Quality of Life in Transfusion-Dependent Thalassemia Patients in Greece Before and During the COVID-19 Pandemic.

OBJECTIVES: The peak of the COVID-19 pandemic was a challenging situation for transfusion-dependent thalassemia (TDT) patients. The objectives of this study were to measure the quality of life (QoL) in TDT patients during the COVID-19 lockdown restriction measures, compare the results with the pre-COVID-19 era, and evaluate the influence of sociodemographic and clinical factors on QoL. METHODS: This was a cross-sectional study of 110 consecutively selected adult TDT patients, during the stringent lockdown restriction measures implemented in Greece. All participants completed a combination of 2 QoL questionnaires, the generic Short-Form Health Survey 36 version 2 and the disease-specific Transfusion-Quality of life (TranQol). We used the "1/2 SD method," a distribution-based approach to calculate minimal clinically important differences and clinically compare the QoL scores between the pre-COVID-19 and post-COVID-19 era. A backward stepwise linear regression was selected to explore the influence of potential predictors on TranQol scores. RESULTS: The Short-Form Health Survey 36 version 2 and TranQol scores remained low but not clinically different compared with the pre-COVID-19 era. Older, married, and higher educated TDT patients exhibited significantly lower TranQol summary scores. The patients who reported a negative effect of the COVID-19 pandemic had significantly lower TranQol scores in summary and all subdomains except for school and career. CONCLUSIONS: During the COVID-19 pandemic, the overall QoL of TDT patients was clinically similar to the status of the pre-COVID-19 era. Nevertheless, most of the significant QoL subdomains were negatively affected, and distinct groups of TDT patients were more vulnerable.

A Cross-Sectional, Multicentric, Disease-Specific, Health-Related Quality of Life Study in Greek Transfusion Dependent Thalassemia Patients.

The assessment of health-related quality of life (HRQoL) in thalassemia offers a holistic approach to the disease and facilitates better communication between physicians and patients. This study aimed to evaluate the HRQoL of transfusion-dependent thalassemia (TDT) patients in Greece. This was a multicentric, cross-sectional study conducted in 2017 involving 283 adult TDT patients. All participants completed a set of two QoL questionnaires, the generic SF-36v2 and the disease-specific TranQol. Demographic and clinical characteristics were used to predefine patient subgroups. Significant factors identified in the univariate analysis were entered into a multivariate analysis to assess their effect on HRQoL. The SF-36 scores of TDT patients were consistently lower compared to the general population in Greece. The mean summary score of TranQol was relatively high (71 ± 14%), exceeding levels observed in national surveys in other countries. Employment emerged as the most significant independent factor associated with better HRQoL, whereas age had the most significant negative effect. This study represents the first comprehensive QoL assessment of a representative sample of the TDT population in Greece. The implementation of TranQol allowed for the quantification of HRQoL in Greece, establishing a baseline for future follow-up, and identifying more vulnerable patient subgroups.

Reporting of adverse events of treatment interventions in multiple myeloma: an overview of systematic reviews.

The present study is an overview of systematic reviews focusing on adverse events of antimyeloma treatments. It provides a systematic description of adverse events as they are reported in the systematic reviews as well as a critical appraisal of included reviews. We conducted a comprehensive literature search in the most widely used electronic databases looking for systematic reviews that had an adverse event of an antimyeloma treatment intervention as primary outcome. Two independent reviewers conducted selection of included studies and data extraction on predesigned online forms and assessed study quality using AMSTAR 2. Overall corrected covered area (CCA) was calculated to examine the overlap of primary studies across systematic reviews. After screening eligible studies, 23 systematic reviews were included in this overview. Seven reviews with overall CCA of 14.7% examined cardiovascular adverse events of different drugs, including immunomodulatory drugs and proteasome inhibitors (mainly carfilzomib). Nine focused on infections, presenting with overall CCA of 5.8%, each one focused on a different drug or drug class. Three studied thromboembolism in patients treated either with lenalidomide, any immunomodulatory drug, or with daratumumab and had an overall CCA equal to 1.5%. Four more reviews focused on bortezomib-associated neurotoxicity, carfilzomib-associated renal toxicity, or second primary malignancies as an adverse event of lenalidomide or anti-CD38 monoclonal antibody treatment. The quality of included studies as judged by AMSTAR 2 was mostly critically low. Absence of a priori registered protocol and formal assessment of risk of bias of included primary studies were the most common shortcomings. Reporting of antimyeloma drug-associated toxicity is supported by multiple systematic reviews; nevertheless, methodological quality of existing reviews is mostly low.

