Mediterranean Journal of Hematology and Infectious Diseases <p style="font-size: 14px;">The Journal publishes original articles and topical reviews concerning both clinical hematology and infectious diseases. A particular attention will be deserved to original articles focusing on the relationship between blood and infectious diseases.</p> <p><strong>The Mediterranean Journal of Hematology and Infectious Diseases has been selected for coverage in </strong><strong>Clarivate Analytics products and services. <br>Beginning with V. 7 (1) 2015, this publication is indexed and abstracted in:</strong></p> <p><strong>♦ Science Citation Index Expanded</strong><br><strong>♦ Journal Citation Reports/InCites</strong> <br><br><strong>♦ First <strong>2017 <strong>official</strong> </strong>Impact Factor: 1.183</strong> <br><strong>♦ Official Impact Factor 2018. 1.586</strong> <br><strong>♦ Official Impact Factor 2019. 1.600</strong></p> <p><span style="font-size: 12px;"><strong><span class="info_label" style="color: #757472; text-transform: none; text-indent: 0px; letter-spacing: normal; font-family: 'Open Sans',sans-serif,icomoon; font-style: normal; word-spacing: 0px; white-space: normal; background-color: #ffffff;">ISI Journal Citation Reports @ Ranking: 2017</span></strong></span></p> <p><strong>List of contents:</strong></p> <p>&nbsp;</p> <p><strong><a title="Volume 12, Year 2020" href="">12:(1) (2020):</a> </strong><strong><a title="Volume 12, Year 2020" href=""><img src="/public/site/images/fguidi/FRECCE0014.gif" alt=""></a> ORIGINAL ARTICLES, REVIEWS:</strong></p> <p><span style="font-weight: bold;">COVID-19</span><strong> and&nbsp;</strong><strong>Reviews</strong><strong>&nbsp;</strong><strong>Topics</strong><strong>:</strong></p> <ul> <li class="show">ANEMIAS DUE TO DEFICIENCY OR DEFECTIVE UTILIZATION OF IRON AND/OR VITAMINS. Guest Editor: Domenico Girelli. <a href="/index.php/mjhid/announcement/view/103">More...</a></li> <li class="show">News on COVID-19 Letters to the Editor of the Mediterranean Journal of Hematology and Infectious Diseases. <a href="/index.php/mjhid/announcement/view/100">More...</a></li> </ul> <p><a title="Volume 11, Year 2019" href=""><strong>11:(1) (2019):</strong></a> <strong><a title="Volume 11, Year 2019" href=""><img src="/public/site/images/fguidi/FRECCE0014.gif" alt=""></a> ORIGINAL ARTICLES, REVIEWS:</strong></p> <p><strong>Reviews&nbsp;</strong><strong>Topics</strong><strong>:</strong></p> <ul> <li class="show">UPDATE ON THALASSEMIA AND HEMOGLOBINOPATHIES. Guest Editor: Raffaella Origa<strong>. </strong><a href="/index.php/mjhid/announcement/view/82">More...</a></li> <li class="show">UPDATE ON&nbsp;HEMOPHILIA. Guest Editor: Giancarlo Castaman<strong style="font-weight: normal;">. </strong><a href="/index.php/mjhid/announcement/view/94">More...</a></li> </ul> <p><strong><a href="">10:(1) (2018):</a> <a title="Volume 10, Year 2018" href=""><img src="/public/site/images/fguidi/FRECCE0014.gif" alt=""></a> ORIGINAL ARTICLES, REVIEWS:</strong></p> <p><strong>Review Topics:</strong></p> <ul> <li class="show">UPDATE ON VIRAL INFECTIONS AND LYMPHOPROLIFERATIVE DISEASES. Guest Editors: M. Luppi and L. Arcaini <a href="/index.php/mjhid/announcement/view/73">More...</a></li> </ul> <p><a href=""><strong>9:(1) (2017): </strong></a><strong><a title="Volume 9, Year 2017" href=""><img src="/public/site/images/fguidi/FRECCE0014.gif" alt=""></a>ORIGINAL ARTICLES, REVIEWS:</strong></p> <p><strong>Review Topics:</strong></p> <ul> <li class="show">UPDATE ON SECONDARY LEUKEMIAS. Guest Editor: Richard Larson <a href="/index.php/mjhid/announcement/view/59">More...</a></li> <li class="show">UPDATE on “Rare Plasma Cell Dyscrasias” Guest Editor: M.T. Petrucci <a href="/index.php/mjhid/announcement/view/49">More...</a></li> </ul> <p><strong><a href="">8:(1) (2016):</a> <a title="Volume 8, Year 2016" href=""><img src="/public/site/images/fguidi/FRECCE0014.gif" alt=""></a> ORIGINAL ARTICLES, REVIEWS:</strong></p> <p><strong>Review Topics:</strong></p> <ul> <li class="show">HEMATOPOIETIC STEM CELL TRANSPLANTATION AND INFECTIONS. Guest Editor: Miguel Sanz <a href="/index.php/mjhid/announcement/view/37">More...</a></li> <li class="show">REVIEW SERIES: UPDATE ON FOLLICULAR LYMPHOMA. Guest Editor: Corrado Tarella <a href="/index.php/mjhid/announcement/view/39">More...</a></li> </ul> <p><strong>8:(Supplementary Issue) (2016): <a href=""><img src="/public/site/images/fguidi/FRECCE0014.gif" alt=""></a> Fifth International Symposium on Secondary Leukemia and Leukemogenesis</strong></p> <p><strong><a href="">7:(1) (2015):</a> <a title="Volume 7, Year 2015" href=""><img src="/public/site/images/fguidi/FRECCE0014.gif" alt=""></a> ORIGINAL ARTICLES, REVIEWS:</strong></p> <p>Review Topics:</p> <ul> <li class="show">MYELODYSPLASTIC SYNDROMES. AN UPDATE. SINCE 2015. Guest Editors: C. Mecucci and M.T. Voso. <a href="">More...</a></li> <li class="show">BACTERIAL INFECTIONS IN HEMATOLOGIC PATIENTS: AN UPDATE. SINCE 2015.Guest Editors F. Aversa and M. Tumbarello <a href="">More...</a></li> </ul> <p><strong><a href="">6:(1) (2014):</a> <a title="Volume 6, Year 2014" href=""><img src="/public/site/images/fguidi/FRECCE0013.gif" alt=""></a> ORIGINAL ARTICLES, REVIEWS:</strong></p> <p>Review Topics:</p> <ul> <li class="show">CHRONIC MYELOID LEUKEMIAS: AN UPDATE. Guest Editors: M. Baccarani and F. Pane. <a href="">More...</a></li> <li class="show">UPDATE IN HODGKIN LYMPHOMA. Guest Editor: A. Gallamini <a href="">More...</a></li> <li class="show">ACUTE LYMPHOID LEUKEMIA IN ADULTS: AN UPDATE. Guest Editors: R. Bassan and A.Rambaldi <a href="">More...</a></li> </ul> <p><strong><a href="">5:(1) (2013):</a> <a title="Volume 5, Year 2013" href=""><img src="/public/site/images/fguidi/FRECCE0012.gif" alt=""></a> ORIGINAL ARTICLES, REVIEWS:</strong></p> <p>Review Topics:</p> <ul> <li class="show">ACUTE MYELOID LEUKEMIA IN THE ELDERLY. Guest Editors: S. Amadori and A. Venditti. <a href="">More...</a></li> <li class="show">VON WILLEBRAND FACTOR UPDATE. Guest Editors: A. Federici and F. Rodeghiero. <a href="">More...</a></li> <li class="show">TUBERCULOSIS UPDATE. Guest Editors: R. Cauda and A. Matteelli. <a href="">More...</a></li> </ul> <p><strong><a href="">4:(1) (2012):</a> <a title="Malaria In The World, Chronic Lymphoid Leukemia, Autologous Hemopoietic Stem Cell Transplantation In Leukemia And Lymphoma" href=""><img src="/public/site/images/fguidi/FRECCE0011.gif" alt=""></a>ORIGINAL ARTICLES, REVIEWS:</strong></p> <p>Review Topics:</p> <ul> <li class="show">MALARIA IN THE WORLD: 2012 Update. Guest Editors: F. Castelli and E. Pizzigallo <a href="">More...</a></li> <li class="show">CHRONIC LYMPHOID LEUKEMIA: Update on Immunological Dysfunctions and Infections. Guest Editors: D. Efremov and L. Laurenti <a href="">More...</a></li> <li class="show">AUTOLOGOUS HEMOPOIETIC STEM CELL TRANSPLANTATION IN LEUKEMIA AND LYMPHOMA: 2012 UPDATE. Guest Editors: G. Meloni and G. Visani <a href="">More...</a></li> </ul> <p><strong><a href="">3:(1) (2011):</a> <a title="Fungal Infections, Thrombosis In The Mediterranean Area, Acute Promyelocytic Leukemia In The Mediterranean Area And In The Developing Countries, Therapy-Related Myeloid Neoplasms." href=""><img src="/public/site/images/fguidi/FRECCE001.gif" alt=""></a> ORIGINAL ARTICLES, REVIEWS:</strong></p> <p>Review Topics:</p> <ul> <li class="show">FUNGAL INFECTIONS. Guest Editor: L. Pagano <a style="color: #990000;" href="">More...</a></li> <li class="show">THROMBOSIS IN THE MEDITERRANEAN AREA. Guest Editor: V. De Stefano <a style="color: #990000;" href="">More...</a></li> <li class="show">ACUTE PROMYELOCYTIC LEUKEMIA IN THE MEDITERRANEAN AREA AND IN THE DEVELOPING COUNTRIES: Guest Editors: F. Lo-Coco and G. Avvisati <a style="color: #990000;" href="">More...</a></li> <li class="show">THERAPY-RELATED MYELOID NEOPLASMS: Guest Editor: R. Larson <a style="color: #990000;" href="">More...</a></li> </ul> Università Cattolica Sacro Cuore, Rome, Italy en-US Mediterranean Journal of Hematology and Infectious Diseases 2035-3006 <p>This is an Open Access article distributed under the terms of the Creative Commons Attribution License (<a href="" target="_blank" rel="noopener"></a>) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</p> <p><strong>Transfer of Copyright and Permission to Reproduce Parts of Published Papers.</strong>&nbsp;Authors will grant copyright of their articles to the Institute of Hematology, Catholic University, Rome . No formal permission will be required to reproduce parts (tables or illustrations) of published papers, provided the source is quoted appropriately and reproduction has no commercial intent.&nbsp;<strong>Reproductions with commercial intent will require written permission and payment of royalties.</strong></p> <div class="grammarly-disable-indicator">&nbsp;</div> CONCISE REVIEW ON THE FREQUENCY, MAJOR RISK FACTORS AND SURVEILLANCE OF HEPATOCELLULAR CARCINOMA (HCC) IN Β-THALASSEMIAS: PAST, PRESENT AND FUTURE PERSPECTIVES <p>Due to the recent alarming increase in the incidence of hepatocellular carcinoma (HCC) in thalassemias, the aim of the present report is to review briefly the frequency, the major risk factors and the surveillance of HCC in β-thalassemias. Over the past 33 years, 153 cases of HCC were reported in patients with thalassemia, mainly in Italy, and Greece. Among HCV-infected patients additional factors promoting development of&nbsp; HCC, included: advanced age, male sex, chronic hepatitis B (CHB) coinfection, and iron overload. For early diagnosis of HCC sequential ultrasound screening&nbsp; is recommended&nbsp; especially for thalassemia patients with chronic hepatitis C (CHC), that coincide with (one or more) additional risk factors for HCC. &nbsp;Here we report also the preliminary data of thalassemic patients, above the age of 30 years, followed in 13 different centers. The total number of enrolled patients was 1,313 (males: 612 and 701 females). The prevalence of HCC in thalassemia major patients [characterized by transfusion-dependency (TDT)] and thalassemia intermedia [characterized by nontransfusion dependency (NTDT)] was 1.68 % and 1.98 % ,respectively The lowest age at diagnosis was 36 years in TDT and 47 years in NTDT patients.We hope that our review can be used to develop more refined and prospective analyses of HCC magnitude and risk in patients with thalassemia, and to define specific international guidelines to support clinicians for an early diagnosis and treatment of HCC in thalassemic patients.