Patients with chronic myeloid leukemia in the blast phase pose a significant therapeutic challenge and have poor survival, even in the tyrosine kinase inhibitor era, according to a new study.

Source: CancerNetworkCategory: Cancer & Oncology Authors: Tags: Chronic Myeloid Leukemia Hematologic Malignancies & Lymphoma News Source Type: news

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Publication date: Available online 23 November 2018Source: Clinical Lymphoma Myeloma and LeukemiaAuthor(s): Brianna Smith, Michael Savona, Rami S. KomrokjiAbstractMyelodysplastic/Myeloproliferative neoplasms (MDS/MPN) are hybrid group of chronic myeloid neoplasms combining features of both MDS and MPN. The world health organization (WHO) classification coined this group designation in 2008 to include chronic myelomonocytic leukemia (CMML), atypical chronic myeloid leukemia (aCML), juvenile myelomoncoytic leukemia (JMML), refractory anemia with ring sideroblasts and thrombocytosis (RARS-T) as provisional entity, and MDS/MPN…

BackgroundChronic neutrophilic leukemia (CNL) and atypical chronic myeloid leukemia (aCML) are rare myeloid malignancies with an estimated median survival of 2 years. No effective therapy has been established. The majority of CNL and

Source: BloodCategory: Hematology Authors: Tags: 634. Myeloproliferative Syndromes: Clinical: Addressing Areas of Unmet Need in Prognostic Assessments and Therapy for MPNs Source Type: research

Conclusion: To sum up, we identified potential pan-inhibitors of the Jumonji domain of histone demethylases. Binding in-vivo is followed by selective killing of MLLr AL cells.Disclosures. No relevant conflicts of interest to declare.DisclosuresNo relevant conflicts of interest to declare.

Source: BloodCategory: Hematology Authors: Tags: 604. Molecular Pharmacology and Drug Resistance in Myeloid Diseases: Poster III Source Type: research

Conclusions: our preliminary results suggested that higher Cmax and AUC24h did not correlate neither to efficacy nor to classical toxicities reported with ibrutinib intake. On one hand, we think that dosing intra-cellular concentrations could be more reliable than in plasma. On the other hand, we could consider TDM of ibrutinib in the context of a clinical trial reducing the doses of drug over time, to limit clinical and financial toxicity of this highly efficient drug.DisclosuresNo relevant conflicts of interest to declare.

Source: BloodCategory: Hematology Authors: Tags: 605. Molecular Pharmacology, Drug Resistance-Lymphoid and Other Diseases: Poster III Source Type: research

Chronic myeloid leukemia (CML) is caused by the oncogenic tyrosine kinase BCR-ABL1, which is uniquely present in the leukemic cells and drives progression of the disease. Small-molecule ABL1 tyrosine kinase inhibitors (TKIs) have transformed prognosis for patients as compared to interferon or standard chemotherapy, with the vast majority of patients achieving deep, long-term remission on treatment (Druker et al., Nature Medicine 2009). However, results from multiple TKI discontinuation studies over the past decade suggest approximately 50-60% of patients must remain on therapy indefinitely, highlighting challenges associat…

Source: BloodCategory: Hematology Authors: Tags: 631. Chronic Myeloid Leukemia: Biology and Pathophysiology, excluding Therapy: Poster III Source Type: research

Background: Various pro-inflammatory and stress-related stimuli activate p38 mitogen-activated protein kinase (p38MAPK), triggering cascades of cell proliferation, differentiation, and apoptosis signaling. We have previously found that inflammatory cytokines promote growth and survival in primary cells from acute myeloid leukemia (AML) patients. The downstream mediator of inflammatory pathways is p38MAPK, and blocking this regulator with kinase inhibitors abrogates inflammation signaling in AML cells.Methods: We used a functional ex vivo screening assay to identify small-molecule targeted inhibitors and inhibitor combinati…

Source: BloodCategory: Hematology Authors: Tags: 616. Acute Myeloid Leukemia: Novel Therapy, excluding Transplantation: Poster II Source Type: research

Conclusion: Both myeloid and lymphoid-derived primary leukemia cells show sensitivity to combined inhibition of BCL2 and BTK with the combination of venetoclax and ibrutinib, suggesting this drug pair may have broad therapeutic indications.DisclosuresTyner: Vivid Biosciences: Membership on an entity’s Board of Directors or advisory committees; Takeda: Research Funding; Genentech: Research Funding; Gilead: Research Funding; Constellation: Research Funding; Janssen: Research Funding; AstraZeneca: Research Funding; Incyte: Research Funding; Array: Research Funding; Aptose: Research Funding. Danilov: TG Therapeutics: Consultan…

Source: BloodCategory: Hematology Authors: Tags: 802. Chemical Biology and Experimental Therapeutics: New Targeted Therapies and Drug Development Source Type: research

Immunotherapy is a promising approach to improve treatment responses in hematological malignancies. Accumulating evidence suggests a role for natural killer (NK) cells in controlling hematological malignancies. However, mechanisms regulating sensitivity or resistance of hematologic cancer cells to the effector function of NK cells are incompletely understood. Here, we performed genome-scale CRISPR-Cas9 loss-of-function screens to systematically map genes that regulate sensitivity of hematologic malignancies to NK cells.To screen for genes involved in the interaction between NK and cancer cells, we infected human cancer cel…

Source: BloodCategory: Hematology Authors: Tags: 203. Lymphocytes, Lymphocyte Activation, and Immunodeficiency, including HIV and Other Infections: Pre-clinical T and NK Cell Immunotherapies Source Type: research

Conclusion: This study has established the responsiveness and MCID for both Part A and Part B of HM-PRO. The HM-PRO is capable of detecting small but clinically important changes in patients’ HRQoL over time. The MCID for Part A based on SEM was 6.2 and for PART B 5.9 points. It would therefore be prudent, for practical reasons, to propose a MCID of ‘6’ for the HM-PRO.DisclosuresOliva: Sanofi: Consultancy, Speakers Bureau; La Jolla: Consultancy; Amgen: Consultancy, Speakers Bureau; Celgene: Consultancy, Other: Royalties, Speakers Bureau; Janssen: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau. Ionova:…

Source: BloodCategory: Hematology Authors: Tags: 904. Outcomes Research-Malignant Conditions: Poster I Source Type: research

IntroductionAdvances in clinical practice for allogeneic hematopoietic cell transplantation (HCT), a potentially curative treatment most frequently indicated for hematologic malignancies, have led to substantial improvements in prognosis. HCT survivors are at risk for a number of post-transplant complications, including the development of new malignancies. Although cutaneous melanoma risk is known to be increased after HCT, no previous study has comprehensively investigated risk factors in order to identify patients at highest risk for melanoma development. The purpose of this study was to identify risk factors for develop…

Source: BloodCategory: Hematology Authors: Tags: 723. Clinical Allogeneic and Autologous Transplantation: Late Complications and Approaches to Disease Recurrence: HSCT Late Effects and Disease Monitoring Source Type: research

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