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Relapsed acute myeloid leukemia

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https://www.readbyqxmd.com/read/28225168/correlations-between-epstein-barr-virus-and-acute-leukemia
#1
Hongzai Guan, Hongxia Miao, Na Ma, Wei Lu, Bing Luo
Infection with Epstein-Barr virus (EBV) may be correlated to the onset of acute leukemia (AL). Studies were performed to investigate the relationship between EBV infection and immunophenotyping of acute lymphoblastic leukemia (ALL) and chromosome aberrations. Additionally, the effects of EBV on clinical prognosis were described. Fluorescence quantitative polymerase chain reaction (FQ-PCR) was used to detect EBV-DNA copy numbers from bone marrow in 110 cases of patients with ALL, 75 cases of patients with myeloid leukemia (AML) and 37 cases of hematologically healthy control subjects...
February 22, 2017: Journal of Medical Virology
https://www.readbyqxmd.com/read/28223278/impact-of-genetic-alterations-in-stem-cell-transplantation-for-myelodysplasia-and-secondary-acute-myeloid-leukemia
#2
Tetsuichi Yoshizato, Yasuhito Nannya, Yoshiko Atsuta, Yusuke Shiozawa, Yuka Iijima-Yamashita, Kenichi Yoshida, Yuichi Shiraishi, Hiromichi Suzuki, Yasunobu Nagata, Yusuke Sato, Nobuyuki Kakiuchi, Keitaro Matsuo, Makoto Onizuka, Keisuke Kataoka, Kenichi Chiba, Hiroko Tanaka, Hiroo Ueno, Masahiro M Nakagawa, Bartlomiej Przychodzen, Claudia Haferlach, Wolfgang Kern, Kosuke Aoki, Hidehiro Itonaga, Yoshinobu Kanda, Mikkael A Sekeres, Jaroslaw P Maciejewski, Torsten Haferlach, Yasushi Miyazaki, Keizo Horibe, Masashi Sanada, Satoru Miyano, Hideki Makishima, Seishi Ogawa
Genetic alterations, including mutations and copy number alterations, are central to the pathogenesis of myelodysplastic syndromes and related diseases (myelodysplasia), but their roles in allogeneic stem-cell transplantation have not fully been studied in a large cohort of patients. We enrolled 797 patients who had been diagnosed with myelodysplasia at initial presentation and received transplantation via the Japan Marrow Donor Program. Targeted-capture sequencing was performed to identify mutations in 69 genes, together with copy number alterations, whose effects on transplantation outcomes were investigated...
February 21, 2017: Blood
https://www.readbyqxmd.com/read/28221862/randomized-phase-ii-study-of-clofarabine-based-consolidation-for-younger-adults-with-acute-myeloid-leukemia-in-first-remission
#3
Xavier Thomas, Stéphane de Botton, Sylvie Chevret, Denis Caillot, Emmanuel Raffoux, Emilie Lemasle, Jean-Pierre Marolleau, Céline Berthon, Arnaud Pigneux, Norbert Vey, Oumedaly Reman, Marc Simon, Christian Recher, Jean-Yves Cahn, Olivier Hermine, Sylvie Castaigne, Karine Celli-Lebras, Norbert Ifrah, Claude Preudhomme, Christine Terré, Hervé Dombret
Purpose To evaluate the efficacy and safety of a clofarabine-based combination (CLARA) versus conventional high-dose cytarabine (HDAC) as postremission chemotherapy in younger patients with acute myeloid leukemia (AML). Patients and Methods Patients age 18 to 59 years old with intermediate- or unfavorable-risk AML in first remission and no identified donor for allogeneic stem-cell transplantation (SCT) were eligible. Two hundred twenty-one patients were randomly assigned to receive three CLARA or three HDAC consolidation cycles...
