Busulfan with 400 centigray of total body irradiation and higher dose fludarabine: An alternative regimen for hematopoietic stem cell transplantation in pediatric acute lymphoblastic leukemia.

BACKGROUND: Hematopoietic stem cell transplantation can be curative for children with difficult-to-treat leukemia. The conditioning regimen utilized is known to influence outcomes. We report outcomes of the conditioning regimen used at the Alberta Children's Hospital, consisting of busulfan (with pharmacokinetic target of 3750 µmol*min/L/day ±10%) for 4 days, higher dose (250 mg/m2 ) fludarabine and 400 centigray (cGy) of total body irradiation. PROCEDURE: This retrospective study involved children receiving transplant for acute lymphoblastic leukemia (ALL). It compared children who fell within the target range for busulfan with those who were either not measured or were measured and fell outside this range. All other treatment factors were identical. RESULTS: Twenty-nine children (17 within target) were evaluated. All subjects engrafted neutrophils with a median [interquartile range] time of 14 days [8-30 days]. The cumulative incidence of acute graft-versus-host disease was 44.8% [95% confidence interval, CI: 35.6%-54.0%], while chronic graft-versus-host disease was noted in 16.0% [95% CI: 8.7%-23.3%]. At 2 years, the overall survival was 78.1% [95% CI: 70.8%-86.4%] and event-free survival was 74.7% [95% CI: 66.4%-83.0%]. Cumulative incidence of relapse was 11.3% [95% CI: 5.1%-17.5%]. There were no statistically significant differences in between the group that received targeted busulfan compared with the untargeted group. CONCLUSION: Our conditioning regiment for children with ALL resulted in outcomes comparable to standard treatment with acceptable toxicities and significant reduction in radiation dose. Targeting busulfan dose in this cohort did not result in improved outcomes.

Neuroimaging and Pathology Findings Associated With Rapid Onset Obesity, Hypothalamic Dysfunction, Hypoventilation, and Autonomic Dysregulation (ROHHAD) Syndrome.

Rapid onset Obesity, Hypothalamic dysfunction, Hypoventilation, and Autonomic Dysregulation (ROHHAD) is a rare syndrome whose underlying pathophysiology and etiology remain elusive. We present the case of a 36-month-old boy with the classic symptoms of ROHHAD and a neuroendocrine tumor, who progressed rapidly and subsequently succumbed to cardiorespiratory arrest because of hypoventilation. His magnetic resonance imaging findings at the initial diagnosis and the brain autopsy results are detailed. The literature was reviewed to summarize the current understanding of the underlying mechanism of this rare disorder.

Racecadotril for the treatment of severe acute watery diarrhoea in children admitted to a tertiary hospital in Kenya.

BACKGROUND: Diarrhoea is the second most common cause of death in children under 5 years of age in Kenya. It is usually treated with oral rehydration, zinc and continued feeding. Racecadotril has been in use for over 2 decades; however, there is a paucity of data regarding its efficacy from Africa. OBJECTIVES: The objectives of this study were: to compare the number of stools in the first 48 hours in children with severe gastroenteritis requiring admission and treated with either racecadotril or placebo, to study the impact of racecadotril on duration of inpatient stay as well as duration of diarrhoea and to describe the side effect profile of racecadotril. METHODS: This was a randomised, double-blinded, placebo-controlled trial. It enrolled children between the age of 3 and 60 months who were admitted with severe acute gastroenteritis. They received either racecadotril or placebo in addition to oral rehydration solution (ORS) and zinc and were followed up daily. RESULTS: 120 children were enrolled into the study. There were no differences in the demographics or outcomes between the 2 groups. Stools at 48 hours: median (IQR) of 5 (3-7) and 5 (2.5-7.5), respectively; p=0.63. The duration of inpatient stay: median (IQR): 4 days (1.5-6.5) and 4.5 (1.8-6.3); p=0.71. The duration of illness: 3 days (2-4) and 2 days (1-3); p=0.77. The relative risk of a severe adverse event was 3-fold higher in the drug group but was not statistically significant (95% CI 0.63 to 14.7); p=0.16. CONCLUSIONS: Racecadotril has no impact on the number of stools at 48 hours, the duration of hospital stay or the duration of diarrhoea in children admitted with severe gastroenteritis and managed with ORS and zinc. TRIAL REGISTRATION NUMBER: PACTR201403000694398; Pre-results.