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Adam Gassas, Ponni Sivaprakasam, Michelle Cummins, Patricia Breslin, Katharine Patrick, Mary Slatter, Roderick Skinner, Geof Shenton, Brenda Gibson, Sarah Lawson, Toni Petterson, Michael Potter, Beki James, Rachael Hough, Prashant Hiwarkar, Ajay Vora, Paul Veys, Josu De La Fuente, Robert Wynn, Persis Amrolia
Paediatric therapy-related acute myeloid leukaemia (t-AML) is rare and the outcome is poor. While allogeneic haematopoietic stem cell transplantation (HSCT) is generally the accepted modality of treatment, data regarding salvage chemotherapy, remission induction, conditioning regimens, transplant-related mortality and outcome is scarce. Between 2000 and2016, 36 children with t-AML were treated in seven UK paediatric HSCT centres. The most common salvage protocol for remission induction was FLAG with or without idarubicin and 28 patients were in complete morphological remission prior to BMT...
March 15, 2018: Bone Marrow Transplantation
Miryoung Kim, Sherry Williams
OBJECTIVE: To evaluate the efficacy and safety of daunorubicin and cytarabine liposome in older adults with newly diagnosed therapy-related acute myeloid leukemia (t-AML) or AML with myelodysplasia-related changes (AML-MRC). DATA SOURCE: A literature search of PubMed and MEDLINE (January 2017 to January 2018) was performed using the terms CPX-351, Vyxeos, daunorubicin and cytarabine liposome, and acute myeloid leukemia. STUDY SELECTION/DATA EXTRACTION: Phase I, II, and III clinical trials evaluating the efficacy and safety of daunorubicin and cytarabine liposome were reviewed with a specific focus on its use in older patients with newly diagnosed AML...
March 1, 2018: Annals of Pharmacotherapy
Chintan Vyas, Sandeep Jain, Gauri Kapoor
Therapy-related acute myeloid leukemia/myelodysplastic syndrome (t-AML/MDS) is a devastating late effect of cancer treatment. There is limited data on incidence of t-AML/MDS from India. We retrospectively studied pediatric t AML/MDS at our institute between January 1996 and December 2015. Among 1285 children, 8 patients developed t-AML with a median age of 15.5 years. Overall incidence of t-AML/MDS was 0.62% [0.99% (4/402) in solid tumours and 0.45% (4/883) in leukemia/lymphoma, P = 0.26] with 6390 patient years of follow up...
January 2018: Indian Journal of Hematology & Blood Transfusion
Juan Qian, Wenyu Shi, Li Yang, Zenghua Lin, Yifeng Cai, Hong Liu
RATIONALE: To investigate the clinical features of treatment-related acute granulocyte-monocytic leukemia (t-AML) from multiple myeloma (MM) thereby improving the understanding of this disease. PATIENT CONCERNS: A 72-year-old woman patient was initially diagnosed as MM. Two years and 7 months after treatment, this patient developed AML M4 as confirmed by the analyses from clinical features, bone marrow morphology, flow cytometry, and cytogenetic examination. DIAGNOSIS: Treatment-related acute myeloid leukaemia (t-AML)...
December 2017: Medicine (Baltimore)
Terrence N Wong, Christopher A Miller, Matthew R M Jotte, Nusayba Bagegni, Jack D Baty, Amy P Schmidt, Amanda F Cashen, Eric J Duncavage, Nichole M Helton, Mark Fiala, Robert S Fulton, Sharon E Heath, Megan Janke, Kierstin Luber, Peter Westervelt, Ravi Vij, John F DiPersio, John S Welch, Timothy A Graubert, Matthew J Walter, Timothy J Ley, Daniel C Link
Hematopoietic clones harboring specific mutations may expand over time. However, it remains unclear how different cellular stressors influence this expansion. Here we characterize clonal hematopoiesis after two different cellular stressors: cytotoxic therapy and hematopoietic transplantation. Cytotoxic therapy results in the expansion of clones carrying mutations in DNA damage response genes, including TP53 and PPM1D. Analyses of sorted populations show that these clones are typically multilineage and myeloid-biased...
January 31, 2018: Nature Communications
Ivanka Nenova, Janet Grudeva-Popova
The growing number of successfully cured cancer patients has created a new field in oncogenesis. The life expectancy of such patients has increased, however this favorable event may create enough time for epigenetic events to occur which can cause a new carcinognic event, i.e. a secondary malignancy. The terms in use are second primary malignancies as well as therapy-related neoplasms in case the treatment of the first neoplasm is a direct cause. Second primary malignancies can be hematological neoplasms or solid tumors, with solid tumors having higher frequency...
November 2017: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
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
Kyung Taek Hong, Jung Yoon Choi, Che Ry Hong, Hyoung Jin Kang, Kyung Duk Park, Hee Young Shin
Therapy-related acute myeloid leukemia (t-AML) has a dismal prognosis and is one of the most frequent second malignant neoplasms which could be encountered by pediatric oncologists. Between October 2000 and September 2016, 16 patients who had primary solid tumors were diagnosed with t-AML at the Seoul National University Children's Hospital. The median patient age at the time of diagnosis of their primary solid tumors was 9.6 years (range, 0.1 to 15.4 y), and that of t-AML was 14.0 years (range, 4.7 to 23...
January 2018: Journal of Pediatric Hematology/oncology
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
T Rolvien, U Kornak, J Stürznickel, T Schinke, M Amling, S Mundlos, R Oheim
Osteogenesis imperfecta (OI) is typically characterized by low bone mass and increased bone fragility caused by heterozygous mutations in the type I procollagen genes (COL1A1/COL1A2). We report two cases of a 56-year-old woman and her 80-year-old mother who suffered from multiple vertebral and non-vertebral fractures with onset in early childhood. A full osteologic assessment including dual-energy X-ray absorptiometry (DXA), high-resolution peripheral quantitative computed tomography (HR-pQCT), and serum analyses pointed to a high bone mineral density (BMD) in the hip (DXA Z-score + 3...
