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acute refractory myeloid leukemia

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https://www.readbyqxmd.com/read/28286924/treatment-of-relapsed-refractory-acute-myeloid-leukemia
#1
REVIEW
Prithviraj Bose, Pankit Vachhani, Jorge E Cortes
Approximately 40-45% of younger and 10-20% of older adults with acute myeloid leukemia (AML) will be cured with current standard chemotherapy. The outlook is particularly gloomy for patients with relapsed and/or refractory disease (cure rates no higher than 10%). Allogeneic hematopoietic stem cell transplantation (HSCT), the only realistic hope of cure for these patients, is an option for only a minority. In recent years, much has been learned about the genomic and epigenomic landscapes of AML, and the clonal architecture of both de novo and secondary AML has begun to be unraveled...
March 2017: Current Treatment Options in Oncology
https://www.readbyqxmd.com/read/28282031/a-phase-1-2-study-of-chemosensitization-with-plerixafor-plus-g-csf-in-relapsed-or-refractory-acute-myeloid-leukemia
#2
G L Uy, M P Rettig, R M Stone, M Y Konopleva, M Andreeff, K McFarland, W Shannon, T R Fletcher, T Reineck, W Eades, K Stockerl-Goldstein, C N Abboud, M A Jacoby, P Westervelt, J F DiPersio
No abstract text is available yet for this article.
March 10, 2017: Blood Cancer Journal
https://www.readbyqxmd.com/read/28278716/efficacy-of-single-agent-decitabine-in-relapsed-and-refractory-acute-myeloid-leukemia
#3
Niloufer Khan, Andrew Hantel, Randall W Knoebel, Andrew Artz, Richard A Larson, Lucy A Godley, Michael J Thirman, Hongtao Liu, Jane E Churpek, Darren King, Olatoyosi Odenike, Wendy Stock
Improving therapy for relapsed/refractory AML remains a challenge. We performed a retrospective analysis of outcomes following decitabine treatment in 34 patients with relapsed/refractory AML (median age, 62; median Charlson comorbidity score, 6). Decitabine, 20 mg/m(2) daily, was given in 5- (25%) or 10-day (75%) cycles. Overall response rate (OR) was 30% with 21% complete remission and 9% partial remission rate. Patients with therapy-related myeloid neoplasm (t-MN) and secondary AML had a significantly higher OR compared to those with de novo AML (70 vs...
February 20, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28275539/a-case-of-acute-myeloid-leukemia-with-e6a2-bcr-abl-fusion-transcript-acquired-after-progressing-from-chronic-myelomonocytic-leukemia
#4
Jinjuan Yao, Dan Douer, Lu Wang, Maria E Arcila, Khedoudja Nafa, April Chiu
Philadelphia (Ph) chromosome is a cytogenetic hallmark of chronic myeloid leukemia (CML). Most patients with CML harbor either the e13a2 or e14a2 BCR-ABL fusion product, while a small subset of the cases expresses e1a2 or e19a2 transcripts. We report a patient with chronic myelomonocytic leukemia (CMML), initially Ph chromosome negative at presentation, with rapid disease progression to acute myeloid leukemia (AML) and appearance of Ph chromosome and BCR-ABL e6a2, a very uncommon fusion transcript. The AML was refractory to treatment with subsequent emergence and dominance of a Ph negative leukemic clone...
2017: Leukemia Research Reports
https://www.readbyqxmd.com/read/28275497/extracorporeal-membrane-oxygenation-as-a-rescue-therapy-for-acute-respiratory-failure-during-chemotherapy-in-a-patient-with-acute-myeloid-leukemia
#5
Sang Won Lee, Youn Seup Kim, Goohyeon Hong
Acute respiratory distress syndrome (ARDS) caused by pneumonia in patients with hematologic malignancies can be life-threatening. Extracorporeal membrane oxygenation (ECMO) is the only temporary treatment for patients with ARDS who are refractory to conventional treatment. However, the immunosuppression and coagulopathies in hematological malignancies such as lymphoma and acute leukemia are relative contraindications for ECMO, due to high risks of infection and bleeding. Here, we report a 22-year-old man with acute myeloid leukemia (AML) who developed pneumonia and ARDS during induction chemotherapy; he was treated with ECMO...
February 2017: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/28271644/a-case-of-disseminated-infection-with-skin-manifestation-due-to-non-neoformans-and-non-gattii-cryptococcus-in-a-patient-with-refractory-acute-myeloid-leukemia
#6
Sun Seob Park, Hyewon Lee, Weon Seo Park, Sang Hyun Hwang, Sang Il Choi, Mi Hong Choi, Si Won Lee, Eun Jung Ko, Young Ju Choi, Hyeon Seok Eom
Cryptococcus spp. other than Cryptococcus neoformans or Cryptococcus gattii were previously considered saprophytes and thought to be non-pathogenic to humans. However, opportunistic infections associated with non-neoformans and non-gattii species, such as Cryptococcus laurentii and Cryptococcus albidus, have increased over the past four decades. We experienced a case of cryptococcosis caused by non-neoformans and non-gattii spp. in a 47-year-old female with refractory acute myeloid leukemia after allogeneic hematopoietic stem cell transplantation...
