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Relapsed acute myeloid leukemia

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https://www.readbyqxmd.com/read/28340210/clinical-significance-of-isolated-myeloperoxidase-expression-in-pediatric-b-lymphoblastic-leukemia
#1
Matthew J Oberley, Sisi Li, Etan Orgel, Choo Phei Wee, Ashley Hagiya, Maurice R G O'Gorman
Objectives: Diagnosis of B-cell acute lymphoblastic leukemia (B-ALL) requires immunophenotypic evidence of B-lineage and absence of specific myeloid or T-lineage markers. Rare cases of otherwise typical B-ALL express myeloperoxidase (MPO) detectable by flow cytometry with an absence of other myeloid markers, but the clinical significance of this finding is not well studied. Methods: A retrospective cohort analysis of flow cytometry and clinical data was performed to investigate the clinical outcome of this specific group of patients...
March 15, 2017: American Journal of Clinical Pathology
https://www.readbyqxmd.com/read/28333413/extramedullary-leukemia-in-children-with-acute-myeloid-leukemia-a-population-based-cohort-study-from-the-nordic-society-of-pediatric-hematology-and-oncology-nopho
#2
Heidi Kristine Støve, Julie Damgaard Sandahl, Jonas Abrahamsson, Peter H Asdahl, Erik Forestier, Shau-Yin Ha, Kirsi Jahnukainen, Ólafur G Jónsson, Birgitte Lausen, Josefine Palle, Bernward Zeller, Henrik Hasle
BACKGROUND: The prognostic significance of extramedullary leukemia (EML) in childhood acute myeloid leukemia is not clarified. PROCEDURE: This population-based study included 315 children from the NOPHO-AML 2004 trial. RESULTS: At diagnosis, 73 (23%) patients had EML: 39 (12%) had myeloid sarcoma, 22 (7%) had central nervous system disease, and 12 (4%) had both. EML was associated with young age (median age: 2.6 years), a high white blood cell count (median: 40 × 10(9) /l), M5 morphology (40%), and 11q23/MLL (KMT2A) rearrangements (34%)...
March 23, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28329410/long-term-outcome-after-a-treosulfan-based-conditioning-regimen-for-patients-with-acute-myeloid-leukemia-a-report-from-the-acute-leukemia-working-party-of-the-european-society-for-blood-and-marrow-transplantation
#3
Arnon Nagler, Myriam Labopin, Dietrich Beelen, Fabio Ciceri, Liisa Volin, Avichai Shimoni, Roberto Foá, Noel Milpied, Jacopo Peccatori, Emmanuelle Polge, Audrey Mailhol, Mohamad Mohty, Bipin N Savani
BACKGROUND: Allogeneic hematopoietic cell transplantation (HCT) is a curative therapy for patients with acute myeloid leukemia (AML). However, post-HCT relapse and regimen-related toxicity remain significant barriers to long-term survival. In recent years, new conditioning regimens have been explored to improve transplantation outcomes in patients with AML. Treosulfan combines a potent immunosuppressive and antileukemic effect with a low toxicity profile. METHODS: To investigate the role of treosulfan-based conditioning, the European Society for Blood and Marrow Transplantation Acute Leukemia Working Party performed a registry analysis of 520 adult patients with AML who received treosulfan-based conditioning and underwent HCT between 2000 and 2012, including 225 patients in first complete remission, 107 in second or later complete remission, and 188 with active/advanced disease 188 (88 with primary refractory disease)...