September 15, 2017: Osteoporosis International
Carsten Rendenbach, Ashkan Rashad, Lara Hansen, Carsten Kohlmeier, Moritz L Dyck, Anna Suling, Alexandre T Assaf, Michael Amling, Max Heiland, Johannes Wikner, Bjoern Riecke, Kilian Kreutzer
OBJECTIVES: The fibula free flap is the workhorse procedure for osseous reconstruction. The objective of this study was to investigate long-term functional outcomes of the harvesting site. PATIENTS AND METHODS: About 19 patients (10 male, 9 female, mean age 58.1 years) were available for the long-term analysis 13-51 months after surgery. Jumping mechanography and balance testing on a ground force reaction plate (Leonardo Mechanograph GFRP) were performed before and surgery...
July 26, 2017: Microsurgery
Naoki Shimada, Nobuhiro Ohno, Ryuji Tanosaki, Shigeo Fuji, Yuhko Suzuki, Koichiro Yuji, Kaoru Uchimaru, Arinobu Tojo
A 61-year-old woman with chronic-type adult T-cell leukemia-lymphoma (ATL) had been taking low-dose oral etoposide for progressive lymphocytosis. After taking this for 3.5 years, she was diagnosed with therapy-related acute myeloid leukemia (t-AML), with a chromosomal translocation of t (6:11) (q27; q23). She thus received remission induction therapy, consolidation therapy, and allogeneic hematopoietic stem cell transplantation. Although both t-AML and ATL were in remissive states, she died of a therapy-related infection within 1 year...
2017: Internal Medicine
S Yamasaki, R Suzuki, K Hatano, K Fukushima, H Iida, S Morishima, Y Suehiro, T Fukuda, N Uchida, H Uchiyama, H Ikeda, A Yokota, K Tsukasaki, H Yamaguchi, J Kuroda, H Nakamae, Y Adachi, K-I Matsuoka, Y Nakamura, Y Atsuta, J Suzumiya
Therapy-related acute myeloid leukemia and myelodysplastic syndrome (t-AML/MDS) represent severe late effects in patients receiving hematopoietic cell transplantation (HCT) for lymphoma. The choice between high-dose therapy with autologous HCT and allogeneic HCT with reduced-intensity conditioning remains controversial in patients with relapsed lymphoma. We retrospectively analyzed incidence and risk factors for the development of t-AML/MDS in lymphoma patients treated with autologous or allogeneic HCT. A total of 13 810 lymphoma patients who received autologous (n=9963) or allogeneic (n=3847) HCT between 1985 and 2012 were considered...
July 2017: Bone Marrow Transplantation
Kenzo Kosugi, Katsuya Saito, Wataru Takahashi, Yukina Tokuda, Hideyuki Tomita
BACKGROUND: Temozolomide (TMZ) is now standard adjuvant therapy in combination with radiotherapy for patients with newly diagnosed malignant glioma. Treatment-related myelodysplastic syndrome and acute treatment-related leukemia (t-AML) associated with TMZ chemotherapy for patients with glioma is quite a rare complication. CASE DESCRIPTION: A 43-year-old man with an anaplastic astrocytoma received radiation therapy synchronized with ranimustine and adjuvant TMZ chemotherapy for 15 cycles...
May 2017: World Neurosurgery
Arnold Ganser, Michael Heuser
PURPOSE OF REVIEW: Advances in the genetic characterization of patients with therapy-related myeloid neoplasms (t-MNs) have changed our understanding of the pathogenesis of these diseases. In addition, extensive sequencing studies have identified recurrent mutations with diagnostic and prognostic impact. Thus, the revised version of the WHO classification combines therapy-related myelodysplastic syndromes (t-MDS) and therapy-related acute myeloid leukemia (t-AML) in the one entity of t-MNs because of their similar pathogenesis, rapid progression from t-MDS to t-AML, and their equally poor prognosis...
March 2017: Current Opinion in Hematology
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
Sarah Bertoli, Arthur Sterin, Suzanne Tavitian, Lucie Oberic, Loïc Ysebaert, Reda Bouabdallah, François Vergez, Audrey Sarry, Emilie Bérard, Françoise Huguet, Guy Laurent, Thomas Prébet, Norbert Vey, Christian Récher
Therapy-related acute myeloid leukemia (t-AML) is a heterogeneous entity most frequently related to breast cancer or lymphoproliferative diseases (LD). Population-based studies have reported an increased risk of t-AML after treatment of lymphomas. The aim of this study was to describe the characteristics and outcome of 80 consecutive cases of t-AML following treatment of LD. t-AML accounted for 2.3% of all AML cases, occurred 60 months after LD diagnosis, and were characterized by a high frequency of FAB M6 AML and poor-risk cytogenetic abnormalities...
December 27, 2016: Oncotarget
T Schmidt, M Amling, F Barvencik
This review presents the current knowledge on the diagnosis and treatment of hypophosphatasia, a rare genetic disease, caused by mutations in the tissue non-specific alkaline phosphatase (TNSALP) gene. The clinical spectrum of hypophosphatasia is highly variable ranging from lethal infantile forms to mild forms diagnosed in adults. Although the disease rarely occurs, correct diagnosis is important to provide appropriate treatment and to avoid worsening by use of harmful drugs such as bisphosphonates. Low serum values of alkaline phosphatase (ALP) is the main feature of HPP, but by itself not sufficient for diagnosis, as it can occur under different conditions...
December 2016: Der Internist
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%)...
November 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...
July 29, 2016: BMC Pediatrics
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