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refractory acute leukemia

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https://www.readbyqxmd.com/read/28646908/comparison-of-matched-sibling-donors-versus-unrelated-donors-in-allogeneic-stem-cell-transplantation-for-primary-refractory-acute-myeloid-leukemia-a-study-on-behalf-of-the-acute-leukemia-working-party-of-the-ebmt
#1
Eolia Brissot, Myriam Labopin, Matthias Stelljes, Gerhard Ehninger, Rainer Schwerdtfeger, Jürgen Finke, Hans-Jochem Kolb, Arnold Ganser, Kerstin Schäfer-Eckart, Axel R Zander, Donald Bunjes, Stephan Mielke, Wolfgang A Bethge, Noël Milpied, Peter Kalhs, Igor-Woflgang Blau, Nicolaus Kröger, Antonin Vitek, Martin Gramatzki, Ernst Holler, Christoph Schmid, Jordi Esteve, Mohamad Mohty, Arnon Nagler
BACKGROUND: Primary refractory acute myeloid leukemia (PRF-AML) is associated with a dismal prognosis. Allogeneic stem cell transplantation (HSCT) in active disease is an alternative therapeutic strategy. The increased availability of unrelated donors together with the significant reduction in transplant-related mortality in recent years have opened the possibility for transplantation to a larger number of patients with PRF-AML. Moreover, transplant from unrelated donors may be associated with stronger graft-mediated anti-leukemic effect in comparison to transplantations from HLA-matched sibling donor, which may be of importance in the setting of PRF-AML...
June 24, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28645776/selective-inhibition-of-flt3-by-gilteritinib-in-relapsed-or-refractory-acute-myeloid-leukaemia-a-multicentre-first-in-human-open-label-phase-1-2-study
#2
Alexander E Perl, Jessica K Altman, Jorge Cortes, Catherine Smith, Mark Litzow, Maria R Baer, David Claxton, Harry P Erba, Stan Gill, Stuart Goldberg, Joseph G Jurcic, Richard A Larson, Chaofeng Liu, Ellen Ritchie, Gary Schiller, Alexander I Spira, Stephen A Strickland, Raoul Tibes, Celalettin Ustun, Eunice S Wang, Robert Stuart, Christoph Röllig, Andreas Neubauer, Giovanni Martinelli, Erkut Bahceci, Mark Levis
BACKGROUND: Internal tandem duplication mutations in FLT3 are common in acute myeloid leukaemia and are associated with rapid relapse and short overall survival. The clinical benefit of FLT3 inhibitors in patients with acute myeloid leukaemia has been limited by rapid generation of resistance mutations, particularly in codon Asp835 (D835). We aimed to assess the highly selective oral FLT3 inhibitor gilteritinib in patients with relapsed or refractory acute myeloid leukaemia. METHODS: In this phase 1-2 trial, we enrolled patients aged 18 years or older with acute myeloid leukaemia who either were refractory to induction therapy or had relapsed after achieving remission with previous treatment...
June 20, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28643044/pd-1-signaling-and-inhibition-in-aml-and-mds
#3
REVIEW
Faysal Haroun, Sade A Solola, Samah Nassereddine, Imad Tabbara
Acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) are clinically and molecularly heterogeneous clonal myeloid disorders with a poor prognosis especially in the relapsed refractory setting and in patients above the age of 60. While allogeneic hematopoietic stem cell transplantation (ASCT) is a potentially curative approach, high relapse, morbidity, and mortality rates necessitate the development of alternative therapies. Immune checkpoint inhibitors unmask tumoral immune tolerance and have demonstrated efficacy in the treatment of chemotherapy-resistant hematologic and solid malignancies...
