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https://www.readbyqxmd.com/read/27910026/recurrent-cytogenetic-abnormalities-in-myelodysplastic-syndromes
#1
Meaghan Wall
Cytogenetic analysis has an essential role in diagnosis, classification, and prognosis of myelodysplastic syndromes (MDS). Some cytogenetic abnormalities are sufficiently characteristic of MDS to be considered MDS defining in the appropriate clinical context. MDS with isolated del(5q) is the only molecularly defined MDS subtype. The genes responsible for many aspects of 5q- syndrome, the distinct clinical phenotype associated with this condition, have now been identified. Cytogenetics forms the cornerstone of the most widely adopted prognostic scoring systems in MDS, the international prognostic scoring system (IPSS) and the revised international prognostic scoring system (IPPS-R)...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27898660/asthma-and-risk-of-myelodysplastic-syndromes-a-population-based-cohort-study
#2
Henrik Frederiksen, Dóra Körmendiné Farkas, Erzsébet Horváth-Puhó, Jan M Nørgaard, Mette Nørgaard, Henrik T Sørensen
BACKGROUND: Risk factors for the development of myelodysplastic syndromes (MDS) include age, exposure to ionising radiation, and cytotoxic drug treatment. Recently, asthma also has been suggested as a risk factor for MDS. METHODS: We undertook this nationwide population-based cohort study on patients with a first-time hospital-based asthma diagnosis during 2002-2013 and followed them for the development of MDS/chronic myelomonocytic leukaemia (CMML). RESULTS: We identified 75 995 patients with incident asthma and no previous MDS/CMML diagnosis...
November 29, 2016: British Journal of Cancer
https://www.readbyqxmd.com/read/27881041/incidence-and-survival-outcomes-of-chronic-myelomonocytic-leukemia-in-the-united-states
#3
Guru Subramanian Guru Murthy, Ishwori Dhakal, Paulette Mehta
Chronic myelomonocytic leukemia (CMML) is an aggressive neoplasm with sparse data on outcomes at a population level. Using Surveillance Epidemiology and End Results (SEER) database, we identified 2238 patients with CMML diagnosed in the period 2003-2013. We found that the disease incidence was significantly higher with advancing age and lower in females, Blacks, and Asian/pacific islanders. Median OS declined significantly with increasing age (age 20-39 - 25 months, age 40-59 - 20 months, age 60-79 - 18 months, and age ≥80 - 11 months, p < ...
November 23, 2016: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/27849645/current-management-of-patients-with-chronic-myelomonocytic-leukemia
#4
Ana Alfonso, Guillermo Montalban-Bravo, Guillermo Garcia-Manero
PURPOSE OF REVIEW: The present review will focus on the current management of patients with chronic myelomonocytic leukemia (CMML) as well as in future therapeutic perspectives. RECENT FINDINGS: CMML is a clonal hematopoietic stem cell disorder characterized by peripheral blood monocytosis and myelodysplastic and myeloproliferative alterations in the bone marrow. Clinical behavior of the disease can be heterogeneous, with some patients having an indolent form of the disease, whereas others experience an aggressive course with decreased survival and eventual transformation to leukemia...
January 2017: Current Opinion in Oncology
https://www.readbyqxmd.com/read/27807503/clinical-management-of-myelodysplastic-syndrome-myeloproliferative-neoplasm-overlap-syndromes
#5
Joseph A Clara, David A Sallman, Eric Padron
The myelodysplastic/myeloproliferative neoplasms (MDS/MPNs) are a unique group of hematologic malignancies characterized by concomitant myelodysplastic and myeloproliferative features. According to the 2008 WHO classification, the category includes atypical chronic myeloid leukemia (aCML), chronic myelomonocytic leukemia (CMML), juvenile myelomonocytic leukemia (JMML), MDS/MPN-unclassifiable (MDS/MPN-U), and the provisional entity refractory anemia with ring sideroblasts and thrombocytosis (RARS-T). Although diagnosis currently remains based on clinicopathologic features, the incorporation of next-generation platforms has allowed for the recent molecular characterization of these diseases which has revealed unique and complex mutational profiles that support their distinct biology and is anticipated to soon play an integral role in diagnosis, prognostication, and treatment...
