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2019年中国中西医结合学会血液病专业委员会学术年会暨浙江省中西医结合学会血液病专业委员会学术年会

作者：孙洁洪明华芦婷黄燕黄维加刘丽珍韩晓雁吴文俊郑伟燕魏国庆罗依施继敏何静松蔡真黄河浙江大学医学院附属第一医院血液科骨髓移植中心

Purpose To compare the clinical characteristics, treatment response, leukemia transformation risks and prognosis between de novo myelodysplastic syndrome with bone marrow(BM) fibrosis(MDS-MF group) and de novo myelodysplastic syndrome without BM fibrosis(MDS group).Patients and Methods 84 consecutive patients were rolled retrospectively from 2010 to 2018 in our institution. All patients were diagnosed as de novo MDS according to WHO 2016 criteria. They were also evaluated BM pathology. Among them 53 Patients were found with marrow fibrosis at different levels(MDS-MF group, MF=1-3) according to the European consensus for bone marrow fibrosis(BMF) grading,while other 31 patients were not(MDS group, MF=0). Two groups were compared on clinical characteristics, cytogenetics, therapeutic effects and clinical outcomes. All the data were statistical analyzed by SPSS 24.0. Results Among 84 de novo MDS patients, most of them were classified as MDS-EB-2(46.4%), followed by MDS-EB-1(31.0%), MDS-SLD(10.7%), MDS-MLD(9.5%) and MDS-RS(2.4%). There were 31 MDS patients with MF=0(MDS group) and 53 cases with MF>0(MDS-MF group). There was no significant difference between MDS and MDS-MF on the clinical characteristics including age, gender, peripheral blood cell counts, MDS sub-classifications, IPSS risk levels and treatment strategies before leukemia transformation. MDS-MF had a lower overall reaction rate(ORR) under all-types therapies, but there was no significant correlation between BM fibrosis and HMAs failure. The rate of poor prognosis chromosome in MDS-MF(MF =2-3) group was significantly higher than that in MDS group and moderate to severe MF(MF =2-3) predicted an inferior overall survival and disease-free survival compared to MDS groups. It should be highlighted that MDS-MF group had significantly increased leukemia transformation rate(26/53, 49.1%), and most cases(14/26, 53.4%)transformed to AML within 6 months. And the half year risk of leukemic transformation was associate

关键词： myelofibrosis myelodysplastic syndrome leukemia transformation

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Hydroxyurea-induced cutaneous squamous cell carcinoma: A case report

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World Journal of Clinical Cases 2019年第23期7卷 4091-4097页

作者： Yan Xu Jian Liu Department of Surgical Oncology The First Affiliated Hospital College of Medicine Zhejiang University

BACKGROUND Hydroxyurea(HU)is a non-alkylating antineoplastic agent that is active in the Sphase of the cell cycle and inhibits the enzyme ribonucleoside *** is currently used to treat leukemia,sickle cell anemia,psoriasis,and chronic myeloproliferative *** HU is easy to use and effective and has high tolerance,there have been numerous reports of cutaneous complications during long-term therapy with *** SUMMARY We report a 67-year-old woman on long-term HU therapy for primary myelofibrosis who developed concurrent skin lesions during *** first skin lesion appeared on the dorsum of her right hand in *** continuous use of HU,her cutaneous changes were *** 3 years ago,she had multiple nodular and keratotic lesions on both hands with sharp margins,branny desquamation,and dotted ***,she developed acutely numerous ulcerative lesions on her hands and *** wound therapy with dressing changes and parenteral antibiotics was applied for management of the *** of the wounds healed after HU *** on both hands were replaced by ***,the wound on her left ankle reached 9 cm×7 cm in size in January *** confirmed welldifferentiated squamous cell carcinoma at the ulcer *** addition,her left foot was severely affected and radical surgery with a below-the-knee amputation was suggested followed by preventive right groin nodal *** In patients receiving continuous HU therapy,close dermatologic follow-up is critical for the early diagnosis and selection of appropriate treatment for cutaneous lesions.