Kidney transplantation in an adult with transfusion-dependent beta thalassemia: A challenging case report and literature review.

The markedly increased survival of transfusion-dependent beta thalassemia patients has led to the recognition of new complications, such as renal disorders. Kidney transplantation is nowadays the preferred treatment option for end-stage kidney disease (ESKD). We describe a case of a 49-year-old woman with ß-Transfusion Dependent Thalassemia, who developed ESKD as a result of focal segmental glomerulosclerosis and received a deceased-donor kidney transplant following hemodialysis for over a decade. The particular challenges of this case are discussed, including the long-term survival in hemodialysis. Our patient had to overcome multiple obstacles, including hypercoagulability issues presented in the form of thromboembolism, infections, such as hepatitis C and gastroenteritis, and the acute T-cell-mediated rejection, which had to be managed postoperatively. A review of the current literature revealed only one previous report of a thalassemia patient who successfully underwent renal transplantation. More than a year after the transplantation our patient presents with a normal glomerular filtration rate (GFR=62ml/min/1.73m2) and creatinine level (Cr=0.96mg/dL) and is transfused every 3 weeks. In conclusion, renal transplantation is possible in patients with TDT and should not be discouraged. Regular transfusions and optimal follow-up for the elimination of post-transplant complications are required.

Immune Response of Adult Sickle Cell Disease Patients after COVID-19 Vaccination: The Experience of a Greek Center.

Vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are essential weapons to control the spread of the coronavirus disease-19 (COVID-19) pandemic and protect immunocompromised patients. With a greater susceptibility to infection, sickle cell disease (SCD) patients are considered as "high risk" patients during the current COVID-19 pandemic. In our study, we try to determine the immune response of adult SCD patients monitored at our center after the first and second dose of the qualified mRNA vaccines available and correlate them to several disease-specific markers, as well as complement activation. The results demonstrate that the levels of neutralizing antibodies (nAbs) against SARS-CoV-2 were adequate for most patients studied after the second dose and there seemed to be a certain association with complement activation. Further studies are critical to determine the durability of this immune response and the potential benefit of a third dose.

Eosinophilic dermatosis in a patient with chronic lymphocytic leukemia: a rare case report.

Chronic lymphocytic leukemia (CLL) is a type of malignant lymphoproliferative disorder characterized by a rapid and uncontrolled increase in lymphoid cells, mostly monoclonal B-cells (B-CLL). Patients with CLL may present cutaneous lesions that can be classified as either "specific" or "non-specific." In CLL patients, specific skin eruptions arise from leukemic cell infiltration, recognized histopathologically in tissue sample biopsy. Non-specific lesions encompass the majority of eruptions in CLL patients and may present as petechiae, purpura, urticaria, exfoliative dermatitis, paraneoplastic pemphigus, vasculitis, or eosinophilic dermatosis. Eosinophilic dermatosis of hematologic malignancy (EDHM) is a rare cutaneous manifestation that presents as an eruption in various locations and is characterized as papular, pruritic, and sometimes vesicular or vesiculobullous. Here we present a rare and interesting case of a 58-year-old woman with a medical history of B-CLL that was examined at our clinic for evaluation of an unspecified diffuse vesicular pruritic rash. The patient was first diagnosed with CLL 3 years earlier and followed a 6-month course of immuno-chemotherapy with rituximab, fludarabine, and cyclophosphamide. We also performed brief review of previous literature and present the results.

Necrobiosis Lipoidica in a Patient with ß-Thalassemia Major: A Case Report and Review of the Literature.

