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Koji Sasaki, Elias Jabbour, Jorge Cortes, Tapan Kadia, Guillermo Garcia-Manero, Gautam Borthakur, Preetesh Jain, Sherry Pierce, Naval Daver, Koichi Takahashi, Susan O'Brien, Hagop Kantarjian, Farhad Ravandi
PURPOSE: To learn whether an antecedent hematologic disorder (AHD) is associated with additional risk in patients with therapy-related acute myeloid leukemia (t-AML). PATIENTS AND METHODS: We reviewed data of 301 patients with newly diagnosed t-AML who sought care from January 2000 to January 2014 (183 t-AML without AHD, 118 t-AML with AHD). Overall, median follow-up was 44 months. RESULTS: The primary malignancy was non-Hodgkin lymphoma in 92 (31%), breast cancer in 80 (27%), and prostate cancer in 49 (16%)...
August 10, 2016: Clinical Lymphoma, Myeloma & Leukemia
Hua Pan, Dong-Ning Feng, Liang Song, Li-Rong Sun
BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a rare, life-threatening disorder characterized by prolonged fever, cytopenia, hepatosplenomegaly, rash, icterus, and other neurological symptoms. Successful treatment of HLH by etoposide has improved outcomes for children with HLH. However, the development of treatment-related acute myeloid leukemia (t-AML) after the usage of this drug is a concern. CASE PRESENTATION: We report a case of acquired EBV-triggered HLH with progression to t-AML following etoposide therapy with cytogenetic abnormality for t (11; 19) (q23; p13) resulting in MLL gene fusion...
2016: BMC Pediatrics
Brian A Jonas, Carl Johnson, Dita Gratzinger, Ravindra Majeti
Acute myeloid leukemia (AML) is a heterogeneous group of aggressive bone marrow cancers arising from transformed hematopoietic stem and progenitor cells (HSPC). Therapy-related AML and MDS (t-AML/MDS) comprise a subset of AML cases occurring after exposure to alkylating chemotherapy and/or radiation and are associated with a very poor prognosis. Less is known about the pathogenesis and disease-initiating/leukemia stem cell (LSC) subpopulations of t-AML/MDS compared to their de novo counterparts. Here, we report the development of mouse models of t-AML/MDS...
2016: PloS One
Mary Theresa Sylvia, Jhansi Rani, Debdatta Basu, Rakhee Kar, Biswajit Dubashi
Therapy related Acute Myeloid Leukemia/Myelodysplastic syndrome (t-AML/MDS) occur due to the direct mutational events of the chemotherapeutic agents and radiotherapy. The disease latency, mutational events and prognosis vary with the type of chemotherapeutic agent. Therapy related Acute Myeloid Leukemia occurring with DNA topoisomerase II inhibitors have a shorter latency period and poor prognosis than anthracyclin based regimens. We report a case of a 9 year old boy who developed t-AML with mixed-lineage-leukemia gene translocation within a year of high dose chemotherapy for stage 4 neuroblastoma...
June 2016: Indian Journal of Hematology & Blood Transfusion
Ana Espírito ESPíRITO Santo, Sérgio Chacim, Isabel Ferreira, Luís Leite, Claudia Moreira, Dulcineia Pereira, Margarida Dantas Dantas Brito, Marta Nunes, Nelson Domingues, Isabel Oliveira, Ilídia Moreira, Angelo Martins, Luísa Viterbo, José Mário Mariz, Rui Medeiros
Therapy-related acute myeloid leukemia (t-AML) is a rare and almost always fatal late side effect of antineoplastic treatment involving chemotherapy, radiotherapy or the two combined. The present retrospective study intended to characterize t-AML patients that were diagnosed and treated in a single referral to an oncological institution in North Portugal. Over the past 10 years, 231 cases of AML were diagnosed and treated at the Portuguese Institute of Oncology of Porto, of which 38 t-AML cases were identified...
July 2016: Oncology Letters
Fei-Fei Tang, Xiao-Jun Huang, Xiao-Hui Zhang, Huan Chen, Yu-Hong Chen, Wei Han, Yao Chen, Feng-Rong Wang, Yu Wang, Jing-Zhi Wang, Chen-Hua Yan, Yu-Qian Sun, Xiao-Dong Mo, Kai-Yan Liu, Lan-Ping Xu
Therapy-related acute myeloid leukemia (T-AML) is associated with poor prognosis after conventional therapy. Allogeneic hematopoietic cell transplantation (allo-HCT) has been proposed as a treatment for T-AML; however, data comparing outcomes of transplants for patients with de novo AML and T-AML are limited. Sixteen adult patients with T-AML during first complete remission after malignant disease received allo-HCT at the Peking University Institute of Hematology between January 1, 2006 and December 31, 2014...
August 2016: Leukemia Research
Li-Jun Wang, Ming-Juan Liu, Xiao-Li Zhao, Jie Ding, Yu Jing, Li Yu
OBJECTIVE: To investigate the clinical features and prognosis of patients with myelodysplastic syndrome (MDS) who received allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: A total of 45 patients with MDS and transformed acute myeloid leukemia (tAML) who received allo-HSCT between January 2009 and December 2014 were enrolled in this study. The effects of different conditioning regimens, donor and chemotherapy before transplantation on the clinical outcome were analyzed retrospectively...
