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https://www.readbyqxmd.com/read/29346478/differentiation-syndrome-associated-with-enasidenib-a-selective-inhibitor-of-mutant-isocitrate-dehydrogenase-2-analysis-of-a-phase-1-2-study
#1
Amir T Fathi, Courtney D DiNardo, Irina Kline, Laurie Kenvin, Ira Gupta, Eyal C Attar, Eytan M Stein, Stephane de Botton
Importance: Enasidenib mesylate, a mutant isocitrate dehydrogenase 2 (IDH2) protein inhibitor that promotes differentiation of leukemic myeloblasts, was recently approved by the US Food and Drug Administration for use in relapsed/refractory (R/R) mutant IDH2 acute myeloid leukemia (AML). During the first study of enasidenib in humans, a minority of patients with advanced myeloid neoplasms experienced unexpected signs/symptoms of a differentiation syndrome (DS), a potentially lethal entity...
January 18, 2018: JAMA Oncology
https://www.readbyqxmd.com/read/29344207/novel-homobarringtonie-containing-therapy-for-the-treatment-of-patients-with-primary-acute-myeloid-leukemia-that-are-resistant-to-conventional-therapy
#2
Jingsong He, Li Li, Jingjing Zhu, Weiyan Zheng, Wenjun Wu, Yanlong Zheng, Xiujin Ye
The current study investigated the efficacy and safety of a novel treatment regime consisting of homobarringtonie, cytosine arabinoside and etoposide (HCE) for the treatment of primary acute myeloid leukemia (AML). In the present study, 141 patients diagnosed with AML were divided into the HCE (n=47) and the conventional AML therapy, consisting of idamycin combined with cytarabine (IA; n=94), treatment groups. The measured patient outcome parameters were the emission and response rates, as well as medication-induced adverse events, with a median follow-up time of 28 months...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29338495/clinical-challenges-in-de-novo-pediatric-acute-myeloid-leukemia
#3
Kim Klein, Valérie de Haas, Gertjan J L Kaspers
Although the prognosis of pediatric acute myeloid leukemia (pAML) has improved, with current survival rates up to 75%, relapse rates remain high. Areas covered: The low number of patients, the heterogeneous genomic landscape of AML, novel diagnostic techniques, divergent available treatment protocols, and dose-limiting toxicity of conventional agents all contribute to the complexity of AML treatment. This review gives an overview of the current clinical challenges with respect to diagnostics, treatment, and supportive care in pAML...
January 17, 2018: Expert Review of Anticancer Therapy
https://www.readbyqxmd.com/read/29337223/sequential-conditioning-with-thiotepa-in-t-cell-replete-hematopoietic-stem-cell-transplantation-for-the-treatment-of-refractory-hematological-malignancies-comparison-with-matched-related-haplo-mismatched-and-unrelated-donors
#4
Rémy Duléry, Anne-Lise Ménard, Sylvain Chantepie, Jean El Cheikh, Sylvie François, Jérémy Delage, Federica Giannotti, Annalisa Ruggeri, Eolia Brissot, Giorgia Battipaglia, Florent Malard, Ramdane Belhocine, Simona Sestili, Anne Vekhoff, François Delhommeau, Oumédaly Reman, Ollivier Legrand, Myriam Labopin, Marie-Thérèse Rubio, Mohamad Mohty
The results of conventional allogeneic stem cell transplantation (SCT) in refractory hematological malignancies are poor. Sequential strategies have shown promising results in refractory acute myeloid leukemia (AML), but have not been validated in a haploidentical (Haplo) setting. We developed a new sequential approach combining chemotherapy with broad anti-tumor activity (thiotepa 10 mg/kg, etoposide 400 mg/m2, cyclophosphamide 1600 mg/m2 from Day-15 to -10), followed after 3 days of rest by reduced-intensity conditioning regimen (fludarabine 150 mg/m2, intravenous busulfan 6...
January 11, 2018: Biology of Blood and Marrow Transplantation
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
#5
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/29324476/revisiting-autologous-transplantation-in-acute-myeloid-leukemia
#6
Chezi Ganzel, Jacob M Rowe
PURPOSE OF REVIEW: Autologous hematopoietic cell transplantation (auto-HCT) has been evaluated as a consolidation treatment for acute myeloid leukemia (AML) in the 1980s and 1990s. These prospective studies from large trials compared auto-HCT with chemotherapy. A comparison was made also with allogeneic hematopoietic cell transplantation (allo-HCT). These studies reported a lower relapse rate with auto-HCT compared with chemotherapy, but without impact on the overall survival. A high transplant-related mortality in that era confounded the relevance of these data...