Necrobiosis lipoidica (NL) is a rare granulomatous disease that predominantly affects middle-aged women and is often associated with diabetes mellitus (DM), rheumatoid arthritis (RA) and other metabolic disorders. Thalassemias are the most common hereditary hemoglobin (Hb) disorders worldwide. A few studies investigated dermatologic problems that coexist with ß-thalassemia major (ß-TM). The most common skin disorders in patients with ß-TM are xerosis, urticaria, pseudoxanthoma, hyperpigmentation, leg ulcers and small-vessel vasculitis. Necrobiosis lipoidica has only been occasionally reported in patients with ß-TM. Herein, we present a female with ß-TM and NL. Furthermore, a brief review of the literature was performed.

Rivaroxaban Use in Patients with Hemoglobinopathies.

The use of rivaroxaban in patients with hemoglobinopathies and thrombotic events has not been studied extensively. Here we present eight cases of such patients, five receiving rivaroxaban for stroke and systemic embolism prevention due to non-valvular atrial fibrillation and three for deep vein thrombosis treatment. The follow-up period ranged from 6 to 34 months. During this period none of the patients experienced any thrombotic or bleeding event.There were no other adverse events reported. Further studies with larger numbers of patients with hemoglobinopathies are needed to determine the use of rivaroxaban and ensure its safety in this patient setting.

Evaluation of the Greek TranQol: a novel questionnaire for measuring quality of life in transfusion-dependent thalassemia patients.

The aim of our study was to evaluate the Greek version of the transfusion-dependent quality of life (TranQol) questionnaire and report our experience of using this novel disease-specific quality of life (QoL) measure in patients with transfusion-dependent thalassemia (TDT). The TranQol and SF-36v2 questionnaires were administered to 94 adult TDT patients with a mean age of 32.1 years (SD = 7, range = 19-58), recruited from the Adult Thalassemia Unit of Hippokration General Hospital of Thessaloniki, Greece. The TranQol was evaluated in terms of construct validity, reliability, and responsiveness. There was a moderately strong correlation between the TranQol summary and both the SF-36v2 physical and mental component summaries (r = 0.4, p < 0.001 and r = 0.5, p < 0.001, respectively). There was also a moderately strong correlation between the physical health scale of TranQol and the relevant SF-36v2 scales, including physical functioning (r = 0.4, p < 0.001), role-physical (r = 0.6, p < 0.001), and bodily pain (r = 0.5, p < 0.001). TranQol also exhibited good internal consistency (Cronbach's alpha coefficient = 0.9) and excellent test-retest reliability (intra-class correlation coefficient = 0.9). The subgroup of patients that reported a better QoL 1 week after transfusion also demonstrated a significant improvement in their TranQol score. These are the first data regarding the administration of the Greek TranQol in a single thalassemia unit. The psychometric properties of the Greek TranQol confirmed it is a valid, reliable, and responsive to change questionnaire, which can be incorporated into future clinical trials.

Presence of the IVS-I-6-Mutated Allele in Beta-Thalassemia Major Patients Correlates with Extramedullary Hematopoiesis Incidence.

Extramedullary hematopoiesis (EMH) results from the extension of hematopoietic tissue beyond the confines of the bones. Since the initiation of regular transfusion programs from an early age for all thalassemia major (ΤΜ) patients, EMH has not been considered a clinical issue anymore. The present study aims to record the prevalence of EMH in chronically transfused ΤΜ patients followed at our institution and to investigate possible risk factors associated with its occurrence. The project was designed as a retrospective, nonexperimental, descriptive, exploratory study. In total, the study enrolled 104 patients. EMH was revealed in 15/104 (14%) patients. The presence of intravening sequence (IVS)-I-6 was significantly related with the development of EMH (p < 0.05). No other demographic or biological factor studied was found to be related with the presence of EMH. The study stresses a profound incidence of asymptomatic EMH in a solid group of well-transfused ΤΜ patients. Given the high incidence of the IVS-I-6 allele in the Mediterranean and Middle Eastern region, high-quality, prospective, multicenter studies could confirm the association of EMH occurrence with the presence of the IVS-I-6 mutation and further evaluate the exact role of this mutation in the EMH process.