April 2016: Zhongguo Shi Yan Xue Ye Xue za Zhi
Q S Lu, N Xu, X Zhou, G X Cai, L Li, Y L Li, Z Y Lu, J X Huang, Q F Liu, X L Liu
OBJECTIVE: To investigate the morbidity, treatment outcomes and prognosis of 35 therapy-related hematological neoplasms patients. METHODS: A total of 35 cases of therapy-related hematological neoplasms were examined genetically and immunologically using flow cytometry, karyotype analysis and FISH, and their clinical data were retrospective analyzed and literatures were reviewed. RESULTS: Among 35 patients, there were 20 cases of therapy-related acute myeloid leukemia (t-AML), 4 cases of therapy-related acute lymphoblastic leukemia (t-ALL), 1 case of acute mixed leukemia, therapy-related non-hodgkin' s lymphoma (t-NHL) in 8 cases and myelodysplastic syndrome (t-MDS) in 2 cases...
March 2016: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
Irappa Madabhavi, Gaurang Modi, Harsha Panchal, Apurva Patel, Asha Anand, Sonia Parikh
Treatment related acute myeloid leukemia (t-AML) is well documented phenomenon after chemotherapy. In this subgroup of patients acute promyelocytic leukemia (APML) due to delayed complication of using anthracycline is very rare occurrence. Very few cases are reported in world literature. We are reporting a rare case of occurrence of t-APML in cured breast cancer patient treated with doxorubicin. 43 year old female presented with triple negative early breast cancer treated initially with Right modified radical mastectomy...
October 1, 2015: International Journal of Hematology-oncology and Stem Cell Research
Junaid Ansari, Hari P Ravipati, Reinhold Munker, James D Cotelingam, Rodney E Shackelford, Leonard A Prouty
Secondary leukemia is a common late complication after exposure to cancer therapies such as chemotherapy and radiotherapy. With the increase in the overall survival of cancer patients over the past 3 decades, treatment-related malignant neoplasms have increased in incidence. Secondary leukemias due to breast cancer and Hodgkin lymphoma have been studied in detail, but to our knowledge only a few case studies have reported secondary leukemias with previous lung cancer.¹⁻⁴ Lung cancer is the leading cause of cancer death in the United States...
November 2015: Journal of Community and Supportive Oncology
Dan Yang, Xiaorui Fu, Xudong Zhang, Wencai Li, Mingzhi Zhang
Due to advances in the treatment of lymphoma, the remission and overall survival rates for this disease have improved in recent years. However, the incidence of therapy-related myelodysplastic syndrome/acute myeloid leukemia (t-MDS/AML) has increased. In order to further the understanding of the mechanisms of t-MDS/AML and reduce its incidence, the present study reports 4 cases of t-AML following treatment for lymphoma. The 4 patients presented aggressive forms of lymphoma in stage III/IV, and 3 were diagnosed with non-Hodgkin's lymphoma...
November 2015: Oncology Letters
Na Liu, Hong-Mei Ning, Liang-Ding Hu, Min Jiang, Chen Xu, Jiang-Wei Hu, Jun Wang, Yu-Hang Li, Bo-Tao Li, Xiao Lou, Fan Yang, Jian-Lin Chen, Yong-Feng Su, Meng Li, Hong-Ye Wang, Jing Ren, Yue-Qian Feng, Bin Zhang, Dan-Hong Wang, Hu Chen
To further find effective method to improve the long term survival of refractory or relapsed acute myeloid leukemia (AML) patients, we retrospectively analyzed the outcomes of myeloablative hematopoietic stem cell transplantation (HSCT) for 133 consecutive patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) therapy related AML(t-AML) in not remission status. The overall 3-year OS and DFS were 40.9% and 35.6% respectively. The variables associated with improved long term DFS were a bone marrow blast cell count less than 20% and an intensified conditioning regimen...
December 2015: Leukemia Research
Adetokunbo Oluwasanjo, Ranjan Pathak, Anene Ukaigwe, Olatunji Alese
BACKGROUND: Therapy-related acute myeloid leukemia (t-AML) associated with radioiodine treatment (RAI) is emerging as an important clinical entity with the rise in incidence of thyroid cancer. DESIGN AND METHODS: We conducted an electronic search of MEDLINE and EMBASE, and also searched reference lists of articles and abstracts from conference proceedings for case reports and review articles on t-AML following radioiodine therapy. A total of 37 patients with acute myeloid neoplasms following radioiodine treatment were analyzed...