June 22, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28637877/ex-vivoexpanded-adaptive-nk-cells-effectively-kill-primary-acute-lymphoblastic-leukemia-cells
#4
Lisa L Liu, Vivien Beziat, Vincent Oei Yi Sheng, Aline Pfefferle, Marie Schaffer, Soren Lehmann, Eva Hellstrom-Lindberg, Stefan Soderhall, Mats Heyman, Dan Grander, Karl-Johan Malmberg
Manipulation of human NK cell repertoires promises more effective strategies for NK cell-based cancer immunotherapy. A subset of highly differentiated NK cells, termed adaptive NK cells, expands naturally in vivo in response to human cytomegalovirus (HCMV) infection, carries unique repertoires of inhibitory killer cell immunoglobulin-like receptors (KIRs), and displays strong cytotoxicity against tumor cells. Here, we established a robust and scalable protocol for ex vivo generation and expansion of adaptive NK cells for cell therapy against pediatric acute lymphoblastic leukemia (ALL)...
June 21, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28631497/cost-effectiveness-of-blinatumomab-versus-salvage-chemotherapy-in-relapsed-or-refractory-philadelphia-chromosome-negative-b-precursor-acute-lymphoblastic-leukemia-from-a-us-payer-perspective
#5
Thomas E Delea, Jordan Amdahl, Diana Boyko, May Hagiwara, Zachary F Zimmerman, Janet L Franklin, Ze Cong, Guy Hechmati, Anthony Stein
Objective To evaluate the cost-effectiveness of blinatumomab (Blincyto) versus standard of care (SOC) chemotherapy in adults with relapsed or refractory (R/R) Philadelphia-chromosome-negative (Ph-) B-precursor acute lymphoblastic leukemia (ALL) based on the results of the phase 3 TOWER study from a US healthcare payer perspective. Methods The Blincyto Global Economic Model (B-GEM), a partitioned survival model, was used to estimate the incremental cost-effectiveness ratio (ICER) of blinatumomab versus SOC. Response rates, event free survival (EFS), overall survival (OS), numbers of cycles of blinatumomab and SOC, and transplant rates were estimated from TOWER...
June 20, 2017: Journal of Medical Economics
https://www.readbyqxmd.com/read/28625976/a-genome-wide-crispr-screen-identifies-genes-critical-for-resistance-to-flt3-inhibitor-ac220
#6
Panpan Hou, Chao Wu, Yuchen Wang, Rui Qi, Dheeraj Bhavanasi, Zhixiang Zuo, Cedric Dos Santos, Shuliang Chen, Yu Chen, Hong Zheng, Hong Wang, Alexander E Perl, Deyin Guo, Jian Huang
Acute myeloid leukemia (AML) is a malignant hematopoietic disease and the most common type of acute leukemia in adults. The mechanisms underlying drug resistance in AML are poorly understood. Activating mutations in FMS-like tyrosine kinase 3 (FLT3) are the most common molecular abnormality in AML. Quizartinib (AC220) is a potent and selective second-generation inhibitor of FLT3. It is in clinical trials for the treatment of relapsed or refractory FLT3-ITD-positive and -negative AML patients and as maintenance therapy...
June 16, 2017: Cancer Research
https://www.readbyqxmd.com/read/28609177/very-low-dose-methadone-to-treat-refractory-neuropathic-pain-in-children-with-cancer
#7
Kevin Madden, Eduardo Bruera
BACKGROUND: Compared with nociceptive pain, neuropathic pain is a challenging diagnosis to make and successfully treat in children with cancer. OBJECTIVE: The objective of this case report was to see whether very-low-dose methadone (VLDM) (defined as <50% of accepted starting analgesic dose of methadone for children) would be an effective strategy to treat refractory neuropathic pain due to vincristine in two children with acute lymphoblastic leukemia. METHODS: This case report is based on the clinical experience and parent-reported outcomes of two children with refractory neuropathic pain who received VLDM...
June 13, 2017: Journal of Palliative Medicine
https://www.readbyqxmd.com/read/28608730/novel-therapy-for-childhood-acute-lymphoblastic-leukemia
#8
Raoul Santiago, Stéphanie Vairy, Daniel Sinnett, Maja Krajinovic, Henrique Bittencourt
During recent decades, the prognosis of childhood acute lymphoblastic leukemia (ALL) has improved dramatically, nowadays, reaching a cure rate of almost 90%. These results are due to a better management and combination of old therapies, refined risk-group stratification and emergence of minimal residual disease (MRD) combined with treatment's intensification for high-risk subgroups. However, the subgroup of patients with refractory/relapsed ALL still presents a dismal prognosis indicating necessity for innovative therapeutic approaches...
