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https://www.readbyqxmd.com/read/29878489/chronic-myelomonocytic-leukemia-2018-update-on-diagnosis-risk-stratification-and-management
#1
Mrinal M Patnaik, Ayalew Tefferi
DISEASE OVERVIEW: Chronic myelomonocytic leukemia (CMML) is a clonal hematopoietic stem cell disorder with overlapping features of myelodysplastic syndromes and myeloproliferative neoplasms, with an inherent risk for leukemic transformation (∼15%-20% over 3-5 years). DIAGNOSIS: Diagnosis is based on the presence of sustained (>3 months) peripheral blood monocytosis (≥1 × 109 /L; monocytes ≥10%), along with bone marrow dysplasia. Clonal cytogenetic abnormalities occur in ∼ 30% of patients, while >90% have gene mutations...
June 2018: American Journal of Hematology
https://www.readbyqxmd.com/read/29866811/how-we-treat-myelofibrosis-after-failure-of-jak-inhibitors
#2
Animesh Pardanani, Ayalew Tefferi
The introduction of JAK inhibitors, leading to regulatory approval of ruxolitinib, represents a major therapeutic advance in myelofibrosis. Most patients experience reduction in splenomegaly and improved quality of life from symptom improvement. It is a paradox however that, despite inhibition of signaling downstream of disease-related driver mutations, JAK inhibitor treatment is not associated with consistent molecular or pathologic responses in myelofibrosis. Furthermore, there are important limitations to JAK inhibitor therapy including development of dose-limiting cytopenias and/or non-hematological toxicities such as neuropathy or opportunistic infections...
June 4, 2018: Blood
https://www.readbyqxmd.com/read/29866419/mayo-alliance-prognostic-model-for-myelodysplastic-syndromes-integration-of-genetic-and-clinical-information
#3
Ayalew Tefferi, Naseema Gangat, Mythri Mudireddy, Terra L Lasho, Christy Finke, Kebede H Begna, Michelle A Elliott, Aref Al-Kali, Mark R Litzow, C Christopher Hook, Alexandra P Wolanskyj, William J Hogan, Mrinal M Patnaik, Animesh Pardanani, Darci L Zblewski, Rong He, David Viswanatha, Curtis A Hanson, Rhett P Ketterling, Jih-Luh Tang, Wen-Chien Chou, Chien-Chin Lin, Cheng-Hong Tsai, Hwei-Fang Tien, Hsin-An Hou
OBJECTIVE: To develop a new risk model for primary myelodysplastic syndromes (MDS) that integrates information on mutations, karyotype, and clinical variables. PATIENTS AND METHODS: Patients with World Health Organization-defined primary MDS seen at Mayo Clinic (MC) from December 28, 1994, through December 19, 2017, constituted the core study group. The National Taiwan University Hospital (NTUH) provided the validation cohort. Model performance, compared with the revised International Prognostic Scoring System, was assessed by Akaike information criterion and area under the curve estimates...
June 1, 2018: Mayo Clinic Proceedings
https://www.readbyqxmd.com/read/29790589/genotype-phenotype-correlation-of-hereditary-erythrocytosis-mutations-a-single-center-experience
#4
Jennifer L Oliveira, Lea M Coon, Lori A Frederick, Molly Hein, Kenneth C Swanson, Michelle E Savedra, Tavanna R Porter, Mrinal M Patnaik, Ayalew Tefferi, Animesh Pardanani, Stefan K Grebe, David S Viswanatha, James D Hoyer
Hereditary erythrocytosis is associated with high oxygen affinity hemoglobin variants (HOAs), 2,3-bisphosphoglycerate deficiency and abnormalities in EPOR and the oxygen-sensing pathway proteins PHD, HIF2α, and VHL. Our laboratory has 40 years of experience with hemoglobin disorder testing and we have characterized HOAs using varied protein and molecular techniques including functional assessment by p50 analysis. In addition, we have more recently commenced adding the assessment of clinically relevant regions of the VHL, BPGM, EPOR, EGLN1 (PHD2), and EPAS1 (HIF2A) genes in a more comprehensive hereditary erythrocytosis panel of tests...
