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Refractory leukemia

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https://www.readbyqxmd.com/read/29773602/clofarabine-high-dose-cytarabine-and-liposomal-daunorubicin-in-pediatric-relapsed-refractory-acute-myeloid-leukemia-a-phase-ib-study
#1
Natasha K A van Eijkelenburg, Mareike Rasche, Essam Ghazaly, Michael N Dworzak, Thomas Klingebiel, Claudia Rossig, Guy Leverger, Jan Stary, Eveline S J M de Bont, Dana A Chitu, Yves Bertrand, Benoit Brethon, Brigitte Strahm, Inge M van der Sluis, Gertjan J L Kaspers, Dirk Reinhardt, C Michel Zwaan
Survival in children with relapsed/refractory acute myeloid leukemia is unsatisfactory. Treatment consists of one course fludarabine, cytarabine and liposomal daunorubicin, followed by fludarabine and cytarabine and stem-cell transplantation. Study ITCC 020/I-BFM 2009-02 aimed to identify the recommended phase 2 dose of clofarabine replacing fludarabine in the abovementioned combination regimen (3+3 design). Escalating dose-levels of clofarabine (20-40mg/m2/day x5days) and liposomal daunorubicin (40-0mg/m2/day) were administered with cytarabine (2g/m2/day x5days)...
May 17, 2018: Haematologica
https://www.readbyqxmd.com/read/29773601/combinatorial-targeting-of-xpo1-and-flt3-exerts-synergistic-anti-leukemia-effects-through-induction-of-differentiation-and-apoptosis-in-flt3-mutated-acute-myeloid-leukemias-from-concept-to-clinical-trial
#2
Weiguo Zhang, Charlie Ly, Jo Ishizawa, Hong Mu, Vivian Ruvolo, Sharon Shacham, Naval Daver, Michael Andreeff
Targeted therapies against FLT3-mutated acute myeloid leukemia have shown limited clinical efficacy primarily because of the acquisition of secondary mutations in FLT3 and persistent activation of downstream pro-survival pathways such as MEK/ERK, PI3K/AKT, and STAT5. Activation of these additional kinases may also result in phosphorylation of tumor suppressor proteins promoting their nuclear export. Thus, co-targeting nuclear export proteins (i.e., XPO1) and FLT3 concomitantly may be therapeutically effective...
May 17, 2018: Haematologica
https://www.readbyqxmd.com/read/29773429/real-life-experience-with-ponatinib-in-chronic-myeloid-leukemia-a-multicenter-observational-study
#3
Adi Shacham-Abulafia, Pia Raanani, David Lavie, Yulia Volchek, Ron Ram, Ilana Helman, Liat Shargian, Anna Gourevitch, Evgeni Chubar, Roy Ratzon, Uri Rozovski
BACKGROUND: The strict recruitment criteria of patients for clinical trials often lead to reduced generalizability of the findings. We studied how ponatinib is used outside clinical trials in patients with chronic myeloid leukemia (CML). PATIENTS AND METHODS: The present retrospective study included all patients with a diagnosis of CML who had received ponatinib in 7 medical centers in Israel. RESULTS: From 2011 to 2016, we identified 37 patients with CML who had received ponatinib, 21 in the chronic phase and 16 in the advanced phase...
May 7, 2018: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/29770715/enasidenib-for-the-treatment-of-acute-myeloid-leukemia
#4
James Dugan, Daniel Pollyea
In August 2017 the United States Federal Drug Administration (FDA) approved enasidenib (Idhifa, Celgene/Agios) for adults with relapsed and refractory acute myelogenous leukemia (AML) with an IDH2 mutation. Enasidenib targets cells with mutant copies of isocitrate dehydrogenase-2 (IDH2), inhibiting the oncometabolite 2-hydroxyglutarte (2-HG) formed by the mutant IDH2. Areas covered: We review the studies leading to enasidenib's approval, as well as common side effects and safety issues experienced during the clinical trials...
May 17, 2018: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/29769206/targeting-the-idh2-pathway-in-acute-myeloid-leukemia
#5
Maria L Amaya, Daniel A Pollyea
Acute myeloid leukemia (AML) is an aggressive disease with a poor prognosis. A large percentage of patients succumb to this disease, in spite of aggressive treatments with chemotherapy. Recent advances with mutational analysis led to the discovery of isocitrate dehydrogenase (IDH) mutations in AML. IDH2 is an enzyme that catalyzes the oxidative decarboxylation of isocitrate to alpha-ketoglutarate; its mutated version leads to the accumulation of the oncometabolite (R)-2 hydroxyglutarate, which disrupts several cell processes and leads to a blockage in differentiation...