March 22, 2017: Cancer
https://www.readbyqxmd.com/read/28322237/characteristics-and-outcome-of-patients-with-therapy-related-acute-promyelocytic-leukemia-front-line-treated-with-or-without-arsenic-trioxide
#4
S Kayser, J Krzykalla, M A Elliott, K Norsworthy, P Gonzales, R K Hills, M R Baer, Z Ráčil, J Mayer, J Novak, P Žák, T Szotkowski, D Grimwade, N H Russell, R B Walter, E H Estey, J Westermann, M Görner, A Benner, A Krämer, B D Smith, A K Burnett, C Thiede, C Röllig, A D Ho, G Ehninger, R F Schlenk, M S Tallman, M J Levis, U Platzbecker
Therapy-related acute promyelocytic leukemia (t-APL) is relatively rare, with limited data on outcome after treatment with arsenic trioxide (ATO) compared to standard intensive chemotherapy (CTX). We evaluated 103 adult t-APL patients undergoing treatment with all-trans retinoic acid (ATRA) alone (n=7) or in combination with ATO (n=24), CTX (n=53), or both (n=19). Complete remissions were achieved after induction therapy in 57% with ATRA, 100% with ATO/ATRA, 78% with CTX/ATRA, and 95% with CTX/ATO/ATRA. Early death rates were 43% for ATRA, 0% for ATO/ATRA, 12% for CTX/ATRA, and 5% for CTX/ATO/ATRA...
March 21, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28321813/harnessing-the-immune-system-against-leukemia-monoclonal-antibodies-and-checkpoint-strategies-for-aml
#5
Lucia Masarova, Hagop Kantarjian, Guillermo Garcia-Mannero, Farhad Ravandi, Padmanee Sharma, Naval Daver
Acute myeloid leukemia (AML) is the most common leukemia among adults and is associated with a poor prognosis, especially in patients with adverse prognostic factors, older age, or relapsed disease. The last decade has seen a surge in successful immune-based therapies in various solid tumors; however, the role of immune therapies in AML remains poorly defined. This chapter describes the rationale, clinical data, and toxicity profiles of immune-based therapeutic modalities in AML including naked and conjugated monoclonal antibodies, bispecific T-cell engager antibodies, chimeric antigen receptor (CAR)-T cells, and checkpoint blockade via blockade of PD1/PDL1 or CTLA4...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28321480/a-new-peptide-vaccine-ocv-501-in-vitro-pharmacology-and-phase-1-study-in-patients-with-acute-myeloid-leukemia
#6
Yukio Kobayashi, Toru Sakura, Shuichi Miyawaki, Kazuyuki Toga, Shinji Sogo, Yuji Heike
Wilms' tumor 1 (WT1) is a promising target of new immunotherapies for acute myeloid leukemia (AML) as well as for other cancers. OCV-501 is a helper peptide derived from the WT1 protein. OCV-501 induced OCV-501-specific Type 1 T-helper (Th1) responses dose-dependently and stimulated helper activity of the specific Th1 cells in peripheral blood mononuclear cells from healthy donors. OCV-501 also enhanced the increase in WT1-killer peptide-specific cytotoxic T lymphocytes. OCV-501 stimulated the OCV-501-specific Th1 clones in an HLA class-II restricted manner and formed a complex with HLA class-II protein...
March 20, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28315400/multicolor-flow-cytometry-and-multi-gene-next-generation-sequencing-are-complementary-and-highly-predictive-for-relapse-in-acute-myeloid-leukemia-following-allogeneic-transplant
#7
Bartlomiej M Getta, Sean M Devlin, Ross L Levine, Maria E Arcila, Abhinita S Mohanty, Ahmet Zehir, Martin S Tallman, Sergio A Giralt, Mikhail Roshal
Minimal Residual disease (MRD) in acute myeloid leukemia (AML) is typically measured using multi-parameter flow cytometry (MFC). Detection of leukemia mutations using multi-gene next generation sequencing (NGS) can potentially be used to measure residual disease. We used a targeted 28-gene NGS panel to detect mutations and different-from-normal 10-colour MFC to measure MRD in AML patients before allogeneic hematopoietic stem cell transplant (HCT). Residual disease was defined when any abnormal blast population was detected using MFC and when any leukemia allele was detected with a variant allele frequency (VAF) ≥5% using NGS...