</p> Vincenzo De Sanctis Copyright (c) 2020 Vincenzo De Sanctis 2020-01-01 2020-01-01 12 1 e2020006 e2020006 10.4084/mjhid.2020.006 MOLECULAR MECHANISMS OF INHIBITOR DEVELOPMENT IN HEMOPHILIA <p>The development of neutralizing antibodies in hemophilia is a serious complication of factor replacement therapy. These antibodies, also known as “inhibitors”, significantly increase morbidity within the hemophilia population and lower the quality of life for these patients. People with severe hemophilia A have an overall 25-40% lifetime risk of inhibitor development, compared to that of 5-15% lifetime risk in those with moderate/mild hemophilia A. The risk is lower in hemophilia B population (about 1-5%) and occurrence of inhibitors is almost only seen in patients with severe hemophilia B. The understanding of the pathophysiological mechanism leading to the development of inhibitors in patients with hemophilia has improved considerably over the last 2 decades. Identification of early biomarkers which predict inhibitor development in previously untreated patients with hemophilia will assist in risk identification and possible early intervention strategies. In this review, we aim to summarize the molecular mechanisms of inhibitor development in hemophilia and to identify potential areas in need of further investigation.</p> Davide Matino Paul Tieu Antony Chan Copyright (c) 2019 Davide Matino, Paul Tieu, Dr., Antony Chan 2020-01-01 2020-01-01 12 1 e2020001 e2020001 10.4084/mjhid.2020.001 THE HISTORY OF DEFERIPRONE (L1) AND THE COMPLETE TREATMENT OF IRON OVERLOAD IN THALASSAEMIA <p>Deferiprone (L1) was originally designed, synthesised and screened in vitro and in vivo in 1981 by Kontoghiorghes G J following his discovery of the novel alpha-ketohydroxypyridine class of iron chelators (1978-1981), which were intended for clinical use. The journey through the years for the treatment of thalassaemia with L1 has been a very difficult one with intriguing turn of events, which continue until today. Despite many complications, such as the wide use of L1 suboptimal dose protocols, the aim of chelation therapy- namely the complete removal of excess iron in thalassaemia major patients, has been achieved following the introduction of specific L1 and L1/deferoxamine combinations. Many such patients continue to maintain normal iron stores. As a result of the introduction of L1, thalassaemia has changed from a fatal to a chronic disease and thalassaemia patients are active professional members in all sectors of society, have their own families with children and grandchildren and their lifespan is approaching that of normal individuals. No changes in the low toxicity profile of L1 have been observed in more than 30 years of clinical use. Thousands of thalassaemia patients are still denied the cardioprotective and other beneficial effects of L1 therapy. The safety of L1 in thalassaemia and other non-iron loaded diseases resulted in its selection as one of the leading therapeutics for the treatment of Friedreich’s ataxia, pantothenate kinase-associated neurodegeneration and other&nbsp;similar cases. There are also increasing prospects for the application of L1 as a main, alternative or adjuvant therapy in many pathological conditions including cancer, infectious diseases and as a general antioxidant for diseases related to free radical pathology.</p> George J Kontoghiorghes Marios Kleanthous Christina N. Kontoghiorghe Copyright (c) 2020 George J Kontoghiorghes, Marios Kleanthous, Christina N. Kontoghiorghe 2020-01-01 2020-01-01 12 1 e2020011 e2020011 10.4084/mjhid.2020.011 THE EVOLVING PHARMACOTHERAPEUTIC LANDSCAPE FOR THE TREATMENT OF SICKLE CELL DISEASE <p>Sickle cell disease (SCD) is an extremely heterogeneous disease that has been associated with global morbidity and early mortality. More effective and inexpensive therapiesare needed. During the last five years the landscape of the pharmacotherapy of SCD has changed dramatically. Currently, there are at least 50 drugs that have been used or under consideration to use for the treatment of SCD. These fall into 3 categories: the first category includes the three drugs (Hydroxyurea, L-Glutamine and Crizanlizumab tmca) that have been approved by the United States Food and Drug Administration (FDA) based on successful clinical trials. The second category includes 22 drugs that failed, discontinued or terminated for now and the third category includes 25 drugs that are actively being considered for the treatment of SCD. New therapies targeting multiple pathways in its complex pathophysiology have been achieved or are under continued investigation. The emerging trend seems to be the use of multimodal drugs (i.e. drugs that have different mechanisms of action) to treat SCD similar to the use of multiple chemotherapeutic agents to treat cancer.</p> Samir Ballas Copyright (c) 2020 Samir Ballas 2020-01-01 2020-01-01 12 1 e2020010 e2020010 10.4084/mjhid.2020.010 FEBRILE NEUTROPENIA IN ACUTE LEUKEMIA. EPIDEMIOLOGY, ETIOLOGY, PATHOPHYSIOLOGY AND TREATMENT <p>Acute leukemias are a group of aggressive malignant diseases associated with a high degree of morbidity and mortality. An important cause of both the latter is infectious complications. Patients with acute leukemia are highly susceptible to infectious diseases due to factors related to the disease itself, factors attributed to treatment, and specific individual risk factors in each patient. Patients with chemotherapy-induced neutropenia are at particularly high risk, and microbiological agents include viral, bacterial and fungal agents. The etiology is often unknown in infectious complications, although adequate patient evaluation and sampling have diagnostic, prognostic and treatment-related consequences. Bacterial infections include a wide range of potential microbes, both Gram-negative and Gram-positive species, while fungal infections include both mold and yeast. A recurring problem is increasing resistance to antimicrobial agents, and in particular, this applies to extended-spectrum beta-lactamase resistance (ESBL), <em>Pseudomonas aeruginosa</em>, methicillin-resistant <em>Staphylococcus aureus</em> (MRSA), vancomycin-resistant <em>Enterococcus</em> (VRE) and even carbapenemase-producing <em>Enterobacteriaceae</em> (CPE). International guidelines for the treatment of sepsis in leukemia patients include the use of broad-spectrum Pseudomonas-acting antibiotics. However, one should implant the knowledge of local microbiological epidemiology and resistance conditions in treatment decisions. Here, we discuss infectious diseases in acute leukemia with a major focus on febrile neutropenia and sepsis, and we problematize the diagnostic, prognostic, and therapeutic aspects of infectious complications in this patient group. Meticulously and thorough clinical and radiological examination combined with adequate microbiology samples are cornerstones of the examination. Diagnostic and prognostic evaluation includes patient review according to the multinational association for supportive care in cancer (MASCC) and sequential organ failure assessment (SOFA) scoring system. Antimicrobial treatments for important etiological agents are presented. The main challenge for reducing the spread of resistant microbes is to avoid unnecessary antibiotic treatment, but without giving to narrow treatment to the febrile neutropenic patient that reduce the prognosis.</p> Bent-Are Hansen Øystein Wendelbo Øyvind Bruserud Anette Lodvir Hemsing Knut Anders Mosevoll Håkon Reikvam Copyright (c) 2020 Bent-Are Hansen, Øystein Wendelbo, Øyvind Bruserud, Anette Lodvir Hemsing, Knut Anders Mosevoll, Håkon Reikvam 2019-12-30 2019-12-30 12 1 e2020009 e2020009 10.4084/mjhid.2020.009 CURRENT ISSUES AND OPTIONS FOR HORMONAL CONTRACEPTION IN ADOLESCENTS AND YOUNG ADULT WOMEN WITH SICKLE CELL DISEASE: AN UPDATE FOR HEALTH CARE PROFESSIONALS <p><strong>Abstract.</strong> Women with sickle cell disease (SCD) are of particular concern due to the significantly increased risk of pregnancy-related morbidity, mortality, and adverse outcomes. They have limited knowledge of the risks of pregnancy and childbirth as well as of the benefits and risks from the use of contraceptives. Thus, there is urgent need for appropriate information about reproductive family planning to reduce unintended pregnancy. Any decision regarding the use of contraceptives has to be based on the efficacy and the risks and benefits of the method used. Both the World Health Organization (WHO) and the Center for Disease Control and Prevention (CDC) have developed, published, and updated evidence-based guidelines for medical providers for the use of contraceptives in patients with specific medical chronic conditions. This article provides an overview of the present knowledge for the use of contraceptives in women with SCD. We believe that the collaboration between health care professionals (hematologists, obstetricians, endocrinologists, and primary care providers) can play a major role in identifying the safer contraceptive method to abolish the risks of unintended pregnancy and preserve the health status of patients with SCD.</p> Vincenzo De Sanctis Copyright (c) 2020 Vincenzo De Sanctis 2020-04-27 2020-04-27 12 1 e2020032 e2020032 10.4084/mjhid.2020.032 IRON DEFICIENCY ANEMIA IN CHILDREN RESIDING IN HIGH AND LOW-INCOME COUNTRIES: RISK FACTORS, PREVENTION, DIAGNOSIS AND THERAPY <p><span lang="EN-US">Iron deficiency and iron deficiency anemia (IDA) affect approximately two billion people worldwide and most of them reside in low- and middle-income countries. In these countries, additional causes of anemia include parasitic infections like malaria, other nutritional deficiencies, chronic diseases, hemoglobinopathies and lead poisoning. Maternal anemia in resource-poor nations is associated with low birth weight, increased perinatal mortality and decreased work productivity. Maintaining a normal iron balance in these settings is challenging, as iron-rich foods with good bioavailability are of animal origin that are expensive and/or available in short supply. Apart from infrequent consumption of meat, inadequate vitamin C intake and diets rich in inhibitors of iron absorption are additional important risk factors for IDA in low-income countries. In-home iron fortification of complementary foods with micronutrient powders has been shown to effectively reduce the risk of iron deficiency and IDA in infants and young children in developing countries but is associated with unfavorable changes in gut flora and induction of intestinal inflammation that may lead to diarrhea and hospitalization. In developed countries, iron deficiency is the only frequent micronutrient deficiency. In the industrialized world, IDA is more common in infants beyond the sixth month of life, in adolescent females with heavy menstrual bleeding, in women of childbearing age and elderly people. Other special at-risk populations for IDA in developed countries are regular blood donors, endurance athletes and vegetarians. Several medicinal ferrous or ferric oral iron products exist, and their use is not apparently associated with harmful effects on the overall incidence of infectious illnesses in sideropenic and/or anemic subjects. Further research is needed to clarify the risks and benefits of supplemental iron for children exposed to parasitic infections in the third world, and for children genetically predisposed to iron overload.