关键词： Hydroxyurea Squamous cell carcinoma Primary myelofibrosis Case report

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Bone marrow metastatic neuroendocrine carcinoma with unknown primary site:A case report and review of the literature

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World Journal of Clinical Cases 2022年第30期10卷 11074-11081页

作者： Xue-Bing Shi Wen-Xia Deng Feng-Xiang Jin Department of Medical Oncology Tongling People’s HospitalTongling 244000Anhui ProvinceChina Department of Hematology Tongling People’s HospitalTongling 244000Anhui ProvinceChina

BACKGROUND Metastatic neuroendocrine carcinoma(NEC) of bone marrow is ***,we report a case of bone marrow metastatic NEC with an unknown primary *** SUMMARY A 73-year-old Chinese woman was admitted to our hospital because marked chest distress and asthma lasting 1 d on March 18,*** was initially diagnosed with pulmonary infection,cardiac insufficiency,thrombocytopenia and severe *** treatment with antibiotic therapy,diuresis and blood transfusion,the patient’s symptoms greatly *** bone marrow examinations,the patient was diagnosed with bone marrow metastatic NEC,bone marrow necrosis(BMN) and secondary myelofibrosis(MF).Further imaging workup did not show the primary tumor,we presumed that the primary site might regress spontaneously or merely be unexplored due to lack of positron emission tomography with gallium ***(10 mg/d) was added to the treatment and the best supportive and symptomatic therapies were also ***,the patient’s condition continued to deteriorate and she died on May 15,*** Bone marrow invasion of NEC is rare and our patient who suffered from bone marrow metastatic NEC as well as secondary BMN and MF had an extremely poor *** marrow biopsy plays an important role in the diagnosis of solid tumors invading bone marrow.

关键词： Neuroendocrine neoplasm Bone marrow metastasis Bone marrow necrosis myelofibrosis Everolimus Case report

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Risk of hepatitis B reactivation in patients with myeloproliferative neoplasms treated with ruxolitinib

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World Journal of Hepatology 2023年第11期15卷 1188-1195页

作者： Adeniyi Abraham Adesola Matei-Alexandru Cozma Yong-Feng Chen Bahadar Singh Srichawla Mihnea-Alexandru Găman Department of Medicine and Surgery Faculty of Clinical SciencesCollege of MedicineUniversity of IbadanIbadanNigeria Faculty of Medicine "Carol Davila"University of Medicine and PharmacyBucharest 050474Romania Department of Gastroenterology Colentina Clinical HospitalBucharest 020125Romania Department of Basic Medical Sciences Medical College of Taizhou UniversityTaizhou 318000Zhejiang ProvinceChina Department of Neurology University of Massachusetts Chan Medical SchoolWorcesterMA 01655United States Department of Hematology Center of Hematology and Bone Marrow TransplantationFundeni Clinical InstituteBucharest 022328Romania Cellular and Molecular Pathology Department Stefan S.Nicolau Institute of VirologyRomanian AcademyBucharest 030304Romania

Classical Philadelphia-negative myeloproliferative neoplasms(MPNs),i.e.,polycythemia vera,essential thrombocythemia,and primary/secondary myelofibrosis,are clonal disorders of the hematopoietic stem cell in which an uncontrolled proliferation of terminally differentiated myeloid cells *** are characterized by mutations in driver genes,the JAK2V617F point mutation being the most commonly detected genetic alteration in these hematological ***,JAK inhibition has emerged as a potential therapeutic strategy in MPNs,with ruxolitinib being the first JAK inhibitor developed,approved,and prescribed in the management of these blood ***,the use of ruxolitinib has been associated with a potential risk of infection,including opportunistic infections and reactivation of hepatitis ***,we briefly describe the association between ruxolitinib treatment in MPNs and hepatitis B reactivation.

关键词： Ruxolitinib Myeloproliferative neoplasms Hepatitis B Polycythemia vera myelofibrosis JAK inhibitor

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Toxicity of targeted anticancer treatments on the liver in myeloproliferative neoplasms

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World Journal of Hepatology 2023年第9期15卷 1021-1032页

作者： Shubhrat Purwar Anam Fatima Himashree Bhattacharyya Lakshmi Venkata Simhachalam Kutikuppala Matei-Alexandru Cozma Bahadar Singh Srichawla Leah Komer Khulud Mahmood Nurani Mihnea-Alexandru Găman Department of Internal Medicine Grant Government Medical CollegeMumbai 400008MaharashtraIndia Department of Internal Medicine Pandit Jawaharlal Nehru Memorial Medical CollegeRaipur 492001ChhattisgarhIndia Department of Community&Family Medicine AIIMS GuwahatiAssam 781101India Department of General Surgery Dr NTR University of Health SciencesVijayawada 521104Andhra PradeshIndia Faculty of Medicine “Carol Davila”University of Medicine and PharmacyBucharest 050474Romania Department of Gastroenterology Colentina Clinical HospitalBucharest 020125Romania Department of Neurology University of Massachusetts Chan Medical SchoolWorcesterMA 01655United States Department of Psychiatry University of TorontoToronto M5G 1V7OntarioCanada Faculty of Health Sciences University of NairobiNairobi 30197-00100Kenya Department of Hematology Center of Hematology and Bone Marrow TransplantationFundeni Clinical InstituteBucharest 022328Romania

