ABSTRACT
Over 50% of patients with systemic LCH are not cured with front-line therapies, and data to guide salvage options are limited. We describe 58 patients with LCH who were treated with clofarabine. Clofarabine monotherapy was active against LCH in this cohort, including heavily pretreated patients with a systemic objective response rate of 92.6%, higher in children (93.8%) than adults (83.3%). BRAFV600E+ variant allele frequency in peripheral blood is correlated with clinical responses. Prospective multicentre trials are warranted to determine optimal dosing, long-term efficacy, late toxicities, relative cost and patient-reported outcomes of clofarabine compared to alternative LCH salvage therapy strategies.
Subject(s)
Clofarabine , Histiocytosis, Langerhans-Cell , Humans , Clofarabine/therapeutic use , Clofarabine/administration & dosage , Histiocytosis, Langerhans-Cell/drug therapy , Male , Female , Adult , Adolescent , Child , Middle Aged , Child, Preschool , Young Adult , Aged , Recurrence , Proto-Oncogene Proteins B-raf/genetics , Infant , Treatment Outcome , Salvage Therapy , Adenine Nucleotides/therapeutic use , Adenine Nucleotides/administration & dosage , Adenine Nucleotides/adverse effects , Arabinonucleosides/therapeutic use , Arabinonucleosides/administration & dosage , Arabinonucleosides/adverse effectsABSTRACT
BACKGROUND: Recombinant factor VIIa is a general hemostatic agent. Randomized trials have demonstrated effectiveness in adults; however, data in children are confined to case reports and series subject to publication bias. PROCEDURES: A consecutive cohort of children treated with rFVIIa was identified via inspection of pharmacy records. Data collected included demographic data, underlying disorders, reason for rFVIIa use, dosing, thrombotic events, and mortality. Efficacy was scored subjectively on a 3-point scale (complete, partial, or no response) and supported by a measurement of transfusion of red cells, platelets, fresh frozen plasma, and cryoprecipitate in the 3 days prior to and following use of rFVIIa. Patients with hemophilia and congenital factor VII deficiency were excluded. RESULTS: Sixty-five percent had a complete response and 26% had a partial response. Following treatment, there was a mean reduction in transfusions of 14.2 ml/kg for red blood cells, 10.9 ml/kg for platelets, 9 ml/kg for fresh frozen plasma, and 4.6 ml/kg for cryoprecipitate. Thrombosis occurred in 4.3% of patients with the highest rate being in neonates (17.6%). CONCLUSIONS: rFVIIa is an effective general hemostatic agent for management of excessive bleeding in children and that with the exception of neonates has excellent safety.