Hemophagocytic Lymphohistiocytosis and Graft Failure Following Unrelated Umbilical Cord Blood Transplantation in Children

Hemophagocytic lymphohistiocytosis (HLH) following hematopoietic stem cell transplantation is closely correlated with graft failure and poor prognosis. Because of its rarity, the incidence, risk factors, and optimal treatment strategy are unclear. We analyzed data from cases of HLH following umbilical cord blood transplantation (UCBT) performed for pediatric patients at our center. Among 66 UCBT recipients, 5 developed HLH and imminent graft failure. The median time of diagnosis of HLH was 22 (range, 19 to 30) days after UCBT, and the cumulative incidence of HLH was 7.6% (95% confidence interval, 2.8-15.7) at day 60. In univariate analysis, the cumulative incidence of HLH was significantly higher in patients with infused CD34(+) cells <1.0x10(5)/kg than in patients with higher CD34(+) cells. Patients with preengraftment infection showed a trend toward higher incidence of HLH compared with patients without any infection. All 5 patients with HLH received corticosteroids and low-dose etoposide (VP-16), with or without high-dose intravenous immunoglobulin. Following these treatments, successful engraftment was observed in 2 patients. Corticosteroids and low-dose VP-16 may be worthy of a trial before attempting salvage hematopoietic stem cell transplantation. Further analyses are required to identify risk factors and to develop methods for prophylaxis, diagnosis, and treatment of HLH.