May 23, 2018: American Journal of Hematology
https://www.readbyqxmd.com/read/29749401/blast-phase-chronic-myelomonocytic-leukemia-mayo-mdacc-collaborative-study-of-171-cases
#5
Mrinal M Patnaik, Ana A Pierola, Rangit Vallapureddy, Fevzi F Yalniz, Tapan M Kadia, Elias J Jabbour, Terra Lasho, Curtis A Hanson, Rhett P Ketterling, Hagop M Kantarjian, Ayalew Tefferi, Guillermo Garcia-Manero
No abstract text is available yet for this article.
April 25, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29712989/a-comparison-of-clinical-and-molecular-characteristics-of-patients-with-systemic-mastocytosis-with-chronic-myelomonocytic-leukemia-to-cmml-alone
#6
Mrinal M Patnaik, Rangit Vallapureddy, Terra L Lasho, Katherine P Hoversten, Christy M Finke, Rhett P Ketterling, Curtis A Hanson, Naseema Gangat, Ayalew Tefferi, Animesh Pardanani
No abstract text is available yet for this article.
April 2, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29708808/mipss70-version-2-0-mutation-and-karyotype-enhanced-international-prognostic-scoring-system-for-primary-myelofibrosis
#7
Ayalew Tefferi, Paola Guglielmelli, Terra L Lasho, Naseema Gangat, Rhett P Ketterling, Animesh Pardanani, Alessandro M Vannucchi
No abstract text is available yet for this article.
April 30, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/29582697/nonhepatosplenic-extramedullary-manifestations-of-chronic-myelomonocytic-leukemia-clinical-molecular-and-prognostic-correlates
#8
Katherine Hoversten, Rangit Vallapureddy, Terra Lasho, Christy Finke, Rhett Ketterling, Curtis Hanson, Naseema Gangat, Ayalew Tefferi, Mrinal M Patnaik
No abstract text is available yet for this article.
March 27, 2018: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/29568091/sex-and-degree-of-severity-influence-the-prognostic-impact-of-anemia-in-primary-myelofibrosis-analysis-based-on-1109-consecutive-patients
#9
Maura Nicolosi, Mythri Mudireddy, Terra L Lasho, Curtis A Hanson, Rhett P Ketterling, Naseema Gangat, Animesh Pardanani, Ayalew Tefferi
No abstract text is available yet for this article.
May 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29535431/u2af1-mutation-types-in-primary-myelofibrosis-phenotypic-and-prognostic-distinctions
#10
Ayalew Tefferi, Christy M Finke, Terra L Lasho, Curtis A Hanson, Rhett P Ketterling, Naseema Gangat, Animesh Pardanani
No abstract text is available yet for this article.
February 27, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29515238/philadelphia-chromosome-negative-classical-myeloproliferative-neoplasms-revised-management-recommendations-from-european-leukemianet
#11
REVIEW
Tiziano Barbui, Ayalew Tefferi, Alessandro M Vannucchi, Francesco Passamonti, Richard T Silver, Ronald Hoffman, Srdan Verstovsek, Ruben Mesa, Jean-Jacques Kiladjian, Rȕdiger Hehlmann, Andreas Reiter, Francisco Cervantes, Claire Harrison, Mary Frances Mc Mullin, Hans Carl Hasselbalch, Steffen Koschmieder, Monia Marchetti, Andrea Bacigalupo, Guido Finazzi, Nicolaus Kroeger, Martin Griesshammer, Gunnar Birgegard, Giovanni Barosi
This document updates the recommendations on the management of Philadelphia chromosome-negative myeloproliferative neoplasms (Ph-neg MPNs) published in 2011 by the European LeukemiaNet (ELN) consortium. Recommendations were produced by multiple-step formalized procedures of group discussion. A critical appraisal of evidence by using Grades of Recommendation, Assessment, Development and Evaluation (GRADE) methodology was performed in the areas where at least one randomized clinical trial was published. Seven randomized controlled trials provided the evidence base; earlier phase trials also informed recommendation development...
May 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29515114/momelotinib-therapy-for-myelofibrosis-a-7-year-follow-up
#12
Ayalew Tefferi, Daniela Barraco, Terra L Lasho, Sahrish Shah, Kebede H Begna, Aref Al-Kali, William J Hogan, Mark R Litzow, Curtis A Hanson, Rhett P Ketterling, Naseema Gangat, Animesh Pardanani
One-hundred Mayo Clinic patients with high/intermediate-risk myelofibrosis (MF) received momelotinib (MMB; JAK1/2 inhibitor) between 2009 and 2010, as part of a phase 1/2 trial (NCT00935987); 73% harbored JAK2 mutations, 16% CALR, 7% MPL, 44% ASXL1, and 18% SRSF2. As of July 2017, MMB was discontinued in 91% of the patients, after a median treatment duration of 1.4 years. Grade 3/4 toxicity included thrombocytopenia (34%) and liver/pancreatic test abnormalities (<10%); grade 1/2 peripheral neuropathy occurred in 47%...
