Cardiac chamber hypertrophy following hematopoietic stem cell transplantation for primary immunodeficiency.

Children with primary immune deficiency (PID) who receive hematopoietic stem cell transplantation (HSCT) often suffer from graft-versus-host disease (GVHD), which is commonly treated with corticosteroids (CS). CS may cause hypertension, development of cardiac chamber hypertrophy (CCH), and left ventricular outflow tract obstruction (LVOTO). We followed the development of CCH and LVOTO by serial echocardiograms in 10 children with PID before and 6 to 12 weeks after HSCT, and correlated their development with age of transplant, GVHD, use of CS and hypertension. CCH developed in all 4 children transplanted before 1 year of age who received high dose CS treatment for grade III or IV acute GVHD (aGVHD), but not in the 6 children who were transplanted at later ages or who had not received high-dose CS (P = .07). Significant correlation (P < .002) was found between CCH and blood pressure measurements that deviated above the 99th percentile. One child also suffered from severe LVOTO. CCH and LVOTO improved when CS treatment was discontinued and blood pressure normalized. We conclude that following HSCT, young children who suffer from aGVHD, treated with high CS doses, and have excessive hypertension are at risk of developing CCH.

Defibrotide for the treatment of hepatic veno-occlusive disease in children.

BACKGROUND: This retrospective report describes experience with defibrotide in children with hepatic veno-occlusive disease (HVOD) following hematopoietic progenitor cell transplant (HPCT) in a single institution. PROCEDURE: Children who had undergone HPCT between February 1999 and June 2001 and between July 2003 and September 2004 and who received defibrotide during their admission were identified. Demographic data and information regarding the clinical course of these patients were abstracted from their health records. RESULTS: Fourteen children (mean age: 9.3 years; range: 0.4-18.1) who underwent HPCT during the study period received defibrotide for the treatment of HVOD; nine were girls. Most patients underwent HPCT for hematologic malignancies (8/14) and received matched unrelated donor transplants (8/14). Conditioning regimens included cyclophosphamide with total body irradiation (5/14) and busulfan followed by cyclophosphamide (7/14). HVOD was diagnosed on transplant day -4 to +33 (median: +10.5); defibrotide was started on transplant day -4 to +40 (median: +12). The median initial defibrotide dose was 33 mg/kg/day (11-40 mg/kg/day); the median maximum defibrotide dose was 38.5 mg/kg/day (11-81 mg/kg/day). The median duration of defibrotide therapy was 16 days (4-37 days). Defibrotide was discontinued due to clinical improvement (9), death (3), drug unavailability (1), and neurological toxicity (1). Gastrointestinal hemorrhage was observed in two patients and intra-cranial hemorrhage was observed in one patient during defibrotide therapy. The survival rate to day +100 was 79%. CONCLUSIONS: Defibrotide appears to be an effective and relatively safe treatment for children with HVOD.