Chronic Myeloproliferative Neoplasm Research This is an RSS file. You can use it to subscribe to this data in your favourite RSS reader or to display this data on your own website or blog.

Compassionate Use of Ropeginterferon-Alfa-2b/P1101 for Treatment of High Risk Polycythemia Vera and Essential Thrombocythemia Patients Previously Controlled on Pegylated Interferon-Alfa-2a/Pegasys(R)
Polycythemia vera (PV) and essential thrombocythemia (ET) are chronic myeloproliferative neoplasms (MPN) associated with morbidity and mortality resulting from thrombosis or transformation to myelofibrosis and/or secondary acute leukemia. The acquired somatic mutation JAK2V617Fhas been observed in 98% of PV patients, and around 50% of ET patients. Interferon is known to be an effective treatment for chronic MPNs, but unlike hydroxyurea (HU, Hydrea®), it has been shown to target the malignant clone by decreasing JAK2V617Fallelic burden, and in some patients restoring polyclonal hematopoiesis. (Liu et al, Blood. 2003;101...
Source: Blood - November 21, 2018 Category: Hematology Authors: Gilreath, J. A., Tashi, T., Kim, S. J., Hickman, K., Prchal, J. T. Tags: 634. Myeloproliferative Syndromes: Clinical Source Type: research

High Mobility Group A1 Chromatin Remodeling Proteins Amplify Inflammatory Networks to Drive Leukemic Transformation in Chronic Myeloproliferative Neoplasia in Humans and JAK2 V617F Transgenic Mouse Models
Conclusions: HMGA1/2 genes are overexpressed in MPN with highest levels in more advanced disease (MF, AML) both in primary human tumors and murine models. Strikingly, silencing HMGA1 or HMGA2 halts proliferation and clonogenicity in vitro and prevents leukemic engraftment in vivo. Further, heterozygous Hmga1 deficiency prolongs survival in a murine model of fulminant MPN AML and decreases tumor burdens. Finally, preliminary RNA-Seq analyses suggest that HMGA1 amplifies transcriptional networks involved in immune cell trafficking and inflammation to drive tumor progression. Unexpectedly, HMGA1 also regulates pathways involv...
Source: Blood - November 21, 2018 Category: Hematology Authors: Resar, L., Williams, D. M., Xian, L., Lu, W., Chisholm, B., Luo, L., Zhao, Z. J., Rogers, O., Spivak, J. L., Moliterno, A. R. Tags: 635. Myeloproliferative Syndromes: Basic Science: Mechanisms of Development and Progression Source Type: research

First-in-Human CLL1-CD33 Compound CAR T Cell Therapy Induces Complete Remission in Patients with Refractory Acute Myeloid Leukemia: Update on Phase 1 Clinical Trial
ConclusionOur first-in-human clinical trial demonstrates promising efficacy of cCAR therapy in treating patients with relapsed/ refractory AML. cCAR is able to eradicate leukemia blasts and leukemia stem cells, exerting a profound tumor killing effect that is superior to single target CAR T cell therapies. cCAR is also shown to induce total myeloid ablation in bone marrow, suggesting that it may act as a safer alternative to avoid the severe toxicities caused by standard bone marrow ablation regimens without sacrificing the anti-tumor efficacy. This strategy will likely benefit patients who are unable to tolerate total bod...
Source: Blood - November 21, 2018 Category: Hematology Authors: Liu, F., Cao, Y., Pinz, K., Ma, Y., Wada, M., Chen, K., Ma, G., Shen, J., Tse, C. O., Su, Y., Xiong, Y., He, G., Li, Y., Ma, Y. Tags: 616. Acute Myeloid Leukemia: Novel Therapy, excluding Transplantation: Immunotherapy Source Type: research

Myelofibrosis Is Initiated and Sustained By Rare Multipotent Stem Cells
Conclusions:Our approach combining high-resolution cell sorting and xenograft assays with genomic interrogation demonstrates that MF is initiated and maintained by rare multipotent MF-HSCs. Our study underscores the complex evolutionary events that occur in the stem cell compartment during disease progression and identifies MF-HSCs as the relevant cellular target for future therapeutic intervention.DisclosuresGupta: Novartis: Consultancy, Honoraria, Research Funding; Incyte: Research Funding. (Source: Blood)
Source: Blood - November 21, 2018 Category: Hematology Authors: Medeiros, J. J. F., Mitchell, A., Trotman-Grant, A., Woo, T., Ho, J. M., Arruda, A., Minden, M. D., Dick, J. E., Gupta, V., Shlush, L. I. Tags: 635. Myeloproliferative Syndromes: Basic Science: Poster I Source Type: research