January 2016: Cancer Causes & Control: CCC
S Burillo-Sanz, R M Morales-Camacho, T Caballero-Velázquez, M T Vargas, J R García-Lozano, J F Falantes, C Prats-Martín, R Bernal, J A Pérez-Simón
INTRODUCTION: Chromosomal rearrangements involving NUP98 gene have been associated with human leukemias such as de novo AML, therapy-related AML (t-AML), myelodysplastic syndrome (MDS), and chronic myeloid leukemia (CML). Genetic fusion NUP98-HOXA9, caused by t(7;11)(p15;p15), is a recurrent cytogenetic alteration in de novo acute myeloid leukemia (AML) usually found in young Asian patients and its description in therapy-related myeloid neoplasms (t-MN) is rare. Only one Asian case with molecular demonstration of the NUP98-HOXA9 fusion has been reported in therapy-related leukemia...
February 2016: International Journal of Laboratory Hematology
John C Nguyen, Melanie J Kubik, H Elizabeth Broome, Peter T Curtin, Marie L Dell'Aquila, Huan-You Wang
Double minute chromosomes (DMs), although relatively frequently encountered in solid tumors, are rare in hematologic neoplasms such as acute myeloid leukemia (AML), and even rarer in lymphoid neoplasms. t(3;3)(q26.2;q21) is a very rare genetic alteration observed in myeloid neoplasm. Herein we report an interesting and unique case of concomitant C-MYC DMs and t(14;18)-containing large B-cell lymphoma, which was successfully treated with R-hyper-CVAD; unfortunately, the patient has developed a therapy-related AML (t-AML) 2 years since the start of his lymphoma treatment...
November 2015: Pathology, Research and Practice
Nicholas J Short, Michael J Keating, William G Wierda, Stefan Faderl, Alessandra Ferrajoli, Zeev Estrov, Susan C Smith, Susan M O'Brien
BACKGROUND: Fludarabine, cyclophosphamide, and rituximab (FCR) result in durable responses in patients with previously untreated chronic lymphocytic leukemia (CLL). Previous reports have suggested that in patients with relapsed CLL, a dose-intensified rituximab regimen increases response rates in comparison with standard-dose rituximab. It is unknown whether rituximab intensification of the FCR regimen will result in improved response rates and patient outcomes in patients with previously untreated CLL...
November 1, 2015: Cancer
Simon B Zeichner, Martha L Arellano
Secondary AML (s-AML) encompasses AML evolving from myelodysplasia (AML-MDS) and treatment-related AML (t-AML) after exposure to chemotherapy, radiation, or environmental toxins. S-AML has traditionally been considered a devastating disease, affecting a vulnerable population of heavily pretreated, older adults. A limited understanding of disease pathogenesis/heterogeneity and lack of effective treatments have hampered overall improvements in patient outcomes. With the recent understanding that the secondary nature of sAML does not by itself incur a poor prognosis and incorporation of cytogenetics and molecular genetics into patient care and the advancement of treatment, including improved supportive care, novel chemotherapeutics agents, and nonmyeloablative conditioning regimens as part of allogeneic hematopoietic cell transplantation (HCT), modest gains in survival and quality of life are beginning to be seen among patients with s-AML...
August 2015: Current Treatment Options in Oncology
N Alam, E G Atenafu, J Kuruvilla, J Uhm, J H Lipton, H A Messner, D H Kim, M Seftel, V Gupta
We studied outcomes of 65 consecutive patients with therapy-related AML/myelodyplastic syndrome (t-AML/MDS) who underwent allogeneic hematopoietic cell transplantation (HCT). Previously published scores of HCT-CI, CIBMTR, EBMT and Comorbidity-age index were also evaluated. Median follow-up of survivors was 72 months (range 16-204). At 2 years, overall survival (OS) was 34% (95% confidence interval (CI) 23-45). Nineteen patients (29%) had monosomal karyotype (MK). Patients with MK had an OS of 21% (95% CI 7-41) at 2 years...
September 2015: Bone Marrow Transplantation
Xinan Holly Yang, Bin Wang, John M Cunningham
BACKGROUND: Therapy-related, secondary acute myeloid leukemia (t-AML) is an increasingly frequent complication of intensive chemotherapy. This malignancy is often characterized by abnormalities of chromosome 7, including large deletions or chromosomal loss. A variety of studies suggest that decreased expression of the EZH2 gene located at 7q36.1 is critical in disease pathogenesis. This histone methyltransferase has been implicated in transcriptional repression through modifying histone H3 on lysine 27 (H3k27)...
2015: BMC Medical Genomics
Chi Young Ok, Keyur P Patel, Guillermo Garcia-Manero, Mark J Routbort, Jie Peng, Guilin Tang, Maitrayee Goswami, Ken H Young, Rajesh Singh, L Jeffrey Medeiros, Hagop M Kantarjian, Rajyalakshmi Luthra, Sa A Wang
BACKGROUND: TP53 mutation is more prevalent in therapy-related myeloid neoplasms (t-MN) than their de novo counterparts; however, the pattern of mutations involving TP53 gene in t-MN versus de novo diseases is largely unknown. METHODS: We collected 108 consecutive patients with therapy-related myelodysplastic syndrome (t-MDS)/acute myeloid leukemia (t-AML). Clinical, hematological, and cytogenetic data were collected by searching the electronic medical record. TP53 sequencing was performed in all patients using a clinically validated next-generation sequencing-based gene panel assay...
2015: Journal of Hematology & Oncology
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