Survival and late effects of hematopoietic cell transplantation in patients with thalassemia major.

In this retrospective study, we evaluated long-term survival and late effects in 137 patients affected by thalassemia major (TM) who received an allogeneic hematopoietic cell transplantation (HCT). Median age at HCT was 10.1 years. After a median follow-up of 30 years, 114 (83.2%) patients are living and 108 (78.8%) are cured. The cumulative incidence of nonrelapse mortality and thalassemia recurrence was 9.5% at 1 year and 10.2% at 39 years respectively. The 39-years cumulative incidence of overall survival and disease-free survival were 81.4% and 74.5%. One hundred twenty-three patients who survived more than 2 years after HCT were evaluated for late effects concerning hematological disorders, iron burden, growth, obesity, diabetes mellitus, thyroid and gonadal function, eye, heart, liver, lung, kidney, gastrointestinal, neurologic and psychiatric system, osteoarticular system, secondary solid cancer (SSC), performance status, and Covid-19 infection. Fertility was preserved in 21 males whose partners delivered 34 neonates and 25 females who delivered 26 neonates. Fifteen cases of SSC were diagnosed for a 39-year cumulative incidence of 16.4%. HCT represents a definitive cure for the majority of TM patients at the price, however, of a non-negligible early and late mortality which in the long run affects survival and disease-free survival.

Possible effects of sirolimus treatment on the long­term efficacy of COVID­19 vaccination in patients with ß­thalassemia: A theoretical perspective.

The pandemic caused by the severe acute respiratory syndrome coronavirus (SARS­CoV­2), responsible for coronavirus disease 2019 (COVID­19) has posed a major challenge for global health. In order to successfully combat SARS­CoV­2, the development of effective COVID­19 vaccines is crucial. In this context, recent studies have highlighted a high COVID­19 mortality rate in patients affected by ß­thalassemia, probably due to their co­existent immune deficiencies. In addition to a role in the severity of SARS­CoV­2 infection and in the mortality rate of COVID­19­infected patients with thalassemia, immunosuppression is expected to deeply affect the effectivity of anti­COVID­19 vaccines. In the context of the interplay between thalassemia­associated immunosuppression and the effectiveness of COVID­19 vaccines, the employment of immunomodulatory molecules is hypothesized. For instance, short­term treatment with mammalian target of rapamycin inhibitors (such as everolimus and sirolimus) has been found to improve responses to influenza vaccination in adults, with benefits possibly persisting for a year following treatment. Recently, sirolimus has been considered for the therapy of hemoglobinopathies (including ß­thalassemia). Sirolimus induces the expression of fetal hemoglobin (and this may contribute to the amelioration of the clinical parameters of patients with ß­thalassemia) and induces autophagy (thereby reducing the excessive levels of α­globin). It may also finally contribute to the mobilization of erythroid cells from the bone marrow (thereby reducing anemia). In the present study, the authors present the hypothesis that sirolimus treatment, in addition to its beneficial effects on erythroid­related parameters, may play a crucial role in sustaining the effects of COVID­19 vaccination in patients with ß­thalassemia. This hypothesis is based on several publications demonstrating the effects of sirolimus treatment on the immune system.

