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AML Treatment

Megan Othus, Mikkael A Sekeres, Sucha Nand, Guillermo Garcia-Manero, Frederick R Appelbaum, Harry P Erba, Eli Estey
Here we quantify and compare the absolute and relative overall survival (OS) benefits conveyed by complete remission (CR) in AML and high-risk MDS, and by CR with incomplete count recovery (CRi) in AML and by hematologic improvement (HI) in MDS, following treatment with 7 + 3 versus azacytidine. We compared patients receiving 7 + 3 in SWOG studies S0106 (n = 301) and S1203 (n = 261) enrolling adults ≤ 60 years, with patients receiving azacytidine therapies in S0703 (n = 133 AML patients ≥ 60) and S1117 (n = 277 MDS patients ≥ 18)...
October 12, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Ping Wang, Xian'gui Peng, Xiaojuan Deng, Li Gao, Xi Zhang, Yimei Feng
RATIONALE: The diagnosis of hematological malignancies depends on laboratory analysis and often requires multiple experimental methods to judge, otherwise misdiagnosis is apt to happen. Lymph node biopsy immunohistochemistry (IHC) for T-lymphoblastic lymphoma (T-LBL) requires the establishment of antibody set screening. For identifying T-LBL and early T-cell precursor acute lymphoblastic leukemia (ETP-ALL) by lymph node biopsy and IHC, WHO has not yet proposed a better IHC antibody combination...
October 2018: Medicine (Baltimore)
Claire Marchal, Maud de Dieuleveult, Claude Saint-Ruf, Nadège Guinot, Laure Ferry, Sara T Olalla Saad, Mariana Lazarini, Pierre-Antoine Defossez, Benoit Miotto
DNA methyltransferase inhibitor (DNMTi) treatments have been used for patients with myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML), and have shown promising beneficial effects in some other types of cancers. Here, we demonstrate that the transcriptional repressor ZBTB38 is a critical regulator of the cellular response to DNMTi. Treatments with 5-azacytidine, or its derivatives decitabine and zebularine, lead to down-regulation of ZBTB38 protein expression in cancer cells, in parallel with cellular damage...
October 11, 2018: Oncogenesis
Phyllis S Y Chong, Jianbiao Zhou, Jing-Yuan Chooi, Zit-Liang Chan, Sabrina Hui Min Toh, Tuan Zea Tan, Sheena Wee, Jayantha Gunaratne, Qi Zeng, Wee-Joo Chng
Aberrant activation of Wnt/β-catenin signaling pathway is essential for the development of AML; however, the mechanistic basis for this dysregulation is unclear. PRL-3 is an oncogenic phosphatase implicated in the development of LSCs. Here, we identified Leo1 as a direct and specific substrate of PRL-3. Serine-dephosphorylated form of Leo1 binds directly to β-catenin, promoting the nuclear accumulation of β-catenin and transactivation of TCF/LEF downstream target genes such as cyclin D1 and c-myc. Importantly, overexpression of PRL-3 in AML cells displayed enhanced sensitivity towards β-catenin inhibition in vitro and in vivo, suggesting that these cells are addicted to β-catenin signaling...
October 10, 2018: Oncogene
Norio Shiba
The pathogenesis of acute myeloid leukemia (AML) is heterogeneous and caused by various chromosomal aberrations, gene mutations or epigenetic modifications, and deregulated or overregulated gene expression, leading to increased proliferation and decreased hematopoietic progenitor cell differentiation. Although most of these aberrations are correlated with prognosis, accurate risk stratification remains challenging even after incorporating these molecular markers. The development of analytical techniques using microarrays and massive parallel sequencing has identified some gene mutations in adult AML, including DNMT3A and TET2 mutations...
