Stalin Ramprakash

A bone marrow transplant recipient on cyclosporine initiated on ciprofloxacin for a renal abscess presented with encephalopathy, right hemiparesis, and multiorgan dysfunction. Imaging revealed white matter signal changes characteristic of cyclosporine leukoencephalopathy. This case illustrates the potential drug interaction of cyclosporine with ciprofloxacin and the need to exercise caution while prescribing antibiotics with cyclosporine.

Severe blood disorders and cancer are the leading cause of death and disability from noncommunicable diseases in the global pediatric population and a major financial burden. The most frequent of these conditions, namely sickle cell disease and severe thalassemia, are highly curable by blood or bone marrow transplantation (BMT) which can restore a normal health-related quality of life and be cost-effective. This position paper summarizes critical issues in extending global access to BMT based on ground experience in the start-up of several BMT units in middle-income countries (MICs) across South-East Asia and the Middle East where close to 700 allogeneic BMTs have been performed over a 10-year period. Basic requirements in terms of support systems, equipment, and consumables are summarized keeping in mind WHO’s model essential lists and recommendations. BMT unit setup and maintenance costs are summarized as well as those per transplant. Low-risk BMT is feasible and safe in MICs with outcomes comparable to high-income countries but at a fraction of the cost. This report might be of assistance to health care institutions in MICs interested in developing hematopoietic stem cell transplantation services and strengthening context appropriate tertiary care and higher medical education.

In spite of advances in chelation therapy and screening of blood, mortality associated with the most common life-threatening noncommunicable disease of children in India, transfusion-dependent thalassemia (TDT), remains poorly defined. This study aims at estimating death rates and mortality risk factors associated with TDT. The clinical records of 1087 patients from S thalassemia centers in India were retrospectively analyzed from 2011 to 2018. Median patient age was 8.5 years, with 107 patients older than 18 years; 656 patients were male and 431 were female. Demographic details and clinical parameters were analyzed at presentation and at last visit. With 41 recorded deaths, actuarial survival at 26.9 years was 50%, and under-5 mortality was 7 times higher than in the general population. Patients with transfusion-transmitted infections (TTIs) had 3.4 times higher risk for death (P - .031). Serum ferritin higher than 4000 ng/dL had 4.6 times higher risk for mortality compared with ferritin lower than 1000 ng/dL (P - .00063). A hemoglobin drop lower than 2 g/dL per week had 7.7 times higher mortality risk compared with a drop of less than 1 g/dL per week (P < .0001). Social determinants (sex, economic status, and distance from center), splenectomy, and even cardiac complications were not associated with higher mortality risk. Main causes of death were infection, iron overload, TTIs, and allo-immunization. Patients who received more than 4 years of adequate care had more than 66% mortality risk reduction (P < .0001) . TDT in India continues to result in high mortality. Ineffective transfusion, TTIs, and chelation continue to be the most significant risk factors. Comprehensive care in dedicated day care centers from early age is likely to improve outcomes.

Introduction: An assessment of morbidity and mortality caused by transfusion dependent thalassemia in India has never really been done despite thalassemia being the most prevalent life threatening non-communicable disorder of childhood. There is little structured understanding identifying the key risk factors feeding into research and policy making for effective management of thalassemia. With an estimated 10,000-12,000 children born with thalassemia each year in India, in addition to increasing focus on early pregnancy targeted screening, it seems critical to increase our understanding of risk factors associated with early mortality and morbidity. This is also relevant to family counselling about management options. Methodology: A retrospective analysis of mortality key risk factors in patients suffering from thalassemia major from 5 thalassemia day care centres in India was carried out. This included a total of 1,087 patients (656 males and 431 females with a median age of 8.6 years) enrolled for care between 1 Jan 2010 - 31 Oct 2018 at these centres. These centres were set up by a non-profit organization in collaboration with blood banks and /hospital facilities with the objective to provide comprehensive thalassemia care; A common web-based application was employed (ThalCare™). This system was used to track information associated with treatment including disease history at enrolment, demographic data and follow-up information. All analyses were performed with R Statistical software (3.5.2). Survival analysis was done from the age at presentation to the centre till October 2018. The reasons for mortality were categorized. Overall survival was also separately analyzed for patients in their 1st,2nd, 3rd or subsequent decades of life. The Cnaan and Ryan approach was used as patients entered and left the study cohort (left censored and right truncated data) and observation began only at enrolment and not at disease onset Results: The median age at enrolment was 5.4 years and the median follow up at the centre was 2.5 years. A total of 86 patients were cured by bone marrow transplantation (BMT), 13 of them moved to other centres for care and 41 patients died during the study period (28 males and 13 females). The median age at death was 15.4 years. Actuarial survival at 26.9 years of age was 50% (Figure 1) and under-five mortality was 7 times higher than the general population. Patients with transfusion-transmitted infections (TTI) had 3.4 times higher risk of death (p=0.031). Serum ferritin >4,000 ng/dL was associated with 4.6 times higher risk of mortality compared to ferritin 2 gm/dL/week had 7.7 times higher mortality risk compared to 2 gm/week (hazard ratio 5.58 ,p=0.0007) and lack of attention towards care for possible prevention from TTI (hazard ratio 2.86, p=0.0004) are factors independently associated with high mortality. Table 2 shows that in patients born after the year 2,000 overall survival is 85.2% compared to 29.4% for patients born earlier. Main causes of death were infection, iron overload, TTIs, and alloimmunization; In a quarter of patients the cause of death was unknown (Figure 2). Patients who received more than 4 years of adequate care had more than 66% mortality risk reduction (p<0.0001). Conclusion: Comprehensive care right from an early age at dedicated management centres is key to improving life expectancy of thalassemia patients in India. Optimizing blood transfusion, intensifying chelation and preventing TTIs seem particularly important. Sustained efforts in these areas coupled with increased prevention and access to safe BMT will ease the burden for both families and public healthcare. Disclosures No relevant conflicts of interest to declare.