptive genetic variants in individuals without a diagnosis of hematologic malignancy. Here we will review the implications of ARCH in the context of HSCT...
November 2018: Current Opinion in Hematology
https://www.readbyqxmd.com/read/30048839/incidence-and-survival-of-therapy-related-myeloid-neoplasm-in-united-states
#3
Guru Subramanian Guru Murthy, Mehdi Hamadani, Binod Dhakal, Parameswaran Hari, Ehab Atallah
BACKGROUND: Therapy related myeloid neoplasm (t-MN) is an emerging challenge in the current era. However, real world data on its incidence and survival at the population level remains sparse. METHODS: Using Surveillance Epidemiology and End Results (SEER-18) database, we identified patients aged ≥20 years with pathologically confirmed t-MN diagnosed between the years 2001-2014 and actively followed. Incidence rate per 100,000 population and incidence rate ratio (IRR) were calculated...
August 2018: Leukemia Research
https://www.readbyqxmd.com/read/29897339/density-functional-study-of-half-metallicity-and-spin-polarization-in-fe-1-x-t-x-s-2-with-t-mn-ni
#4
Abdesalem Houari, Peter E Blöchl
Alloying effects by Mn and Ni substitution on FeS2 have been studied using density-functional calculations. Standard generalized gradient approximation (GGA) and local hybrid functional have been utilized to account for exchange-correlations. The alloys Fe1-x T x S2 with T  =  Mn,Ni have been investigated for concentrations [Formula: see text] together with the ground states of the pure compounds. The electronic structure is discussed with the main goal to identify candidates for ferromagnetic half-metals, which are of interest for spintronics applications...
August 1, 2018: Journal of Physics. Condensed Matter: An Institute of Physics Journal
https://www.readbyqxmd.com/read/29862538/improved-long-term-survival-in-all-sanz-risk-patients-of-newly-diagnosed-acute-promyelocytic-leukemia-treated-with-a-combination-of-retinoic-acid-and-arsenic-trioxide-based-front-line-therapy
#5
Yinjun Lou, Ying Lu, Zhijuan Zhu, Yafang Ma, Shanshan Suo, Yungui Wang, Dong Chen, Hongyan Tong, Wenbin Qian, Haitao Meng, Wenyuan Mai, Wenjun Yu, Weilai Xu, Lei Wang, Liping Mao, Renzhi Pei, Jie Jin
Limited data was available for long-term follow-up in newly diagnosed acute promyelocytic leukemia (APL) patients treated with all-trans-retinoic acid (ATRA) plus intravenously arsenic trioxide (ATO)-based front-line therapy. The aim of this work was to retrospectively analyze the long-term survival rate and frequency of therapy-related myeloid neoplasia (t-MN) occurring in a large cohort of APL patients. A total of 760 newly diagnosed patients with APL between January 1999 and May 2016 were evaluated. The early death rate was 9...
June 3, 2018: Hematological Oncology
https://www.readbyqxmd.com/read/29666007/mutation-analysis-of-therapy-related-myeloid-neoplasms
#6
Takahiro Nishiyama, Yuichi Ishikawa, Naomi Kawashima, Akimi Akashi, Yoshiya Adachi, Hikaru Hattori, Yoko Ushijima, Hitoshi Kiyoi
We analyzed the genetic mutation status of 13 patients with therapy-related myeloid neoplasms (t-MN). Consistent with previous reports, t-MN cells preferentially acquired mutations in TP53 and epigenetic modifying genes, instead of mutations in tyrosine kinase and spliceosome genes. Furthermore, we compared the mutation status of three t-MN cells with each of the initial lymphoid malignant cells, and identified common mutations among t-MN and the initial malignant cells in two patients. In a patient who developed chronic myelomonocytic leukemia (CMML) after follicular lymphoma (FL), TET2 mutation was identified in both CMML and FL cells...
April 2018: Cancer Genetics
https://www.readbyqxmd.com/read/29423555/second-malignancies-after-hematopoietic-stem-cell-transplantation
#7
REVIEW
Ivetta Danylesko, Avichai Shimoni
Second malignancies are a rare but well-defined late complication after autologous and allogeneic hematopoietic stem-cell transplantation (SCT). Solid malignancies occur in up to 15% of patients 15 years after SCT with myeloablative conditioning, with no plateau in the incidence rates. They are responsible for 5-10% of late deaths after SCT. The incidence is increased with advanced age at SCT. The major risk factors are the use of total body irradiation, which is associated with adenocarcinomas and with chronic graft-versus-host disease which is associated with squamous cell cancers...