2018: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
Toru Kiguchi
Acute promyelocytic leukemia (APL) with PML-RARA is an acute myeloid leukemia (AML) with a predominance of abnormal promyelocytes. Both hypergranular (typical) and microgranular (hypogranular) types exist. Previously, APL was associated with an extremely high mortality rate due to hemorrhage. However, since the advent of anthracycline, all-trans retinoic acid (ATRA) has been introduced into therapy, resulting in the transformation of APL into AML with a higher probability of cure. Furthermore, for the last 30 years, molecular-targeted drugs, such as arsenic acid (ATO), tamibarotene (Am80), and gemtuzumab ozogamicin (GO), have been developed in succession in addition to ATRA...
2018: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
Yuichi Ishikawa
Core binding factor-acute myeloid leukemia (CBF-AML) comprises AML with t (8;21) (p22;q22) and inv16 (q16q16) /t (16;16) (q16;q16) and accounts for 20% of AML cases. The 2016 WHO classification categorized CBF-AML under AML with recurrent genetic abnormalities and considered it as a favorable risk group with a higher remission rate and better overall survival with high-dose cytarabine post-remission therapy. However, relapse occurs in approximately 40% of patients, thereby necessitating the establishment of risk stratification and risk-adapted therapy in CBF-AML...
2018: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
Takahiro Yamauchi
The mainstay of therapeutic modalities of acute myeloid leukemia (AML) includes intensive chemotherapies and allogeneic hematopoietic cell transplantation. The gold standard of the induction treatment is a regular dose of cytarabine plus anthracycline, and several courses of consolidation therapy are administered. Allogeneic hematopoietic cell transplantation is employed in patients with intermediate-poor risks. No new drugs have been introduced to the treatment of AML for nearly 30 years. However, in 2017, the US Food and Drug Administration approved four novel drugs for treating AML: FLT3 inhibitor midostaurin, IDH2 inhibitor enasidenib, liposomal cytarabine-daunorubicin CPX-351, and revived antibody-drug conjugate gemtuzumab ozogamicin...
2018: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
Michael Dickinson, Honar Cherif, Pierre Fenaux, Moshe Mittelman, Amit Verma, Maria Socorro O Portella, Paul Burgess, Pedro Marques Ramos, Jeea Choi, Uwe Platzbecker
Azacitidine treatment for (MDS) generally exacerbates thrombocytopenia during the first treatment cycles. SUPPORT, a Phase III, randomized, double-blind, placebo-controlled study (NCT02158936), investigated the platelet supportive effects of eltrombopag given concomitantly with azacitidine. IPSS intermediate-1, intermediate-2 or high-risk MDS patients with baseline platelets <75x109 /L were randomized 1:1 to eltrombopag (starting 200 mg/day [East Asians: 100 mg/day], maximum 300 mg/day [East Asians: 150 mg/day]) or placebo, plus azacitidine (75 mg/m2 sc once daily for 7 days, every 28 days)...
October 10, 2018: Blood
Mehmet Canpolat, Hakan Gumus, Sefer Kumandas, Abdulhakim Coskun, Huseyin Per
PURPOSE: The purpose of this study was to evaluate the long-term results of eight cases diagnosed with tuberous sclerosis complex (TSC) and receiving rapamycin therapy because of epileptic seizures and/or accompanying TSC findings. METHOD: Rapamycin therapy was initiated at a dose of 1.5 mg/m2 . Seizure frequency, electroencephalographic (EEG) findings, renal and cranial imaging findings, and cutaneous lesions over 3- to 6-month periods during follow-up and treatment were evaluated...
October 7, 2018: Epilepsy & Behavior: E&B
Johanna S Ungerstedt
Myeloid hematological malignancies are clonal bone marrow neoplasms, comprising of acute myeloid leukemia (AML), the myelodysplastic syndromes (MDS), chronic myelomonocytic leukemia (CMML), the myeloproliferative neoplasms (MPN) and systemic mastocytosis (SM). The field of epigenetic regulation of normal and malignant hematopoiesis is rapidly growing. In recent years, heterozygous somatic mutations in genes encoding epigenetic regulators have been found in all subtypes of myeloid malignancies, supporting the rationale for treatment with epigenetic modifiers...