February 21, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28220349/clofarabine-based-chemotherapy-as-a-bridge-to-transplant-in-the-setting-of-refractory-or-relapsed-acute-myeloid-leukemia-after-at-least-one-previous-unsuccessful-salvage-treatment-containing-fludarabine-a-single-institution-experience
#4
Alfredo Molteni, Marta Riva, Emanuele Ravano, Laura Marbello, Valentina Mancini, Giovanni Grillo, Elisa Zucchetti, Rosa Greco, Roberto Cairoli
For refractory or relapsed acute myeloid leukemia patients, allogeneic hematopoietic stem cell transplantation is the only curative treatment option, but the disease must be in remission before this can be attempted. "Salvage" therapy regimens containing high-dose cytarabine plus fludarabine or cladribine with or without anthracyclines or plus mitoxantrone and etoposide fail in 30-50% of cases. We report the outcome of 14 patients treated with a clofarabine-based treatment administered after at least one failed fludarabine-based "salvage" attempt in a "real life" (outside a clinical trial) context...
February 20, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28219393/molecular-and-genetic-alterations-associated-with-therapy-resistance-and-relapse-of-acute-myeloid-leukemia
#5
REVIEW
Hubert Hackl, Ksenia Astanina, Rotraud Wieser
BACKGROUND: The majority of individuals with acute myeloid leukemia (AML) respond to initial chemotherapy and achieve a complete remission, yet only a minority experience long-term survival because a large proportion of patients eventually relapse with therapy-resistant disease. Relapse therefore represents a central problem in the treatment of AML. Despite this, and in contrast to the extensive knowledge about the molecular events underlying the process of leukemogenesis, information about the mechanisms leading to therapy resistance and relapse is still limited...
February 20, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28219225/-effect-of-nccn-2015-risk-stratification-on-prognosis-of-patients-with-acute-myeloid-leukemia-after-allogeneic-hematopoietic-stem-cell-transplantation
#6
Y Lu, T Wu, Y L Zhao, X Y Cao, D Y Liu, J P Zhang, M Xiong, J R Zhou, R J Sun, Z J Wei, H Wang, H X Liu, T Wang, C R Tong, S Q Ji, D P Lu
Objective: To analyze the effect of NCCN (2015) risk stratification on prognosis of patients with acute myeloid leukemia (AML) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) . Methods: Retrospective analysis of 258 patients with AML in CR (186 cases in CR(1), 72 cases in CR(2)) who underwent allogeneic HSCT in our hospital between April 2012 and March 2015 according to NCCN (2015) risk stratification. Of them, 63 cases were classified as low risk, 112 cases intermediate risk and 83 cases high risk...
January 14, 2017: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/28219003/targeting-the-cxcl12-cxcr4-axis-in-acute-myeloid-leukemia-from-bench-to-bedside
#7
Byung-Sik Cho, Hee-Je Kim, Marina Konopleva
The interactions between the cancerous cells of acute myeloid leukemia (AML) and the bone marrow (BM) microenvironment have been postulated to be important for resistance to chemotherapy and disease relapse in AML. The chemokine receptor CXC chemokine receptor 4 (CXCR4) and its ligand, CXC motif ligand 12 (CXCL12), also known as stromal cell-derived factor 1α, are key mediators of this interaction. CXCL12 is produced by the BM microenvironment, binds and activates its cognate receptor CXCR4 on leukemic cells, facilitates leukemia cell trafficking and homing in the BM microenvironment, and keeps leukemic cells in close contact with the stromal cells and extracellular matrix that constitutively generate growth-promoting and anti-apoptotic signals...
