Summary:Veno-occlusive disease (VOD) of the liver is a complication observed particularly in patients undergoing hematopoietic stem cell transplantation (HSCT). Defibrotide (DF) is a polydeoxyribonucleotide with aptameric activity on endothelium. We evaluated in a retrospective analysis the efficacy of DF in pediatric patients developing hepatic VOD after HSCT. A total of 45 patients between 0.2 and 20 years (median age: 8.2 years) with hepatic VOD were treated with DF: 22 patients (49%) met risk criteria for severe or progressive disease and 23 (51%) for moderately severe and mild disease. The median duration of DF treatment was 17 days. In all, 34 patients (76%) achieved complete response (CR) with a survival rate of 64% at day 100. CR rate in patients with severe disease was 50% with longterm survival of 36%. The average DF dose in the CR group was 45 mg/kg/day and in the no responder (NR) group 27 mg/kg/day. The use of additional drugs besides DF to treat VOD made no difference in the outcome compared to DF alone. The average interval from diagnosis to start of DF was 1 day in the CR and 5.5 days in NR group. In multivariate analysis, early intervention remained the only significant factor for a CR.

Renotubular handling of sodium, potassium (K) calcium (Ca), phosphate, hydrogen ions and glucose, and urinary concentrating ability were studied in three children (aged 8, 8.5, 11 years) with renal magnesium (Mg) loss, persisting for more than 2 years after discontinuation of cisplatin treatment for neuroblastoma. A group of healthy children served as controls. Besides renal Mg wasting, a clear-cut tendency towards reduced calciuria associated with normal or slightly elevated plasma Ca was observed. Plasma K tended to be low (3.4-3.7 mmol/l), and plasma chloride was normal. Plasma bicarbonate (HCO3) ranged from 24.9 to 27.8 mmol/l, and urinary pH was always less than 6.0, indicating a renal HCO3 threshold exceeding 24 mmol/l. Plasma creatinine levels, glucosuria and phosphaturia, and urinary concentrating capacity were adequate. Comparable features were found in three children (aged 4.5, 9, 13 years) with primary renotubular hypomagnesaemia-hypokalaemia and hypocalciuria. This study complements the picture of chronic cisplatin tubulopathy in childhood demonstrating that, apart from Mg wasting, a reduced Ca excretion, and a tendency to hypokalaemia and metabolic alkalosis exist. Thus cisplatin may induce renal functional damage identical to that found in primary renotubular hypomagnesaemia--hypokalaemia with hypocalciuria.

Information on persisting renal sequelae after cisplatin in children and adolescents is limited. Twelve patients aged 4–20 years had been treated with cisplatin and were healthy 4–43 months after stopping chemotherapy. Plasma creatinine, calcium, albumin and hydrogen ion concentration, plasma and urinary sodium, chloride, phosphate and urate, and urinary magnesium and potassium were comparable in patients and controls. However, mean calciuria, magnesemia and potassemia were significantly reduced and bicarbonatemia increased in the patients. Calciuria, magnesemia, potassemia and bicarbonatemia were normal in 3 patients only, calciuria was below – 2 SD control in 9 patients, renal magnesium deficiency was demonstrated in 5 patients (all with hypocalciuria as well), and 4 patients presented with hypokalemic metabolic alkalosis (all with magnesium deficiency and hypocalciuria). Conclusions: (1) Renotubular dysfunctions persist very often after cisplatin; (2) hypocalciuria is more frequent than hypomagnesemia; (3) the most severe tubulopathy after cisplatin includes hypocalciuria, renal magnesium deficiency and hypokalemic metabolic alkalosis.

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