September 2016: Cancer Biology & Medicine
https://www.readbyqxmd.com/read/27789175/-juvenile-myelomonocytic-leukemia-a-three-case-series
#6
I Ghariani, N Jmili-Braham, H Regaieg, B Achour, Y Ben Youssef, H Sendi, L Bakir, M Kortas
Juvenile myelomonocytic leukemia (JMML), previously known as juvenile chronic myeloid leukemia (JCML), is a rare, myelodysplastic-myeloproliferative disease typically presenting in early childhood. This disorder is difficult to distinguish from other myeloproliferative syndromes such as chronic myeloid leukemia (CML) because of the similarities in their clinical and bone marrow findings. However, because of its unique biological characteristics such as absolute monocytosis with dysplasia, absence of Philadelphia chromosome or BCR-ABL fusion protein, hypergammaglobulinemia, and raised fetal hemoglobin level, this disorder does not satisfy the criteria for inclusion in the CML or chronic myelomonocytic leukemia (CMML) group, as seen in adult patients...
October 24, 2016: Archives de Pédiatrie: Organe Officiel de la Sociéte Française de Pédiatrie
https://www.readbyqxmd.com/read/27781377/a-variant-c-kit-mutation-d816h-fundamental-to-the-sequential-development-of-an-ovarian-mixed-germ-cell-tumor-and-systemic-mastocytosis-with-cmml
#7
Sarah G Mitchell, Silvia T Bunting, Debra Saxe, Thomas Olson, Frank G Keller
An activating point mutation of the c-KIT tyrosine kinase receptor gene, D816H, has been described in germ cell tumors (GCTs). We report an adolescent diagnosed with an ovarian mixed GCT and systemic mastocytosis with chronic myelomonocytic leukemia (SM-CMML). The teratoma and dysgerminoma differed by copy number aberrations via single nucleotide polymorphism (SNP) microarray, but were inclusive of the same c-KIT D816H point mutation (c.2446G>C) also identified in blood and bone marrow mast cells. These findings indicate not only a clonal origin of the GCT and hematologic malignancy, but also suggest a rare KIT mutation may be playing a fundamental role in malignancy development...
October 26, 2016: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/27777939/tet2-mutations-were-predictive-of-inferior-prognosis-in-the-presence-of-asxl1-mutations-in-patients-with-chronic-myelomonocytic-leukemia
#8
Yajuan Cui, Hongyan Tong, Xin Du, Bing Li, Robert Peter Gale, Tiejun Qin, Jinqin Liu, Zefeng Xu, Yue Zhang, Gang Huang, Jie Jin, Liwei Fang, Hongli Zhang, Lijuan Pan, Naibo Hu, Shiqiang Qu, Zhijian Xiao
BACKGROUND: Somatic mutations involving epigenetic regulators, histone modification and chromatin regulation, splicing components, transcription factors and signaling regulator genes are common in chronic myelomonocytic leukemia (CMML) patients. It has been consensus that ASXL1 mutations have adversely impact on overall survival (OS), while the effect of TET2 mutations remains controversial and undefined. METHODS: ASXL1 and TET2 mutations were analyzed in 141 patients with CMML using Sanger sequencing, with the aim to identify the interplay of ASXL1 and TET2 mutations in the prognosis of CMML...
2016: Stem Cell Investigation
https://www.readbyqxmd.com/read/27760943/-chronic-myelomonocytic-leukemia-with-myelofibrosis-resulting-in-sudden-massive-pleural-effusion-during-cytoreductive-therapy-with-hydroxycarbamide
#9
Yoshitaka Sunami, Akihiko Gotoh, Naoki Watanabe, Yoko Edahiro, Yasuharu Hamano, Hironori Harada, Norio Komatsu
Pleural effusion may occur as a rare complication associated with myeloid hematological malignancies. However, it occasionally occurs in patients with myelodysplastic/myeloproliferative neoplasms(MDS/MPN), especially in chronic myelomonocytic leukemia(CMML)with marked leukocytosis. Pleural effusion can also develop in hematological disorders with bone marrow fibrosis. Here, we report a case of CMML with bone marrow fibrosis, in which massive pleural effusion developed rapidly during cytoreductive therapy with hydroxycarbamide(HU)...