May 16, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29760835/cutaneous-mucormycosis-following-a-bullous-pemphigoid-flare-in-a-chronic-lymphocytic-leukemia-patient-on-ibrutinib
#6
Matthew K Stein, Saradasri Karri, Jackson Reynolds, Jeff Owsley, Austin Wise, Mike G Martin, Fereshteh Zare
While the recent development of novel therapeutics in oncology, such as small molecule kinase inhibitors (SMKIs), has enabled our ability to target disease-specific molecular pathways, the prolonged impact of these agents on the immune system and infectious risk remains to be seen. We present a 68-year-old male with refractory chronic lymphocytic leukemia (CLL) on ibrutinib monotherapy for 3 years who developed extensive cutaneous mucormycosis following a severe bullous pemphigoid (BP) flare. He received amphotericin B for 4 weeks and was continued on posaconazole with resolution of his mucormycosis infection...
April 2018: World Journal of Oncology
https://www.readbyqxmd.com/read/29759975/restoring-the-switch-for-cancer-cell-death-targeting-the-apoptosis-signaling-pathway
#7
REVIEW
Clement Chung
PURPOSE: The relevance of apoptosis to cancer development and pharmacologic agents that target this pathway in selected malignancies are described. SUMMARY: Apoptosis is a tightly regulated biological process mediated by both proapoptotic (i.e., prodeath) and antiapoptotic (i.e., prosurvival) proteins. While apoptosis represents a well-established effector mechanism induced by conventional chemotherapy in many malignancies, the development of apoptosis-based targeted therapy is relatively new...
May 14, 2018: American Journal of Health-system Pharmacy: AJHP
https://www.readbyqxmd.com/read/29757455/cells-cytokines-chemokines-and-cancer-stress-a-biobehavioral-study-of-patients-with-chronic-lymphocytic-leukemia
#8
Barbara L Andersen, Neha Godiwala Goyal, David M Weiss, Travis D Westbrook, Kami J Maddocks, John C Byrd, Amy J Johnson
BACKGROUND: Chronic lymphocytic leukemia (CLL) is the most prevalent adult leukemia, with profound disease-related cellular, humoral, and innate immune suppression. The objective of this study was to study the correlations between stress and disease-specific, negative prognostic cellular, cytokine, and chemokine markers in patients with CLL. METHODS: A single-group, observational design was used. Patients with relapsed/refractory CLL (N = 96) who were entering a phase 2 trial of an experimental therapy (ibrutinib) were studied...
May 14, 2018: Cancer
https://www.readbyqxmd.com/read/29755706/infectious-risks-and-complications-in-adult-leukemic-patients-receiving-blinatumomab
#9
Wonhee So, Shuchi Pandya, Rod Quilitz, Bijal Shah, John N Greene
Background: Blinatumomab is an anti-CD19 immunotherapy approved for relapsed/refractory B-cell acute lymphoblastic leukemia (ALL) with significantly increased survival rate. While blinatumomab showed lower rates of infection, neutropenia and mucosal barrier injury versus chemotherapy, its infection risks are not well described. Methods: All patients who received blinatumomab for ≥ seven days at an academic cancer center from May 2015 to April 2017 were included...
2018: Mediterranean Journal of Hematology and Infectious Diseases
https://www.readbyqxmd.com/read/29752743/therapy-related-acute-myeloid-leukemia-and-myelodysplastic-syndrome-among-refractory-germ-cell-tumor-patients
#10
Yuta Inoue, Terukazu Nakamura, Hiroyuki Nakanishi, Masakatsu Oishi, Fumiya Hongo, Koji Okihara, Shinsuke Mizutani, Junya Kuroda, Osamu Ukimura
OBJECTIVES: To analyze cases of therapy-related acute myeloid leukemia and myelodysplastic syndrome diagnosed after chemotherapy for refractory testicular and extragonadal germ cell tumor in our experience. METHODS: A total of 171 consecutive patients who were diagnosed and treated as refractory germ cell tumor and had records of detailed chemotherapy doses between April 1998 and December 2015 were retrospectively reviewed. RESULTS: Four testicular tumor patients (4/171, 2...