</span></p> ELPIS MANTADAKIS Copyright (c) 2020 ELPIS MANTADAKIS 2020-06-28 2020-06-28 12 1 e2020041 e2020041 10.4084/mjhid.2020.041 CHILDREN IN CORONAVIRUSES’ WONDERLAND: WHAT CLINICIANS NEED TO KNOW <p>Human coronaviruses (HCoVs) commonly cause mild upper-respiratory tract illnesses but can lead to more severe and diffusive diseases. A variety of signs and symptoms may be present, and infections can range in severity from common cold and sore throat to more serious laryngeal or tracheal infections, bronchitis, and pneumonia. Among the seven coronaviruses that affect humans, (SARS)-CoV, the Middle East respiratory syndrome (MERS)-CoV and the most recent coronavirus disease 2019 (COVID-19) represent potential life-threatening diseases worldwide. In adults they may cause severe pneumonia that evolve in distress respiratory syndrome and multiorgan failure with a high mortality rate. Children appear to be less susceptible to develop severe clinical disease and present usually with mild and aspecific symptoms similar to other respiratory infections typical of childhood. However, some children such as infants, adolescents or those with underlying diseases may be more at-risk categories and require greater caution from clinicians. Available data on pediatric coronavirus infections are rare and scattered in the literature. The purpose of this review is to provide to clinicians a complete and updated panel useful to recognize and characterize the broad spectrum of clinical manifestations of coronavirus infections in the pediatric age.</p> Giuseppe Lassandro Valentina Palladino Anna Amoruso Viviana Palmieri Giovanna Russo Paola Giordano Copyright (c) 2020 Giuseppe Lassandro, Valentina  Palladino, Anna Amoruso, Viviana Palmieri, Giovanna Russo, Paola Giordano 2020-06-28 2020-06-28 12 1 e2020042 e2020042 10.4084/mjhid.2020.042 COBALAMIN DEFICIENCY IN THE ELDERLY <p>Older people are at risk for cobalamin (vitamin B<sub>12</sub>) deficiency because of a number of common disorders (e.g. autoimmune gastritis) and drugs (e.g. antacids) that may alter its absorption and utilization. The prevalence of cobalamin deficiency increases with age, resulting particularly elevated in frail and institutionalized subjects. At variance with common sense, the diagnosis is far from simple and requires a high degree of suspicion, due to heterogeneity and non-specificity of the signs and symptoms, ranging from macrocytosis (with or without anemia) to neuropsychiatric manifestations, that characterize several other aging-related disorders, like hematological malignancies, diabetes, hypothyroidism or vasculopathies. Furthermore, the detection of low levels of serum vitamin B<sub>12</sub> appears poorly sensitive and specific. Other biomarkers, like serum homocysteine or methylmalonic acid, have improved the diagnostic possibilities but are expensive, not widely available and may be influenced by some confounders (e.g. folate deficiency, or chronic renal failure). Early recognition and treatment are crucial, since a proportion of patients develop severe complications, such as bone marrow failure and irreversible neurological impairment. High-dose oral treatment has proven to be as effective as the parenteral route even in subjects with malabsorption, ensuring the complete resolution in the majority of cases. In this review, we trace the essential role of cobalamin in humans, the possible causes and impact of deficiency, the diagnostic challenges and the therapeutic options, between old and emerging concepts, with a particular focus on the elderly.</p> Giacomo Marchi Fabiana Busti Acaynne Lira Zidanes Alice Vianello Domenico Girelli Copyright (c) 2020 Giacomo Marchi, Fabiana Busti, Acaynne Lira Zidanes, Alice Vianello, Domenico Girelli 2020-06-28 2020-06-28 12 1 e2020043 e2020043 10.4084/mjhid.2020.043 ACQUIRED HAEMOPHILIA A: AN INTRIGUING DISEASE <p>Acquired Haemophilia A is a rare acquired bleeding disorder caused by autoantibodies directed against Factor VIII, which neutralize FVIII activity. These inhibitors differ from alloantibodies against FVIII which can occur in congenital Haemophilia A after repeated exposures to plasma-derived or recombinant FVIII products. In most cases the disease occurs suddenly in subjects without personal or familiar history of bleedings, with symptoms that may be mild, moderate or severe. However, only laboratory alterations are present in&nbsp; &nbsp;̴ 30% of patients. The incidence varies from 1 to 4 cases per million/year; more than 80% of patients are elderly, males and females are similarly affected. There is a small peak of incidence related to pregnancy in young women aged 20–40 years. The disease may be underdiagnosed in the elderly. The diagnostic algorithm is based on an isolated prolonged activated partial thromboplastin time, normal thrombin time, absence of Lupus Anticoagulant and a mixing test that reveals the presence of an inhibitor: the finding of reduced FVIII activity and the detection of neutralising autoantibodies against FVIII lead to diagnosis. The disease is idiopathic in &nbsp;&nbsp;44%-63% of cases, while in the others etiological factors are present. Bleeding prevention and treatment are based on therapeutic tools as bypassing agents, recombinant porcine FVIII concentrate or, in a limited number of cases, FVIII concentrates and desmopressin. As soon as the diagnosis has been made, immunosuppressive therapy must be started to eradicate the inhibitor. Better knowledge of the disease, optimal management of bleeding and eradication of the inhibitor have significantly reduced morbidity and mortality in most patients.&nbsp;</p> <p>&nbsp;</p> <p>Keywords: autoantibodies against FVIII, bleeding symptoms, bleeding treatment, eradication therapy.&nbsp;</p> Maria Gabriella Mazzucconi Erminia Baldacci Antonietta Ferretti Cristina Santoro Copyright (c) 2020 Maria Gabriella Mazzucconi, Erminia Baldacci, Antonietta Ferretti, Cristina Santoro 2020-06-28 2020-06-28 12 1 e2020045 e2020045 10.4084/mjhid.2020.045 - KAWASAKI DISEASE AS THE IMMUNE-MEDIATED ECHO OF A VIRAL INFECTION <p>Although etiology of Kawasaki disease remains elusive, the available evidence indicates that the primum movens might be a dysregulation of immune responses to various microbes, i.e. a kind of immune-mediated response induced by a viral infection. Even if several data might suggest that Kawasaki disease is an infection-related clinical syndrome, which can develop only in children with a predisposing genetic background, our knowledge on both the infectious agents involved and the genetic characteristics of children prone to the disease remains poor.</p> Donato Rigante Copyright (c) 2020 Donato Rigante 2020-06-28 2020-06-28 12 1 e2020039 e2020039 10.4084/mjhid.2020.039 CARDIOVASCULAR RISK IN ESSENTIAL THROMBOCYTHEMIA AND POLYCYTHEMIA VERA: THROMBOTIC RISK AND SURVIVAL <p class="western"><span style="color: #1c1d1e;"><span style="font-family: Arial, serif;"><span style="font-size: large;"><span lang="en-US"><strong>Abstract</strong></span></span></span></span></p> <p class="western" align="justify"><a name="tw-target-text"></a> <span style="color: #000000;"><span style="font-family: Arial, serif;"><span style="font-size: large;"><span lang="en-US">Thromboembolic and bleeding events pose a severe risk for patients with Polycythemia Vera (PV) and Essential Thrombocythemia (ET). Many factors can contribute to determine the thrombotic event, including the interaction between platelets, leukocytes and endothelium alterations. Moreover, a very important role can be played by cardiovascular risk factors (CV.R) such as cigarette smoking habits, hypertension, diabetes, obesity and dyslipidemia. In this study we evaluated the impact that CV.R plays on thrombotic risk and survival in patients with PV and ET.</span></span></span></span></p> Vincenzo Accurso Marco Santoro Salvatrice Mancuso Angelo Davide Contrino Paolo Casimio Mariano Sardo Simona Raso Florinda Di Piazza Alessandro Perez Marco Bono Antonio Russo Sergio Siragusa Copyright (c) 2020 Vincenzo Accurso, Maro Santoro, Salvatrice Mancuso, Angelo Davide Contrino, Paolo Casimio, Mariano Sardo, Simona Raso, Florinda Di Piazza, Alessandro Perez, Marco Bono, Antonio Russo, Sergio Siragusa 2020-01-01 2020-01-01 12 1 e2020008 e2020008 10.4084/mjhid.2020.008 CANDIDEMIA IN PATIENTS WITH ACUTE LEUKEMIA: ANALYSIS OF SEVEN YEARS’ EXPERIENCE AT A SINGLE CENTER IN CHINA <p>The study of candidemia in Chinese leukemia patients has been limited. This retrospective study aims to investigate the characteristics and prognostic factors of candidemia among leukemia patients in a Chinese chemotherapy center.</p> <p>From 2009 to 2015, 30 isolates of candidemia were detected in 19 patients with acute leukemia after chemotherapy. The overall incidence of candidemia was 2.12 episode per 1000 admissions<em>. </em><em>Candida tropicalis</em> was the most common <em>Candida</em> species (n = 17; 89.5%), followed by <em>Candida albicans</em> (n = 2; 10.5%). The most common underlying disease was acute myeloid leukemia (94.7%) and induction chemotherapy phase was the most susceptible stage. The vast majority of candidal infections are endogenous rather than central venous catheter-related. The overall 30-day crude mortality rate was 31.6%. Neutrophil recovery (P = 0.000) and initiation of empiric antifungal treatment before first positive blood culture (P = 0.041) were associated with a significant improvement in overall survival.</p> <p>Although the incidence of candidaemia appears to be quite low in patients with leukemia submitted to intensive chemotherapy, its high mortality rate continues to be a crucial problem despite the availability of new effective antifungal drugs. Early diagnosis followed by rapid antifungal treatment remains the cornerstone of successful management. Catheter removal should be considered on an individual basis. The widespread use of newer antifungal agents as prophylaxis among patients with acute leukemia may result in a decreased candidemia incidence.</p> Xiaoyuan Gong mianzeng yang Dong Lin Hui Wei Ying Wang Bingchen Liu Chunlin Zhou Kaiqi Liu Shuning Wei Benfa Gong Guancji Zhang Yuntao Liu Yan Li Xingli Zao Shaowei Qiu Ruxia Gu Yingchang Mi Jianxiang Wang Copyright (c) 2020 Xiaoyuan Gong, mianzeng yang, Dong Lin, Hui Wei, Ying Wang, Bingchen Liu, Chunlin Zhou, Kaiqi Liu, Shuning Wei, Benfa Gong, Guancji Zhang, Yuntao Liu, Yan Li, Xingli Zao, Shaowei Qiu, Ruxia Gu, Yingchang Mi, Jianxiang Wang 2020-01-01 2020-01-01 12 1 e2020003 e2020003 10.4084/mjhid.2020.003 THE PROGNOSTIC SIGNIFICANCE OF TET2 SINGLE NUCLEOTIDE POLYMORPHISM IN EGYPTIAN CHRONIC MYELOID LEUKEMIA <p><strong>Background: </strong>Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm. The pathogenesis of CML is based on the oncoprotein termed BCR‐ABL1. TET2 initiates DNA demethylation and is frequently mutated in hematological malignancies including CML.<sup>(1)</sup> The relation between TET2 acquisition and CML transformation and/or imitinab resistance is needed to be investigated. <strong><sup>(2)</sup></strong></p> <p><strong>Aim:</strong> To evaluate Ten Eleven Translocation 2 gene (TET2) single nucleotide polymorphism (SNP) (rs2454206, rs34402524, rs61744960) in chronic myeloid leukemia (CML) in relation to the disease prognostic criteria.