June 13, 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28597329/safety-and-efficacy-of-mogamulizumab-in-patients-with-adult-t-cell-leukemia-lymphoma-in-japan-interim-results-of-postmarketing-all-case-surveillance
#9
Kenji Ishitsuka, Satoshi Yurimoto, Kouichi Kawamura, Yukie Tsuji, Manabu Iwabuchi, Takeshi Takahashi, Kensei Tobinai
We present the interim results of a postmarketing all-case surveillance study in patients with C-C chemokine receptor 4 (CCR4)-positive, relapsed or refractory adult T-cell leukemia-lymphoma (ATL) treated with the anti-CCR4 monoclonal antibody mogamulizumab since its 2012 launch in Japan. The safety and efficacy analysis populations comprised 484 and 442 patients, respectively. The ATL subtype was acute in 58.9% and lymphoma in 34.2% of patients. All patients were scheduled to receive intravenous infusions of mogamulizumab (1...
June 9, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28592975/prognostic-factors-and-treatment-of-pediatric-acute-lymphoblastic-leukemia
#10
REVIEW
Jae Wook Lee, Bin Cho
The event-free survival (EFS) for pediatric acute lymphoblastic leukemia (ALL) has shown remarkable improvement in the past several decades. In Korea also, a recent study showed 10-year EFS of 78.5%. Much of the improved outcome for pediatric ALL stems from the accurate identification of prognostic factors, the designation of risk group based on these factors, and treatment of appropriate duration and intensity according to risk group, done within the setting of cooperative clinical trials. The schema of first-line therapy for ALL remains mostly unchanged, although many groups have now reported on the elimination of cranial irradiation in all patients with low rates of central nervous system relapse...
May 2017: Korean Journal of Pediatrics
https://www.readbyqxmd.com/read/28592755/acute-myeloid-leukemia-developing-secondary-immune-thrombocytopenia-after-umbilical-cord-blood-transplantation
#11
Rena Matsumoto, Kazuhiro Ito, Naoko Hosono, Yasufumi Matsuda, Katsunori Tai, Ippei Sakamaki, Goh Aoki, Hirohito Yamazaki, Shinji Nakao, Takahiro Yamauchi
A 64-year-old man was diagnosed with acute myeloid leukemia M2 (FLT3-ITD-positive). After induction chemotherapy and four courses of consolidation therapy, he underwent umbilical cord blood transplantation (CBT) in his first remission. He developed acute graft-versus-host disease (skin stage 2) after successful engraftment. On post-transplantation day 147, he was admitted to the hospital suffering from pneumonia. During the treatment, drastic thrombocytopenia was observed on day 251. Both platelet-associated immunoglobulin G and platelet antibody producing B cells were detected, and he was diagnosed with immune thrombocytopenia (ITP)...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/28588617/outcomes-of-six-dose-high-dose-cytarabine-as-a-salvage-regimen-for-patients-with-relapsed-refractory-acute-myeloid-leukemia
#12
Brandi Anders, Lauren Veltri, Abraham S Kanate, Alexandra Shillingburg, Nilay Shah, Michael Craig, Aaron Cumpston
Relapsed/refractory acute myeloid leukemia (RR-AML) is associated with poor prognosis and long-term disease-free survival requires allogeneic hematopoietic cell transplantation (allo-HCT). Limited data exists, regarding the optimal regimen to obtain remission prior to allo-HCT. Single agent high-dose cytarabine (10-12 doses administered every 12 hours) has been previously used as induction therapy. Six-dose high-dose cytarabine (HiDAC-6), commonly used as a consolidation regimen, has never been evaluated as induction therapy...
