Plasticity after allogeneic hematopoietic stem cell transplantation

The postulated almost unlimited potential of transplanted hematopoietic stem cells (HSCs) to transdifferentiate into cell types that do not belong to the hematopoietic system denotes a complete paradigm shift of the hierarchical hemopoietic tree. In several studies during the last few years, donor cells have been identified in almost all recipient tissues after allogeneic HSC transplantation (HSCT), supporting the theory that any failing organ could be accessible to regenerative cell therapy. However, the putative potential ability of the stem cells to cross beyond lineage barriers has been questioned by other studies which suggest that hematopoietic cells might fuse with non-hematopoietic cells and mimic the appearance of transdifferentiation. Proof that HSCs have preserved the capacity to transdifferentiate into other cell types remains to be demonstrated. In this review, we focus mainly on clinical studies addressing plasticity in humans who underwent allogeneic HSCT. We summarize the published data on non-hematopoietic chimerism, donor cell contribution to tissue repair, the controversies related to the methods used to detect donor-derived non-hematopoietic cells and the functional impact of this phenomenon in diverse specific target tissues and organ

Breaking stereotypes - Polycythemia secondary to shisha smoking in a middle-age Swiss woman.

The diagnosis of polycythemia, particularly the secondary forms, can be challenging. The distinction between primary and secondary polycythemia is relevant and has management implications. A systematic diagnostic work-up algorithm and a good anamnesis are of paramount relevance. More than one cause may be involved in the development of polycythemia, identifying all of them will be the key to better understanding and eventually solving the polycythemia. We describe a case of a 53-year-old Swiss woman with polycythemia and a high level of carboxyhemoglobin. Her medical story included obesity and obstructive sleep apnea. The anamnesis ruled out the habit of smoking cigarettes, however, the patient reported that she was on a trip to Egypt 10 years before and bought herself a shisha, since then she used to smoke shisha daily, at home, alone. After drastically reducing and then stopping the shisha smoking, 7 months later her blood count and carboxyhemoglobin completely normalized

"The long journey of unexplained erythrocytosis". Erythrocytosis due to high oxygen affinity hemoglobinopathy - hemoglobin variant Little Rock (HBB: c.432C>A) - A report of a Swiss Family and review of the literature.

The differential diagnosis of erythrocytosis is complex, involving a tailored algorithm. Congenital causes are rare and such patients commonly face a long journey looking for diagnosis. This diagnosis requires expertise and accessibility to modern diagnostic tools. We present the case of a young Swiss man with long-standing erythrocytosis of unknown origin and his family. The patient had an episode of malaise as he went skiing above 2,000m altitude. In the blood gas analysis, the p50 was low (16 mmHg) and erythropoietin was normal. Using Next Generation Sequencing (NGS) a mutation in the Hemoglobin subunit beta gene was found, a pathogenic variant known as Hemoglobin Little Rock causing high oxygen affinity. Some family members also had unexplained erythrocytosis, therefore the mutational status of the family was analyzed, the grandmother and mother showed the presence of the same mutation. The use of modern technology offered finally a diagnosis to this family

When Should We Think of Myelodysplasia or Bone Marrow Failure in a Thrombocytopenic Patient? A Practical Approach to Diagnosis.

Thrombocytopenia can arise from various conditions, including myelodysplastic syndromes (MDS) and bone marrow failure (BMF) syndromes. Meticulous assessment of the peripheral blood smear, identification of accompanying clinical conditions, and characterization of the clinical course are important for initial assessment of unexplained thrombocytopenia. Increased awareness is required to identify patients with suspected MDS or BMF, who are in need of further investigations by a step-wise approach. Bone marrow cytomorphology, histopathology, and cytogenetics are complemented by myeloid next-generation sequencing (NGS) panels. Such panels are helpful to distinguish reactive cytopenia from clonal conditions. MDS are caused by mutations in the hematopoietic stem/progenitor cells, characterized by cytopenia and dysplasia, and an inherent risk of leukemic progression. Aplastic anemia (AA), the most frequent acquired BMF, is immunologically driven and characterized by an empty bone marrow. Diagnosis remains challenging due to overlaps with other hematological disorders. Congenital BMF, certainly rare in adulthood, can present atypically with thrombocytopenia and can be misdiagnosed. Analyses for chromosome fragility, telomere length, and germline gene sequencing are needed. Interdisciplinary expert teams contribute to diagnosis, prognostication, and choice of therapy for patients with suspected MDS and BMF. With this review we aim to increase the awareness and provide practical approaches for diagnosis of these conditions in suspicious cases presenting with thrombocytopenia

Unstable hemoglobin Montreal II uncovered in an adult with unexplained hemolysis exacerbated by a presumed viral infection: a case report.

