Swiss Survey on current practices and opinions on clinical constellations triggering the search for PNH clones.

UNLABELLED This national survey investigated the current practice in Switzerland by collecting participants' opinions on paroxysmal nocturnal hemoglobinuria (PNH) clone assessment and clinical practice. AIM This study aimed to investigate clinical indications prompting PNH clones' assessment and physician's accessibility of a flow cytometry facility, and also to understand clinical attitudes on the follow-up (FU) of patients with PNH clones. METHODS The survey includes 16 multiple-choice questions related to PNH and targets physicians with a definite level of experience in the topic using two screener questions. Opinion on clinical management was collected using hypothetical clinical situations. Each participant had the option of being contacted to further discuss the survey results. This was an online survey, and 264 physicians were contacted through email once a week for 5 weeks from September 2020. RESULTS In total, 64 physicians (24.2%) from 23 institutions participated (81.3% hematologists and 67.2% from university hospitals). All had access to flow cytometry for PNH clone testing, with 76.6% having access within their own institution. The main reasons to assess for PNH clones were unexplained thrombosis and/or hemolysis, and/or aplastic anemia (AA). Patients in FU for PNH clones were more likely to be aplastic anemia (AA) and symptomatic PNH. In total, 61% of the participants investigated PNH clones repetitively during FU in AA/myelodysplastic syndromes patients, even when there was no PNH clone found at diagnosis, and 75% of the participants tested at least once a year during FU. Opinions related to clinical management were scattered. CONCLUSION The need to adhere to guidelines for the assessment, interpretation, and reporting of PNH clones emerges as the most important finding, as well as consensus for the management of less well-defined clinical situations. Even though there are several international guidelines, clear information addressing specific topics such as the type of anticoagulant to use and its duration, as well as the indication for treatment with complement inhibitors in some borderline situations are needed. The analysis and the discussion of this survey provide the basis for understanding the unmet needs of PNH clone assessment and clinical practice in Switzerland

Myeloproliferative neoplasms in young patients: clinical features and specific management

Myeloproliferative neoplasms (MPN) are a group of clonal haematopoietic stem cell diseases usually associated with increased production of blood cells (red blood cells, white blood cells, and platelets), splenomegaly, and other symptoms (fatigue, pruritus, night seat, early satiety, abdominal discomfort, weight loss, and recurrent fever). In addition, the main complications of MPN involve thrombotic (venous and arterial) events and less frequent progression to acute leukaemia and death. Usually, MPN are diagnosed during the 6th decade, but it is now wellrecognised that a small proportion of patients (<20%) are diagnosed below the age of 40 years. The diagnosis of MPN in young patients, in addition to the extension of life expectancy, has revealed emergent questions regarding thrombotic risk, progression, disease evolution, and pregnancies. Data on young MPN are limited, and this original thesis presents three papers illustrating two aspects of this population. The first two papers focus on the description of this population regarding characteristics of diagnosis, management, and prognosis. Moreover, the first paper presents the largest real-world study of young patients diagnosed with MPN and provides reliable information on this population. Finally, the third paper focused on the management of pregnancy in this population. MPN are associated with a high risk of foetal and maternal complications. The use of interferon is part of the treatment to reduce complications during pregnancy. This paper presents the first and largest series of patients treated with peginterferon alfa-2a during pregnancy, a more recently developed form of interferon with better tolerance than the previously used interferon alfa-2a. This selected work is put into perspective with the current knowledge of this rare population of young patients with MPN and its management

Validation de l'index de risque lié à la pathologie chez les patients ayant bénéficié d'une allogreffe de cellules souches hématopoïétiques partiellement déplétée en lymphocytes T in vitro