January 10, 2018: Current Opinion in Hematology
https://www.readbyqxmd.com/read/29318584/treatment-of-relapsed-refractory-acute-myeloid-leukaemia-in-adults
#7
REVIEW
Armin Rashidi, Daniel J Weisdorf, Nelli Bejanyan
The prognosis of relapsed acute myeloid leukaemia (AML) is poor and treatment is challenging. While the most potent treatment modality for patients who achieve a complete remission after relapse is still allogeneic haematopoietic cell transplantation (allo-HCT), both transplant-related mortality and relapse rates are high and many patients are not candidates for this approach. After a few decades of relative stasis in this field, a large number of novel approaches have become available to tackle this highly fatal disease...
January 9, 2018: British Journal of Haematology
https://www.readbyqxmd.com/read/29316944/car-t-cells-targeting-cll-1-as-an-approach-to-treat-acute-myeloid-leukemia
#8
Jinghua Wang, Siyu Chen, Wei Xiao, Wende Li, Liang Wang, Shuo Yang, Weida Wang, Liping Xu, Shuangye Liao, Wenjian Liu, Yang Wang, Nawei Liu, Jianeng Zhang, Xiaojun Xia, Tiebang Kang, Gong Chen, Xiuyu Cai, Han Yang, Xing Zhang, Yue Lu, Penghui Zhou
BACKGROUND: Acute myeloid leukemia (AML) is one of the most common types of adult acute leukemia. Standard chemotherapies can induce complete remission in selected patients; however, a majority of patients eventually relapse and succumb to the disease. Thus, the development of novel therapeutics for AML is urgently needed. Human C-type lectin-like molecule-1 (CLL-1) is a type II transmembrane glycoprotein, and its expression is restricted to myeloid cells and the majority of AML blasts...
January 10, 2018: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/29304116/the-sorafenib-anti-relapse-effect-after-allohsct-is-associated-with-heightened-alloreactivity-and-accumulation-of-cd8-pd-1-cd279-lymphocytes-in-marrow
#9
Andrzej Lange, Emilia Jaskula, Janusz Lange, Grzegorz Dworacki, Dorota Nowak, Aleksandra Simiczyjew, Monika Mordak-Domagala, Mariola Sedzimirska
We studied three FLT3 ITD acute myeloid leukemia (AML) patients who relapsed after allogeneic haematopoietic stem cell transplantation (alloHSCT) and received multikinase inhibitor (MKI) sorafenib as part of salvage therapy. MKI was given to block the effect of FLT3 ITD mutation which powers proliferation of blast cells. However, the known facts that sorafenib is more effective in patents post alloHSCT suggested that this MKI can augment the immune system surveillance on leukaemia. In the present study, we investigated in depth the effect of sorafenib on the alloreactivity seen post-transplant including that on leukaemia...
2018: PloS One
https://www.readbyqxmd.com/read/29296747/single-umbilical-cord-blood-with-or-without-cd34-cells-from-a-third-party-donor-in-adults-with-leukemia
#10
Jaime Sanz, Mi Kwon, Guiomar Bautista, Miguel A Sanz, Pascual Balsalobre, José Luis Piñana, Carlos Solano, Rafael Duarte, Christelle Ferrá, Ignacio Lorenzo, Carmen Martín, Pere Barba, María Jesús Pascual, Rodrigo Martino, Jorge Gayoso, Ismael Buño, Carmen Regidor, Almudena de la Iglesia, Juan Montoro, José Luis Díez-Martín, Guillermo F Sanz, Rafael Cabrera
We retrospectively compared the clinical outcomes of adults with acute leukemia who received single-unit umbilical cord blood (UCB) transplantation (sUCBT) (n = 135) or stem cell transplant using coinfusion of a UCB graft with CD34+ cells from a third-party donor (Haplo-Cord) (n = 72) at different institutions within the Grupo Español de Trasplante Hematopoyético. In multivariable analysis, patients in the Haplo-Cord group showed more rapid neutrophil (hazard ratio [HR], 2.3; 95% confidence interval [CI], 1...
June 27, 2017: Blood Advances
https://www.readbyqxmd.com/read/29289758/comparison-of-autologous-stem-cell-transplantation-versus-haploidentical-donor-stem-cell-transplantation-for-favorable-and-intermediate-risk-acute-myeloid-leukemia-patients-in-first-complete-remission
#11
Jia Chen, Lingyi Yang, Yi Fan, Yang Xu, Yue Han, Xiaowen Tang, Huiying Qiu, Chengcheng Fu, Miao Miao, Feng Chen, Depei Wu
Stem cell transplantation (SCT) is an attractive post-remission treatment option for patients with intermediate-risk acute myeloid leukemia (AML) and for some favorable-risk AML patients with additional non-genetic risk factors. Autologous SCT (auto-SCT) and haplo-identical donor SCT (haplo-SCT) are the widely used alternatives in case of a lack of a human leukocyte antigen (HLA)-matched donor. However, limited data have been published on the direct comparison between these two transplant types. Based on the transplantation database in our center, we conducted a retrospective study involving patients with favorable- and intermediate-risk AML in first complete remission (CR1), according to the NCCN guideline...