January 16, 2017: Infection & Chemotherapy
https://www.readbyqxmd.com/read/28261852/acute-leukemia-with-a-pure-erythroid-phenotype-underrecognized-morphologic-and-cytogenetic-signatures-universally-associated-with-primary-refractory-disease-and-a-dismal-clinical-outcome
#7
David C Park, Neval Ozkaya, Scott B Lovitch
AIMS: Pure erythroid leukemia (PEL) is a very rare and aggressive subtype of acute myeloid leukemia defined by the World Health Organization (WHO) as a neoplastic proliferation of immature cells committed exclusively to the erythroid lineage comprising >80% of bone marrow cells and not meeting criteria of other well-defined myeloid neoplasms. The aim of this study was to describe the clinicopathologic features of acute leukemias with a pure erythroid phenotype (ALPEP) irrespective of their WHO classification and determine if ALPEP represents a distinct clinicopathologic entity...
March 6, 2017: Histopathology
https://www.readbyqxmd.com/read/28260960/clinical-hematological-and-cytogenetic-profile-of-adult-myelodysplastic-syndrome-in-a-tertiary-care-center
#8
Santhosh Narayanan
BACKGROUND: Myelodysplastic syndrome (MDS), a disorder of clonal hematopoiesis, is an important clinical entity, but most of the studies available are conducted among the Western population. Its etiological factors and clinicohematological profile in the Indian population are quite diverse. The information regarding its prognostic factors and cytogenetics is very scarce. OBJECTIVES: (1) To assess the clinicohematological profile, cytogenetics, prognostic factors, and outcome of MDS and (2) to study its progression to acute myeloid leukemia (AML) in the selected patients over the study period...
2017: Journal of Blood Medicine
https://www.readbyqxmd.com/read/28260453/first-report-on-stem-cell-transplant-from-iraq
#9
Abdul Majeed A Hammadi, Waleed A Azeez, Firas Hashim Jasim, Nadher Alshammary, Adel D Sewan, Khudhair Alrawaq, Ala Makki, Ahmed Mubarak, Amel Ameen, Andolina Marino, Ahmed Khudhair, Nedhal K Alrahhal
The Iraqi Bone Marrow Transplantation Center is located in the medical city complex of Bab Almuadham in Baghdad, Iraq. It was established on March 11, 2002, and performed its first mini-allotransplant for acute myeloid leukemia on January 24, 2003. Among 16 patients who received hematopoietic stem cell transplant between January 2003 and January 2010, one patient underwent allogeneic bone marrow transplant for acute myeloid leukemia and 15 patients received autologous bone marrow transplant for the following indications: 5 had multiple myeloma, 9 had lymphoma (8 with Hodgkin disease and 1 with non- Hodgkin lymphoma), and 1 had rhabdomyosarcoma...
February 2017: Experimental and Clinical Transplantation
https://www.readbyqxmd.com/read/28244979/allogeneic-hematopoietic-cell-transplantation-in-patients-with-aml-not-achieving-remission-potentially-curative-therapy
#10
REVIEW
B Gyurkocza, H M Lazarus, S Giralt
Patients with acute myeloid leukemia (AML) who fail to achieve complete remission (CR) have a dismal prognosis. Although data suggest that durable remissions can be achieved in approximately 30% of patients with refractory or relapsed AML after allogeneic hematopoietic cell transplantation (HCT), only a small fraction of those patients are offered this therapeutic option. Importantly, patients with primary refractory AML have distinctly better outcomes following allogeneic HCT than those with refractory relapse...
February 27, 2017: Bone Marrow Transplantation
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
#11
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/28218757/allogeneic-stem-cell-transplantation-for-refractory-acute-myeloid-leukemia-in-pediatric-patients-the-uk-experience
#12
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/28211885/the-novel-bmi-1-inhibitor-ptc596-downregulates-mcl-1-and-induces-p53-independent-mitochondrial-apoptosis-in-acute-myeloid-leukemia-progenitor-cells
#13
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/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
#14
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/28187034/detection-of-novel-t-12-17-p12-p13-in-relapsed-refractory-acute-myeloid-leukemia-by-anchored-multiplex-pcr-amp-based-next-generation-sequencing
#15
Talha Badar, Laura Johnson, Katelyn Trifilo, Helen Wang, Brian A Kudlow, Eric Padron, Peter R Pappenhausen, Mohammad O Hussaini
Although several technologies can be used to detect gene fusions, anchored multiplex PCR next-generation sequencing (AMP-NGS) offers the advantage of novel fusion detection and the ability to multiplex multitudinous genes. We applied AMP-NGS technology in the evaluation of a 56-year-old gentleman with myelodysplastic syndrome transformed acute myeloid leukemia (AML). Patient was initially diagnosed with low-risk myelodysplastic syndrome-refractory cytopenias and multilineage dysplasia (MDS-RCMD), progressed to AML after failing hypomethylating agent therapy...