Understanding the impact of COVID-19 pandemic on health-related quality of life amongst Iranian patients with beta thalassemia major: a grounded theory.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic and the resulting measures can impact daily life and healthcare management amongst patients with beta thalassemia major. METHODS: The Corbin and Strauss method of grounded theory was used to explore the impact of the COVID-19 pandemic on health-related quality of life (HRQoL) amongst Iranian patients with beta thalassemia major. Semi-structured interviews with 16 patients with thalassemia major in the eastern of Iran were performed. Data collection was conducted from 19 September through 18 November 2020. Collected data were recorded, transcribed, and coded to develop themes and subthemes. Paradigm components were sought to find out what happened to these patients and explore the process and events. RESULTS: Insights from these interviews led to five major themes: 'changing physical health', 'emotional and psychological reactions', 'changing the nature of relationships and the scope of social support', 'metamorphosis of ongoing healthcare, and 'functionality and adaptation to new realities.' The emerging core concept was labelled: 'maintaining well-being balance.' The COVID-19 pandemic disturbed the balance of life and health of the patients. Multiple strategies to maintain balance and reduce the negative effects of the COVID-19 pandemic on HRQoL were used by the patients, the healthcare team, and support systems. CONCLUSIONS: Due to the fear of COVID-19, the patients with beta thalassemia were less likely to contact healthcare professionals. They considered postponing blood transfusion and abandoned evaluating disease complications. Reduced access to the healthcare system and shifting resources from existing programmes to COVID-19 by the healthcare system were incompatible policies. These policies and strategies had strong and negative effects on the physical domain of HRQoL. The patients experienced a deterioration of emotional functioning. They reported a strong reduction in social functioning and felt lonely. Online interventions supporting mental health and social interactions and telemedicine can help during the times of social distancing and lockdowns.

SARS-CoV-2 infection in patients with ß-thalassemia: The French experience.

INTRODUCTION: Because of iron overload complications, thrombosis and infectious predisposition, patients with severe forms of thalassemia are likely to be at increased risk of COVID-19 complications. RESULTS: A national survey conducted during the year 2020 across the French reference centers for hemoglobinopathies identified 16 cases of COVID-19 confirmed by RT-PCR in beta-thalassemia patients. Their age ranged from 11 months to 60 years. 15 patients were transfusion-dependent and 6 were splenectomized. Concerning iron overload related complications, none had diabetes or cirrhosis and only one had experienced heart failure. All 4 pediatric patients were pauci-symptomatic during the viral episode. Three patients (41, 49 and 57 years old) developed COVID-19 pneumonia requiring oxygen therapy without the need for mechanical ventilation. Neutropenia (absolute neutrophils count <0.5 10 9/L) was observed in 2 patients receiving long-term treatment with hydroxycarbamide and deferiprone. No thrombosis event, organ failure or death occurred. All patients recovered. CONCLUSION: Severity of COVID-19 in this population of young and middle-aged patients appeared increased compared to the general population but remained mild to moderate as already described in the few series reported in the literature. Occurrence of adverse events related to chronic treatment administered in thalassemia disease may be favored by the infectious episode.

The impact of COVID-19 on transfusion-dependent thalassemia patients of Karachi, Pakistan: A single-center experience.

OBJECTIVES: With the advent of COVID-19 in Pakistan, the already fragmented blood transfusion services (BTS) received a severe blow, putting the lives of transfusion-dependent thalassemia children on stake. This study aimed to assess the impact of the COVID-19 on blood transfusion therapy (BTT) of thalassemia patients and suggest ways to ensure safe and reliable blood supplies amid such health crises. MATERIAL AND METHODS: A retrospective, cross-sectional study was conducted from October 2019 (before COVID-19) to July 2020 (during COVID-19) based on the data provided by a thalassemia center, named Help International Welfare Trust, Karachi, Pakistan. SPSS version 24.0 was used for the data analysis. Data were described in the form of means and percentages. RESULTS: There was a significant reduction in the consumption of PRBCs bags after the emergence of COVID-19 (P=0.002). Moreover, the number of thalassemia patients receiving BTT was dropped by 10.56% during the pandemic. There was a strong negative correlation observed between the rising cases of COVID-19 in Pakistan and the number of patients missing their therapy sessions (r=-0.914, P=0.030). A considerable decline in the reserves of all Rhesus-negative blood groups amid the COVID-19 outbreak was also observed. CONCLUSION: The COVID-19 pandemic adversely affected the already suboptimal care catered to thalassemia patients in Karachi, Pakistan. The fear of the virus contraction coupled with the lockdown and restricted mobility has disrupted the entire transfusion chain from donor to the recipient. Collaborated efforts by the government and healthcare authorities are essential to ensure sufficient blood for thalassemia patients amid the pandemic.