October 9, 2018: International Journal of Molecular Sciences
Yimamu Maimaitili, Aki Inase, Yoshiharu Miyata, Akihito Kitao, Yu Mizutani, Seiji Kakiuchi, Yohei Shimono, Yasuyuki Saito, Takashi Sonoki, Hironobu Minami, Hiroshi Matsuoka
Gemtuzumab ozogamicin (GO), the first antibody-drug conjugate (ADC), has attracted the interest of hematologists because more than 90% of acute myeloid leukemia (AML) blasts express its target, CD33. Although GO and subsequently developed ADCs depend on lysosomes for activation, lysosome number and activity in tumor cells has not been well elucidated. In this study, we investigated whether an mTORC1/2 kinase inhibitor, PP242, which was reported to activate lysosomal function, potentiates the cytotoxicity of GO in AML cells...
October 2, 2018: Leukemia Research
Omer Jamy, Sejong Bae, Luciano J Costa, Harry P Erba, Nikolaos Papadantonakis
BACKGROUND: Patients with acute myeloid leukemia (AML) treated with intensive chemotherapy may require re-induction based on the evaluation of day 14 bone marrow biopsy. METHODS: A retrospective chart review was performed to evaluate adult patients with AML who received re-induction with fludarabine, high dose cytarabine and granulocyte colony stimulating factor (FLAG) regimen for residual disease (≥ 5% blasts by morphology) on day 14 bone marrow examination between September 2012 and July 2017 at our institution...
September 27, 2018: Leukemia Research
Natalia Martinez-Soria, Lynsey McKenzie, Julia Draper, Anetta Ptasinska, Hasan Issa, Sandeep Potluri, Helen J Blair, Anna Pickin, Asmida Isa, Paulynn Suyin Chin, Ricky Tirtakusuma, Daniel Coleman, Sirintra Nakjang, Salam Assi, Victoria Forster, Mojgan Reza, Ed Law, Philip Berry, Dorothee Mueller, Alex Elder, Simon N Bomken, Deepali Pal, James M Allan, Gareth J Veal, Peter N Cockerill, Christian Wichmann, Josef Vormoor, Georges Lacaud, Constanze Bonifer, Olaf Heidenreich
Oncogenic transcription factors such as the leukemic fusion protein RUNX1/ETO, which drives t(8;21) acute myeloid leukemia (AML), constitute cancer-specific but highly challenging therapeutic targets. We used epigenomic profiling data for an RNAi screen to interrogate the transcriptional network maintaining t(8;21) AML. This strategy identified Cyclin D2 (CCND2) as a crucial transmitter of RUNX1/ETO-driven leukemic propagation. RUNX1/ETO cooperates with AP-1 to drive CCND2 expression. Knockdown or pharmacological inhibition of CCND2 by an approved drug significantly impairs leukemic expansion of patient-derived AML cells and engraftment in immunodeficient murine hosts...
October 8, 2018: Cancer Cell
Xuchun He, Jiadi Chen
OBJECTIVE: To explore the genetic and clinical features of patients with acute myeloid leukemia (AML) and near-tetraploidy/tetraploidy (NT/T) karyotype. METHODS: Cytogenetic findings of 1836 cases of primary AML were retrospectively analyzed. Karyotypes of the identified cases were confirmed by fluorescence in situ hybridization (FISH). Clinical data including gender, age, morphology, immunophenotype, genetics, and prognosis were reviewed. RESULTS: Nine male and two female patients with NT/T were identified with a median age of 63 years...