February 8, 2018: Current Treatment Options in Oncology
https://www.readbyqxmd.com/read/29326802/allogeneic-hematopoietic-stem-cell-transplantation-in-therapy-related-myeloid-neoplasms-t-mn-of-the-adult-monocentric-observational-study-and-review-of-the-literature
#8
Elisabetta Metafuni, Patrizia Chiusolo, Luca Laurenti, Federica Sorà, Sabrina Giammarco, Andrea Bacigalupo, Giuseppe Leone, Simona Sica
Background: Therapy related myeloid neoplasms (t-MN) occur due to direct mutational events of chemotherapeutic agents and radiotherapy. Disease latency, mutational events and prognosis vary with drugs categories. Methods: We describe a cohort of 30 patients, 18 females and 12 males, with median age of 52.5 years (range, 20 to 64), submitted to allogeneic stem cell transplantation (HSCT) in our department between September 1999 and March 2017. Patients had a history of solid tumour in 14 cases, haematological disease in 15 cases and both of them in one case...
2018: Mediterranean Journal of Hematology and Infectious Diseases
https://www.readbyqxmd.com/read/29299118/identification-of-a-cytogenetic-and-molecular-subgroup-of-acute-myeloid-leukemias-showing-sensitivity-to-l-asparaginase
#9
Salvatore Nicola Bertuccio, Salvatore Serravalle, Annalisa Astolfi, Annalisa Lonetti, Valentina Indio, Anna Leszl, Andrea Pession, Fraia Melchionda
L-Asparaginase (L-Asp) is an enzyme that catalyzes the hydrolysis of L-asparagine to L-aspartic acid, and its depletion induces leukemic cell death. L-Asp is an important component of treatment regimens for Acute Lymphoblastic Leukemia (ALL). Sensitivity to L-Asp is due to the absence of L-Asparagine synthetase (ASNS), the enzyme that catalyzes the biosynthesis of L-asparagine. ASNS gene is located on 7q21.3, and its increased expression in ALLs correlates with L-Asp resistance. Chromosome 7 monosomy (-7) is a recurrent aberration in myeloid disorders, particularly in adverse-risk Acute Myeloid Leukemias (AMLs) and therapy-related myeloid neoplasms (t-MN), that leads to a significant downregulation of the deleted genes, including ASNS ...
December 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/29296745/copy-number-alterations-detected-as-clonal-hematopoiesis-of-indeterminate-potential
#10
Koichi Takahashi, Feng Wang, Hagop Kantarjian, Xingzhi Song, Keyur Patel, Sattva Neelapu, Curtis Gumbs, Latasha Little, Samantha Tippen, Rebecca Thornton, Courtney D DiNardo, Farhad Ravandi, Carlos Bueso-Ramos, Jianhua Zhang, Xifeng Wu, Guillermo Garcia-Manero, P Andrew Futreal
Recent studies have revealed that clonal hematopoiesis of indeterminate potential (CHIP) is an important risk factor for therapy-related myeloid neoplasms (t-MNs). CHIP is currently defined as a clonal hematopoietic population carrying somatic point mutations in 1 of the leukemia-associated genes. Patients with t-MNs often present with chromosomal abnormalities in addition to somatic point mutations. It remains unclear whether chromosomal abnormalities can cooccur with point mutations as part of CHIP. Here we report that 3 of 14 patients with t-MNs had low amplitude but detectable chromosome arm-level copy number alterations (CNAs) in the peripheral blood samples that were taken at the time of their primary cancer diagnosis and before exposure to therapy...
June 27, 2017: Blood Advances
https://www.readbyqxmd.com/read/29155023/therapy-related-myeloid-neoplasm-in-an-18-year-old-boy-with-b-lymphoblastic-leukemia
#11
Xin Qing, Eduard Panosyan, Changjun Yue, Ping Ji, Moran Gotesman, Samuel French, Junchao Cai
BACKGROUND: Acute lymphoblastic leukemia (ALL) is the most common pediatric malignancy. Acute myeloid leukemia or myelodysplastic syndrome during the course of ALL is a rare entity. Some of these cases are therapy-related while the others occur due to lineage switch. The correct diagnosis relies on comparing the immunophenotypes and cytogenetic/molecular alterations of the myeloid neoplasm and the ALL. We present the clinical, pathologic and cytogenetic features of a case of an 18-year-old male with prior treatment for B-lymphoblastic leukemia (B-ALL) who developed therapy-related myeloid neoplasm (t-MN) 4-5years after his initial diagnosis of B-ALL...