March 14, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28302711/precision-and-prognostic-value-of-clone-specific-minimal-residual-disease-in-acute-myeloid-leukemia
#8
Pierre Hirsch, Ruoping Tang, Nassera Abermil, Pascale Flandrin, Hannah Moatti, Fabrizia Favale, Ludovic Suner, Florence Lorre, Christophe Marzac, Fanny Fava, Anne-Claire Mamez, Simona Lapusan, Françoise Isnard, Mohamad Mohty, Ollivier Legrand, Luc Douay, Chrystele Bilhou-Nabera, François Delhommeau
The genetic landscape of adult acute myeloid leukemias has been recently unraveled. However, due to their genetic heterogeneity, only a handful of markers are currently used for the evaluation of minimal residual disease. Recent studies using multi-target strategies indicate that detection of residual mutations in less than 5% of cells in complete remission is associated with a better survival. Here, in a series of 69 acute myeloid leukemias with known clonal architecture, we design a clone-specific strategy based on fluorescent in situ hybridization and high-sensitivity next generation sequencing to detect chromosomal aberrations and mutations, respectively, in follow-up samples...
March 16, 2017: Haematologica
https://www.readbyqxmd.com/read/28297624/genomics-of-acute-myeloid-leukemia-diagnosis-and-pathways
#9
Lars Bullinger, Konstanze Döhner, Hartmut Döhner
In recent years, our understanding of the molecular pathogenesis of myeloid neoplasms, including acute myeloid leukemia (AML), has been greatly advanced by genomics discovery studies that use novel high-throughput sequencing techniques. AML, similar to most other cancers, is characterized by multiple somatically acquired mutations that affect genes of different functional categories, a complex clonal architecture, and disease evolution over time. Patterns of mutations seem to follow specific and temporally ordered trajectories...
March 20, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28286924/treatment-of-relapsed-refractory-acute-myeloid-leukemia
#10
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/28283965/treatment-of-acute-myeloid-leukemia-with-the-flt3-gene-mutation
#11
REVIEW
Carlos Best-Aguilera, O Rodrigo Gómez-Vázquez, A Elizabeth Guzmán-Hernández, R Monserrat Rojas-Sotelo
In acute myeloid leukemia (AML), mutations of the Fms-like tyrosine kinase 3 receptor (FLT3) and its overexpression are related with hyperleukocytosis, higher risk of relapse, and decrease of both disease-free survival and overall survival. It has been suggested that this phenomenon confers proliferative and survival advantages to the malignant blast cells. As a consequence, it is an attractive therapeutic target. As the best treatment strategy for mutated FLT3 AML remains to be defined, the addition of FLT3 inhibitor drugs to chemotherapy or to the bone marrow transplant approach has become a growing strategy...
March 2017: Current Oncology Reports
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
#12
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/28279035/-effect-of-minimal-residual-disease-monitoring-by-multiparameter-flow-cytometry-pre-conditioning-on-prognosis-of-acute-myeloid-leukemia-after-allogeneic-hematopoietic-stem-cell-transplantation
#13
Y Lu, T Wu, H Wang, Y L Zhao, X Y Cao, D Y Liu, J P Zhang, M Xiong, J R Zhou, R J Sun, Z J Wei, S Q Ji, D P Lu
Objective: To investigate the effect of minimal residual disease (MRD) monitoring by multiparameter flow cytometry (MFC) pre-conditioning on prognosis of acute myeloid leukemia in first complete remission (CR(1)-AML) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) , and to explore the value of MRD monitoring by MFC in the prognosis evaluation on allo-HSCT in CR(1)-AML. Methods: Between April 2012 and March 2015, consecutive 186 patients with CR(1)-AML who underwent allo-HSCT were analyzed retrospectively...
February 14, 2017: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/28278729/genomic-instability-is-a-principle-pathologic-feature-of-flt3-itd-kinase-activity-in-acute-myeloid-leukemia-leading-to-clonal-evolution-and-disease-progression
#14
Melanie T Rebechi, Keith W Pratz
Acute Myeloid Leukemia with FLT3 ITD mutations are associated with a poor prognosis characterized by a higher relapse rate, shorter relapse free survival, and decreased likelihood of response to therapy at relapse. FLT3 ITD signaling drives cell proliferation and survival. FLT3 ITD AML disease progression is associated with cytogenetic evolution and acquired tyrosine kinase inhibitor (TKI) resistance suggesting a potential role of genomic instability. There is growing evidence demonstrating a relationship between FLT3 signaling and increased DNA damage, specifically through increased reactive oxygen species (ROS) resulting in double-strand breaks (DSB), as well as impaired DNA repair, involving deficiencies in the non-homologous end joining (NHEJ), alternative non-homologous end joining (ALT NHEJ) and homologous recombination (HR) pathways...