May 11, 2018: International Journal of Urology: Official Journal of the Japanese Urological Association
https://www.readbyqxmd.com/read/29750747/haploidentical-donor-transplantation-using-a-novel-clofarabine-containing-conditioning-regimen-for-very-high-risk-hematologic-malignant-neoplasms
#11
Akshay Sharma, Guolian Kang, Anusha Sunkara, Hiroto Inaba, Sima Jeha, Shane J Cross, Terrence Geiger, Brandon Triplett
Recurrent/refractory hematologic malignancies have a poor prognosis, and there is a need for novel treatment regimens that can be tolerated by this heavily pretreated patient group. Clofarabine has antileukemic activity with an acceptable toxicity profile. In a phase I clinical trial (NCT00824135), we substituted clofarabine for fludarabine in a well-established reduced-intensity conditioning regimen for a T cell-depleted, mismatched-related (haploidentical) donor transplant backbone and explored the maximum tolerated dose of clofarabine in this combination in 15 patients undergoing hematopoietic cell transplantation for recurrent/refractory or secondary leukemia...
May 10, 2018: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/29744126/htlv-1-atll-refractory-hypercalcaemia-and-hiv-1-co-infection
#12
Abdullah E Laher, Feroza Motara, Muhammed Moolla, Osman Ebrahim
Adult T-cell lymphoma/leukemia (ATLL) is a rare tumour of T-lymphocytes that is associated with human T-lymphotrophic virus type 1 (HTLV-1) infection as well as severe/refractory hypercalcaemia. Human immunodefficiency virus type 1 (HIV-1) infected individuals are at increased risk of acquiring co-infection with HTLV-1. We present the case of a 37 -year -old HIV-1 positive and antiretroviral therapy naive woman who was admitted to the ICU with delirium, a generalised maculopapular rash, severe hypercalcaemia of 4...
January 2018: Oxford Medical Case Reports
https://www.readbyqxmd.com/read/29743722/management-of-patients-with-acute-promyelocytic-leukemia
#13
REVIEW
Sabine Kayser, Richard F Schlenk, Uwe Platzbecker
With the introduction of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) acute promyelocytic leukemia (APL) has become from a detrimental to one of the most curable malignant diseases in humans. In particular, the chemotherapy-free regimen with ATO/ATRA has been proven to be highly effective in de novo APL and has become standard first-line therapy in younger adult, non-high-risk patients. Nevertheless, early death is still a major issue in APL, particularly in older patients, emphasizing the need of rapid diagnostics and supportive care together with immediate access to ATRA-based therapy...
April 24, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29743405/-recurrent-spi1-fusions-in-pediatric-t-cell-acute-lymphoblastic-leukemia-novel-mutations-with-poor-prognosis
#14
Masafumi Seki, Junko Takita
The outcome of treatment-refractory and/or relapsed pediatric T-cell acute lymphoblastic leukemia (T-ALL) is extremely poor, and the genetic basis of these cases remains poorly understood. Here, we report comprehensive profiling of 121 cases of pediatric T-ALL using RNA sequencing and/or targeted capture sequencing through which we identified new recurrent gene fusions involving SPI1 (STMN1-SPI1 and TCF7-SPI1). Cases positive for fusions involving SPI1 (encoding PU.1), which accounted for 3.9% (7/181) of the total examined pediatric T-ALL cases, had uniformly poor overall survival...
2018: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/29743403/-role-of-anti-ccr4-antibody-in-the-treatment-of-transplant-eligible-patients-with-aggressive-adult-t-cell-leukemia-lymphoma
#15
Shigeo Fuji
Adult T-cell leukemia/lymphoma (ATL) is a peripheral T-cell lymphoma caused by the human T-cell lymphotropic virus type I. Patients with aggressive ATL show dismal prognoses, even with intensive dose-dense chemotherapy. Such patients often show chemo-refractoriness. Mogamulizumab (Moga) is a potent treatment option for patients with relapsed or refractory ATL. However, use of Moga before allo-HSCT could theoretically increase the risk of post-transplant complications like graft-versus-host disease (GVHD) as Moga depletes regulatory T-cells (Tregs)...