October 10, 2018: Zhonghua Yi Xue Yi Chuan Xue za Zhi, Zhonghua Yixue Yichuanxue Zazhi, Chinese Journal of Medical Genetics
Rosa Pennisi, Jacopo Albanesi, Paolo Ascenzi, Clara Nervi, Alessandra di Masi
Acute myeloid leukemia (AML) is a genetically heterogeneous malignancy characterized by the expansion of hematopoietic stem/progenitor cells (HPCs) blocked at different stages of maturation/differentiation. The poor outcome of AMLs necessitates therapeutic improvement. In AML, genes encoding for myeloid transcription factors, signaling receptors regulating cell proliferation, and epigenetic modifiers can be mutated by somatically acquired genetic mutations or altered by chromosomal translocations. These mutations modify chromatin organization at genes sites regulating HPCs proliferation, terminal differentiation, and DNA repair, contributing to the development and progression of the disease...
October 8, 2018: IUBMB Life
Peng Hu, Tong-Hua Yang, Ren-Bin Zhao, Ke-Qian Shi, Yan-Mei Yang, Xun Lai
OBJECTIVE: To investigate the efficacy of hematopoietic stem cells cryopreserved by ladder-style freezing from low temperature refrigerator to liquid nitrogen in treatment of hematological malignancies, and to analyze the survival condition of patients after hematopoietic stem cell transplantation. METHODS: The coyoprotectant formed by 3% hydroxyethyl starch, 4% albumin and 5% dimethyl sulfoxide (DMSO) was need for cryopreservation of hematopoietic stem cells,which were first placed in -800 C low temperature refrigerator and then were stored in -1960 C liquid nitrogen tank...
October 2018: Zhongguo Shi Yan Xue Ye Xue za Zhi
Zong Zhang, Wei Gui, Min Bai, Li Ma, Li-Ping Su, Tao Guan
OBJECTIVE: To investigate the diagnosis and treatment of patients with T-lymphoblastic lymphoma(T-LBL)combined with acute myeloid leukemia(AML). METHODS: The clinical features of 4 patients with T-LBL combined with AML were retrospectively analyzed, Among them the case 1 and 2 were synchronous occurrence,and case 3 and 4 were sequentially occurred. Especially for former 2 patients,the dliagnosis differentiated from the involved lymph node of AML is important...
October 2018: Zhongguo Shi Yan Xue Ye Xue za Zhi
Ben-Fa Gong, Dong Lin, Hui Wei, Ying Wang, Bing-Cheng Liu, Chun-Lin Zhou, Kai-Qi Liu, Shu-Ning Wei, Guang-Ji Zhang, Yun-Tao Liu, Xiao-Yuan Gong, Yan Li, Xing-Li Zhao, Shao-Wei Qiu, Run-Xia Gu, Ying-Chang Mi, Jian-Xiang Wang
OBJECTIVE: To evaluate the efficacy of primary prophylaxis of voriconazole against invasive infection of pulmonary aspergillosis (IPA) during remission-induction chemotherapy (RIC) of patients with acute myeloid leukemia (AML). METHODS: Clinical data of 102 de novo AML patients who received primary anti-IPA prophylaxis during the first induction chemotherapy were analyzed retrospectively. All the cases were divided into voriconazole-treated group and posaconazole-treated group according to the prophylactic agent...
October 2018: Zhongguo Shi Yan Xue Ye Xue za Zhi
M Ruan, B Q Qi, F Liu, T F Liu, X M Liu, X J Chen, W Y Yang, Y Guo, L Zhang, Y Zou, Y M Chen, X F Zhu
Objective: To investigate the efficacy and the prognostic factors of Chinese Academy of Medical Sciences 2005 (CAMS-2005) regimen in the treatment of pediatric acute myeloid leukemia (AML). Methods: Eighty-eight cases of newly-diagnosed AML patients, who were treated with the CAMS-2005 regimen from April 2005 to July 2009, were enrolled in this case observational study. Clinical characteristics, long-term prognosis and prognostic factors were analyzed retrospectively. Overall survival (OS) and event free survival (EFS) rates were estimated by the Kaplan-Meier method...
October 2, 2018: Zhonghua Er Ke za Zhi. Chinese Journal of Pediatrics
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