A Case of Fatal Agranulocytosis That Developed in a Patient with ß-Thalassemia Major Treated with Deferiprone.

A 29-year-old male with transfusion-dependent ß-thalassemia major (ß-TM), splenectomized and on chelation therapy with deferiprone (DFP or L1) due to heart and liver hemosiderosis, presented with high fever and agranulocytosis. Deferiprone was discontinued and a broad spectrum antibiotic therapy was started intravenously. The patient remained febrile and showed no recovery of neutrophil count even after the initiation of granulocyte colony-stimulation factor (G-CSF). After 12 days at the hospital, he developed respiratory failure and was transferred to the intensive care unit (ICU) where he developed multi-organ failure and died 3 days later. To investigate the mechanism of agranulocytosis, bone marrow mononuclear cells of a healthy volunteer were plated on culture dishes, with or without the patient's serum. The observation of colony forming units of progenitor cells in dishes that contained the patient's serum, provided inconclusive explanation of the possible mechanism of DFP-induced agranulocytosis. This is a case of fatal agranulocytosis developing in a patient being treated with DFP, a well recognized but rare complication of this drug. Further studies are required in order to elucidate the possible pathogenic mechanism of agranulocytosis due to DFP and to provide clear guidelines in order to best care for the patient.

Five Years of Deferasirox Therapy for Cardiac Iron in ß-Thalassemia Major.

Myocardial siderosis in ß-thalassemia major (ß-TM) remains the leading cause of death. Deferasirox (DFX), a new iron chelation treatment, has proved to be effective in reducing or preventing cardiac iron burden in thalassemic patients according to clinical trials with maximum duration of up to 3 years except one that was recently published and lasted 5 years. The aim of this study was to evaluate the efficacy of DFX in reducing or preventing cardiac iron burden in 23 patients with ß-TM after 5 years of therapy. All patients had a magnetic resonance imaging (MRI) T2* evaluation of their cardiac iron load before starting DFX therapy and after a period of 5 years. Ferritin levels and left ventricular ejection fraction (LVEF) were also evaluated at the same time. Deferasirox was administered in a starting dose of 30 mg/kg/day and never increased to more than 40 mg/kg/day. The MRI T2* cardiac iron load mean values before DFX was 32.82 ± 10.86 ms, and after 32.13 ± 7.74 ms, showing a stability in MRI T2* myocardial value but a significant improvement in two patients with an intermediate iron load (12 vs. 23 ms). The mean LVEF value was 68.43 ± 7.08% before treatment with DFX and 67.95 ± 5.94% after DFX therapy without significant change. Our results confirm previous studies that DFX is considered an effective chelating agent used as monotherapy for at least 5 years and is more efficacious in moderate to severe cardiac iron loaded thalassemic patients.

Pure red cell aplasia and lymphoproliferative disorders: an infrequent association.

Pure red cell aplasia (PRCA) is a rare bone marrow failure syndrome defined by a progressive normocytic anaemia and reticulocytopenia without leukocytopenia and thrombocytopenia. Secondary PRCA can be associated with various haematological disorders, such as chronic lymphocytic leukaemia (CLL) or non-Hodgkin lymphoma (NHL). The aim of the present review is to investigate the infrequent association between PRCA and lymphoproliferative disorders. PRCA might precede the appearance of lymphoma, may present simultaneously with the lymphoid neoplastic disease, or might appear following the lymphomatic disorder. Possible pathophysiological molecular mechanisms to explain the rare association between PRCA and lymphoproliferative disorders are reported. Most cases of PRCA are presumed to be autoimmune mediated by antibodies against either erythroblasts or erythropoietin, by T-cells secreting factors selectively inhibiting erythroid colonies in the bone marrow or by NK cells directly lysing erythroblasts. Finally, focus is given to the therapeutical approach, as several treatment regimens have failed for PRCA. Immunosuppressive therapy and/or chemotherapy are effective for improving anaemia in the majority of patients with lymphoma-associated PRCA. Further investigation is required to define the pathophysiology of PRCA at a molecular level and to provide convincing evidence why it might appear as a rare complication of lymphoproliferative disorders.