The liver has a central role in metabolism,therefore,it is susceptible to harmful effects of ingested medications(drugs,herbs,and nutritional supplements).Druginduced liver injury(DILI)comprises a range of unexpected reactions that occur after exposure to various classes of *** though most cases consist of mild,temporary elevations in liver enzyme markers,DILI can also manifest as acute liver failure in some patients and can be associated with ***,we briefly review available data on DILI induced by targeted anticancer agents in managing classical myeloproliferative neoplasms:Chronic myeloid leukemia,polycythemia vera,essential thrombocythemia,and myelofibrosis.

关键词： Myeloproliferative neoplasms Chronic myeloid leukemia myelofibrosis Polycythemia vera Essential thrombocythemia Hepatotoxicity Drug-induced liver injury

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Acute myocardial infarction in myeloproliferative neoplasms

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World Journal of Cardiology 2023年第11期15卷 571-581页

作者： Muhammad Romail Manan Vincent Kipkorir Iqra Nawaz Maryann Wanjiku Waithaka Bahadar Singh Srichawla Amelia Maria Găman Camelia Cristina Diaconu Mihnea-Alexandru Găman Services Institute of Medical Sciences Lahore 54000Pakistan Department of Human Anatomy and Physiology University of NairobiNairobi 00100Kenya Quaid-e-Azam Medical College Bahawalpur 63100Pakistan Department of Neurology University of Massachusetts Chan Medical SchoolWorcesterMA 01655United States Department of Pathophysiology University of Medicine and Pharmacy of CraiovaCraiova 200143Romania Clinic of Hematology Filantropia City HospitalCraiova 200143Romania Department of Internal Medicine Faculty of Medicine“Carol Davila”University of Medicine and PharmacyBucharest 050474Romania Internal Medicine Clinic Clinical Emergency Hospital of BucharestBucharest 105402Romania Faculty of Medicine “Carol Davila”University of Medicine and PharmacyBucharest 050474Romania Department of Hematology Center of Hematology and Bone Marrow TransplantationFundeni Clinical InstituteBucharest 022328Romania Department of Cellular and Molecular Pathology Stefan S.Nicolau Institute of VirologyRomanian AcademyBucharest 030304Romania

Myeloproliferative neoplasms(MPNs)are a heterogeneous group of hematologic malignancies characterized by an abnormal proliferation of cells of the myeloid *** individuals are at increased risk for cardiovascular and thrombotic *** infarction(MI)may be one of the earliest clinical manifestations of MPNs or may be a thrombotic complication that develops during the natural course of the *** the present review,we examine the epidemiology,pathogenesis,clinical presentation,and management of MI in MPNs based on the available ***,we review potential biomarkers that could mediate the MI-MPNs crosstalk,from classical biochemical tests,e.g.,lactate dehydrogenase,creatine kinase and troponins,to pro-inflammatory cytokines,oxidative stress markers,and clonal hematopoiesis.

关键词： Myeloproliferative neoplasms Polycythemia vera Essential thrombocythemia myelofibrosis Myocardial infarction Acute coronary syndrome Biomarker Clonal hematopoiesis

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PVSG and WHO vs European Clinical,Molecular and Pathological Criteria for prefibrotic myeloproliferative neoplasms

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World Journal of Hematology 2013年第3期2卷 71-88页

作者： Jan Jacques Michiels Zwi Berneman Wilfried Schroyens King H Lam Hendrik De Raeve Department of Hematology University Hospital AntwerpWilrijkstraat 10B-2650 EdegemAntwerpBelgium European Working Group on Myeloproliferative Neoplasms Goodheart InstituteErasmus TowerVeenmos 133069 ATRotterdamThe Netherlands Department of Pathology Erasmus University Medical Center RotterdamDr.Molewaterplein 503015 GD RotterdamThe Netherlands Department of Pathology OLV Hospital Aalst and University Hospital Brussels OLV ZiekenhuisMoorselbaan 164B-9300 AalstBelgium