COVID-19 Pandemic and Thalassemia Major Patients: Transfusion Practice and Treatment Assessment.

BACKGROUND: When the COVID-19 epidemic occurred for the first time in December 2019, the governments worldwide took some restriction measures for slowing the spread of novel coronavirus. Eventually, there was a considerable decrease in volunteer blood donations. Regular transfusions and follow-up of patients with thalassemia major (TM) should be maintained during this period. It is possible that the treatment of the patients with TM may hinder due to the difficulty of reaching the treatment center and the difficulty of blood supply. Thus, in this study, we aimed to investigate whether there were any differences in the follow-up and treatment of the patients with TM during the outbreak. MATERIALS AND METHODS: Sixty-one patients with TM who were followed up in our center without COVID-19 contact history and symptoms were included in this study. The demographic features and red blood cell volume per kilogram they received, pretransfusion hemoglobin, serum ferritin (SF) level, biochemical parameters, and transfusion interval were recorded. The difference between the arithmetic mean of the data before and during the pandemic was evaluated. RESULTS: In this study, 61 patients with TM (32 males/29 females, mean age 13.9±6.8 y) were evaluated. The mean pretransfusion hemoglobin value was 9.14±0.77 g/dL and 8.87± 0.80 g/dL before and during the pandemic, respectively (P=0.023). There was no difference between before and during the pandemic concerning transfusion interval and transfusion volume. However, SF levels increased above 1000 ng/mL in 16.6% of patients. CONCLUSION: Although blood donation decreased significantly during the pandemic, it was observed in this study that the blood needs of patients with TM could be provided. The results of the SF level showed that the management of chelation therapy should be more meticulous. However, we should be ready for the challenges in the transfusion practice of patients with TM due to fluctuations in the COVID-19 pandemic.

Prevalence and severity of Coronavirus disease 2019 (COVID-19) in Transfusion Dependent and Non-Transfusion Dependent ß-thalassemia patients and effects of associated comorbidities: an Iranian nationwide study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) outbreak is a global and challenging disease that is accompany with mortality and morbidity. AIM OF STUDY: We evaluated the prevalence and the impact of comorbidities in thalassemia Iranian patients affected by COVID-19.  Methods: A multicenter, retrospective, cross-sectional study was conducted across all comprehensive thalassemia centers in Iran, from January to June 15th, 2020. RESULTS: Forty-three confirmed COVID-19 thalassemia patients (32 TDT, and 11 NTDT) were detected. The mean age of patients was 35.3 ± 11.5 years (range 9 - 67); 21 females and 22 males. Overall, 78.1% of TDT and 90.9% of NTDT patients were complicated with at least one comorbidity (P: 0.656). The overall mortality rate of thalassemia patients with COVID-19 was 18.6% while 27.3% was in NTDT patients compared to 15.6% in TDT patients (P:0.401). The dead group had a non-significant higher frequency of endocrinopathies compared to the recovered group (62.5% versus 45.7% P:0.457). Ten female thalassemia patients with positive COVID-19 had hypogonadism, six patients were receiving hormone replacement therapy and all of them recovered (zero death) compared to two deaths from 4 patients who were not receiving hormone replacement therapy (P:0.133). Furthermore, the prevalence of COVID-19 in NTDT patients was significantly higher than the general population (45 per 10,000 versus 22.29 per 10,000 respectively, P:0.018) while the prevalence of TDT was almost similar to the normal population (P:0.539). The mortality rate of COVID-19 was 4.71% in the normal Iranian population compared to 18.6% in ß-thalassemias (P: <0.001) at the same date. CONCLUSIONS: It is important to acknowledge that ß-thalassemia patients, especially young adults/adults, have a chronic condition which may contribute to increase susceptibility to SARS-CoV-2 infection. A higher susceptibility to the infection was observed in patients with NTDT and in untreated hypogonadal female thalassemic patients. However, to confirm these data, more accurate designed studies are needed.