Unexpected Low Expression of Platelet Fibrinogen Receptor in Patients with Chronic Myeloproliferative Neoplasms: How Does It Change with Aspirin?
CONCLUSIONIn untreated MPNs, a large amount of platelets are resting in a conformation that is unable to bind fibrinogen, as demonstrated by the low PAC-1 expression in cytofluorimetry. This lack of activity can be reversed by administering ASA, which is also known for its fibrinolytic and hypoprothrombinemic effects. We hypotesize that the hypercoagulable states observed in these patient could depend on a primarly plasma-driven impairment of fibrin turnover and thrombin generation. Further investigations are going to be promoted by our Group. PAC-1 could be at the same time a good marker of aspirin resistance in patients ...
Source: Blood - November 21, 2018 Category: Hematology Authors: Lucchesi, A., Carloni, S., Ghetti, M., De Matteis, S., Musuraca, G., Augello, A. F., Fattori, P. P., Martinelli, G., Napolitano, R. Tags: 635. Myeloproliferative Syndromes: Basic Science: Poster I Source Type: research

Large Genomic Alterations Occurring in the Transition from Chronic to Blast Phase of Chronic Myeloproliferative Neoplasms
CONCLUSION All together, this data indicate that genomic instability is a hallmark of leukemic transformation of MPN and for the first time identify regions that may be recurrently associated with disease progression from CP to BP, potentially representing novel biomarkers. These finding require confirmation in larger series.DisclosuresNo relevant conflicts of interest to declare. (Source: Blood)
Source: Blood - November 21, 2018 Category: Hematology Authors: Bartalucci, N., Magi, A., Contini, E., Bolognini, D., Romagnoli, S., Guglielmelli, P., Vannucchi, A. M. Tags: 634. Myeloproliferative Syndromes: Clinical: Poster II Source Type: research

Excess Mortality in Polycythemia Vera and Essential Thrombocythemia
Conclusion. From the population viewpoint, ET and PV do not carry an increased excess mortality until late in the second follow-up decade or later. Nevertheless, appearance of a thrombotic event significantly increases the subsequent excess mortality.Figure 1DisclosuresHernandez Boluda: Incyte: Consultancy; Novartis: Consultancy. Ferrer Marin: Novartis: Consultancy, Research Funding; Incyte: Consultancy. Gómez-Casares: Bristol-Myers Squibb: Speakers Bureau; Incyte: Speakers Bureau; Novartis: Speakers Bureau. Cervantes: Celgene: Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria,...
Source: Blood - November 21, 2018 Category: Hematology Authors: Pereira, A., Besses Raebel, C., Hernandez Boluda, J. C., Ferrer Marin, F., Garcia-Hernandez, C., Gomez-Casares, M. T., Perez-Encinas, M., Noya, M.-S., Cuevas, B., Caballero, G., Mata, M., Cervantes, F., Alvarez-Larran, A. Tags: 634. Myeloproliferative Syndromes: Clinical: Poster II Source Type: research

Survey of Integrative Medicine in Myeloproliferative Neoplasms (The SIMM Study-2)
Conclusion:In a geographically diverse MPN patient population, and when adjusting for healthy lifestyle practices overall, patterns of lower symptom burden, fatigue, depression, and higher QoL were revealed with integrative medicine utilization. Although limited by gender discrepancy and patient reported data, this study may offer a foundation to structure future integrative medicine trials to complement standard therapies in MPN patients.DisclosuresGowin: Incyte: Consultancy, Other: Scientific Advisory Board, Speakers Bureau. Mesa: UT Health San Antonio - Mays Cancer Center: Employment; Promedior: Research Funding; NS Pha...
Source: Blood - November 21, 2018 Category: Hematology Authors: Gowin, K. L., Langlais, B. T., Millstine, D., Kosiorek, H. E., Huberty, J., Eckert, R., Mesa, R. A. Tags: 634. Myeloproliferative Syndromes: Clinical: Poster II Source Type: research

Whole Blood Transcriptional Profiling Reveals Highly Deregulated Atherosclerosis Genes in Myeloproliferative Cancer
In conclusion, we have for the first time shown massive deregulation of atherosclerosis genes in MPNs, likely reflecting the inflammatory state in MPNs in association with in vivo activation of the cell types (leukocytes, platelets, endothelial cells) being deeply involved in the atherosclerotic process. The significance of our observations should be further explored and confirmed in other MPN-cohorts and the impact of cytoreductive therapy (e.g interferon-alpha2) and statins upon deregulated genes as well.DisclosuresHasselbalch: Novartis: Research Funding. (Source: Blood)
Source: Blood - November 21, 2018 Category: Hematology Authors: Skov, V., Thomassen, M., Kjaer, L., Riley, C., Larsen, T. S., Bjerrum, O. W., Kruse, T. A., Hasselbalch, H. C. Tags: 635. Myeloproliferative Syndromes: Basic Science: Poster II Source Type: research