The Polycythemia Vera Study Group(PVSG),World Health Organization(WHO) and European Clinical,Molecular and Pathological(ECMP) classifications agree upon the diagnostic criteria for polycythemia vera(PV) and advanced primary myelofibrosis(MF). Essential thrombocythemia(ET) according to PVSG and 2007/2008 WHO criteria comprises three variants of JAK2V617 F mutated ET when the ECMP criteria are applied. These include normocellular ET,hypercellular ET with features of early PV(prodromal PV),and hypercellular ET due to megakaryocytic,granulocytic myeloprolifera-tion(***). Evolution of prodromal PV into overt PV is common. Development of MF is rare in normocellular ET(WHO-ET) but rather common in hypercellular ***. The JAK2V617 F mutation burden in heterozygous mutated normocellular ET and in heterozygous/homozygous or homozygous mutated PV and *** is of major prognostic significance. JAK2/MPL wild type ET associated with prefibrotic primary megakaryocytic and granulocytic myeloproliferation(PMGM) is characterized by densely clustered immature dysmorphic megakaryocytes with bulky(bulbous) hyperchromatic nuclei,which are never seen in JAK2V617 F mutated ET,and PV and also not in MPL515 mutated normocellular ET(WHO-ET). JAK2V617 mutation burden,spleen size,LDH,circulating CD34+ cells,and pre-treatment bone marrow histopathology are mandatory to stage the myeloproliferative neoplasms ET,PV,PMGM for proper prognosis assessment and therapeutic implications. MF itself is not a disease because reticulin fibrosis and reticulin/collagen fibrosis are secondary responses of activated polyclonal fibroblasts to cytokines released from the clonal myeloproliferative granulocytic and megakaryocytic progenitor cells in ***,PV and PMGM.

关键词： Myeloproliferative neoplasms Essential thrombocythemia Prodromal polycythemia vera Polycythemia vera myelofibrosis JAK2V617F mutation JAK2 wild type myeloproliferative neoplasm Bone marrow pathology

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Leukemogenic Fusion Gene (p190 BCR-ABL) Transduction into Hematopoietic Stem/Progenitor Cells in the Common Marmoset

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Open Journal of Blood Diseases 2012年第1期2卷 1-10页

作者： Yan Dong Seiichiro Kobayashi Yamin Tian Manabu Ozawa Takafumi Hiramoto Kiyoko Izawa Yuansong Bai Yasushi Soda Erika Sasaki Toshio Itoh Yoshiro Maru Satoshi Takahashi Kaoru Uchimaru Naoki Oyaizu Arinobu Tojo Chieko Kai Kenzaburo Tani Central Institute for Experimental Animals Kawasaki Japan Department of Laboratory Medicine Research Hospital Institute of Medical Science the University of Tokyo Tokyo Japan Department of Molecular Genetics Medical Institute of Bioregulation Kyushu University Fukuoka Japan Department of Pharmacology Tokyo Woman’s Medical University Japan Division of Molecular Therapy Institute of Medical Science the University of Tokyo Tokyo Japan Laboratory Animal Research Center Institute of Medical Science the University of Tokyo Tokyo Japan.

Patients with Philadelphia chromosome (p190 BCR-ABL fusion gene)-positive acute lymphoblastic leukemia have a poor prognosis despite intensive therapeutic *** this study, we attempted to develop a leukemia nonhuman primate model that mimics various human systems. Hematopoietic stem/progenitor cells in the common marmoset were transduced with a lentiviral vector containing the p190 BCR-ABL fusion gene by ex vivo transduction or in vivo direct bone marrow injection. In the latter model, BCR-ABL gene expression was maintained for more than one and a half years. One marmoset unexpectedly developed myelofibrosis-like disease. However, none of the marmosets have developed leukemia to date. In conclusion, we successfully achieved sustained p190 BCR-ABL gene expression in vivo. However, a genetic mutation in addition to p190 BCR-ABL may be required for the malignant transformation of hematopoietic stem/progenitor cells in the common marmoset during the short observation period. This novel in vivo approach will help develop a marmoset leukemia model in the future.