February 6, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28278716/efficacy-of-single-agent-decitabine-in-relapsed-and-refractory-acute-myeloid-leukemia
#15
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/28270496/jab1-csn5-thioredoxin-signaling-in-relapsed-acute-monocytic-leukemia-under-oxidative-stress
#16
Fuling Zhou, Yunbao Pan, Yongchang Wei, Ronghua Zhang, Gaigai Bai, Qiuju Shen, Shan Meng, Xiao-Feng Le, Michael Andreeff, Francois X Claret
PURPOSE: High levels of ROS and ineffective antioxidant systems contribute to oxidative stress, which affects the function of hematopoietic cells in acute myeloid leukemia (AML); however, the mechanisms by which ROS lead to malignant transformation in relapsed AML-M5 are not completely understood. We hypothesized that alterations in intracellular ROS would trigger AML-M5 relapse by activating the intrinsic pathway. EXPERIMENTAL DESIGN: We studied ROS levels and conducted JAB1/COPS5 and TRX gene expression analyses with blood samples obtained from 60 matched AML-M5 patients at diagnosis and relapse and conducted mechanism studies of Jab1's regulation of Trx in leukemia cell lines...
March 7, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28270436/focal-adhesion-kinase-as-a-potential-target-in-aml-and-mds
#17
Bing Z Carter, Po Yee Mak, Xiangmeng Wang, Hui Yang, Guillermo Garcia-Manero, Duncan Mak, Hong Mu, Vivian Ruvolo, Yihua Qiu, Kevin Coombes, Nianxiang Zhang, Brittany Ragon, David T Weaver, Jonathan A Pachter, Steven Kornblau, Michael Andreeff
Although overexpression/activation of focal adhesion kinase (FAK) is widely known in solid tumors to control cell growth, survival, invasion, metastasis, gene expression, and stem cell self-renewal, its expression and function in myeloid leukemia are not well investigated. Using reverse-phase protein arrays in large cohorts of newly diagnosed acute myeloid leukemia (AML) and myeloid dysplastic syndrome (MDS) samples, we found that high FAK expression was associated with unfavorable cytogenetics (P = 2 x 10-4) and relapse (P = 0...
March 7, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28266766/early-mixed-t-cell-chimerism-is-predictive-of-pediatric-aml-or-mds-relapse-after-hematopoietic-stem-cell-transplant
#18
Larisa Broglie, Irene Helenowski, Lawrence J Jennings, Kristian Schafernak, Reggie Duerst, Jennifer Schneiderman, William Tse, Morris Kletzel, Sonali Chaudhury
Patients with acute myeloid leukemia (AML) who relapse after hematopoietic stem cell transplantation (HCT) have dismal outcomes. Our ability to predict those at risk for relapse is limited. We examined chimerism trends post-HCT in 63 children who underwent HCT for AML or myelodysplastic syndrome (MDS). Mixed T-cell chimerism at engraftment and absence of chronic graft versus host disease (cGVHD) were associated with relapse (P = 0.04 and P = 0.02, respectively). Mixed T-cell chimerism at engraftment was predictive in patients without cGVHD (P = 0...
March 7, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28261562/inhibition-of-dna-and-histone-methylation-by-5-aza-2-deoxycytidine-decitabine-and-3-deazaneplanocin-a-on-antineoplastic-action-and-gene-expression-in-myeloid-leukemic-cells
#19
Richard L Momparler, Sylvie Côté, Louise F Momparler, Youssef Idaghdour
Epigenetic alterations play an important role in the development of acute myeloid leukemia (AML) by silencing of genes that suppress leukemogenesis and differentiation. One of the key epigenetic changes in AML is gene silencing by DNA methylation. The importance of this alteration is illustrated by the induction of remissions in AML by 5-aza-2'-deoxycytidine (5-AZA-CdR, decitabine), a potent inhibitor of DNA methylation. However, most patients induced into remission by 5-AZA-CdR will relapse, suggesting that a second agent should be sought to increase the efficacy of this epigenetic therapy...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28260453/first-report-on-stem-cell-transplant-from-iraq
#20
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
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