</p> <p><strong>Materials &amp; Method:</strong> The study included 84 subjects; 54 CML in chronic phase and 30 healthy subjects as control group matched for age and sex. Routine investigations including CBC, bone marrow aspiration, biochemical investigations and molecular study were performed in CML patients to identify the disease stage. DNA extraction and SNP assay for TET2 gene polymorphism was done using (Thermo-Fisher predesigned SNP, USA) PCR prism 7500.</p> <p><strong>Results:</strong> The mean age was 45.98±15.7 yrs in CML patients and&nbsp;&nbsp; 39.3±6.587 yrs in control group (p&gt;0.05). TET2 SNP rs 34402524 was either heterozygous and homozygous in CML (48%,and 46.2%) but was mainly homozygous among control (80%) group (p=0.012). TET2 SNP rs 2454206 cases within CML (65.4%) and control (63.3%) group had wild patterns (p=0.046). TET2 SNP rs 61744960 showed a homozygous pattern among all groups (CML and control) showing no statistical significance (p=0.528). TET2 SNP in CML cases did not alter the prognostic criteria as no statistical significance was noted (p&gt;0.05) yet, it was significantly related to spleen size in rs 34402524 where homozygous group had huger sizes and higher BCR-ABL1 levels 6 months after starting TKIs (p&lt;0.05).</p> <p><strong>Conclusions/Recommendation:</strong> TET2 SNP is a common in Egyptian chronic myeloid leukemia. TET2 SNP rs 3442524 was associated with huger spleen size and higher BCR-ABL1 levels after 6 months of starting TKIs suggesting disease progression.</p> Enas A Dammag Nahla A.M. Hamed Nabil A El Halawani Heba S Kassem Mona W Ayad Copyright (c) 2020 Enas A Dammag, Nahla A.M. Hamed, Professor, Nabil A El Halawani, Professor, Heba S Kassem, Professor, Mona W Ayad, Professor 2020-01-01 2020-01-01 12 1 e2020004 e2020004 10.4084/mjhid.2020.004 MICRORNA-181A-3P AS A DIAGNOSTIC AND PROGNOSTIC BIOMARKER FOR ACUTE MYELOID LEUKEMIA <p><strong>Background:</strong> Micro (mi)RNAs play an important role in the pathogenesis and development of acute myeloid leukemia (AML), and their abnormal expression may be sufficient to predict the prognosis and outcomes in AML patients. We evaluated the clinical diagnostic value of miRNA-181a-3p in predicting prognosis and outcomes in patients with AML.</p> <p><strong>Methods: </strong>A total of 119 newly diagnosed adult patients with AML and 60 healthy controls were recruited. Blood specimens were obtained from all AML patients at diagnosis, and 10 blood specimens were obtained on day 28 after induction chemotherapy. The controls also provided blood samples. MiR-181a-3p expression was quantified by PCR, and relative&nbsp;miRNA&nbsp;expression&nbsp;was determined using the comparative Ct method.</p> <p><strong>Results:</strong> Compared with healthy controls, the expression of miRNA-181a-3p was significantly increased in patients with AML. MiR-181a-3p expression could be used to discriminate AML patients from controls, with up-regulated expression correlating with favorable prognosis. Moreover, miRNA-181a-3p expression was significantly decreased in patients who achieved a complete response after induction chemotherapy. The multivariate Cox analysis highlighted the prognostic value of miR-181a-3p for patients with AML.</p> <p><strong>Conclusions:</strong> MiR-181a-3p may be clinically useful as a disease marker for AML, and enhanced the prediction of patient outcomes to chemotherapy.</p> Xiaoling Ma Copyright (c) 2020 Xiaoling Ma 2020-02-26 2020-02-26 12 1 e2020012 e2020012 10.4084/mjhid.2020.012 The PARTIAL ACHIEVEMENT OF THE 90-90-90 UNAIDS TARGET IN A COHORT OF HIV INFECTED PATIENTS FROM CENTRAL ITALY. <p>Despite progress in the prevention and treatment of HIV, persistent issues concerning the evaluation of continuum in care from the serological diagnosis to virologic success remain.</p> <p>Considering the UNAIDS target 90-90-90 for 2020 for treatment and viral suppression of people living with HIV (PLVH), our purpose was to verify if, starting from diagnosis, the viral suppression rate of our cohort of new PLWH satisfied the above targets.</p> <p>The aim of this retrospective study was to compare 2005-2017 data collected at the Perugia Infectious Diseases Clinic with the 2020 UNAIDS 90 targets and to identify risk factors that could be associated with failure to reach these targets.</p> <p>Methods:&nbsp; We included all patients aged ≥15 undergoing HIV test at our clinic between January 2005 and December 2017. We evaluated the unclaimed tests, linkage to care, retention in ART and the viral suppression at 1 and 2 years from starting ART. Data were analyzed between Italians and foreigners.</p> <p>Results: We observed 592 new diagnoses for HIV infection: 61.4% on Italian-natives, 38.5% on foreigners. Considering the continuum of care from diagnosis, 88 (15%) PLWHIV were lost to engagement in care: 55 (9.2%) patients didn’t withdraw the test and 33 (5.5%) &nbsp;didn’t link to care.</p> <p>An antiretroviral treatment was started only on 78.8% of the new diagnoses (467/592) and a viral suppression was obtained at 2 years on 82% of PLWH who had started ART (383/467) namely only 64.7% of the new diagnoses instead of the hoped-for 81% of the UNAIDS target. We found no significant differences between Italians and foreigners</p> <p>Conclusions</p> <p>UNAIDS goal was very far to be reached. The main challenges were unreturned tests as well as the retention in ART. Rapid tests for a test-treat strategy and frequent phone communications in the first ART years could facilitate UNAIDS target achievement.</p> Elisabetta Schiaroli Copyright (c) 2020 Elisabetta Schiaroli 2020-02-26 2020-02-26 12 1 e2020017 e2020017 10.4084/mjhid.2020.017 CHARACTERISTICS AND PROGNOSIS OF HEPATOCELLULAR CARCINOMA IN MULTI-TRANSFUSED PATIENTS WITH THALASSEMIA MAJOR. EXPERIENCE OF A SINGLE TERTIARY CENTER. <p><strong>Background: </strong>In this retrospective study, records of patients with thalassemia major (TM) diagnosed with hepatocellular carcinoma (HCC) from 2008‐2018 were reviewed in order to determine the survival rate and evaluate possible etiological factors associated with survival.</p> <p><strong>Methods:</strong> Forty-two TM patients who were diagnosed with HCC have been included in the study. Most of our patients (78.5%) were anti-HCV positive, while 16.5% had evidence of resolved HBV infection. At the time of HCC diagnosis, 78.5% of our patients were diagnosed with cirrhosis, while the vast majority (98%) had normal or mild elevated liver iron concentration (LIC) values. According to Barcelona Clinic Liver Cancer (BCLC) grading system patients were classified as 0-A: 28.5%, B: 57% and as C-D: 14.5%.&nbsp; HCC has been treated with loco-regional treatment in 78.5% of our patients, while the rest have been treated with sorafenib.</p> <p><strong>Results:</strong> Twenty-eight patients (66.5%) have eventually died with a median survival time of 6 months (range: 2-60). Using the Cox proportional hazard model, the only factors who have been associated with poor survival were BCLC stages C and D.</p> <p><strong>Conclusions:</strong> In conclusion, BCLC staging is the main prognostic factor of survival in patients with TM who develop HCC, with a median survival time of six months.</p> Nikolaos Papadopoulos Dimitrios Kountouras Katerina Malagari Maria Tampaki Maria Theochari John Koskinas Copyright (c) 2020 Nikolaos Papadopoulos, Dimitrios Kountouras, Katerina Malagari, Maria Tampaki, Maria Theochari, John Koskinas 2020-02-26 2020-02-26 12 1 e2020013 e2020013 10.4084/mjhid.2020.013 FINE MAPPING OF GLUCOSE 6 PHOSPHATE DEHYDROGENASE (G6PD) DEFICIENCY IN RURAL AREA OF SOUTH WEST ODISHA USING THE CLINICAL, HEMATOLOGICAL AND MOLECULAR APPROACH <p><strong>Introduction</strong>: The aim of the study was to enumerate the clinical, hematological and molecular spectrum of G6PD deficiency in malaria endemic regions of south west Odisha.</p> <p><strong>Methods</strong>: Diagnosis of G6PD deficiency was made by using the Di-chloroindophenol Dye test in from two south west districts (Kalahandi and Rayagada) of Odisha State. Demographic and clinical history was taken from each individual using a pre-structured questionnaire. Molecular characterization of G6PD deficiency was done using PCR-RFLP and Sanger sequencing.</p> <p><strong>Results</strong>:&nbsp; A total of 1981 individuals were screened, out of which 59 (2.97%) individuals were found G6PD deficient. Analysis revealed that G6PD deficiency was more in males (4.0%) as compared to females (2.3%). G6PD deficiency was significantly higher in tribal population (4.8%) as compared to non-tribal populations (2.4%) (p=0.012, OR=2.014, 95%CI =1.206-3.365). Individuals with history of malaria and G6PD deficiency have high risk of need of blood transfusion than G6PD normal individuals (p=0.026, OR=3.816, 95%CI=1.079-13.496). Molecular analysis revealed G6PD Orissa as the most common (88%) mutation 88% in the studied cohort. G6PD Kaiping (n=3), G6PD Coimbra (n=2) and G6PD Union (n=1) were also identified in studied cohort.&nbsp;</p> <p><strong>Conclusion</strong>: The cumulative prevalence of G6PD deficiency the present is below the estimated national prevalence. G6PD deficiency was higher in tribes as compared to non-tribes. Rare G6PD Kaiping and G6PD Union variants have been identified.</p> Ravindra Kumar MPSS Singh Soumendu Mahapatra Sonam Chourasia Malay Kumar Tripathi John Oommen Praveen Kumar Bharti Rajasubramaniam Shanmugam Copyright (c) 2020 Ravindra Kumar, MPSS Singh, Soumendu Mahapatra, Sonam Chourasia, Malay Kumar Tripathi, John Oommen, Praveen Kumar Bharti, Rajasubramaniam Shanmugam 2020-02-26 2020-02-26 12 1 e2020015 e2020015 10.4084/mjhid.2020.015 THE IMPACT OF CHEMOTHERAPY AFTER PEDIATRIC MALIGNANCY ON HUMORAL IMMUNITY TO VACCINE-PREVENTABLE DISEASES <div>Abstract.Background/Aim: The antibody titer of vaccine-preventable disease in pediatric patients who underwent chemotherapy was assessed in order to evaluate the seroprotection after treatment and the feasibility and the efficacy of a policy of revaccination.Methods: Serum antibody titers of55 patients for hepatitis B (HBV), rubella, varicella-zoster (VZV), measles, mumps, polioviruses, Clostridium tetani(C. tetani)and Streptococcus pneumoniae(S. pneumoniae) were analysed.Results: After chemotherapy, a lack of protective antibody titers against HBV, rubella, VZV, measles, mumps, polioviruses, C. tetani, and S. pneumonia was found in 53%, 45%, 46%, 46%, 43%, 21-26%, 88% and 55% of patients, respectively. In 49 of 55 patients who were tested both before and after chemotherapy for at least a pathogen, the loss of immunity for HBV, rubella, VZV, measles, mumps, polioviruses and C. tetani was respectively 39%, 43%, 38%, 42%, 32%, 33%, and 80%. A low number of B-lymphocytes was associated with the loss of immunity against measles (p=0.04) whereas a high number of CD8+ T-lymphocytes was associated with the loss of immunity against VZV (p=0.03). A single booster of vaccine dose resulted in a seroprotection for HBV, rubella, VZV, measles, mumps, polioviruses, C. tetani and S. pneumoniae in 67%, 83%, 80%, 67%, 33%, 100%, 88% and 67% of patients, respectively. Conclusions: We confirm that seroprotection for vaccine-preventable diseases is affected by treatment for pediatric malignancy. A single booster dose of vaccine might be a practical way to restore vaccine immunity in patients after chemotherapy.