关键词： Leukemia Lentiviral Vector myelofibrosis Common Marmoset

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Overview of dyslipidemia and metabolic syndrome in myeloproliferative neoplasms

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World Journal of Clinical Oncology 2024年第6期15卷 717-729页

作者： Mihnea-Alexandru Găman Bahadar Singh Srichawla Yong-Feng Chen Poulami Roy Arkadeep Dhali Ahmed Nahian Muhammad Romail Manan Vincent Kipkorir Richard Christian Suteja Lakshmi Venkata Simhachalam Kutikuppala Amelia Maria Găman Camelia Cristina Diaconu Faculty of Medicine “Carol Davila”University of Medicine and PharmacyBucharest 050474Romania Department of Hematology Center of Hematolog Department of Cellular and Molecular Pathology Stefan S Nicolau Institute of VirologyRomanian AcademyBucharest 030304Romania Department of Neurology University of Massachusetts Chan Medical SchoolWorcesterMA 01655United States Department of Basic Medical Sciences School of Medicine of Taizhou UniversityTaizhou UniversityTaizhou 318000Zhejiang ProvinceChina Department of Medicine North Bengal Medical College and HospitalWest Bengal 734012India Academic Department of Gastroenterology Sheffield Teaching Hospitals NHS Foundation TrustSheffield S57AUUnited Kingdom Lecom at Seton Hill GreensburgPA 15601United States Faculty of Medicine Services HospitalLahore 54000Pakistan Department of Human Anatomy and Physiology University of NairobiNairobi 00100Kenya Faculty of Medicine Udayana UniversityDenpasarBali 80361Indonesia Department of General Surgery Dr.NTR University of Health SciencesVijayawada 520008Andhra PradeshIndia Department of Pathophysiology University of Medicine and Pharmacy of CraiovaCraiova 200349Romania Clinic of Hematology Filantropia City HospitalCraiova 200143Romania Department of Internal Medicine Faculty of Medicine“Carol Davila”University of Medicine and PharmacyBucharest 050474Romania Internal Medicine Clinic Clinical Emergency Hospital of BucharestBucharest 105402Romania

Myeloproliferative neoplasms(MPNs)occur due to the abnormal proliferation of one or more terminal myeloid cell lines in peripheral *** suffering from MPNs display a high burden of cardiovascular risk factors,and thrombotic events are often the cause of death in this population of ***,we provide a brief overview of dyslipidemia and metabolic syndrome and their epidemiology in MPNs and examine the common molecular mechanisms between dyslipidemia,metabolic syndrome,and MPNs,with a special focus on cardio-vascular risk,atherosclerosis,and thrombotic ***,we investigate the impact of dyslipidemia and metabolic syndrome on the occurrence and survival of thrombosis in MPN patients,as well as the management of dyslipidemia in MPNs,and the impact of MPN treatment on serum lipid concentrations,particularly as side/adverse effects reported in the context of clinical trials.

关键词： Polycythemia vera Essential thrombocythemia myelofibrosis Cardiovascular disease Hypercholesterolemia Hypertriglyceridemia Obesity Diabetes Inflammation Oxidative stress

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Hematological disorders and pulmonary hypertension

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World Journal of Cardiology 2016年第12期8卷 703-718页

作者： Rajamma Mathew Jing Huang Joseph M Wu John T Fallon Michael H Gewitz Department of Physiology New York Medical College Section of Pediatric Cardiology New York Medical College Department of Biochemistry and Molecular Biology New York Medical College Department of Pathology New York Medical College

Pulmonary hypertension(PH),a serious disorder with a high morbidity and mortality rate,is known to occur in a number of unrelated systemic *** hematological disorders such as sickle cell disease,thalassemia and myeloproliferative diseases develop PH which worsens the *** oxidant injury and vascular inflammation cause endothelial damage and *** vascular endothelial damage/dysfunction is an early event in PH resulting in the loss of vascular reactivity,activation of proliferative and antiapoptotic pathways leading to vascular remodeling,elevated pulmonary artery pressure,right ventricular hypertrophy and premature *** observed in hematological disorders leads to free hemoglobin which rapidly scavenges nitric oxide(NO),limiting its bioavailability,and leading to endothelial *** addition,hemolysis releases arginase into the circulation which converts L-arginine to ornithine,thus bypassing NO ***,treatments for hematological disorders such as immunosuppressive therapy,splenectomy,bone marrow transplantation,and radiation have been shown to contribute to the development of *** studies have shown deregulated iron homeostasis in patients with cardiopulmonary diseases including pulmonary arterial hypertension(PAH).Several studies have reported low iron levels in patients with idiopathic PAH,and iron deficiency is an important risk *** article reviews PH associated with hematological disorders and its mechanism:and iron homeostasis and its relevance to PH.

关键词： Anemia Hemolysis Iron homeostasis myelofibrosis Pulmonary hypertension

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