BACKGROUND Unstable hemoglobinopathies are rare inherited disorders of hemoglobin causing a reduction of hemoglobin molecule solubility. This results in an unstable hemoglobin tetramer/globin polypeptide, which precipitates within the red blood cell. Affected red blood cells have a reduced lifespan due to oxidative stress and cellular rigidity, and tend to be phagocytized by spleen macrophages more rapidly. Unstable hemoglobin is frequently under- or misdiagnosed, because its clinical presentation varies broadly. Therefore, testing for unstable hemoglobinopathies is indicated in cases of unexplained hemolytic anemia. However, this approach is not systematically followed in clinical practice. CASE REPORT A 25-year-old Caucasian man with a recent history of a presumed viral upper respiratory infection was referred to the hematology outpatient clinic because of hemolytic anemia. The patient had scleral icterus, moderate splenomegaly, and mild macrocytic anemia with high reticulocyte count. Unconjugated bilirubin and lactate dehydrogenase were elevated. Haptoglobin was undetectable. Direct antiglobulin test was negative. Blood smear examination revealed anisopoikilocytosis, polychromasia, bite cells, and basophilic stippling, but no Heinz bodies. High-performance liquid chromatography and capillary electrophoresis showed slightly increased hemoglobin A2, normal fetal hemoglobin, and a variant hemoglobin. Deoxyribonucleic Acid sequencing revealed the heterozygous mutation c430delC in the beta-globin gene hallmark of hemoglobin Montreal II and the heterozygous mutation c287C>T in the alpha-globin gene corresponding to hemoglobin G-Georgia, indicative of the not yet described combination of double-heterozygous hemoglobin Montreal II and hemoglobin G-Georgia variants. Hemoglobinopathy Montreal II was here not associated with β-thalassemia syndrome, and carriers did not show ineffective erythropoiesis. In addition to the case report, we provide information about the largest pedigree with hemoglobinopathy Montreal II identified to date. CONCLUSION We emphasize that a transitory acute condition may uncover an underlying inherited red blood cell disorder. In this regard, awareness should be raised among hematologists caring for adult patients that unstable hemoglobinopathies should be considered in the differential diagnosis of unexplained hemolytic anemias

Real-world impact of primary immune thrombocytopenia and treatment with thrombopoietin receptor agonists on quality of life based on patient-reported experience: Results from a questionnaire conducted in Switzerland, Austria, and Belgium.

AIMS OF THE STUDY Thrombopoietin receptor agonists (TPO-RAs) are approved for immune thrombocytopenia (ITP), but their impact on health-related quality of life (HRQoL) remains poorly investigated in clinical practice. This observational study aimed to gain insight into real-world patient-reported experiences of the burden of ITP and TPO-RAs. METHOD An online questionnaire of closed questions was used to collect views of patients with primary ITP from Switzerland, Austria, and Belgium, between September 2018 and April 2020. RESULTS Of 46 patients who completed the questionnaire (total cohort), 41% were receiving TPO-RAs. A numerically higher proportion of patients reported being free from symptoms at the time of the questionnaire (54%) than at diagnosis (24%), irrespective of treatment type. Bleeding, the most frequently reported symptom at diagnosis (59%), was reduced at the time of the questionnaire (7%). Conversely, fatigue was reported by approximately 40% of patients at both diagnosis and the time of the questionnaire. Having a normal life and their disease under control was reported by 83% and 76%, respectively, but 41% were worried/anxious about their condition. Nearly 50% reported that ITP impaired their engagement in hobbies/sport or energy levels and 63% reported no impact on employment. When stratified by TPO-RA use, bleeding was better controlled in those receiving TPO-RAs than not (0% vs 11%). A numerically lower proportion receiving TPO-RAs than not reported worry/anxiety about their condition (16% vs 59%) and shifting from full-time to part-time employment (11% vs 22%). Similar proportions were satisfied with their therapy whether they were receiving TPO-RAs or not (89% vs 85%). CONCLUSIONS Many factors affect HRQoL in patients with ITP. Of patients receiving TPO-RAs, none experienced bleeding at the time of the questionnaire; they also showed a more positive perspective for some outcomes than those not using TPO-RAs. However, fatigue was not reduced by any treatment

Hematocrit Self-Testing in Patients with Polycythemia Vera and Other Hematological Conditions: Assessing the Accuracy of the StatStrip Xpress® 2 LAC/Hb/Hct Device and User Opinion about the Device in Real-World Clinical Practice.