</div> <div>&nbsp;</div> Chiara Garonzi Rita Balter Gloria Tridello Anna Pegoraro Manuela Pegoraro Monia Pacenti Novella Scattolo Simone Cesaro Copyright (c) 2020 Chiara Garonzi, Rita Balter, Gloria Tridello, Anna Pegoraro, Manuela Pegoraro, Monia Pacenti, Novella Scattolo, Simone Cesaro 2020-02-26 2020-02-26 12 1 e2020014 e2020014 10.4084/mjhid.2020.014 DEVELOPMENT OF AN IMPROVED EPSTEIN-BARR VIRUS (EBV) NEUTRALIZING ANTIBODY ASSAY TO FACILITATE DEVELOPMENT OF A PROPHYLACTIC GP350-SUBUNIT EBV VACCINE <p>No licensed vaccine is available for prevention of EBV-associated diseases, and robust, sensitive, and high-throughput bioanalytical assays are needed to evaluate immunogenicity of gp350 subunit-based candidate EBV vaccines. Here we have developed and improved analytical tools for such a vaccine’s pre-clinical and clinical validation including a gp350-specific antibody detection assay and an EBV-GFP based neutralization assay for measuring EBV specific antibodies in human donors. The sensitivity of our previously published high-throughput EBV-GFP fluorescent focus (FFA)-based neutralization assay was further improved when guinea pig complement was supplemented using a panel of healthy human sera. Anti-gp350 antibody titers, which were evaluated using an anti-gp350 IgG ELISA assay optimized for capture and detection conditions, were moderately correlated to the FFA-based neutralization titers. Overall, these sensitive, and high-throughput bioanalytical assays are capable of characterizing the serologic response to natural EBV infection, with applications in evaluating EBV antibody status in epidemiologic studies and immunogenicity of candidate gp350-subunit EBV vaccines in clinical studies.</p> Hui Liu Lorraine Gemmell Rui Lin Fengrong Zuo Henry H. Balfour Jennifer C. Woo Gregory M. Hayes Copyright (c) 2020 Hui Liu, Henry H. Balfour, Gregory M. Hayes 2020-02-26 2020-02-26 12 1 e2020016 e2020016 10.4084/mjhid.2020.016 DISCOVERY OF TYPE 3 VON WILLEBRAND DISEASE IN A COHORT OF PATIENTS WITH SUSPECTED HEMOPHILIA A IN CÔTE D’IVOIRE <p><strong>Abstract</strong></p> <p><strong>Aim&nbsp;:</strong> Type 3 von Willebrand disease (VWD) is the most severe form of VWD, characterized by a near-total absence of von Willebrand factor (vWF) leading to a huge deficiency in plasmatic factor VIII (FVIII). VWD may be confused with hemophilia A, sometimes leading to misdiagnosis. The purpose of this work was to finalize the biological diagnosis of patients with FVIII activity deficiency in Abidjan, in order to guide the best type of management. <strong>Methods:</strong> We conducted a cross-sectional descriptive study from June 2018 to April 2019. Forty-nine patients, all of whom had lower FVIII levels or had been referred for bleeding disorder, were monitored in the clinical hematology service. Pro-coagulant activity of coagulation factors was performed in Abidjan. The assays for von Willebrand antigen and activity were performed at Nîmes University Hospital in France. <strong>Results:</strong> The mean age of patients was 13.8 years (1 – 65) and 86% were Ivorian. FVIII deficiency was discovered during a biological checkup, circumcision or post-traumatic bleeding, in 33%, 31% and 29% respectively. The FVIII level of patients was classified as severe (89.8%), moderate (8.2%) and mild (2%). Only one patient had a quantitative deficiency of von Willebrand factor (vWF: Ag &lt;3%) with undetectable von Willebrand factor activity (vWF: Ac) and an FVIII level &lt;1%. <strong>Conclusion:</strong> Not all of the constitutive deficits of FVIII are hemophilia A. It was very important to assess the Willebrand factor of these patients followed in Côte d'Ivoire for whom hemophilia A had been suspected.</p> Adia Eusèbe Adjambri Sylvie Bouvier Roseline N'guessan Emma N’draman-Donou Mireille Yayo-Ayé Marie-France Meledje Missa Louis Adjé Duni Sawadogo Copyright (c) 2020 Adia Eusèbe Adjambri, Sylvie Bouvier, Roseline N'guessan, Emma N’draman-Donou, Mireille Yayo-Ayé, Marie-France Meledje, Missa Louis Adjé, Duni Sawadogo 2020-02-26 2020-02-26 12 1 e2020019 e2020019 10.4084/mjhid.2020.019 THALIDOMIDE FOR PATIENTS WITH THALASSEMIA INTERMEDIA: A RETROSPECTIVE MULTICENTER CLINICAL STUDY <p><strong>Objective</strong><strong>: </strong>This study focused on the efficacy and safety of thalidomide for patients with thalassemia intermedia (TI) in a multicenter trial.</p> <p><strong>Methods</strong><strong>:</strong>Clinical and laboratory data of 62 patients subjected to thalidomide therapy in four centers were retrospectively analyzed. We evaluated the efficacy and safety of thalidomide in the short-term (three months) and long-term follow-up (12 and 24 months). Response to thalidomide was defined as follows: Main Responder (MaR) showing an increase in Hb level of &gt;2.0 g/dl or removal from blood transfusion and Minor Responder (MiR) achieving elevated hemoglobin (Hb) level of 1.0-2.0 g/dl or ≥50% reduction in blood transfusion frequency.</p> <p><strong>Results</strong><strong>:</strong>The overall response rate (ORR) of 62 patients with TI was 93.5% (58/62), with MaR and MiR rates accounting for 62.9% (39/62) and 30.6% (19/62) in short-term follow-up and 66.1% (41/62) and 27.4% (17/62) in long-term follow-up, respectively. The clinical response during long-term follow-up was maintained and the Hb level remained stable during the observation period. The response was still observed in patients with dose reduction despite a slight decrease in Hb level. However, Hb decreased rapidly to the baseline level after drug discontinuation. No effect of thalidomide on spleen size in nonsplenectomized patients was evident. Minimal side-effects were documented throughout, except peripheral neurotoxicity in one patient. Nevertheless, the mean serum ferritin (SF) level was significantly increased after treatment.</p> <p><strong>Conclusion:</strong> Thalidomide had significant therapeutic effects on patients with TI, and the response was sustained with acceptable short-term and long-term adverse reactions. While these preliminary results support the potential long-term efficacy and safety of thalidomide as a therapeutic agent for TI, several issues need to be addressed before its application in the clinic.</p> Kun Yang Yi Wu Yali Zhou Tianhong Zhou Li Wang Zhili Geng Xiaolin Yin Copyright (c) 2020 Kun Yang, Yi Wu, Yali Zhou, Tianhong Zhou, Li Wang, Zhili Geng, Xiaolin Yin 2020-04-27 2020-04-27 12 1 e2020021 e2020021 10.4084/mjhid.2020.021 LYON-UNIVERSITY HOSPITAL EXPERIENCE WITH GEMTUZUMAB OZOGAMICIN THERAPY IN ACUTE MYELOID LEUKEMIA: A ‘REAL-LIFE’ STUDY <p>One-hundred and four adults with newly diagnosed or relapsed/refractory acute myeloid leukemia (AML) were treated with fractionated doses of gemtuzumab ozogamicin (GO) at one-single French center over a 10-year period. We attempted to define predictive factors for response and survival. The overall response rate was 70% (86% in newly diagnosed and 67% in relapsed/refractory AML). Disease-free survival (DFS) and overall survival at 3 years after GO treatment was 31% and 29%, respectively. Mortality during induction was 7%. Among remitters, allogeneic hematopoietic stem cell transplantation can be performed in 33 cases (45%). DFS at 3 years was 54%. Incidences of transplant-related mortality, grade ≥ 3 acute graft-versus-host (GvH) disease, and extensive chronic GvH disease were 15%, 12%, and 27%, respectively.No sinusoidal obstruction syndromes were reported among allografted patients as among the other patients in the studied cohort. GO-based chemotherapy is a viable option for treatment of newly diagnosed and relapsed/refractory AML patients, and is a feasible schedule as a bridge to allogeneic transplant.</p> Xavier Thomas Marica Laurino sandrine loron marie-virginie larcher gaëlle fossard mohamed elhamri alexandre deloire marie balsat fiorenza barraco hélène labussière sophie ducastelle myriam renault eric wattel maël heiblig gilles salles Copyright (c) 2020 Xavier Thomas, Marica Laurino, sandrine loron, marie-virginie larcher, gaëlle fossard, mohamed elhamri, alexandre deloire, marie balsat, fiorenza barraco, hélène labussière, sophie ducastelle, myriam renault, eric wattel, maël heiblig, gilles salles 2020-04-27 2020-04-27 12 1 e2020020 e2020020 10.4084/mjhid.2020.020 The COST-UTILITY ANALYSIS OF FOUR CHELATION REGIMENS FOR Β-THALASSEMIA MAJOR: A CHINESE PERSPECTIVE <p><strong>Background:</strong> The four most commonly used chelation regimens for β-thalassemia major patients in China are a combination therapy of deferoxamine and deferiprone (DFO+DFP), deferoxamine(DFO) monotherapy, deferiprone(DFP) monotherapy and deferasirox(DFX) monotherapy. Such patients use iron chelators their whole lives, resulting in enormous treatment costs. This study analyses the cost-utility of these four regimens from the Chinese healthcare system perspective.</p> <p><strong>Methods:</strong> A Markov decision model was used over a 70-year time horizon and was populated using clinical data from a systematic literature review. We obtained utility data from local and previous research. Costs were estimated using Chinese national sources.</p> <p><strong>Results:</strong> From the base-case analysis results, DFP was the most cost-effective chelation regimen, followed by DFO+DFP, DFO and DFX. DFP had a 99.60%, 78.10% and 64.40% likelihood of being cost-effective versus DFX, DFO and DFO+DFP, respectively, at a payment threshold of 193,932.00 CNY/QALY.</p> <p><strong>Conclusions:</strong> DFP was the most cost-effective chelation regimen for β-thalassemia major patients, followed by DFO+DFP, DFO and DFX. Using DFP as the primary treatment regimen may potentially result in cost-savings and QALY gains for the Chinese healthcare system. To increase these benefits, the Chinese government and clinicians should lower drug costs, increase drug utility and reduce mortality and morbidity. Changes in influential parameters easily affect the results of DFO+DFP versus DFP and of DFP versus DFO; clinicians should focus on such parameters and adjust the regimens accordingly.</p> Jialian Li Copyright (c) 2020 Jialian Li 2020-04-27 2020-04-27 12 1 e2020029 e2020029 10.4084/mjhid.2020.029 CLINICAL USEFULNESS OF BROCHOALVEOLAR LAVAGE IN THE MANAGEMENT OF PULMONARY INFILTRATES IN ADULTS WITH HAEMATOLOGICAL MALIGNANCIES AND STEM CELL TRANSPLANTATION <p class="AbstractCxSpFirst"><span lang="EN-GB">Introduction: Pulmonary complications are frequent in patients with hematologic malignancies and stem cell transplantation. Regardless of the microbiological usefulness of bronchoalveolar lavage (BAL), little information exists on both its benefits as a guide for therapeutic decisions and its impact on patients’ clinical outcome.