March 7, 2018: Blood Cancer Journal
https://www.readbyqxmd.com/read/29512199/chronic-neutrophilic-leukemia-2018-update-on-diagnosis-molecular-genetics-and-management
#13
Michelle A Elliott, Ayalew Tefferi
DISEASE OVERVIEW AND DIAGNOSIS: Chronic neutrophilic leukemia (CNL) is a potentially aggressive myeloproliferative neoplasm, for which current WHO diagnostic criteria include leukocytosis of ≥ 25 x 109 /L of which ≥ 80% are neutrophils, with < 10% circulating neutrophil precursors with blasts rarely observed. In addition, there is no dysplasia, nor clinical or molecular criteria for other myeloproliferative neoplasms. UPDATE ON DIAGNOSIS: Previously the diagnosis of CNL was often as one of exclusion based on no identifiable cause for physiologic neutrophilia in patients fulfilling the aforementioned criteria...
August 2018: American Journal of Hematology
https://www.readbyqxmd.com/read/29486060/prevention-of-liver-cancer-with-new-curative-hepatitis-c-antivirals-real-world-challenges
#14
EDITORIAL
Vicente Soriano, Ayalew Tefferi
No abstract text is available yet for this article.
April 15, 2018: Cancer
https://www.readbyqxmd.com/read/29472717/revised-cytogenetic-risk-stratification-in-primary-myelofibrosis-analysis-based-on-1002-informative-patients
#15
Ayalew Tefferi, Maura Nicolosi, Mythri Mudireddy, Terra L Lasho, Naseema Gangat, Kebede H Begna, Curtis A Hanson, Rhett P Ketterling, Animesh Pardanani
Current cytogenetic risk stratification in primary myelofibrosis (PMF) is two-tiered: 'favorable' and 'unfavorable'. Recent studies have suggested prognostic heterogeneity within the unfavorable risk category. In 1002 consecutive patients, we performed stepwise analysis of impact on survival from individual and prognostically ordered cytogenetic abnormalities, leading to a revised three-tiered risk model: 'very high risk (VHR)'-single/multiple abnormalities of -7, i(17q), inv(3)/3q21, 12p-/12p11.2, 11q-/11q23, or other autosomal trisomies not including + 8/ + 9 (e...
May 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29467191/targeted-next-generation-sequencing-in-blast-phase-myeloproliferative-neoplasms
#16
Terra L Lasho, Mythri Mudireddy, Christy M Finke, Curtis A Hanson, Rhett P Ketterling, Natasha Szuber, Kebede H Begna, Mrinal M Patnaik, Naseema Gangat, Animesh Pardanani, Ayalew Tefferi
Among 248 consecutive patients with blast phase myeloproliferative neoplasm (MPN-BP), DNA collected at the time of blast transformation was available in 75 patients (median age, 66 years; 64% men). MPN-BP followed primary myelofibrosis in 39 patients, essential thrombocythemia in 20 patients, and polycythemia vera in 16 patients. A myeloid neoplasm-relevant 33-gene panel was used for next-generation sequencing. Driver mutation distribution was JAK2 57%, CALR 20%, MPL 9%, and triple-negative 13%. Sixty-four patients (85%) harbored other mutations/variants, including 37% with ≥3 mutations; most frequent were ASXL1 47%, TET2 19%, RUNX1 17%, TP53 16%, EZH2 15%, and SRSF2 13%; relative mutual exclusivity was expressed by TP53 , EZH2 , LNK , RUNX1 , SRSF2 , and NRAS/KRAS mutations...