2017: Advances in Hematology
https://www.readbyqxmd.com/read/28588020/enasidenib-in-mutant-idh2-relapsed-or-refractory-acute-myeloid-leukemia
#13
Eytan M Stein, Courtney D DiNardo, Daniel A Pollyea, Amir T Fathi, Gail J Roboz, Jessica K Altman, Richard M Stone, Daniel J DeAngelo, Ross L Levine, Ian W Flinn, Hagop M Kantarjian, Robert Collins, Manish R Patel, Arthur E Frankel, Anthony Stein, Mikkael A Sekeres, Ronan T Swords, Bruno C Medeiros, Christophe Willekens, Paresh Vyas, Alessandra Tosolini, Qiang Xu, Robert D Knight, Katharine E Yen, Sam Agresta, Stéphane de Botton, Martin S Tallman
Recurrent mutations in isocitrate dehydrogenase 2 (IDH2) occur in ~12% of patients with acute myeloid leukemia (AML). Mutated IDH2 proteins neomorphically synthesize 2-hydroxyglutarate resulting in DNA and histone hypermethylation, leading to blocked cellular differentiation. Enasidenib (AG-221/CC-90007) is a first-in-class, oral, selective inhibitor of mutant-IDH2 enzymes. This first-in-human, phase 1/2 study assessed the maximum tolerated dose (MTD), pharmacokinetic and pharmacodynamic profiles, safety, and clinical activity of enasidenib in patients with mutant-IDH2 advanced myeloid malignancies...
June 6, 2017: Blood
https://www.readbyqxmd.com/read/28588019/enasidenib-induces-acute-myeloid-leukemia-cell-differentiation-to-promote-clinical-response
#14
Michael D Amatangelo, Lynn Quek, Alan Shih, Eytan M Stein, Mikhail Roshal, Muriel D David, Benoit Marteyn, Noushin Rahnamay Farnoud, Stephane de Botton, Olivier A Bernard, Bin Wu, Katharine E Yen, Martin S Tallman, Elli Papaemmanuil, Virginie Penard-Lacronique, Anjan Thakurta, Paresh Vyas, Ross L Levine
Recurrent mutations at R140 and R172 in isocitrate dehydrogenase 2 (IDH2) occur in many cancers, including ~12% of acute myeloid leukemia (AML). In preclinical models these mutations cause accumulation of the oncogenic metabolite R-2-hydroxyglutarate (2-HG) and induce hematopoietic differentiation block. Single-agent enasidenib (AG-221/CC-90007), a selective mutant IDH2 (mIDH2) inhibitor, produced an overall response rate of 40.3% in relapsed/refractory AML patients with mIDH2 in a phase 1 trial. However, its mechanism of action and biomarkers associated with response remain unclear...
June 6, 2017: Blood
https://www.readbyqxmd.com/read/28583018/a-review-of-cd19-targeted-immunotherapies-for-relapsed-or-refractory-acute-lymphoblastic-leukemia
#15
Ryan K DasGupta, Bernard L Marini, Joslyn Rudoni, Anthony J Perissinotti
Aim Novel immunotherapies have generated high response rates and unique adverse effects among patients with relapsed or refractory acute lymphoblastic leukemia. Therapies engaging endogenous T-cells against acute lymphoblastic leukemia are emerging for children and adults with various poor prognostic factors, thus accurate knowledge of immunotherapies is necessary for their effective implementation in the future. In this review, we evaluate clinical trial data regarding chimeric antigen receptor T-cells and blinatumomab, for the treatment of relapsed or refractory acute lymphoblastic leukemia...
January 1, 2017: Journal of Oncology Pharmacy Practice
https://www.readbyqxmd.com/read/28582843/acute-lymphoblastic-leukemia-and-genetic-variations-in-bhmt-gene-case-control-study-and-computational-characterization
#16
Ravishankara Bellampalli, Manik Vohra, Kashish Sharma, Nalini Bhaskaranand, Kamalakshi G Bhat, Krishna Prasad, Anu R Sharma, Kapaettu Satyamoorthy, Padmalatha S Rai
BACKGROUND: Remethylation of homocysteine is catalyzed by B12 dependent methionine synthase (MTR) in all types of cells and by B12 non-dependent betaine homocysteine methyltransferase (BHMT) in liver and kidney cells. Of many etiologies of cancer, an unexplored area is the variations of genes implicated in methylation reaction. OBJECTIVE: The study evaluated the association of BHMT (rs3733890) with acute lymphoblastic leukemia (ALL), followed by in-silico characterization of variations in BHMT gene...
