Risk factors affecting outcome of unrelated cord blood transplantation for children with familial haemophagocytic lymphohistiocytosis

Abstract

Allogeneic haematopoietic stem cell transplantation is still the only available curative option for Familial Haemophagocytic Lymphohistiocytosis (FHLH). Most studies report outcomes after bone marrow or peripheral blood stem cell transplantation. We analysed the outcomes of 118 children with FHLH undergoing single-unit umbilical cord blood transplantation performed from 1996 to 2014. Myeloablative conditioning regimen was given to 90% of the patients, and was mostly busulfan-based (n = 81, 76%), including anti-thymocyte globulin or alemtuzumab (n = 102, 86%). The cumulative incidence of Day 60 neutrophil engraftment was 85%; and that of non-relapse mortality and acute graft-versus-host disease (GvHD) was 21% and 33% at 100 days, respectively. The 6-year cumulative incidence of chronic GvHD was 17% and the 6-year probability of overall survival was 55%. In multivariate analysis, children receiving a graft with a total nucleated cell dose greater than 9Á9 9 10 7 /kg had a better overall survival (hazard ratio [HR]: 0Á49, 95% CI: 0Á27-0Á88, P = 0Á02). Degree of human leucocyte antigen (HLA) matching was associated with improved disease-free survival (5/6 vs. 6/6 HR: 2Á11, 95% confidence interval [CI]: 1Á01-4Á4, P = 0Á05 and ≤4/6 vs. 6/6, HR: 2Á82, CI: 1Á27-6Á23, P = 0Á01). Umbilical cord blood transplantation with a high cell dose and good HLA match is a suitable alternative option to haematopoietic stem cell transplantation in children with FHLH who lack a HLA-matched donor.

Risk factors for mixed chimerism in children with hemophagocytic lymphohistiocytosis after reduced toxicity conditioning

“…In a small cohort of only 12 patients receiving unrelated cord blood transplantation and variable reduced intensitiy conditioning regimen, full chimerism could be achieved in most patients with familial hemophagocytic lymphohistiocytosis (FHL). 7 Serotherapy is likely to be a crucial factor regarding mixed chimerism. Alemtuzumab has been widely used in HLH conditioning regimens.…”

“…This is in keeping with most publications, 4,31 while this effect could not be shown in a cohort of unrelated cord blood transplantations in HLH. 7 In summary, the appearance of substantial recipient chimerism remains a major challenge in HSCT of HLH (when using reduced toxicity regimes). We demonstrated that an HLA-mismatched donor is an independent risk factor and confirmed that active disease at start of conditioning is a poor prognostic factor.…”

“…[3][4][5][6] Single-unit cord blood transplantation with an overall survival (OS) rate of 55% after MAC yielded a comparable outcome. 7 Reduced toxicity conditioning regimens with melphalan as alkylating agent in combination with fludarabine were established, with a favorable toxicity profile. 3,8,9 Later, treosulfan was introduced for conditioning in malignant and nonmalignant diseases and has been reported to have a low toxicity profile.…”

Haematopoietic Stem Cell Transplantation for Primary Haemophagocytic Lymphohistiocytosis

“…Alternative donors should therefore be considered early. Unrelated umbilical cord blood transplantation may provide a readily available alternative donor source, and 6-year overall survival of 55% has been reported in a recent analysis of 118 patients receiving mostly busulfan-based conditioning (32).…”

Current status of umbilical cord blood transplantation in children

“…Finally, for familial haemophagocytic lymphohistiocytosis (HLH), although the best results are obtained with MSD transplantation, unrelated UCB can be used as a source of HSC, with OS from 55% to 76% (Table D). A recent study by Eurocord reported an OS of 55% in children with familial HLH transplanted from unrelated UCB, with best results with higher cell dose (OS 65% with TNC >9.9 10 7 /kg) and better HLA match (DFS 69% with 6/6 HLA‐match) (Furtado‐Silva et al , ). A smaller Japanese study, moreover, showed that UCBT may be feasible even after RIC in HLH patients with established organ dysfunction (Sawada et al , ).…”