</span></p> <p class="AbstractCxSpMiddle"><span lang="EN-GB">Methods: A prospective observational single center study was performed between July 2011 and July 2015. Consecutive episodes of pulmonary infiltrates were analyzed in subjects over 18 years of age who presented hematologic malignancies and underwent chemotherapy or stem cell transplantation. </span></p> <p class="AbstractCxSpLast"><span lang="EN-GB">Results: Ninety-six episodes of pulmonary infiltrates were analyzed. Acute leukemia was the most frequent underlying condition. Thirty-seven patients (38.5%) received a stem cell transplant. Sixty-one (62.9%) were neutropenic at the moment of inclusion in the study. A definitive etiologic diagnosis was obtained in 41 cases (42.7%), where infection accounted for the vast majority of causes (33 cases, 80.5%). Definitive diagnosis was reached by non-invasive methods in 13 cases (13.5%). BAL was performed in 47 cases, and led to a diagnosis in 40.4% of the cases. BAL results led to therapeutic changes in 27 cases (57.4%), including the addition of new antimicrobials to empiric treatments in 10. Regarding BAL’s safety, 2 patients experienced minor adverse events and 1 a severe adverse event; no procedure-related deaths were observed. </span></p> <p><span lang="EN-GB">Conclusions: Infection was the leading cause of pulmonary infiltrates in patients with hematologic malignancies and stem cell transplantation. BAL was a useful decision-making diagnostic tool, with minor adverse events</span></p> Laura Jorge Diego Torres Agustín Languasco Pablo Rodriguez Pablo Bonvehí Elena Temporiti Silvia Relloso Cristina Videla Fabián Herrera Copyright (c) 2020 Laura Jorge, Diego Torres, Agustín Languasco, Pablo Rodriguez, Pablo Bonvehí, Elena Temporiti, Silvia Relloso, Cristina Videla, Fabián Herrera 2020-05-01 2020-05-01 12 1 e2020025 e2020025 10.4084/mjhid.2020.025 HEMATOPOIETIC STEM CELL TRANSPLANTATION IN EGYPT CHALLENGES AND OPPORTUNITIES <p>Hematopoietic stem cell transplantation (HSCT) is now an established treatment modality with definitive indications for many hematological disorders. However, this line of treatment requires tremendous resources, and it becomes increasingly difficult for transplanters&nbsp; practicing in the developing world to reconcile the difference between what is possible and what is available. On the basis of 30 years of experience and more than 4250 transplants , this article will focus on the challenges faced our HSCT program and how they were solved. The HSCT program in Egypt started in 1989 on a narrow scale and since that time we faced many challenges.In 1997, the transplant rate increased dramatically with the opening of&nbsp; many HSCT units distributed allover Egypt. Our team is registered in the Center for International Blood and Marrow Transplant Research ,and the number of transplants performed till December 2019 exceeded 4000 cases (60% allogeneic and 40% autologous)<strong>.</strong></p> Hossam Kamel Mahmoud Gamaleldin Mohamed Fathy Alaa Elhaddad Omar Abdelrahman Fahmy Mohamed Abdelmooti Raafat Abdelfattah Mahmoud Tarek Sayed Ahmed Bokhary Copyright (c) 2020 Hossam Kamel Mahmoud, Gamaleldin Mohamed Fathy, Alaa Elhaddad, Omar Abdelrahman Fahmy, Mohamed Abdelmooti, Raafat Abdelfattah, Mahmoud Tarek Sayed Ahmed Bokhary 2020-04-27 2020-04-27 12 1 e2020023 e2020023 10.4084/mjhid.2020.023 HEALTH-RELATED QUALITY OF LIFE IN THAI CHILDREN WITH THALASSEMIA AS EVALUATED BY PEDSQL AND EQ-5D-Y: A SINGLE CENTER EXPERIENCE <p><strong>Background</strong><strong>: </strong>Thalassemia remains a chronic challenging disease in Thailand, but national prenatal screening along with better treatment and management may have improved health-related quality of life (HRQoL) for pediatric patients. We aimed to measure the HRQoL of transfusion dependent (TDT) and non-transfusion dependent (NTDT) of these pediatric patients at our institute.</p> <p><strong>Methods</strong><strong>: </strong>We included all patients 2 – 18 years old, with TDT and NTDT, using the Pediatric Quality of Life Inventory 4.0 Generic Core Scales (PedsQL) and the EuroQol Group’s Five Dimensions for Youth (EQ-5D-Y) instruments. Patients and caregivers responded as appropriate for age.</p> <p><strong>Results</strong><strong>: </strong>Mean PedsQL total summary scores (TSS) (SD) of child self-reports and parent proxy-reports were 81.00 (10.94) and 78.84 (16.72) from 150 participants. Mean EQ-5D-Y VAS (SD) for children was 89.27 (11.56) and 86.72 (10.62) for parent proxies. The most problematic EQ-5D-Y dimension was “having pain or discomfort”. These scores had significant correlations between child and parental proxy perspectives, as well as between the PedsQL and EQ-5D-Y. An age of 8 - 12 years and oral chelation therapy predicted lower self-reported PedsQL TSS. Parental proxy-report predictors for reduced PedsQL TSS and EQ-5D-Y VAS were primary school education for children, parental proxy secondary school education, Universal Coverage insurance, and TDT.</p> <p><strong>Conclusion: </strong>HRQoL scores of our pediatric thalassemia patients had improved from the&nbsp;previous decade, and these findings may represent our better standard of care. Some sociodemographic and clinical characteristics may present negative impacts on HRQoL.</p> Pacharapan Surapolchai Phakatip Sinlapamongkolkul Copyright (c) 2020 Pacharapan Surapolchai, Phakatip Sinlapamongkolkul 2020-06-28 2020-06-28 12 1 e2020036 e2020036 10.4084/mjhid.2020.036 Association of VDBP rs4701 variant, but not VDR/RXR-α over-expression with bone mineral density in pediatric β-Thalassemia patients <p><strong>Introduction:</strong> The reduced rate of bone formation despite the availability of vitamin D has been reported in β-thalassemia.&nbsp; This suggests genetic factors together with environmental one can be implicated in this condition. Since vitamin D binding protein (VDBP) maintains bioavailability of vitamin D which binds to vitamin D receptor (VDR)-retinoid X receptor alpha (RXRA) heterodimer to exert its molecular actions, we speculated that vitamin D metabolic-axis expression signature and variants could be potential molecular candidates for bone turnover/disease in thalassemia. To this end, this study aims to analyze <em>VDR</em>/<em>RXRA </em>expression signature, and two <em>VDBP</em> variants in a pilot sample of Egyptian β-thalassemia children in correlation with bone mineral density (BMD).</p> <p><strong>Patients and methods:</strong> Forty-four β-thalassemia children and 40 unrelated controls were enrolled. The serum bone chemistry profile was measured. Peripheral blood mononuclear cells (PBMN) <em>VDR</em>/<em>RXRA </em>expression levels were quantified by Real-Time quantitative reverse transcription-polymerase chain reaction (qRT-PCR). <em>VDBP</em> rs7041 and rs4588 variants were identified by Real-Time allelic discrimination assay. All patients were subjected to lumbar-spine Dual-energy X-ray absorptiometry (DEXA).</p> <p><strong>Results:</strong> <em>VDR</em>/<em>RXRA</em> expressions were significantly higher in β-thalassemia children compared to controls (<em>P </em>= 0.001 and &lt;0.001, respectively) and showed higher values in β-thalassemia major relative to β-thalassemia intermedia. Expression levels of both genes were not associated with sex or BMD. However, <em>VDBP </em>rs4701 genotyping revealed lower BMD-L4 and a higher frequency of osteoporosis.</p> <p><strong>Conclusions:</strong> β-Thalassemia children had higher expression levels of PBMN <em>VDR</em>/<em>RXRA</em>. <em>VDBP </em>rs4701 variant was associated with osteoporosis in our β-thalassemia patients on vitamin D supplementation. Further large-scale studies in other ethnic populations are warranted.</p> Shaimaa Sahmoud Mostafa Ibrahim Eman Toraih Noha Kamel Manal Fawzy Samar Elfiky Copyright (c) 2020 Shaimaa Sahmoud, Mostafa Ibrahim, Eman Toraih, Noha Kamel, Manal Fawzy, Samar Elfiky 2020-06-28 2020-06-28 12 1 e2020037 e2020037 10.4084/mjhid.2020.037 A SEROPREVALENCE OF HBV, HCV AND HIV-1 AND CORRELATION WITH MOLECULAR MARKERS AMONG MULTI-TRANSFUSED THALASSEMIA PATIENTS IN WESTERN INDIA <p><strong>Background: </strong>Blood transfusion is a lifesaving therapy for patients with hemoglobinopathies. However, the need of frequent transfusion carries the risk of transfusion-transmitted infections (TTIs). This study was aimed to determine the seroprevalence of Hep-B, Hep-C and HIV-1infections among the multi-transfused Beta-thalassemic patients and correlate the same with NAT testing.</p> <p><strong>Methods: </strong>Total 196 patients with Beta-thalassemia were included in the study. Patients were screened for the presence of viral markers by third generation ELISA test as well as for viral DNA/RNA by NAT.&nbsp;</p> <p><strong>Results:</strong> Among these 196 multi-transfused Beta-thalassemia patients, 32.1% were females and 67.8% were males. A total of 100 (51.1%) patients were found to be anti-HCV antibody reactive, while HCV-RNA was positive in 66 (33.7 %) of the 196 patients tested. There were 6 (3.1%) patients reactive for anti-HIV-1 antibody, while 8 (4.1%) were positive for HIV-RNA. There were only 3 (1.5%) patients that were found to be reactive for HBsAg, however 5 (2.5%) were positive for HBV-DNA. Two (1%) patients had co-infection of anti-HCV antibody and HBsAg,whereas 6 patients were found co-infected by NAT testing, in-which 3 (1.5%) were positive for HBV-DNA and HCV-RNA, 1 (0.5%) was positive for HIV-RNA and HBV-DNA, and 2 (1%) had co-infection of HIV-RNA and HCV RNA.</p> <p><strong>Conclusion: </strong>Prevalence of HCV among multi-transfused Beta-thalassemia patients is significantly higher than the normal population. On the other hand, the study showed low prevalence of HBV. Therefore, a follow-up schedule and administration of booster dose of HBV vaccine is strongly recommended for thalassemia patients. To the best of our knowledge, this is the foremost work that shows prevalence of HIV, HBV and HCV in thalassemia patients using both serology and molecular markers in Western India.</p> Kanchan Mishra Avani Shah Krima Patel Kanjaksha Ghosh Sumit Bharadva Copyright (c) 2020 Kanchan Mishra, Avani Shah, Krima Patel, Kanjaksha Ghosh, Sumit Bharadva 2020-06-28 2020-06-28 12 1 e2020038 e2020038 10.4084/mjhid.2020.038 A A Multicentre ICET-A Study of Confirmed SARS-CoV-2 Infection in Patients with Hemoglobinopathies: Preliminary Data from 10 Countries <p><strong>Objectives: </strong>This study aims to investigate, retrospectively, the epidemiological and clinical characteristics, laboratory results, radiologic findings and outcomes of novel coronavirus disease-19 (COVID-19) in patients with transfusion dependent β thalassemia (β-thalassemia major-TM), non-transfusion dependent β thalassemia (β-thalassemia intermedia -TI) and sickle cell disease (SCD). <strong>Design, setting: </strong>A total of 17 Centers, from 10 countries, following 9,499 patients with hemoglobinopathies participated in the survey. <strong>Main outcome measures: </strong>Clinical, laboratory and radiologic findings and outcomes of patients with COVID-19 were collected<strong> from m</strong>edical records and summarized. <strong>Results: </strong>A total of 13 patients, 7 with TM, 3 with TI and 3 with SCD, with confirmed COVID-19, were identified from 6 Centers from different countries. The overall mean age of patients was 33.7±12.3 years (range:13-66); 9/13 (69.2%) patients were females. The commonest symptoms in the 10 symptomatic patients were: fever (80%), cough (70%), headache (60%), fatigue (60%), gastrointestinal symptoms (diarrhea /vomiting/abdominal pain; 50%), tachypnea/dyspnea (40%), and sore throat (40%). Six patients had pneumonia (unilateral, bilateral or multiple opacity) and 4 needed oxygen therapy. An oxygen saturation ≤ 93% was documented in 3 patients at diagnosis. 