Atypical Chronic Myeloid Leukemia
We present one of the rare presentations of aCML in an elderly patient.Case: A 76 year old male presented to the Hematology clinic for consultation after discharge from local hospital for elevated WBC count. Past medical history was significant for COPD, acid reflux, peripheral arterial disease and hypertension. Physical exam was unremarkable. Initial labs were significant for leukocytosis of 30 k/cu mm, anemia with Hb 10 gm/dl, thrombocytosis 695,000 with neutrophilia of ANC 25,200. Peripheral blood was negative for JAK2 V617F and BCR-ABL. Peripheral blood flow cytometry showed granulocytic left shift with 1.5% myeloblast...
Source: Blood - November 21, 2018 Category: Hematology Authors: Ashangari, C., Tumula, P. K. Tags: 632. Chronic Myeloid Leukemia: Therapy Source Type: research

Direct Oral Anticoagulants in Patients with Myeloproliferative Neoplasms: A Single Institution Retrospective Study
Discussion: Our limited data suggests that use of DOACs in patients with MPN is feasible with an acceptable balance between risk of hemorrhage and recurrent thrombosis. Additional data on long term outcomes of DOACs in MPNs are needed.DisclosuresNo relevant conflicts of interest to declare. (Source: Blood)
Source: Blood - November 21, 2018 Category: Hematology Authors: Deloughery, E. P., McBane, R. D., Ashrani, A. A., Tefferi, A., Slusser, J. P., Pruthi, R. K. Tags: 332. Antithrombotic Therapy Source Type: research

A Family with a Novel Mutation and Polycythemia Vera
Discussion.Literature review showed 2 previous reports of c.136G>A mutation in the EPO gene. In 2015, Taylor et al described the mutation in two families with erythrocytosis. Their project was aimed at evaluating whole-genome sequencing for diagnosis of families with high suspicion of a genetic component to their clinical presentation with no previously identified pathogenic variants. They concluded that c.136G>A is of autosomal dominant inheritance. Later described in 2016 by Camps et al., the variant was also found in 4 different non-related patients after whole genome sequencing. None of the previous citations dem...
Source: Blood - November 21, 2018 Category: Hematology Authors: Robinson, M. C., Ghanim, M. T., Bergmann, S. Tags: 101. Red Cells and Erythropoiesis, Structure and Function, Metabolism, and Survival, Excluding Iron Source Type: research

The Impact of the Mutational Landscape upon the Molecular Responses to Interferon-Alfa2 in Calr-Mutated MPN Patients
Conclusions: In the present study, ASXL1, DNMT3A, and TET2 were frequently mutated possibly due to the high number of pts with pre-PMF and PMF. An association between poor response to IFN and ASXL1 mutations was recently reported in PMF. Indeed, we found a possible association between ASXL1 mutations and non-MR with increased or unchanged %ASXL1 during IFN therapy. However, in one MR and one non-MR, we recorded a marked decline in %ASXL1 but a sustained decrease or increase in %CALR, respectively. These results might imply a pt specific clonal heterogeneity. CUX1 is a transcription factor regulating TP53. We show that pts ...
Source: Blood - November 21, 2018 Category: Hematology Authors: Skov, V., Kjaer, L., Thomassen, M., Koschmieder, S., Czech, J., Chatain, N., Pallisgaard, N., Cordua, S., Kruse, T. A., Hasselbalch, H. C. Tags: 635. Myeloproliferative Syndromes: Basic Science: Poster III Source Type: research

Disease and Clinical Characteristics of Patients with Essential Thrombocythemia Enrolled in the MOST Study
Conclusions: Prior real-world data in ET has predominately been generated outside of the United States or has been reported from single institutional experiences. The MOST study will provide a more complete picture of the patient characteristics and outcomes of patients receiving ET-directed therapy in the United States. Ultimately, these data will be important for determining ET treatment gaps and areas of unmet need.DisclosuresYacoub: Cara Therapeutics: Equity Ownership; Inycte: Honoraria, Speakers Bureau; Novartis: Honoraria, Speakers Bureau; Ardelyx, INC.: Equity Ownership; Seattle Genetics: Honoraria, Speakers Bureau;...
Source: Blood - November 21, 2018 Category: Hematology Authors: Yacoub, A., Lyons, R. M., Verstovsek, S., Shao, R., Chu, D. T., Agrawal, A., Sivaraman, S., Colucci, P., Yao, P., Mascarenhas, J. Tags: 634. Myeloproliferative Syndromes: Clinical: Poster III Source Type: research

A Nationwide Analysis of Outcomes of Stroke in Hospitalized Patients with Essential Thrombocythemia: 2006 to 2014
Conclusions:Patients with ET who are hospitalized with stroke have significantly worse outcomes. This study demonstrated that a statistically significant difference exists among different age groups of patients with ET and stoke who died during hospitalization when stratification is made using age groups and Charlson Score. This study may serve as an initial point to include new risk factors for further risk stratification. Early identification of patients at higher risk may reduce the incidence and decrease the morbidity of stroke in patients with ET.DisclosuresKota: BMS: Honoraria; Novartis: Honoraria; Xcenda: Honoraria;...
Source: Blood - November 21, 2018 Category: Hematology Authors: Ajebo, G., Badin, K., Forehand, W., Guddati, A. K., Kota, V. Tags: 634. Myeloproliferative Syndromes: Clinical: Poster III Source Type: research