May 19, 2017: Cancer Biomarkers: Section A of Disease Markers
https://www.readbyqxmd.com/read/28579617/hdac1-2-inhibition-and-doxorubicin-impair-mre11-dependent-dna-repair-and-disc-to-override-bcr-abl1-driven-dsb-repair-in-philadelphia-chromosome-positive-b-cell-precursor-acute-lymphoblastic-leukemia
#17
S T Promod, D P Johnson, S E Bennett, E M Dennis, B G Banowsky, S S Jones, J R Shearstone, S N Quayle, C Min, M Jarpe, T Mosbruger, A D Pomicter, R R Miles, W Y Chen, K N Bhalla, P A Zweidler-McKay, D C Shrieve, M W Deininger, M B Chandrasekharan, S Bhaskara
Philadelphia chromosome-positive (Ph+) B-cell precursor acute lymphoblastic leukemia expressing BCR-ABL1 oncoprotein is a major subclass of ALL with poor prognosis. BCR-ABL1-expressing leukemic cells are highly dependent on double-strand break (DSB) repair signals for their survival. Here, we report that a first-in-class HDAC1,2 selective inhibitor and doxorubicin (a hyper-CVAD chemotherapy regimen component) impair DSB repair networks in Ph+ B-cell precursor ALL cells using common as well as distinct mechanisms...
June 5, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28569787/inflammatory-mediator-ultra-low-molecular-weight-hyaluronan-triggers-necrosis-of-b-precursor-leukemia-cells-with-high-surface-cd44-expression
#18
Shin Kasai, Yoshiyuki Furuichi, Norie Ando, Keiko Kagami, Masako Abe, Takaya Nakane, Kumiko Goi, Takeshi Inukai, Sei Saitoh, Shinichi Ohno, Shogo Okazaki, Osamu Nagano, Hideyuki Saya, Kanji Sugita
Acute lymphoblastic leukemia (ALL) with mixed lineage leukemia (MLL) gene rearrangements (MLL+ALL) has a dismal prognosis and is characterized by high surface CD44 expression. Known that CD44 has the specific binding sites for a natural ligand hyaluronan (HA), we investigated biological effects of HA with different molecular sizes on MLL+ALL cell lines, and found that the addition of ultra-low-molecular-weight (ULMW)-HA strongly suppressed their thymidine uptakes. The MLL+ALL cell line lacking surface CD44 expression established by genome editing showed no suppression of thymidine uptake...
June 1, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28567238/vosaroxin-in-relapsed-refractory-acute-myeloid-leukemia-efficacy-and-safety-in-the-context-of-the-current-treatment-landscape
#19
REVIEW
Valeriy Sedov, Robert K Stuart
Treatment for acute myeloid leukemia (AML) generally consists of a combination of cytarabine and an anthracycline. Although induction therapy leads to complete remission (CR) for most patients, refractoriness to chemotherapy or relapse after initial response is associated with poor outcomes. The 1-year survival rates after first relapse have been reported at 29%, declining to 11% at 5 years. Prognosis is particularly poor among older patients whose higher prevalence of unfavorable cytogenetics and high frequency of comorbidities diminish their ability to tolerate intensive chemotherapy...
June 2017: Therapeutic Advances in Hematology
https://www.readbyqxmd.com/read/28560733/complete-remission-with-romidepsin-in-a-patient-with-t-cell-acute-lymphoblastic-leukemia-refractory-to-induction-hyper-cvad
#20
Mark W Brunvand, John Carson
T-cell acute lymphoblastic leukemia (T-ALL) and T-cell lymphoblastic lymphoma (T-LBL) are neoplasms that originate from T-cell precursors. Outcomes in adult patients with T-ALL/LBL remain unsatisfactory; early relapse following intensive induction chemotherapy is a concern, and patients with relapsed or refractory disease have a poor prognosis. Romidepsin is a potent, class 1 selective histone deacetylase inhibitor approved for the treatment of patients with peripheral T-cell lymphoma who have had ≥1 prior therapy and patients with cutaneous T-cell lymphoma who have had ≥1 prior systemic therapy...
May 30, 2017: Hematological Oncology
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