February 27, 2018: Blood Advances
https://www.readbyqxmd.com/read/29459662/blast-phase-myeloproliferative-neoplasm-mayo-agimm-study-of-410-patients-from-two-separate-cohorts
#17
Ayalew Tefferi, Mythri Mudireddy, Francesco Mannelli, Kebede H Begna, Mrinal M Patnaik, Curtis A Hanson, Rhett P Ketterling, Naseema Gangat, Meera Yogarajah, Valerio De Stefano, Francesco Passamonti, Vittorio Rosti, Maria Chiara Finazzi, Alessandro Rambaldi, Alberto Bosi, Paola Guglielmelli, Animesh Pardanani, Alessandro M Vannucchi
A total of 410 patients with blast phase myeloproliferative neoplasm (MPN-BP) were retrospectively reviewed: 248 from the Mayo Clinic and 162 from Italy. Median survival was 3.6 months, with no improvement over the last 15 years. Multivariable analysis performed on the Mayo cohort identified high risk karyotype, platelet count < 100 × 109 /L, age > 65 years and transfusion need as independent risk factors for survival. Also in the Mayo cohort, intensive chemotherapy resulted in complete remission (CR) or CR with incomplete count recovery (CRi) rates of 35 and 24%, respectively; treatment-specified 3-year/5-year survival rates were 32/10% for patients receiving allogeneic stem cell transplant (AlloSCT) (n = 24), 19/13% for patients achieving CR/CRi but were not transplanted (n = 24), and 1/1% in the absence of both AlloSCT and CR/CRi (n = 200) (p < 0...
May 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29440636/chronic-neutrophilic-leukemia-new-science-and-new-diagnostic-criteria
#18
REVIEW
Natasha Szuber, Ayalew Tefferi
Chronic neutrophilic leukemia (CNL) is a distinct myeloproliferative neoplasm defined by persistent, predominantly mature neutrophil proliferation, marrow granulocyte hyperplasia, and frequent splenomegaly. The seminal discovery of oncogenic driver mutations in CSF3R in the majority of patients with CNL in 2013 generated a new scientific framework for this disease as it deepened our understanding of its molecular pathogenesis, provided a biomarker for diagnosis, and rationalized management using novel targeted therapies...
February 13, 2018: Blood Cancer Journal
https://www.readbyqxmd.com/read/29426921/the-2016-who-classification-and-diagnostic-criteria-for-myeloproliferative-neoplasms-document-summary-and-in-depth-discussion
#19
REVIEW
Tiziano Barbui, Jürgen Thiele, Heinz Gisslinger, Hans Michael Kvasnicka, Alessandro M Vannucchi, Paola Guglielmelli, Attilio Orazi, Ayalew Tefferi
The new edition of the 2016 World Health Organization (WHO) classification system for tumors of the hematopoietic and lymphoid tissues was published in September 2017. Under the category of myeloproliferative neoplasms (MPNs), the revised document includes seven subcategories: chronic myeloid leukemia, chronic neutrophilic leukemia, polycythemia vera (PV), primary myelofibrosis (PMF), essential thrombocythemia (ET), chronic eosinophilic leukemia-not otherwise specified and MPN, unclassifiable (MPN-U); of note, mastocytosis is no longer classified under the MPN category...
February 9, 2018: Blood Cancer Journal
https://www.readbyqxmd.com/read/29417633/mutations-and-prognosis-in-myelodysplastic-syndromes-karyotype-adjusted-analysis-of-targeted-sequencing-in-300-consecutive-cases-and-development-of-a-genetic-risk-model
#20
Naseema Gangat, Mythri Mudireddy, Terra L Lasho, Christy M Finke, Maura Nicolosi, Natasha Szuber, Mrinal M Patnaik, Animesh Pardanani, Curtis A Hanson, Rhett P Ketterling, Ayalew Tefferi
To develop a genetic risk model for primary myelodysplastic syndromes (MDS), we queried the prognostic significance of next-generation sequencing (NGS)-derived mutations, in the context of the Mayo cytogenetic risk stratification, which includes high-risk (monosomal karyotype; MK), intermediate-risk (non-MK, classified as intermediate/poor/very poor, per the revised international prognostic scoring system; IPSS-R), and low-risk (classified as good/very good, per IPSS-R). Univariate analysis in 300 consecutive patients with primary MDS identified TP53, RUNX1, U2AF1, ASXL1, EZH2, and SRSF2 mutations as "unfavorable" and SF3B1 as "favorable" risk factors for survival; for the purposes of the current study, the absence of SF3B1 mutation was accordingly dubbed as an "adverse" mutation...
May 2018: American Journal of Hematology
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