February 21, 2017: Korean Journal of Internal Medicine
https://www.readbyqxmd.com/read/28218757/allogeneic-stem-cell-transplantation-for-refractory-acute-myeloid-leukemia-in-pediatric-patients-the-uk-experience
#8
P O'Hare, G Lucchini, M Cummins, P Veys, M Potter, S Lawson, A Vora, R Wynn, A Peniket, K Kirkland, R Pearce, J Perry, P J Amrolia
We report outcomes for 44 children who underwent stem cell transplantation (SCT) for refractory AML in the UK between 2000 and 2012. Median age at SCT was 11.5 years. Twenty-three patients had primary refractory and 21 relapsed refractory AML. Refractory disease was confirmed by cytogenetics/molecular genetics in 24 cases. Median follow-up of the whole cohort is 6.8 years (2.1-14.9 years). Thirty patients (68%) achieved a CR following SCT. Transplant-related mortality at 1 year was 18%. Acute GVHD incidence was 52% (grade ⩾III 19%), chronic 7%...
February 20, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28217708/aberrant-rna-splicing-and-mutations-in-spliceosome-complex-in-acute-myeloid-leukemia
#9
COMMENT
Jianbiao Zhou, Wee-Joo Chng
The spliceosome, the cellular splicing machinery, regulates RNA splicing of messenger RNA precursors (pre-mRNAs) into maturation of protein coding RNAs. Recurrent mutations and copy number changes in genes encoding spliceosomal proteins and splicing regulatory factors have tumor promoting or suppressive functions in hematological malignancies, as well as some other cancers. Leukemia stem cell (LSC) populations, although rare, are essential contributors of treatment failure and relapse. Recent researches have provided the compelling evidence that link the erratic spicing activity to the LSC phenotype in acute myeloid leukemia (AML)...
2017: Stem Cell Investigation
https://www.readbyqxmd.com/read/28215705/kras-allelic-imbalance-enhances-fitness-and-modulates-map-kinase-dependence-in-cancer
#10
Michael R Burgess, Eugene Hwang, Rana Mroue, Craig M Bielski, Anica M Wandler, Benjamin J Huang, Ari J Firestone, Amy Young, Jennifer A Lacap, Lisa Crocker, Saurabh Asthana, Elizabeth M Davis, Jin Xu, Keiko Akagi, Michelle M Le Beau, Qing Li, Benjamin Haley, David Stokoe, Deepak Sampath, Barry S Taylor, Marie Evangelista, Kevin Shannon
Investigating therapeutic "outliers" that show exceptional responses to anti-cancer treatment can uncover biomarkers of drug sensitivity. We performed preclinical trials investigating primary murine acute myeloid leukemias (AMLs) generated by retroviral insertional mutagenesis in Kras(G12D) "knockin" mice with the MEK inhibitor PD0325901 (PD901). One outlier AML responded and exhibited intrinsic drug resistance at relapse. Loss of wild-type (WT) Kras enhanced the fitness of the dominant clone and rendered it sensitive to MEK inhibition...
February 16, 2017: Cell
https://www.readbyqxmd.com/read/28211885/the-novel-bmi-1-inhibitor-ptc596-downregulates-mcl-1-and-induces-p53-independent-mitochondrial-apoptosis-in-acute-myeloid-leukemia-progenitor-cells
#11
Y Nishida, A Maeda, M J Kim, L Cao, Y Kubota, J Ishizawa, A AlRawi, Y Kato, A Iwama, M Fujisawa, K Matsue, M Weetall, M Dumble, M Andreeff, T W Davis, A Branstrom, S Kimura, K Kojima
Disease recurrence is the major problem in the treatment of acute myeloid leukemia (AML). Relapse is driven by leukemia stem cells, a chemoresistant subpopulation capable of re-establishing disease. Patients with p53 mutant AML are at an extremely high risk of relapse. B-cell-specific Moloney murine leukemia virus integration site 1 (BMI-1) is required for the self-renewal and maintenance of AML stem cells. Here we studied the effects of a novel small molecule inhibitor of BMI-1, PTC596, in AML cells. Treatment with PTC596 reduced MCL-1 expression and triggered several molecular events consistent with induction of mitochondrial apoptosis: loss of mitochondrial membrane potential, BAX conformational change, caspase-3 cleavage and phosphatidylserine externalization...