L’allogreffe de cellules souches hématopoïétiques (HSCT) est l’un des seuls traitements à visée curative dans de nombreuses pathologies hématologiques malignes. Ce traitement est associé à une mortalité et une morbidité importantes, principalement liées à la maladie du greffon contre l’hôte (GVHD). Dans l’unité de transplantation des Hôpitaux Universitaires de Genève, nous utilisons une technique de déplétion partielle en lymphocytes T in vitro (pTDEP) pour diminuer l’incidence de GVHD. Cependant, cette technique est peu rependue et les études cliniques, n’incluent habituellement pas de patients ayant bénéficié de cette technique. Au fil des ans, de nombreux scores pronostiques ont été développés dans l’HSCT, afin d’estimer le risque lié à cette procédure et d’aider le clinicien. L’équipe de P. Armand (Dana-Farber Cancer Institute, Boston,) a développé deux scores pronostique basé spécifiquement sur la pathologie au moment de l’HSCT. Ces scores, n’ont pas été validés chez des patients ayant bénéficié d’une pTDEP. Nous avons donc décidé d’appliquer ces scores aux patients ayant bénéficié de cette procédure

Acute respiratory distress syndrome in a patient with primary myelofibrosis after ruxolitinib treatment discontinuation

Ruxolitinib is a Janus kinase (JAK) inhibitor used for the treatment of myelofibrosis with demonstrated efficacy for the alleviation of disease-related symptoms and splenomegaly. Anemia and thrombocytopenia are the main secondary effects. However, there are case reports of rare but serious adverse events following drug withdrawal. We present a case of a 76-year-old man diagnosed with primary myelofibrosis who presented with constitutional symptoms and symptomatic splenomegaly. Ruxolitinib was started (15 mg twice daily) and his disease-related symptoms disappeared. Six weeks later, he developed grade 4 thrombocytopenia and grade 3 anemia. Ruxolitinib was stopped and corticosteroid treatment (prednisone 1 mg/kg/day) was started to avoid a cytokine-rebound reaction. The patient then developed fever, chills, a biological inflammatory syndrome, and an acute respiratory disease syndrome. Full workup excluded an infection and we concluded that ruxolitinib withdrawal syndrome was the likely cause. Continued treatment with corticosteroids, as well as oxygen supply and continuous positive airway pressure, allowed an alleviation of his symptoms. This case report describes acute respiratory distress syndrome as another potential complication of ruxolitinib withdrawal syndrome

Pacritinib: a new agent for the management of myelofibrosis?

Myelofibrosis (MF) is a clonal haematological disease associated with recurrent somatic gene mutations (JAK2V617F, MPL, CALR) and constitutive activation of the Janus kinase (JAK)/Signal Transducer and Activator of Transcription pathway. MF is often characterised by debilitating symptoms and JAK inhibitors (JAKIs) have revolutionised available therapeutic options. Ruxolitinib, a JAK1 and 2 inhibitor, is the only currently approved agent. Several other JAKIs are undergoing evaluation in the clinical trial setting and Pacritinib , a novel JAK2 and FLT3 inhibitor, is at an advanced stage of investigation with recent completion of a Phase III trial and another ongoing

COVID‐19 infection and treatment with hydroxychloroquine cause severe haemolysis crisis in a patient with glucose‐6‐phosphate dehydrogenase deficiency

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an inherited genetic disorder caused by red cell enzymatic defects and is associated with haemolytic crisis when patients are exposed to oxidative agents (fava beans, drugs, infections). Hydroxychloroquine is suspected to trigger haemolytic crisis in G6PD-deficient patients, and off-label administration of this drug to patients infected with the novel coronavirus (SARS-CoV-2) could cause concern. We report here the first case of severe haemolytic crisis in a patient with G6PD deficiency, initiated by severe COVID-19 infection and hydroxychloroquine use. With worldwide spread of COVID-19, especially in regions with a high prevalence of G6PD deficiency, our case should alert physicians to this possible correlation

Surveillance biologique des héparines et du fondaparinux

Anticoagulation with unfractionated heparin, low molecular weight heparin or fondaparinux is common practice in thromboembolic disease, atrial fibrillation and mechanical heart valves. Some of these molecules, with specific pharmacokinetic, requires specific monitoring. Unfractionated heparin requires close monitoring by aPTT and/or anti-FXa activity while LMWH and fondaparinux do not require biological surveillance except in a few specific situations