October 2016: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/27733013/dnmt3a-mutations-are-associated-with-inferior-overall-and-leukemia-free-survival-in-chronic-myelomonocytic-leukemia
#10
Mrinal M Patnaik, Daniela Barraco, Terra L Lasho, Christy M Finke, Curtis A Hanson, Rhett P Ketterling, Naseema Gangat, Ayalew Tefferi
DNMT3A mutations are seen in ∼5% of patients with chronic myelomonocytic leukemia (CMML) and thus far, have had an indeterminate prognostic impact on survival. We carried out this study to assess the prognostic impact of DNMT3A mutations on a larger informative cohort of CMML patients (n=261). DNMT3A mutations were seen in 6% (n=16); 56% (n=9) male, with a median age of 64 years. Eighty-one % of DNMT3A mutations were missense, with the Arg882 mutational hot spot accounting for 63% of all changes. Five (31%) patients had an abnormal karyotype whereas concurrent gene mutations (SF3B1/SRSF2/U2AF1-56%, TET2-50%, and ASXL1-25%) were seen in all patients...
October 12, 2016: American Journal of Hematology
https://www.readbyqxmd.com/read/27707735/when-clinical-heterogeneity-exceeds-genetic-heterogeneity-thinking-outside-the-genomic-box-in-chronic-myelomonocytic-leukemia
#11
Markus Ball, Alan F List, Eric Padron
Exome sequencing studies in Chronic Myelomonocytic Leukemia (CMML) illustrate a mutational landscape characterized by few somatic mutations involving a subset of recurrent gene mutations in ASXL1, SRSF2, and TET2, each approaching 40% in incidence. This has led to the clinical implementation of next generation sequencing panels that effectively identify clonal monocytosis and complement clinical prognostic scoring systems in most patients. However, most murine models based on single gene mutations fail to recapitulate the CMML phenotype and many gene mutations are loss-of-function making the identification of traditional therapeutic vulnerabilities challenging...
October 5, 2016: Blood
https://www.readbyqxmd.com/read/27693133/changes-in-the-updated-2016-who-classification-of-the-myelodysplastic-syndromes-and-related-myeloid-neoplasms
#12
John M Bennett
In comparison with the 2008 World Health Organization "Blue Book" on hematopoietic neoplasms, a small number of changes have been made in the classification. In the lower-risk patients, Refractory Cytopenias with Multilineage Dysplasia and Ring Sideroblasts (RCMD-RS) has been separated from RCMD to recognize the importance of the SF3B1 mutation. Often there has been confusion as to the degree of morphologic dysplasia and/or cytopenias to define some of the lower-risk subtypes. In addition, the type of dysplasia or cytopenias is not always concordant...
November 2016: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/27687869/allogeneic-hematopoietic-stem-cell-transplant-in-adult-patients-with-myelodysplastic-syndrome-myeloproliferative-neoplasm-mds-mpn-overlap-syndromes
#13
Prashant Sharma, Shivani S Shinde, Moussab Damlaj, Mehrdad Hefazi Rorghabeh, Shahrukh K Hashmi, Mark R Litzow, William J Hogan, Naseema Gangat, Michelle A Elliott, Aref Al-Kali, Ayalew Tefferi, Mrinal M Patnaik
MDS/MPN (myelodysplastic syndrome/myeloproliferative neoplasm) overlap syndromes are myeloid malignancies for which allogeneic hematopoietic stem cell transplant (allo-HSCT) is potentially curative. We describe transplant outcomes of 43 patients - 35 with chronic myelomonocytic leukemia, CMML (of which 17 had blast transformation, BT) and eight with MDS/MPN-unclassifiable (MDS/MPN,U). At median follow-up of 21 months, overall survival (OS), cumulative incidence of relapse (CIR) and non-relapse mortality (NRM) were 55%, 29%, and 25% respectively in CMML without BT and 47%, 40%, and 34% respectively in CMML with BT...
August 11, 2016: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/27664113/an-exercise-in-extrapolation-clinical-management-of-atypical-cml-mds-mpn-unclassifiable-and-mds-mpn-rs-t
#14
Chetasi Talati, Eric Padron
According to the recently published 2016 World Health Organization (WHO) classification of myeloid malignancies, myelodysplastic/myeloproliferative neoplasms (MDS/MPN) include atypical chronic myeloid leukemia (aCML), MDS/MPN-unclassifiable (MDS/MPN-U), chronic myelomonocytic leukemia (CMML), juvenile myelomonocytic leukemia (JMML), and MDS/MPN ring sideroblasts with thrombocytosis (MDS/MPN-RS-T). MDS/MPN-RS-T was previously a provisional category known as refractory anemia with ring sideroblasts with thrombocytosis (RARS-T) which has now attained a distinct designation in the 2016 WHO classification...