February 17, 2017: Blood Cancer Journal
https://www.readbyqxmd.com/read/28209655/mutational-analysis-in-serial-marrow-samples-during-azacitidine-treatment-in-patients-with-post-transplant-relapse-of-acute-myeloid-leukemia-or-myelodysplastic-syndromes
#12
Janghee Woo, Nicholas P Howard, Barry E Storer, Min Fang, Cecilia C Yeung, Bart L Scott, H Joachim Deeg
No abstract text is available yet for this article.
February 16, 2017: Haematologica
https://www.readbyqxmd.com/read/28207808/autologous-hematopoietic-stem-cell-transplantation-in-lymphoma-patients-is-associated-with-a-decrease-in-the-double-strand-break-repair-capacity-of-peripheral-blood-lymphocytes
#13
Sandrine Lacoste, Smita Bhatia, Yanjun Chen, Ravi Bhatia, Timothy R O'Connor
Patients who undergo autologous hematopoietic stem cell transplantation (aHCT) for treatment of a relapsed or refractory lymphoma are at risk of developing therapy related- myelodysplasia/acute myeloid leukemia (t-MDS/AML). Part of the risk likely resides in inherent interindividual differences in their DNA repair capacity (DRC), which is thought to influence the effect chemotherapeutic treatments have on the patient's stem cells prior to aHCT. Measuring DRC involves identifying small differences in repair proficiency among individuals...
2017: PloS One
https://www.readbyqxmd.com/read/28206975/long-term-clinical-outcomes-of-hematopoietic-cell-transplantation-for-intermediate-to-poor-risk-acute-myeloid-leukemia-during-first-remission-according-to-available-donor-types
#14
Jae-Ho Yoon, Hee-Je Kim, Sung-Soo Park, Young-Woo Jeon, Sung-Eun Lee, Byung-Sik Cho, Ki-Seong Eom, Yoo-Jin Kim, Seok Lee, Chang-Ki Min, Seok-Goo Cho, Dong-Wook Kim, Jong-Wook Lee, Woo-Sung Min
Standard therapy for acute myeloid leukemia (AML) consists of hematopoietic cell transplantation (HCT) including autologous-HCT (AUTO) and allogeneic-HCT from a matched-sibling donor (MSD) or well-matched unrelated donor (WM-URD). When a conventional donor is not available, HCT from a partially-matched (PM)-URD or familial-mismatched donor (FMMD) is typically considered. We analyzed 561 patients with intermediate to poor-risk molecular cytogenetics who underwent transplant from 2002 to 2013 in their first remission...
February 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28203579/rhabdomyolysis-following-initiation-of-posaconazole-use-for-antifungal-prophylaxis-in-a-patient-with-relapsed-acute-myeloid-leukemia-a-case-report
#15
Mayur D Mody, Deepak Ravindranathan, Harpaul S Gill, Vamsi K Kota
Posaconazole is a commonly used medication for antifungal prophylaxis in patients with high-risk acute leukemia, such as acute myeloid leukemia. Despite clinical data that show that posaconazole is superior to other antifungal prophylaxis medications, posaconazole is known to have many side effects and drug-drug interactions. We present a patient who developed rhabdomyolysis after being started on posaconazole for prophylaxis in the setting of relapsed acute myeloid leukemia.
January 2017: Journal of Investigative Medicine High Impact Case Reports
https://www.readbyqxmd.com/read/28197208/molecular-mutations-and-their-cooccurrences-in-cytogenetically-normal-acute-myeloid-leukemia
#16
REVIEW
Mengning Wang, Chuanwei Yang, Le Zhang, Dale G Schaar
Adult acute myeloid leukemia (AML) clinically is a disparate disease that requires intensive treatments ranging from chemotherapy alone to allogeneic hematopoietic cell transplantation (allo-HCT). Historically, cytogenetic analysis has been a useful prognostic tool to classify patients into favorable, intermediate, and unfavorable prognostic risk groups. However, the intermediate-risk group, consisting predominantly of cytogenetically normal AML (CN-AML), itself exhibits diverse clinical outcomes and requires further characterization to allow for more optimal treatment decision-making...