2018: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/29743205/preclinical-development-of-a-bispecific-antibody-that-safely-and-effectively-targets-cd19-and-cd47-for-the-treatment-of-b-cell-lymphoma-and-leukemia
#16
Vanessa Buatois, Zoë Johnson, Susana Salgado-Pires, Anne Papaïoannou, Eric Hatterer, Xavier Chauchet, Françoise Richard, Leticia Barba, Bruno Daubeuf, Laura Cons, Lucile Broyer, Matilde D'Asaro, Thomas Matthes, Simon LeGallou, Thierry Fest, Karin Tarte, Robert K Clarke Hinojosa, Eulàlia Genescà Ferrer, José María Ribera, Aditi Dey, Katharine Bailey, Adele K Fielding, Linda Eissenberg, Julie Ritchey, Michael Rettig, John F DiPersio, Marie H Kosco-Vilbois, Krzysztof Masternak, Nicolas Fischer, Limin Shang, Walter G Ferlin
CD47, a ubiquitously expressed innate immune checkpoint receptor that serves as a universal "don't eat me" signal of phagocytosis, is often up-regulated by hematological and solid cancers to evade immune surveillance. Development of CD47-targeted modalities is hindered by the ubiquitous expression of the target, often leading to rapid drug elimination and hemotoxicity including anemia. To overcome such liabilities, we have developed a fully human bispecific antibody, NI-1701, designed to co-engage CD47 and CD19 selectively on B cells...
May 9, 2018: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29743179/a-cd19-cd3-bispecific-antibody-for-effective-immunotherapy-of-chronic-lymphocytic-leukemia-in-the-ibrutinib-era
#17
Hannah R Robinson, Junpeng Qi, Erika M Cook, Cydney Nichols, Eman L Dadashian, Chingiz Underbayev, Sarah E M Herman, Nakhle S Saba, Keyvan Keyvanfar, Clare Sun, Inhye E Ahn, Sivasubramanian Baskar, Christoph Rader, Adrian Wiestner
The Bruton's tyrosine kinase inhibitor ibrutinib induces high rates of clinical response in chronic lymphocytic leukemia (CLL). However, there remains a need for adjunct treatments to deepen response and to overcome drug resistance. Blinatumomab, a CD19/CD3 bispecific antibody (bsAb) designed in the BiTE® format, is FDA approved for the treatment of relapsed or refractory B-cell precursor acute lymphoblastic leukemia. Due to its short half-life of 2.1 hours, blinatumomab requires continuous intravenous dosing for efficacy...
May 9, 2018: Blood
https://www.readbyqxmd.com/read/29741514/management-of-acute-lymphoblastic-leukemia-in-young-adults
#18
Lori S Muffly, Natalie Reizine, Wendy Stock
Substantial interest in acute lymphoblastic leukemia (ALL) in young adults (YAs) and investigations focused on this patient population have resulted in therapeutic advancements that are changing the management paradigm and improving outcomes. The pediatric ALL approach is feasible and effective when administered by medical oncologists. Advanced diagnostics and minimal residual disease measurements aid in prognostication and have resulted in shifting recommendations regarding allogeneic hematopoietic cell transplant in first remission...
February 2018: Clinical Advances in Hematology & Oncology: H&O
https://www.readbyqxmd.com/read/29741506/recent-advances-in-the-cellular-and-molecular-understanding-of-myelodysplastic-syndromes-implications-for-new-therapeutic-approaches
#19
Andrew M Brunner, David P Steensma
It has been more than 10 years since any new disease-modifying therapies have received regulatory approval for indications related to myelodysplastic syndromes (MDS). Advances in our collective biological understanding of MDS in the last decade, however, have made it possible to hope that effective therapeutics can be designed to improve MDS-associated cytopenias and patients' quality of life, and perhaps even delay clonal progression and extend survival. Classes of MDS-associated mutations and disordered biological pathways targeted by developmental therapeutics include the following: aberrant messenger RNA splicing, neomorphic enzymes in the citric acid cycle with oncogenic activity, overactivated tyrosine and serine-threonine kinases, epigenetic and chromatin remodeling alterations, abnormal telomere dynamics, and failed protection of DNA integrity...
January 2018: Clinical Advances in Hematology & Oncology: H&O
https://www.readbyqxmd.com/read/29739753/health-related-quality-of-life-in-adults-with-relapsed-refractory-acute-lymphoblastic-leukemia-treated-with-blinatumomab
#20
Max S Topp, Zachary Zimmerman, Paul Cannell, Hervé Dombret, Johan Maertens, Anthony Stein, Janet Franklin, Qui Tran, Ze Cong, Andre C Schuh
In the phase 3 TOWER study, blinatumomab significantly improved overall survival in adults with relapsed or refractory (R/R) Philadelphia chromosome-negative (Ph-) B-cell precursor acute lymphoblastic leukemia (BCP-ALL) relative to standard-of-care chemotherapy. A secondary objective of this study was to assess the impact of blinatumomab on health-related quality of life (HRQL) as measured by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30). This analysis included the 342 of 405 randomized patients for whom baseline and ≥1 post-baseline result were available in any EORTC multi-item scale or single-item measure...
May 8, 2018: Blood
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