6/10 patients had an exacerbation of anemia (2 with SCD, associated with back and chest pain in 1 patient), and 3 (&lt;30%) had a decreased absolute number of lymphocytes. Increased C-reactive protein and D-dimers were the most common laboratory findings (66.6 %). <strong>Conclusions: </strong>The clinical presentation for COVID-19 in patients with β-thalassemia and SCD varies. Patients with mild/ordinary COVID-19 infection appear to have clinical symptoms and laboratory findings common to other viral respiratory infections. One 30 year old TM female patient with diabetes and chronic kidney disease. For a better understanding of COVID-19 in patients with hemoglobinopathies, further epidemiologic and clinical studies in a larger cohort of patients are required.</p> Vincenzo De Sanctis Copyright (c) 2020 Vincenzo De Sanctis 2020-06-28 2020-06-28 12 1 e2020046 e2020046 10.4084/mjhid.2020.046 Archi-Prevaleat project. A National Register of color-Doppler ultrasonography of the epi-aortic vessels in Patients Living with HIV <p>Persons Living with HIV (PLWH) are at higher risk of cardiovascular disease (CVD) than the general population. &nbsp;Carotid ultrasound is a non-invasive diagnostic tool, aimed at the assessment of vascular anatomy and function.&nbsp; Our present aim is to generate a National Register of color-Doppler ultrasonography (Archi-Prevaleat) to better evaluate the characteristics of vascular lesions in PLWH on a large number of data.</p> S Martini S Ferrara C Bellacosa B M Ceresia F Taccari G Di Filippo A Tartaglia G Gaeta Paolo Maggi Copyright (c) 2020 S Martini, S Ferrara, C Bellacosa, B M Ceresia, F Taccari, G Di Filippo, A Tartaglia, G Gaeta, Paolo Maggi 2020-02-26 2020-02-26 12 1 e2020018 e2020018 10.4084/mjhid.2020.018 Calreticulin mutation survey by high resolution melting method associated with unique presentations in essential thrombocythemic patients <p>Somatic mutations of exon 9 of calreticulin gene (CALR) were diagnosis and prognosis importance found in patients with JAK2V617F-negative essential thrombocythemia (ET). We survey CALR and JAK2 mutations in our ET patients and study the relationship between mutations and clinical presentations.</p> <p>A total of 60 ET patients were enrolled in the study, and CALR mutations were studied by high resolution melting (HRM) methods and sequencing in JAK2V617F-negative group retrospectively. Clinical manifestations were reviewed retrospectively from chart records.</p> <p>Twenty-one CALR mutations showed eight types of specific melting curves detected by the HRM method and sequencing validation among 26 JAK2 V617F-negative patients. Compared with JAK2 mutations, patients with CALR mutations were younger and had a higher platelet count, lower white cell counts, and lower hemoglobin levels significantly (<em>p</em>&lt;0.05).</p> <p>From our study, HRM methods revealed unique curve types in screening for CALR mutations screening even for complicated mutations. The mutations can be identification rapidly, and cost-effectively by HRM method than other tools. The clinical presentations of CALR mutations from JAK2 mutations showed significant differences and should be checked in ET patients.</p> Yi-Chang Liu Ching-Ping Lee Tsung-Jang Yeh Yuh-Ching Gau Chieh-Yu Hsieh Ya-Lun Ke Jeng-Shiun Du Ming-Hui Lin Hui-Ching Wang Shih-Hao Tang Shih-Feng Cho Jui-Feng Hsu Samuel Yien Hsiao Chin-Mu Hsu Hui-Hua Hsiao Copyright (c) 2020 Yi-Chang Liu, Ching-Ping Lee, Tsung-Jang Yeh, Yuh-Ching Gau, Chieh-Yu Hsieh, Ya-Lun Ke, Jeng-Shiun Du, Ming-Hui Lin, Hui-Ching Wang, Shih-Hao Tang, Shih-Feng Cho, Jui-Feng Hsu, Samuel Yien Hsiao, Chin-Mu Hsu, Hui-Hua Hsiao 2020-04-27 2020-04-27 12 1 e2020022 e2020022 10.4084/mjhid.2020.022 Limiting the Impact of Methicillin Resistant Staphylococcus Aureus in Patients Undergoing Haploidentical Transplantation SUPARNO CHAKRABARTI Sarita Rani Jaiswal Gitali Bhagwati Copyright (c) 2020 SUPARNO CHAKRABARTI, Sarita Rani Jaiswal, Gitali Bhagwati 2020-04-27 2020-04-27 12 1 e2020024 e2020024 10.4084/mjhid.2020.024 Extending Long Term Follow-up of Patient With Acute Myeloid Leukemia after Autologous Stem Cell Transplantation: disclosing late mortality and causes of death. Federica Sorà Patrizia Chiusolo luca laurenti idanna innocenti francesco autore andrea corbingi andrea corbingi sabrina giammarco elisabetta metafuni andrea bacigalupo simona sica Copyright (c) 2020 Federica Sorà, Patrizia Chiusolo, luca laurenti, idanna innocenti, francesco autore, andrea corbingi, andrea corbingi, sabrina giammarco, elisabetta metafuni, andrea bacigalupo, simona sica 2020-04-27 2020-04-27 12 1 e2020030 e2020030 10.4084/mjhid.2020.030 Focusing On A Unique Innate Memory Cell Population Of Natural Killer Cells In The Fight Against COVID-19: Harnessing The Ubiquity Of Cytomegalovirus Exposure SUPARNO CHAKRABARTI Copyright (c) 2020 SUPARNO CHAKRABARTI 2020-06-28 2020-06-28 12 1 e2020047 e2020047 10.4084/mjhid.2020.047 Chronic-graft-versus-host-disease-related polymyositis: a 17-months-old child with a rare and late complication of haematopoietic stem cell transplantation. <p align="justify"><a name="__DdeLink__174_756140867"></a> <span style="color: #000000;"><span style="font-family: Courier, 'Courier New', serif;"><span style="font-size: small;"><span style="font-family: 'Times New Roman', serif;"><span style="font-size: medium;"><span lang="en-GB"><strong>Background: </strong></span></span></span><span style="font-family: 'Times New Roman', serif;"><span style="font-size: medium;"><span lang="en-GB">Chronic graft versus host disease (cGVHD) occurs in 20-30% of paediatric patients receiving haemopoietic stem cell transplantation (HSCT). Neuromuscular disorders such as polymyositis are considered a rare and distinctive but non-diagnostic manifestation of cGVHD and, in absence of other characteristic signs and symptoms, biopsy is highly recommended to exclude other causes. </span></span></span></span></span></span></p> <p align="justify"><span style="color: #000000;"><span style="font-family: Courier, 'Courier New', serif;"><span style="font-size: small;"><span style="font-family: 'Times New Roman', serif;"><span style="font-size: medium;"><span lang="en-GB"><strong>Case report:</strong></span></span></span><span style="font-family: 'Times New Roman', serif;"><span style="font-size: medium;"><span lang="en-GB"> We report a case of a 17-months-old child </span></span></span><span style="font-family: 'Times New Roman', serif;"><span style="font-size: medium;"><span lang="en-GB">affected by hemophagocytic </span></span></span><span style="font-family: 'Times New Roman', serif;"><span style="font-size: medium;"><span lang="en-GB">lymphohistiocytosis who</span></span></span> <span style="font-family: 'Times New Roman', serif;"><span style="font-size: medium;"><span lang="en-GB">underwent a matched </span></span></span><span style="font-family: 'Times New Roman', serif;"><span style="font-size: medium;"><span lang="en-GB">unrelated donor </span></span></span><span style="font-family: 'Times New Roman', serif;"><span style="font-size: medium;"><span lang="en-GB">haematopoietic stem cell transplantation (</span></span></span><span style="font-family: 'Times New Roman', serif;"><span style="font-size: medium;"><span lang="en-GB">HSCT). She </span></span></span><span style="font-family: 'Times New Roman', serif;"><span style="font-size: medium;"><span lang="en-GB">developed a severe cGVHD-related polymyositis that was successfully treated with high-dose steroid therapy, rituximab and sirolimus. </span></span></span></span></span></span></p> <p class="western" lang="en-GB" align="justify"><span style="color: #000000;"><span style="font-family: 'Times New Roman', serif;"><strong>Conclusions: </strong></span></span><span style="color: #000000;"><span style="font-family: 'Times New Roman', serif;"><span style="font-size: medium;">This is the first case of cGVHD-related-polymyositis described in a pediatric patient which was successfully treated with rituximab.</span></span></span></p> Matteo Chinello Rita Balter Massimiliano De Bortoli Virginia Vitale Ada Zaccaron Elisa Bonetti Paola Tonin Gaetano Vattemi Valeria Guglielmi Simone Cesaro Copyright (c) 2020 Matteo Chinello, Rita Balter, Massimiliano De Bortoli, Virginia Vitale, Ada Zaccaron, Elisa Bonetti, Paola Tonin, Gaetano Vattemi, Valeria Guglielmi, Simone Cesaro 2020-01-01 2020-01-01 12 1 e2020002 e2020002 10.4084/mjhid.2020.002 Successful planned pregnancy through vitrified-warmed embryo transfer in a woman with chronic myeloid leukemia: case report and literature review <p>A 35-year-old female patient with chronic myeloid leukemia wanted to have a child. She had been treated with imatinib and had achieved major molecular remission, after which imatinib was intentionally discontinued and interferon-α treatment was initiated. After three failed cycles of artificial insemination with her husband’s semen, the patient underwent treatment with assisted reproductive technology. After two cycles of <em>in vitro</em> fertilization, two embryos (8-cell stage and blastocyst) were cryopreserved. The patient again had elevated <em>BCR/ABL</em> mRNA levels; thus, infertility treatment was discontinued. After 18 months of dasatinib treatment, major molecular remission was observed and the patient underwent vitrified–warmed embryo transfer with a single blastocyst. Thereafter, she became pregnant. Discontinuation of tyrosine kinase inhibitors combined with the timely initiation of infertility treatments, including assisted reproductive technology, may be useful for treating women with CML who wish to become pregnant.</p> Toshifumi Takahashi Copyright (c) 2020 Toshifumi Takahashi 2020-01-01 2020-01-01 12 1 e2020005 e2020005 10.4084/mjhid.2020.005 Hepatic Infiltration with Malignant T-cells Manifesting as Impending Acute Liver failure in Mycosis Fungoides with Large Cell Transformation <p>Here we described a patient with a history of mycosis fungoides who developed large cell transformation manifesting with generalized erythroderma, lymphocytosis, lymphadenopathy and impending acute liver failure (ALF). Three-phase computed tomography of the liver showed neither mass nor hepatomegaly. Liver biopsy confirmed infiltration with malignant CD4+ clonal T-cells. Combination chemotherapy with gemcitabine, dexamethasone, and cisplatin (GDP) resulted in the recovery of liver function and resolution of skin involvement. In Foundation Medicine Hematology Gene Panel, 31 genetic alterations with 11 clinically relevant mutations were identified including ARID2 mutation frequently observed in hepatocellular carcinoma but rarely observed in hematologic malignancies.