2017: Stem Cells International
https://www.readbyqxmd.com/read/28196625/-did-he-who-made-the-lamb-make-thee-new-developments-in-treating-the-fearful-symmetry-of-acute-myeloid-leukemia
#17
REVIEW
Gabriela Brumatti, Najoua Lalaoui, Andrew H Wei, John Silke
Malignant cells must circumvent endogenous cell death pathways to survive and develop into cancers. Acquired cell death resistance also sets up malignant cells to survive anticancer therapies. Acute Myeloid Leukemia (AML) is an aggressive blood cancer characterized by high relapse rate and resistance to cytotoxic therapies. Recent collaborative profiling projects have led to a greater understanding of the 'fearful symmetry' of the genomic landscape of AML, and point to the development of novel potential therapies that can overcome factors linked to chemoresistance...
February 11, 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28193998/inhibition-of-serotonin-receptor-type-1-in-acute-myeloid-leukemia-impairs-leukemia-stem-cell-functionality-a-promising-novel-therapeutic-target
#18
A Etxabe, M C Lara-Castillo, J M Cornet-Masana, A Banús-Mulet, M Nomdedeu, M A Torrente, M Pratcorona, M Díaz-Beyá, J Esteve, R M Risueño
Acute myeloid leukemia (AML) is a clinically and molecularly heterogeneous neoplasia with poor outcome, organized as a hierarchy initiated and maintained by a subpopulation with differentiation and self-renewal capacities called leukemia stem cells (LSCs). Although currently used chemotherapy is capable of initially reducing the tumor burden producing a complete remission, most patients will ultimately relapse and will succumb to their disease. As such, new therapeutic strategies are needed. AML cells differentially expressed serotonin receptors type 1 (HTR1) compared to healthy blood cells and the most primitive hematopoietic fraction; in fact, HTR1B expression on AML patient samples correlated with clinical outcome...
February 14, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28190862/acute-myeloid-leukemia-with-t-3-21-q13-q22-a-novel-simple-variant-of-the-21q22-runx1-translocation
#19
Yuka Tsuruoka, Hirotaka Sakai, Akiko Uchida, Yu Uemura, Kazuyuki Sato, Satoshi Yokoi, Yuji Nishio, Manabu Matsunawa, Yoshinori Suzuki, Yasushi Isobe, Masayuki Kato, Naoto Tomita, Yasuyuki Inoue, Ikuo Miura
A 69-year-old man diagnosed with leukocytosis was referred to our hospital in July 201X. The patient was diagnosed as having a myelodysplastic/myeloproliferative neoplasm. However, he presented with leukemia 2 months later. Chromosomal analysis of a bone marrow sample documented that this patient had a normal karyotype. The patient was successfully treated with idarubicin and cytarabine, and he underwent three courses of consolidation therapy. However, he suffered a relapse in May of the following year. A cytogenetic analysis revealed the presence of a t (3;21) (q13;q22) translocation, and fluorescence in situ hybridization of metaphase spreads detected three signals corresponding to the runt related transcription factor 1 (RUNX1) on the derivative chromosomes 3 and 21, besides the normal chromosome 21...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/28190619/bone-marrow-evaluation-for-diagnosis-and-monitoring-of-acute-myeloid-leukemia
#20
REVIEW
Mary-Elizabeth Percival, Catherine Lai, Elihu Estey, Christopher S Hourigan
The diagnosis of acute myeloid leukemia (AML) can be made based on peripheral blood or bone marrow blasts. In this review, we will discuss the role of bone marrow evaluation and peripheral blood monitoring in the diagnosis, management, and follow up of AML patients. For patients with circulating blasts, it is reasonable to perform the necessary studies needed for diagnosis and risk stratification, including multiparametric flow cytometry, cytogenetics, and molecular analysis, on a peripheral blood specimen...
February 2, 2017: Blood Reviews
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