December 2017: Experimental and Molecular Pathology
https://www.readbyqxmd.com/read/29023992/therapy-related-chronic-myelomonocytic-leukemia-cmml-molecular-cytogenetic-and-clinical-distinctions-from-de-novo-cmml
#12
Mrinal M Patnaik, Rangit Vallapureddy, Fevzi F Yalniz, Curtis A Hanson, Rhett P Ketterling, Terra L Lasho, Christy Finke, Aref Al-Kali, Naseema Gangat, Ayalew Tefferi
Therapy related myeloid neoplasms (t-MN) including therapy related myelodysplastic syndromes (t-MDS) and acute myeloid leukemia (t-AML) are associated with aggressive disease biologies and poor outcomes. In this large (n = 497) and informative (inclusive of molecular and cytogenetic information) chronic myelomonocytic leukemia (CMML) patient cohort, we demonstrate key biological insights and an independent prognostic impact for t-CMML. T-CMML was diagnosed in 9% of patients and occurred approximately 7 years after exposure to prior chemotherapy and/or radiation therapy...
January 2018: American Journal of Hematology
https://www.readbyqxmd.com/read/28835720/therapy-related-myeloid-neoplasms-when-genetics-and-environment-collide
#13
REVIEW
Megan E McNerney, Lucy A Godley, Michelle M Le Beau
Therapy-related myeloid neoplasms (t-MN) arise as a late effect of chemotherapy and/or radiation administered for a primary condition, typically a malignant disease, solid organ transplant or autoimmune disease. Survival is measured in months, not years, making t-MN one of the most aggressive and lethal cancers. In this Review, we discuss recent developments that reframe our understanding of the genetic and environmental aetiology of t-MN. Emerging data are illuminating who is at highest risk of developing t-MN, why t-MN are chemoresistant and how we may use this information to treat and ultimately prevent this lethal disease...
August 24, 2017: Nature Reviews. Cancer
https://www.readbyqxmd.com/read/28278716/efficacy-of-single-agent-decitabine-in-relapsed-and-refractory-acute-myeloid-leukemia
#14
Niloufer Khan, Andrew Hantel, Randall W Knoebel, Andrew Artz, Richard A Larson, Lucy A Godley, Michael J Thirman, Hongtao Liu, Jane E Churpek, Darren King, Olatoyosi Odenike, Wendy Stock
Improving therapy for relapsed/refractory AML remains a challenge. We performed a retrospective analysis of outcomes following decitabine treatment in 34 patients with relapsed/refractory AML (median age, 62; median Charlson comorbidity score, 6). Decitabine, 20 mg/m2 daily, was given in 5- (25%) or 10-day (75%) cycles. Overall response rate (OR) was 30% with 21% complete remission and 9% partial remission rate. Patients with therapy-related myeloid neoplasm (t-MN) and secondary AML had a significantly higher OR compared to those with de novo AML (70 vs...
September 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28196090/the-uniqueness-of-morphological-features-of-pure-erythroid-leukemia-in-myeloid-neoplasm-with-erythroid-predominance-a-reassessment-using-criteria-revised-in-the-2016-world-health-organization-classification
#15
Po-Shen Ko, Yao-Chung Liu, Chiu-Mei Yeh, Jyh-Pyng Gau, Yuan-Bin Yu, Liang-Tsai Hsiao, Cheng-Hwai Tzeng, Po-Min Chen, Tzeon-Jye Chiou, Chia-Jen Liu, Jin-Hwang Liu
We reviewed 97 consecutive cases of myeloid neoplasm with erythroid predominance (MN-EP) between 2000 and 2015. Following 2016 WHO classification, MN-EP patients were classified into four groups. Eight pure erythroid leukemia (PEL) (including t-MN and AML-MRC morphologically fulfilled criteria for PEL) patients had dismal outcomes (median OS: 1 month) and showed more bone marrow fibrosis, worse performance status (PS) and higher serum lactate dehydrogenase (LDH) at diagnosis than the other groups. In the univariate analysis, risks of death in MN-EP patients included the morphologic features of PEL, very poor cytogenetic risk by IPSS-R, bone marrow fibrosis, leukocytosis, anemia, hypoalbuminemia, high LDH, and poor PS...