September 24, 2016: Current Hematologic Malignancy Reports
https://www.readbyqxmd.com/read/27659716/disease-modifying-activity-of-ruxolitinib-in-a-patient-with-jak2-negative-cmml-2
#15
Silvan Francke, Anna Mies, Manja Meggendorfer, Uta Oelschlaegel, Ekaterina Balaian, Silke Gloaguen, Torsten Haferlach, Gerhard Ehninger, Martin Bornhäuser, Uwe Platzbecker
No abstract text is available yet for this article.
September 23, 2016: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/27609540/putting-it-all-together-in-cmml-risk-stratification
#16
David P Steensma
No abstract text is available yet for this article.
September 8, 2016: Blood
https://www.readbyqxmd.com/read/27597907/simultaneous-manifestation-of-chronic-myelomonocytic-leukemia-and-multiple-myeloma-during-treatment-by-prednisolone-and-eltrombopag-for-immune-mediated-thrombocytopenic-purpura
#17
Masao Hagihara, Morihiro Inoue, Kenichiro Kodama, Tomoyuki Uchida, Jian Hua
An 80-year-old man was admitted to our hospital because of severe thrombocytopenia. He was diagnosed with idiopathic thrombocytopenia, and prednisolone together with eltrombopag was started, leading to significant improvement of platelet counts. Four years later, there was a prominent increase of peripheral blood monocytes, which was accompanied by recurrence of thrombocytopenia. Bone marrow aspirates and serum electrophoresis revealed coexistence of chronic myelomonocytic leukemia (CMML) and multiple myeloma (MM)...
2016: Case Reports in Hematology
https://www.readbyqxmd.com/read/27551000/a-phase-i-study-of-topotecan-carboplatin-and-the-parp-inhibitor-veliparib-in-acute-leukemias-aggressive-myeloproliferative-neoplasms-and-chronic-myelomonocytic-leukemia
#18
Keith W Pratz, Michelle A Rudek, Ivana Gojo, Mark R Litzow, Michael A McDevitt, Jiuping Jay Ji, Larry Karnitz, James G Herman, Robert Kinders, B Douglas Smith, Steven D Gore, Hetty Carraway, Margaret M Showel, Douglas E Gladstone, Mark J Levis, Hua-Ling Tsai, Gary L Rosner, Alice Chen, Scott H Kaufmann, Judith Karp
PURPOSE: The poly(ADP-ribose) polymerase (PARP) inhibitor veliparib delays DNA repair and potentiates cytotoxicity of multiple classes of chemotherapy drugs, including topoisomerase I inhibitors and platinating agents. This study evaluated veliparib incorporation into leukemia induction therapy using a previously described topotecan/carboplatin backbone. EXPERIMENTAL DESIGN: Employing a 3+3 trial design, we administered escalating doses of veliparib combined with topotecan + carboplatin in relapsed or refractory acute leukemias, aggressive myeloproliferative neoplasms (MPNs) and chronic myelomonocytic leukemia (CMML)...
August 22, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27521328/eltrombopag-use-in-patients-with-chronic-myelomonocytic-leukemia-cmml-a-cautionary-tale
#19
Hanadi Ramadan, Vu H Duong, Najla Al Ali, Eric Padron, Ling Zhang, Jeffrey E Lancet, Alan F List, Rami S Komrokji
INTRODUCTION: Eltrombopag used for thrombocytopenia in myelodysplastic syndrome (MDS) patients is being explored in clinical trials including those with chronic myelomonocytic leukemia (CMML). PATIENTS AND METHODS: We report our experience treating patients with CMML enrolled in a sequential 2-stage dose escalation study with eltrombopag in patients with MDS after hypomethylating agent failure. Patients with CMML were compared with patients with MDS in respect to response and adverse events...
August 2016: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/27496968/acute-leukaemia-and-myelodysplastic-syndromes-with-chromosomal-rearrangement-involving-11q23-locus-but-not-mll-gene
#20
Wenli Zuo, Sa A Wang, Courtney DiNardo, Mariko Yabe, Shaoying Li, L Jeffrey Medeiros, Guilin Tang
AIMS: Chromosome 11q23 translocations, resulting in MLL (KMT2A) rearrangement, have been well characterised in acute myeloid leukaemia (AML) and acute lymphoblastic leukaemia (ALL). However, little is known of haematopoietic neoplasms associated with 11q23 translocation but without MLL rearrangement (11q23+/MLL-). The aim of this study is to characterise such cases with 11q23+/MLL-. METHODS AND RESULTS: We retrospectively searched our database for cases with haematopoietic malignancies with 11q23+/MLL-...
August 5, 2016: Journal of Clinical Pathology
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