December 28, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29286515/cortisol-level-as-risk-factor-for-malignant-hematologic-pathology-in-children-exposed-to-ionizing-radiation-after-chornobyl-accident
#12
V G Bebeshko, K M Bruslova, T I Pushkareva, N M Tsvietkova, L O Lyashenko, A S Sergeeva, V F Kuzmenko, S M Iatsemyrskiy, Yu M Samson, V G Boyarsky, I V Tryhlіb
OBJECTIVE: Determination of serum cortisol level in the initial period of acute leukemia in children, who exposed to ion izing radiation and other factors of Chornobyl accident, depending on their age and prognosis of disease. MATERIALS AND METHODS: The study involved 283 children residents of Kyiv, Zhytomyr and Chernihiv regions. There were 90 acute leukemia patients(AL) (ALL - 56, AML - 34), and 193 people of comparison group with anemia, leukemoid reactions and lymphadenopathy...
December 2017: Problemy Radiat︠s︡iĭnoï Medyt︠s︡yny Ta Radiobiolohiï
https://www.readbyqxmd.com/read/29249818/persistence-of-pre-leukemic-clones-during-first-remission-and-risk-of-relapse-in-acute-myeloid-leukemia
#13
M Rothenberg-Thurley, S Amler, D Goerlich, T Köhnke, N P Konstandin, S Schneider, M C Sauerland, T Herold, M Hubmann, B Ksienzyk, E Zellmeier, S K Bohlander, M Subklewe, A Faldum, W Hiddemann, J Braess, K Spiekermann, K H Metzeler
Some patients with acute myeloid leukemia (AML) who are in complete remission after induction chemotherapy harbor persisting pre-leukemic clones, carrying a subset of leukemia-associated somatic mutations. There is conflicting evidence on the prognostic relevance of these clones for AML relapse. Here, we characterized paired pre-treatment and remission samples from 126 AML patients for mutations in 68 leukemia-associated genes. Fifty patients (40%) retained ⩾1 mutation during remission at a variant allele frequency of ⩾2%...
December 18, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29244983/allogeneic-stem-cell-transplant-for-acute-myeloid-leukemia-evolution-of-an-effective-strategy-in-india
#14
Abhijeet Ganapule, Sandeep Nemani, Anu Korula, Kavitha M Lakshmi, Aby Abraham, Alok Srivastava, Poonkuzhali Balasubramanian, Biju George, Vikram Mathews
Purpose There are limited data from developing countries on the role and cost-effectiveness of allogeneic stem cell transplantation (allo-SCT) for patients with acute myeloid leukemia (AML). Patients and Methods We undertook a retrospective descriptive study of all patients with AML who underwent allo-SCT from 1994 to 2013 at our center to evaluate the clinical outcomes and cost-effectiveness of this therapeutic modality. Results Two hundred fifty-four consecutive patients, median age 34 years, who underwent allo-SCT at our center were included in this study...
December 2017: Journal of Global Oncology
https://www.readbyqxmd.com/read/29232178/rapid-decrease-in-krt14-and-tp53-mrna-expression-in-the-buccal-mucosa-of-patients-receiving-total-body-irradiation-for-allogeneic-stem-cell-transplantation
#15
J Chmara, J W L Browning, H Atkins, M Sabloff, B C McKay
The only curative treatment option for relapsed patients with acute myeloid leukemia (AML) is allogeneic stem cell transplantation. Depletion of hematopoietic stem cells and leukemic blast cells is achieved through the systemic administration of DNA damaging agents, including total-body irradiation (TBI) prior to transplantation. Since other tissues are radiosensitive, the identification of biomarkers could facilitate the management of additional toxicities. Buccal keratinocytes are readily accessible and could provide a source of cells for RNA analysis...