2017: PloS One
https://www.readbyqxmd.com/read/28090486/therapy-related-myeloid-neoplasms-in-children-and-adolescents
#16
Hee Won Cho, Young Bae Choi, Eun Sang Yi, Ji Won Lee, Ki Woong Sung, Hong Hoe Koo, Keon Hee Yoo
BACKGROUND: This retrospective study aimed to characterize and analyze the outcome of therapy-related myeloid neoplasms (t-MNs) in children and adolescents. METHODS: The medical records of 16 patients under 21 years of age at the time of t-MN diagnosis were reviewed. RESULTS: The median patient age was 11.5 years (range, 1.6-20.4 yr). Twelve patients had therapy-related acute myeloid leukemia, 3 patients had myelodysplastic syndrome, and 1 patient had chronic myelomonocytic leukemia...
December 2016: Blood Research
https://www.readbyqxmd.com/read/28076841/clonal-evolution-in-therapy-related-neoplasms
#17
Emiliano Fabiani, Giulia Falconi, Luana Fianchi, Marianna Criscuolo, Tiziana Ottone, Laura Cicconi, Stefan Hohaus, Simona Sica, Massimiliano Postorino, Antonino Neri, Marta Lionetti, Giuseppe Leone, Francesco Lo-Coco, Maria Teresa Voso
Therapy-related myeloid neoplasms (t-MN) may occur as a late effect of cytotoxic therapy for a primary malignancy or autoimmune diseases in susceptible individuals. We studied the development of somatic mutations in t-MN, using a collection of follow-up samples from 14 patients with a primary hematologic malignancy, who developed a secondary leukemia (13 t-MN and 1 t-acute lymphoblastic leukemia), at a median latency of 73 months (range 18-108) from primary cancer diagnosis.Using Sanger and next generation sequencing (NGS) approaches we identified 8 mutations (IDH1 R132H, ASXL1 Y591*, ASXL1 S689*, ASXL1 R693*, SRSF2 P95H, SF3B1 K700E, SETBP1 G870R and TP53 Y220C) in seven of thirteen t-MN patients (54%), whereas the t-ALL patient had a t(4,11) translocation, resulting in the KMT2A/AFF1 fusion gene...
February 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28028303/dismal-outcome-of-therapy-related-myeloid-neoplasm-associated-with-complex-aberrant-karyotypes-and-monosomal-karyotype-a-case-report
#18
Y L Tang, W K Chia, E C S W Yap, M I Julia, C F Leong, S Salwati, C L Wong
INTRODUCTION: Individuals who are exposed to cytotoxic agents are at risk of developing therapyrelated myeloid neoplasms (t-MN). Cytogenetic findings of a neoplasm play an important role in stratifying patients into different risk groups and thus predict the response to treatment and overall survival. CASE REPORT: A 59-year-old man was diagnosed with acute promyelocytic leukaemia. Following this, he underwent all-trans retinoic acid (ATRA) based chemotherapy and achieved remission...
December 2016: Malaysian Journal of Pathology
https://www.readbyqxmd.com/read/27913458/therapy-related-myeloid-neoplasms-does-knowing-the-origin-help-to-guide-treatment
#19
REVIEW
Michael Heuser
Therapy-related myeloid neoplasms (t-MN) combine t-MDS and therapy related acute myeloid leukemia (t-AML) patients in one entity because of their similar pathogenesis, rapid progression from t-MDS to t-AML, and their equally poor prognosis. Treatment with epipodophyllotoxins like etoposide has been associated with a short interval between treatment and development of t-AML, with fusion oncogenes like KMT2A/MLL-MLLT3 and a better prognosis. In contrast, treatment with alkylating agents has been associated with a longer latency, an initial MDS phase, adverse cytogenetics, and a poor prognosis...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27353035/myeloid-neoplasms-after-chemotherapy-and-prrt-myth-and-reality
#20
COMMENT
Lisa Bodei, Irvin M Modlin, Markus Luster, Flavio Forrer, Marta Cremonesi, Rodney J Hicks, Samer Ezziddin, Mark Kidd, Arturo Chiti
Peptide receptor radionuclide therapy (PRRT) with (90)Y-octreotide or (177)Lu-octreotate is an effective treatment for inoperable or metastatic neuroendocrine tumors (NETs), particularly well-differentiated gastroenteropancreatic or bronchopulmonary NETs. PRRT is generally extremely well tolerated, with modest toxicity to target organs, kidney and bone marrow. Nevertheless, a priori concerns regarding long-term effects lead clinicians such as Brieau and coworkers, in this ERC issue, to ascribe to the combination of alkylating agents and PRRT the apparently high occurrence (n=4) of myeloproliferative events (therapy-related myeloid neoplasms (t-MNs)) in a small cohort of 20 progressive, advanced digestive NETs treated with PRRT after chemotherapy...
August 2016: Endocrine-related Cancer
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