Maintaining hematocrit (Hct) levels below 45% can reduce morbidity and mortality in patients with polycythemia vera (PV). A device that patients can use to self-monitor Hct levels could enable timely interventions if Hct levels increase above 45%, and could improve quality of life (QoL). This study evaluated the accuracy of the StatStrip Xpress® 2 LAC/Hb/Hct meter (Hb/Hct meter) when used by healthcare professionals (HCPs) or patients in clinical practice. Blood samples from 68 visits for 60 patients with PV or other hematological conditions were collected and analyzed by HCPs using a laboratory hematological analyzer, and by patients (self-test) and HCPs (professional test) using the Hb/Hct meter at two Swiss centers. Accuracy was assessed as the mean difference in readings between two users/methods (mdiff, 90% confidence interval; Spearman correlation [r]). The Hct values were similar between the professional test and analyzer (n = 66 comparisons, mdiff = 0.1% [-0.5 to 0.8]; r = 0.95, p < 0.001), the self-test and professional test (n = 62 comparisons, mdiff = -0.2% [-1.1 to 0.7]; r = 0.93, p < 0.001), and the self-test and analyzer (n = 63 comparisons, mdiff = 0.0% [-0.8 to 0.7]; r = 0.94, p < 0.001). The hemoglobin values across users/methods were also similar. Reporting their opinion on the Hb/Hct meter at visit 1, 100% of the patients found it easy to use, and 97% were willing to use it at home. Of the patients with PV, approximately 71% and 56%, respectively, stated that they would feel safer using a self-testing device, and that it would improve their QoL. These findings demonstrate the potential of the Hb/Hct meter for HCP and patient use in real-world settings

"Don't add fuel to the fire"- Hyperhemolysis Syndrome in a pregnant woman with compound Sickle cell disease/ß0-thalassemia - Case report and review of the literature

Hyperhemolysis Syndrome (HHS) is a rare and severe post-transfusion complication characterized by the destruction of both recipient and donor red blood cells (RBC). The underlying mechanism of HHS is not fully understood and proper management can be difficult. Furthermore, there are few reports regarding HHS in pregnancy. We report on the development and management of HHS in a pregnant woman with known compound Sickle cell disease/ß-0-thalassemia after transfusion of not fully compatible packed red blood cells (PRBC). We aim to raise awareness on this diagnostically challenging and life-threatening type of hemolysis with this report, and to stress the need to consider the diagnosis of HHS in SCD patients with progressive anemia despite PRBC administration

Feasibility of electronic patient-reported outcome monitoring and self-management program in aplastic anemia and paroxysmal nocturnal hemoglobinuria-a pilot study (ePRO-AA-PNH).

INTRODUCTION Electronic patient-reported outcomes (ePRO) are increasingly recognized in health care, as they have been demonstrated to improve patient outcomes in cancer, but have been less studied in rare hematological diseases. The aim of this study was to develop and test the feasibility of an ePRO system specifically customized for aplastic anemia (AA) and paroxysmal nocturnal hemoglobinuria (PNH). METHODS After performing a user-centered design evaluation an ePRO system for AA and PNH patients could be customized and the application was tested by patients and their medical teams for 6 months. Symptom-reporting triggered self-management advice for patients and prompts them to contact clinicians in case of severe symptoms, while the medical team received alerts of severe symptoms for patient care. RESULTS All nine included patients showed a high adherence rate to the weekly symptom-reporting (72%) and reported high satisfaction. The system was rated high for usage, comprehensibility, and integration into daily life. Most patients (78%) would continue and all would recommend the application to other AA/PNH patients. Technical performance was rarely a barrier and healthcare providers saw ePRO-AA-PNH as a useful supplement, but the lacking integration into the hospital information system was identified as a major barrier to usage. CONCLUSION An ePRO system customized for AA and PNH was feasible in terms of adherence, satisfaction, and performance, showing a high potential for these rare conditions in terms of data collection and patient guidance. However, the integration into clinical workflows is crucial for further routine use. TRIAL REGISTRATION ClinicalTrials.gov NCT04128943

JAK2 Unmutated Polycythaemia-Real-World Data of 10 Years from a Tertiary Reference Hospital.

(1) Background: Polycythaemia is defined by an increase in haemoglobin (Hb) concentration, haematocrit (Hct) or red blood cell (RBC) count above the reference range adjusted to age, sex and living altitude. JAK2 unmutated polycythaemia is frequent but under-investigated in original publications. In this retrospective cohort study, we investigated the clinical and laboratory data, underlying causes, management and outcomes of JAK2 unmutated polycythaemia patients. (2) Methods: The hospital database was searched to identify JAK2 unmutated patients fulfilling WHO 2016 Hb/Hct criteria for PV (Hb >16.5 g/dL in men and >16 g/dL in women, or Hct > 49% in men and >48% in women, or RBC mass > 25% above mean normal predicted value) between 2008 and 2019. Clinical and laboratory data were collected and analysed. (3) Results: From 727,731 screened patients, 294 (0.04%) were included, the median follow-up time was 47 months. Epo and P50 showed no clear pattern in differentiating causes of polycythaemia. In 30%, the cause remained idiopathic, despite extensive work-up. Sleep apnoea was the primary cause, also in patients under 30. Around 20% had received treatment at any time, half of whom had ongoing treatment at the end of follow-up. During follow-up, 17.2% developed a thromboembolic event, of which 8.5% were venous and 8.8% arterial. The mortality was around 3%. (4) Conclusions: Testing for Epo and P50 did not significantly facilitate identification of underlying causes. The frequency of sleep apnoea stresses the need to investigate this condition. Idiopathic forms are common. A diagnostic flowchart based on our data is proposed here. NGS testing should be considered in young patients with persisting polycythaemia, irrespective of Epo and P50 levels