December 12, 2017: Radiation Research
https://www.readbyqxmd.com/read/29222236/how-and-when-to-decide-between-epigenetic-therapy-and-chemotherapy-in-patients-with-aml
#16
REVIEW
Hervé Dombret, Raphael Itzykson
Remission induction with chemotherapy has long been the frontline treatment of acute myeloid leukemia (AML). However, intensive therapy is limited in frail patients by its associated toxicity and higher rates of failure or relapse in patients with chemoresistant disease, such as secondary AML or poor-risk cytogenetics. Frailty and chemoresistance are more frequent in older adults with AML. In recent years, epigenetic therapies with the hypomethylating agents decitabine and azacitidine have been thoroughly explored in AML...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/29218851/clinical-experience-with-the-bcl2-inhibitor-venetoclax-in-combination-therapy-for-relapsed-and-refractory-acute-myeloid-leukemia-and-related-myeloid-malignancies
#17
Courtney D DiNardo, Caitlin R Rausch, Christopher Benton, Tapan Kadia, Nitin Jain, Naveen Pemmaraju, Naval Daver, Wendy Covert, Kayleigh R Marx, Morgan Mace, Elias Jabbour, Jorge Cortes, Guillermo Garcia-Manero, Farhad Ravandi, Kapil N Bhalla, Hagop Kantarjian, Marina Konopleva
INTRODUCTION: Venetoclax (VEN), a selective BCL2 inhibitor, has single-agent activity in relapsed and refractory (R/R) acute myeloid leukemia (AML) and efficacy in lower-intensity combinations for treatment-naïve elderly AML patients. VEN treatment combinations in R/R AML have not been previously reported. METHODS: All R/R myeloid patients (including AML, myelodysplastic syndrome (MDS), and blastic plasmacytoid dendritic cell neoplasm (BPDCN)) treated with VEN combinations in the salvage setting were reviewed...
December 8, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/29214689/distinct-factors-determine-the-kinetics-of-disease-relapse-in-adults-transplanted-for-acute-myeloid-leukaemia
#18
C Craddock, J Versluis, M Labopin, G Socie, A Huynh, E Deconinck, L Volin, N Milpied, J H Bourhis, A Rambaldi, P Chevallier, D Blaise, M Manz, E Vellenga, M-C Vekemans, J Maertens, J Passweg, P Vyas, C Schmid, B Löwenberg, G Ossenkoppele, M Mohty, J J Cornelissen, A Nagler
Disease recurrence remains the major cause of death in adults with acute myeloid leukemia (AML) treated using either intensive chemotherapy (IC) or allogenic stem cell transplantation (allo-SCT). The timely delivery of maintenance drug or cellular therapies represent emerging strategies with the potential to reduce relapse after both treatment modalities, but whilst the determinants of overall relapse risk have been extensively characterized the factors determining the timing of disease recurrence have not been characterized...
December 7, 2017: Journal of Internal Medicine
https://www.readbyqxmd.com/read/29212421/antineoplastic-chemotherapy-in-jehovah-s-witness-patients-with-acute-myelogenous-leukemia-refusing-blood-products-a-matched-pair-analysis
#19
Stefan Wilop, Rainhardt Osieka
BACKGROUND: Acute myelogenous leukemia (AML) may be cured in a substantial number of patients using intensive chemotherapeutic regimens leading to temporary severe myelosuppression. Patients belonging to the denomination of Jehovah's Witnesses (JW), however, are bound by their religious convictions not to accept blood products and are therefore at higher risk for life-threatening events. Reports how to handle this challenge are mainly anecdotal. MATERIAL AND METHODS: We here report in much more detail about our experience with nine patients belonging to the denomination of JW who were treated for AML in our department from 1998 to 2007 and who explicitly wished to receive chemotherapy without blood transfusions...
December 7, 2017: Hematology (Amsterdam, Netherlands)
https://www.readbyqxmd.com/read/29212418/clinical-characteristics-and-outcome-of-childhood-acute-promyelocitic-leukemia-apl-in-saudi-arabia-a-multicenter-saphos-leukemia-group-study
#20
Wasil Jastaniah, Abdulrahman Alsultan, Saad Al Daama, Walid Ballourah, Mohamed Bayoumy, Faisal Al-Anzi, Omar Al Shareef, Mohammed Burhan Abrar, Reem Al Sudairy, Ibrahim Al Ghemlas
BACKGROUND: Acute promyelocytic leukemia (APL) is a rare form of acute myelogenous leukemia (AML). Survival rates exceed 80% in developed countries. Successful treatments rely on all-trans retinoic acid with anthracycline-based chemotherapy. Availability of modern care and public knowledge play important roles in pediatric APL survival. METHOD: A cytogenetic diagnosis of APL was confirmed in 30 (14.5%) out of 207 children consecutively diagnosed with de novo AML between January 2005 and December 2012 at nine cancer care centers in Saudi Arabia...
December 7, 2017: Hematology (Amsterdam, Netherlands)
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