Lawrence Faulkner

Background: Central nervous system (CNS) complications after bone marrow transplant (BMT) for benign hematological diseases mainly Thalassemia major have a major impact on overall survival, disease‐free survival, and transplant‐related mortality. Method: Retrospective data analysis of 595 patients after first matched‐related BMT in four participating centers in the subcontinent from 2010 to 2023 was done to assess the incidence, associated risk factors and outcome of transplant‐related intracranial hemorrhage (ICH). Result: The mean age of the patient population at transplant was 8.32 ± 4.09 years. The incidence of ICH was 4.7%. ICH presented with headache (60%) and hypertension (57%) mostly in the early post‐transplant period (< 28 days post‐BMT). Age at transplant was the positive predictor of developing ICH after BMT. Transplant‐related mortality and rejection was higher in patients with ICH than in the other patients. The overall survival and disease‐free survival of 28 patients with ICH out of 595 patients was 51% and 37%, respectively, as compared to 88% and 76% in the rest of the patients. Transplant‐related mortality was higher in patients with ICH than in the other patients, but there was no statistically significant difference in rejection between the two groups. Conclusion: Transplant‐related ICH affects the overall survival, disease‐free survival, and transplant‐related mortality. ICH presented early post‐BMT with headache and hypertension. Age at BMT was the main predictor that emerged at the time of developing ICH.

Thalassemia and sickle cell disease remain the most common life-threatening non-communicable diseases in children worldwide and an increasing burden on affected families and health services. Significant progress has been made in terms of technologies to improve access to a cure by both allogeneic and autologous gene-modified hematopoietic stem cell transplantation (HSCT). However, the high cost of cutting-edge treatments often places them beyond the reach of individual families or even national healthcare systems. Advances in frugal innovation and simplified HSCT procedures for low-risk transplants have significantly reduced the costs and complexities associated with HSCT without compromising on quality and outcomes. Because of the geographical distribution of hemoglobinopathies, i.e., largely in low- and middle-income countries (LMICs), HSCT cost optimization has the potential to impact a huge number of patients, increasing hope for a cure and health-related quality of life normalization, which in turn may affect supportive care compliance. Furthermore, because of the high burden of disease, LMIC transplant centers are rapidly increasing in number and developing unique expertise for the cure of thalassemia and sickle cell disease, particularly in India, where the Sankalp India Foundation with the support of DKMS and Cure2Children has implemented several cost-conscious transplant services. In fact, the very high success rate, increasing cost-effectiveness of transplantation, as well as the chronic nature of these conditions make them ideal initial candidates for start-up transplant centers, so it is likely that the global capacity for a cure for severe hemoglobinopathies will substantially increase in the years to come.

Even though hematopoietic cell transplant (HCT) has been in vogue for more than six decades as a curative therapy for many hematological disorders, with increasing trends in all parts of the world (Fig. 69.1), the density of HCT services is low and access to existing services remain an unmet need in the resource-constrained settings (RCSs) of low- and middle-income countries (LMICs) (Niederwieser et al. 2022). The silver lining though is that within these limitations, there are several examples of high-quality HCT services functioning in several countries, some with full national/international accreditation showing that even in those circumstances this is possible (Damodar et al. 2021). The goal of this chapter will be to discuss how good HCT services may be established and sustained in RCSs (Pasquini et al. 2019; Faulkner et al. 2021).

Diamond Blackfan anemia (DBA) is a rare congenital syndrome presenting primarily as pure red cell aplasia with constitutional abnormalities and cancer predisposition. Established treatment options are corticosteroids, regular erythrocyte transfusions with iron chelation therapy, and hematopoietic stem cell transplantation (HSCT). To date, HSCT is the only definitive curative treatment for the hematological phenotype of DBA, but there is little experience with its use. Given the rarity of the disease and its unique features, an expert panel agreed to draw up a set of recommendations on the use of HSCT in DBA to guide clinical decision-making and practice. The recommendations address indications, pretransplant patient evaluation, donor selection, stem cell sources, conditioning regimens, prophylaxis of rejection and graft versus host disease, and post-transplant follow-up.

Background: Patients with tunnelled CVL may develop blood stream infections which at times are difficult to control without line removal. Concomitant severe thrombocytopenia with platelet transfusion refractoriness is often considered a hard contraindication to any procedure involving a major blood vessel. There is very little literature on the actual clinical risks of tunnelled central line removal in febrile pancytopenic patients. Procedure: We analysed complications and outcomes in all or patients, a total of 52, who underwent CVL removal with platelets <20,000/uL. Results: No bleeding episodes or unplanned transfusions could be associated with CVL removal. No other complications were also reported. All patients had time to hemostasis within 5 minutes of catheter removal. A total 31 patients were febrile at the time of CVL removal, of which 17 became afebrile within 2 days. We found no difference in response when comparing those whose antibiotic therapy was change/escalation versus those who did not. Removal of CVL under local anaesthesia remained complication-free even at platelets counts less than 20.000/uL. With only RDP support 17 lines were pulled out without any complications when platelets were below 5.000. Conclusion: Our findings suggest that central lines can be safely removed with platelet counts less than 20.000/ul and that this may result in enhanced blood stream infection control. This might be particularly relevant to neutropenic patients in this day and age of MDR germs emergence and paucity of new effective antibiotics.

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.