Outcomes Of Unrelated Cord Blood Transplantation For Familial Hemophagocytic Lymphohistiocytosis: Risk Factors And Long Term Follow-Up. An Analysis On Behalf Of Eurocord, Cord Blood Committee Of Cellular Therapy And Immunobiology Working Party Of The Ebmt And Inborn Errors Working Party Of The Ebmt

Familial Hemophagocytic Lymphohistiocytosis (FHLH) is a systemic hyperinflammatory syndrome caused by excessive activation of lymphocytes and macrophages that produce high levels of cytokines as a result of genetic defects affecting the granule-mediated cytotoxicity pathway. Allogeneic hematopoietic stem cell transplantation (HSCT) is so far the only available curative option for the disease and the majority of studies have been conducted in patients given either bone marrow or peripheral blood transplantation. Previous case series of unrelated umbilical cord blood transplants (UCBT) reported survival rates ranging from 25%-85%. We analyzed the outcomes of 118 children from 43 EBMT centers with HLH undergoing single UCBT and reported to Eurocord. The median year of UCBT was 2010 (range 1996-2014). The median follow-up was 75 months (range 3.3-211). The majority of patients had genetic diagnosis of familial HLH (64%) of which 37.4% were due to perforin defect, 30.6% due to Munc 13-4 defect, 25.3% due to Munc 18-2, 5.4% due to syntaxin 11 and 1.3% due to perforin and syntaxin 11 defects. The median age at diagnosis and at UCBT were 0.3 years (range 0-14) and 1 year (range 0.1-14), respectively. The median time from diagnosis to UCBT was 5.3 months (range 0-57). Amongst 113 patients with known disease status, most patients underwent UCBT in complete remission 68/113 (60%) with 25/113 (22%) in partial remission and 20/113 (18%) having active disease at the time of transplant. Conditioning regimen was Busulfan or Treosulfan-based myeloablative in 78% of the patients while 22% received a reduced intensity conditioning. Seventeen (14%) children did not receive serotherapy as part of conditioning. Thirty-five patients (30%) received a 6/6 HLA matched cord blood unit, 56 (48%) received a 5/6 HLA mismatched cord blood unit, 24 (21%) received a 4/6 (21%) and 1 patient received 3/6 (1%) HLA mismatched graft. The median number of total nucleated cells (TNC) infused was 9.9 x107/kg (range 1.26 - 42.5 x107/kg).