</p> Yumeng Zhang Jinming Song David Rutenberg Lubomir Sokol Copyright (c) 2020 Yumeng Zhang, Jinming Song, David Rutenberg, Lubomir Sokol 2020-01-01 2020-01-01 12 1 e2020007 e2020007 10.4084/mjhid.2020.007 Isavuconazole therapy of disseminated and encephalic Saprochaete capitata infection in an acute myeloid leukemia patient treated with midostaurin. <p>BACKGROUND<em> Saprochaete capitata</em> is a rare and emerging opportunistic fungus, involving immunocompromised hosts, in particular neutropenic patients after chemotherapy. CASE REPORT We report a case of disseminated and cerebral infection by <em>Saprochaete capitata, </em>in a 68-year-old woman affected by acute myeloid leukemia that was successfully managed with liposomal amphotericin B and isavuconazole. CONCLUSION this case illustrates the feasibility of isavuconazole therapy in the treatment of a <em>S.capitata</em> infection when co-administered with midostaurin.</p> Salvatore Perrone Chiara Lisi Elettra Ortu La Barbera Cristina Luise Miriam Lichtner Corrado Girmenia Giuseppe Cimino Copyright (c) 2020 Salvatore Perrone, Chiara Lisi, Elettra Ortu La Barbera, Cristina Luise, Miriam Lichtner, Corrado Girmenia, Giuseppe Cimino 2020-04-27 2020-04-27 12 1 e2020026 e2020026 10.4084/mjhid.2020.026 The First Case of Concomitant Mycobacterium genavense lymphadenitis and EBV-positive lymphoproliferative disorder <p>This is the first case of concurrent <em>Mycobacterium genavense</em> lymphadenitis and Epstein-Barr virus (EBV)-positive lymphoproliferative disorder (LPD) in the same lymph node with no immunocompromised history. <em>M. genavense</em> infection is a rare opportunistic infection mainly for human immunodeficiency virus (HIV)-infected patients. Although no immunodeficiency was detected in our patient, our case indicates that the immunodeficiency in the background of EBV latency type III and the immunosuppression by malignant lymphoma itself might induce the <em>M. genavense</em> lymphadenitis. This case highly alerts clinicians the immunosuppressive state of EBV-positive LPD with latency type III even if any serological immunodeficient factors are not detected.</p> Yusuke Ito Kensuke Takaoka Kazuhiro Toyama Yoshitaka Wakabayashi Aya Shinozaki-Ushiku Aiko Okazaki Kinuyo Chikamatsu Satoshi Mitarai Tetsuo Ushiku Mineo Kurokawa Copyright (c) 2020 Yusuke Ito, Kensuke Takaoka, Kazuhiro Toyama, Yoshitaka Wakabayashi, Aya Shinozaki-Ushiku, Aiko Okazaki, Kinuyo Chikamatsu, Satoshi Mitarai, Tetsuo Ushiku, Mineo Kurokawa 2020-06-28 2020-06-28 12 1 e2020035 e2020035 10.4084/mjhid.2020.035 Impressive continuous complete response after mogamulizumab in a heavily pre-treated Sézary syndrome patient <p><strong>Background</strong>: Sézary syndrome (SS) is a rare lymphoproliferative neoplasm, almost incurable outside the setting of allogeneic transplantable patients. Prognosis for relapse/refractory patient remains poor, as the available drugs confer short lasting remission. In this setting, the anti-chemokine receptor type 4 (CCR4) monoclonal antibody mogamulizumab demonstrated efficacy in an international, open label, randomized controlled phase 3 trial (MAVORIC) versus vorinostat.</p> <p><strong>Case description: </strong>A heavily pretreated 57-year-old SS woman (stage IVA) was randomized in the mogamulizumab arm of MAVORIC at our Institution. She quickly achieved a response but after 30 cycles she was discontinued from therapy due to cutaneous toxicity. Nevertheless, she is still in complete response (CR).</p> <p><strong>Conclusions</strong>: mogamulizumab is an anti-CCR4 monoclonal antibody that can induce long lasting response also in very heavily pre-treated patients not responding to any previous treatment. The extraordinary characteristic of our patient is that she is still in CR after 2.5 years since treatment discontinuation.</p> Pier Luigi Zinzani Ginevra Lolli Beatrice Casadei Lisa Argnani Laura Nanni Michele Cavo Copyright (c) 2020 Pier Luigi Zinzani, Ginevra Lolli, Beatrice Casadei, Lisa Argnani, Laura Nanni, Michele Cavo 2020-06-28 2020-06-28 12 1 e2020040 e2020040 10.4084/mjhid.2020.040 Successful Outcomes of Severe COVID-19 in Patient with Chronic Lymphocytic Leukemia: Diagnostic Challenges in Immunocompromised Hosts <p>The emergence and spread of 2019 novel coronavirus has led to an unprecedented public health crisis around the globe and has threatened the life of millions of people. We report a severe case of COVID-19 in a patient with chronic lymphocytic leukemia and describe primarily the clinical presentation and the challenges encountered in the COVID-19 diagnosis, treatment and specimens sampling pitfalls. This case highlights the importance of a comprehensive diagnostic approach of pneumonia in immunocompromised hosts, including timely and safe bronchoscopy, because the broad differential diagnosis, more challenging with the current outbreak of COVID-19.</p> Alexandre Malek Copyright (c) 2020 Alexandre Malek 2020-06-28 2020-06-28 12 1 e2020044 e2020044 10.4084/mjhid.2020.044 The efficacy and safety of intralesional sodium stibogluconate for the treatment of cutaneous Leishmaniasis in children under the age of two years Nawfal R Hussein ibrahim naqid Haval Salih Copyright (c) 2020 Nawfal R Hussein, ibrahim naqid, Haval Salih 2020-04-27 2020-04-27 12 1 e2020027 e2020027 10.4084/mjhid.2020.027 Covid-19 and Children with Immune Thrombocytopenia: emerging issues <p>Letter to Editor</p> Giuseppe Lassandro Valentina Palladino Viviana Palmieri Anna Amoruso Giovanni Del Vecchio Paola Giordano Copyright (c) 2020 Giuseppe Lassandro, Valentina Palladino, Viviana Palmieri, Anna Amoruso, Giovanni Del Vecchio, Paola Giordano 2020-04-27 2020-04-27 12 1 e2020028 e2020028 10.4084/mjhid.2020.028 SARS-CoV-2 (COVID-19) and Chronic Myeloid Leukemia (CML): a case report and review of ABL kinase involvement in viral infection <p>no abstract available</p> <p>Aknowledgements:</p> <p>We thank professor Nathan Tubliz, dept. Biology, University of Oregon, for his insightful support.</p> Elisabetta Abruzzese luigia luciano Francesco D'Agostino Malgorzata Monika Trawinska Fabrizio Pane Paolo de Fabritiis Copyright (c) 2020 Elisabetta Abruzzese, luigia luciano, Francesco D'Agostino, Malgorzata Monika Trawinska, Fabrizio Pane, Paolo de Fabritiis 2020-04-27 2020-04-27 12 1 e2020031 e2020031 10.4084/mjhid.2020.031 Delivery in asymptomatic Italian woman with SARS-CoV-2 infection. <p>We report a case of a 33-year-old Italian pregnant at 40 weeks of gestation affected by asymptomatic SARS-CoV-2 infection delivering a healthy baby with no evidence of Coronavirus Disease 2019 (COVID-19). Vaginal delivery was uncomplicated, the breastfeeding was permitted under strict measures of infection control. The breast milk was negative for SARS-CoV-2. Control at 7 and 15 days indicated mother and baby good clinical condition, no signs of neonatal infection demonstrated by news oropharyngeal and rectal swab test negative for SARS-CoV-2.</p> Giuseppe Vittorio De Socio Lisa Malincarne Saverio Arena Stefania Troiani Sara Benedetti Barbara Camilloni Giorgio Epicoco Antonella Mencacci Daniela Francisci Copyright (c) 2020 Giuseppe Vittorio De Socio, Lisa Malincarne, Saverio Arena, Stefania Troiani, Sara Benedetti, Barbara Camilloni, Giorgio Epicoco, Antonella Mencacci, Daniela Francisci 2020-04-27 2020-04-27 12 1 e2020033 e2020033 10.4084/mjhid.2020.033 Burkitt lymphoma as fourth neoplasia in a patient affected by Cowden Syndrome with a novel PTEN germline pathogenic variant <p>x</p> Eugenio Galli Francesco D’Alò Annarosa Cuccaro Eleonora Alma Elena Maiolo Fulvia Brugnoletti Luigi Maria Larocca Marcella Zollino Andrea Paolo Bacigalupo Stefan Hohaus Copyright (c) 2020 Eugenio Galli, Francesco D’Alò, Annarosa Cuccaro, Eleonora Alma, Elena Maiolo, Fulvia Brugnoletti, Luigi Maria Larocca, Marcella Zollino, Andrea Paolo Bacigalupo, Stefan Hohaus 2020-06-28 2020-06-28 12 1 e2020034 e2020034 10.4084/mjhid.2020.034 MANAGEMENT OF PEDIATRIC RHEUMATOLOGICAL DISEASES DURING THE OUTBREAK OF COVID-19: OUR EXPERIENCE <p>Since the COVID-19 epidemic has evolved rapidly also in Italy, specialists in pediatric rheumatology have found themselves addressing the problems of their patients and in particular how to manage the risk of infection and immunosuppressive treatment.&nbsp;This work aims to make known the experience of our center.</p> Romina Gallizzi Diana Sutera Francesca Mazza Alessandra Spagnolo Giovanni Battista Pajno Copyright (c) 2020 Romina Gallizzi, Diana Sutera, Francesca Mazza, Alessandra Spagnolo, Giovanni Battista Pajno 2020-06-28 2020-06-28 12 1 e2020049 e2020049 10.4084/mjhid.2020.049 A socioeconomic paradox in the COVID-19 pandemic in Italy: a call to study determinants of disease severity in high and low income Countries <p>N/A</p> Marialaura Bonaccio Licia Iacoviello Maria Benedetta Donati Giovanni de Gaetano Copyright (c) 2020 Marialaura Bonaccio, Licia Iacoviello, Maria Benedetta Donati, Giovanni de Gaetano 2020-06-28 2020-06-28 12 1 e2020051 e2020051 10.4084/mjhid.2020.051 Spontaneous and severe haematomas in patients with COVID-19 on low-molecular-weight heparin for paroxysmal atrial fibrillation <p>x</p> Maria Mazzitelli Francesca Serapide Bruno Tassone Domenico Laganà Enrico Maria Trecarichi Carlo Torti Copyright (c) 2020 Maria Mazzitelli, Francesca Serapide, Bruno Tassone, Domenico Laganà, Enrico Maria Trecarichi, Carlo Torti 2020-06-28 2020-06-28 12 1 e2020054 e2020054 10.4084/mjhid.2020.054 Guidance for Facing Dilemmas of Hematopoietic Stem Cell Transplant Clinicians in the Coronavirus Disease 2019 (COVID-19) Pandemic: An Iranian Consensus Seied Asadollah Mousavi Soroush Rad Tahereh Rostami Mohammad Vaezi Hosein Kamranzadeh Davood Babakhani Sahar Tavakoli Maryam Barkhordar Tanaz Bahri Amirabbas Hedayatiasl azade kiumarsi Copyright (c) 2020 Seied Asadollah Mousavi, Soroush Rad, Tahereh Rostami, Mohammad Vaezi, Hosein Kamranzadeh, Davood Babakhani, Sahar Tavakoli, Maryam Barkhordar, Tanaz Bahri, Amirabbas Hedayatiasl, azade kiumarsi 2020-06-28 2020-06-28 12 1 e2020050 e2020050 10.4084/mjhid.2020.050 Severe autoimmune hemolytic anemia in Covid-19 infection <p>xx</p> Fehmi Hindilerden Ipek Yonal-Hindilerden Emre Akar Zuhal Yesilbag Kadriye Kart-Yasar Copyright (c) 2020 Fehmi Hindilerden, Ipek Yonal-Hindilerden, Emre Akar, Zuhal Yesilbag, Kadriye Kart-Yasar 2020-06-28 2020-06-28 12 1 e2020053 e2020053 10.4084/mjhid.2020.053 Impact of SARS CoV-2 in hemoglobinopathies: a protective mechanism being from Beta chain Hemoglobin defects? <p>Not required for Letters</p> Lorenza Torti Laura Maffei Francesco Sorrentino Paolo De Fabritiis Rossella Miceli Elisabetta Abruzzese Copyright (c) 2020 Lorenza Torti 2020-06-28 2020-06-28 12 1 e2020052 e2020052 10.4084/mjhid.2020.052 Pidotimod in paucisymptomatic SARS-CoV2 infected patients <p><strong>B</strong></p> Claudio Ucciferri Barone Mirko Jacopo Vecchiet Katia Falasca Copyright (c) 2020 Claudio Ucciferri, Barone Mirko, Jacopo Vecchiet, Katia Falasca 2020-06-28 2020-06-28 12 1 e2020048 e2020048 10.4084/mjhid.2020.048 Cover <p>Printable Cover Vol 12, Year 2020</p> Francesco Guidi Copyright (c) 2020 Francesco Guidi 2020-03-14 2020-03-14 12 1