February 9, 2017: Applied Immunohistochemistry & Molecular Morphology: AIMM
https://www.readbyqxmd.com/read/28159598/predictive-value-of-pretransplantation-molecular-minimal-residual-disease-assessment-by-wt1-gene-expression-in-flt3-positive-acute-myeloid-leukemia
#16
Anna Candoni, Federico De Marchi, Francesca Zanini, Maria Elena Zannier, Erica Simeone, Eleonora Toffoletti, Alexsia Chiarvesio, Michela Cerno, Carla Filì, Francesca Patriarca, Renato Fanin
The FMS-like tyrosine kinase 3 (FLT3) mutation in acute myeloid leukemia (AML) is a negative prognostic factor and, in these cases, allogeneic stem cell transplantation (allo-SCT) can represent an important therapeutic option, especially if performed in complete remission (CR). However, it is increasingly clear that not all cytological CRs (cCRs) are the same and that minimal residual disease (MRD) before allo-SCT could have an impact on AML outcome. Unfortunately, FLT3, due its instability of expression, is still not considered a good molecular MRD marker...
February 1, 2017: Experimental Hematology
https://www.readbyqxmd.com/read/28143565/disulfiram-overcomes-bortezomib-and-cytarabine-resistance-in-down-syndrome-associated-acute-myeloid-leukemia-cells
#17
Ranjan Bista, David W Lee, Oliver B Pepper, David O Azorsa, Robert J Arceci, Eiman Aleem
BACKGROUND: Children with Down syndrome (DS) have increased risk for developing AML (DS-AMKL), and they usually experience severe therapy-related toxicities compared to non DS-AMKL. Refractory/relapsed disease has very poor outcome, and patients would benefit from novel, less toxic, therapeutic strategies that overcome resistance. Relapse/resistance are linked to cancer stem cells with high aldehyde dehydrogenase (ALDH) activity. The purpose of the present work was to study less toxic alternative therapeutic agents for relapsed/refractory DS-AMKL...
February 1, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28138829/metabolism-and-disposition-of-the-anticancer-quinolone-derivative-vosaroxin-a-novel-inhibitor-of-topoisomerase-ii
#18
C M Nijenhuis, L Lucas, H Rosing, A D R Huitema, M Mergui-Roelvink, G C Jamieson, J A Fox, D R Mould, J H M Schellens, J H Beijnen
Background Vosaroxin is a first-in-class anticancer quinolone derivative that is being investigated for patients with relapsed or refractory acute myeloid leukemia (AML). The primary objective of this study was to quantitatively determine the pharmacokinetics of vosaroxin and its metabolites in patients with advanced solid tumors. Methods This mass balance study investigated the pharmacokinetics (distribution, metabolism, and excretion) of vosaroxin in cancer patients after a single dose of 60 mg/m(2 14)C-vosaroxin, administered as short intravenous injection...
January 31, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28138160/impact-of-salvage-regimens-on-response-and-overall-survival-in-acute-myeloid-leukemia-with-induction-failure
#19
M Wattad, D Weber, K Döhner, J Krauter, V I Gaidzik, P Paschka, M Heuser, F Thol, T Kindler, M Lübbert, H R Salih, A Kündgen, H-A Horst, P Brossart, K Götze, D Nachbaur, C-H Köhne, M Ringhoffer, G Wulf, G Held, H Salwender, A Benner, A Ganser, H Döhner, R F Schlenk
We evaluated the impact of salvage regimens and allogeneic hematopoietic cell transplantation (allo-HCT) in acute myeloid leukemia (AML) with induction failure. Between 1993 and 2009, 3324 patients with newly diagnosed AML were enrolled in 5 prospective treatment trials of the German-Austrian AML Study Group. After first induction therapy with idarubicin, cytarabine and etoposide (ICE), 845 patients had refractory disease. In addition, 180 patients, although responding to first induction, relapsed after second induction therapy...
February 10, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28137265/targeting-acute-myeloid-leukemia-stem-cell-signaling-by-natural-products
#20
REVIEW
Kodappully Sivaraman Siveen, Shahab Uddin, Ramzi M Mohammad
Acute myeloid leukemia (AML) is the most commonly diagnosed leukemia in adults (25%) and comprises 15-20% in children. It is a genetically heterogeneous aggressive disease characterized by the accumulation of somatically acquired genetic changes, altering self-renewal, proliferation, and differentiation of hematopoietic progenitor cells, resulting in uncontrolled clonal proliferation of malignant progenitor myeloid cells in the bone marrow, peripheral blood, and occasionally in other body tissues. Treatment with modern chemotherapy regimen (cytarabine and daunorubicin) usually achieves high remission rates, still majority of patients are found to relapse, resulting in only 40-45% overall 5 year survival in young patients and less than 10% in the elderly AML patients...
January 30, 2017: Molecular Cancer
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