Reduced toxicity conditioning for hematopoietic stem cell transplantation in children with Diamond-Blackfan anemia.

Not available.

Acute Lymphoblastic Leukemia with Central Nervous System Involvement-Challenges in Management.

The survival of patients with acute lymphoblastic leukemia (ALL) has dramatically improved during the last six decades. This improvement is secondary to improved diagnostics, risk stratification of treatment by biological features and response to treatment, improved supportive care, and the introduction of new treatment modalities such as immunotherapy and molecular targeted therapy. However, many questions remain concerning the involvement of the central nervous system (CNS) in leukemia, including ones pertaining to the risk factors for CNS involvement and relapse, the optimal treatment strategy to prevent relapse, and the role of newer therapies. This review discusses these questions by addressing the diagnosis of CNS leukemia, the current clinical trial data for treatment regimens with CNS activity, and issues specific to treatment in low- and middle-income countries (LMICs).

Hematopoietic cell transplantation and gene therapy for Diamond-Blackfan anemia: state of the art and science.

Diamond-Blackfan anemia (DBA) is one of the most common inherited causes of bone marrow failure in children. DBA typically presents with isolated erythroid hypoplasia and anemia in infants. Congenital anomalies are seen in 50% of the patients. Over time, many patients experience panhematopoietic defects resulting in immunodeficiency and multilineage hematopoietic cytopenias. Additionally, DBA is associated with increased risk of myelodysplastic syndrome, acute myeloid leukemia and solid organ cancers. As a prototypical ribosomopathy, DBA is caused by heterozygous loss-of-function mutations or deletions in over 20 ribosomal protein genes, with RPS19 being involved in 25% of patients. Corticosteroids are the only effective initial pharmacotherapy offered to transfusion-dependent patients aged 1 year or older. However, despite good initial response, only ~20-30% remain steroid-responsive while the majority of the remaining patients will require life-long red blood cell transfusions. Despite continuous chelation, iron overload and related toxicities pose a significant morbidity problem. Allogeneic hematopoietic cell transplantation (HCT) performed to completely replace the dysfunctional hematopoietic stem and progenitor cells is a curative option associated with potentially uncontrollable risks. Advances in HLA-typing, conditioning regimens, infection management, and graft-versus-host-disease prophylaxis have led to improved transplant outcomes in DBA patients, though survival is suboptimal for adolescents and adults with long transfusion-history and patients lacking well-matched donors. Additionally, many patients lack a suitable donor. To address this gap and to mitigate the risk of graft-versus-host disease, several groups are working towards developing autologous genetic therapies to provide another curative option for DBA patients across the whole age spectrum. In this review, we summarize the results of HCT studies and review advances and potential future directions in hematopoietic stem cell-based therapies for DBA.

Predictors of emesis in children undergoing procedural sedation with intramuscular ketamine in a paediatric emergency department.

INTRODUCTION: Emesis is one of the most common adverse events associated with ketamine sedation. However, its predictors have not been clearly studied among Asian children. This study aimed to determine the incidence and predictors of emesis in children undergoing intramuscular (IM) ketamine sedation in an emergency department (ED) in Singapore and to identify high-risk groups, so that antiemetics may be administered prophylactically. METHODS: In a prospective observational study, all children requiring procedural sedation with IM ketamine in the paediatric ED between 1 April 2013 and 31 January 2015 were included. All cases of emesis following ketamine sedation were prospectively documented. Univariate and multivariate logistic regression analyses were performed to identify the predictors of emesis. RESULTS: 2,502 sedations were performed using IM ketamine in the ED during the study period. Overall incidence of emesis associated with IM ketamine sedation was 8.4%. Children aged ≥ 8 years were significantly associated with increased risk of emesis (odds ratio 4.636, 95% confidence interval 3.271-6.570; p < 0.001), with an emesis rate of 19.6%. Other variables such as initial dose (3 mg/kg vs. 4 mg/kg), total dosage (including top-ups), type and site of procedure, gender and ethnicity were not significant predictors. The number needed to treat for antiemetics in children aged ≥ 8 years was five. CONCLUSION: Age is a significant predictor of emesis. We recommend conducting a randomised controlled trial to compare the effects of prophylactic oral ondansetron in patients stratified into the age groups of ≥ 8 years and < 8 years.