Outcomes after Allogeneic Stem Cell Transplantation in Adults for Histiocytic Disorders Including Hemophagocytic Lymphohistiocytosis

Histiocytic disorders are rare but often fatal illnesses.  Within these, familial and secondary hemophagocytic lymphohistiocytosic disorders (HLH) are primarily diagnosed in childhood, and there have been few large analyses of outcomes in adults with HLH.  The widely-accepted HLH-94 treatment regimen consisting of dexamethasone, etoposide and cyclosporine therapy followed by allogeneic stem cell transplantation (SCT) has been employed primarily in children.  In the largest series to date of 113 children under 15 years of age, a 3 year survival rate of 55% overall and 62% for those receiving allogeneic SCT was seen (Henter. Blood 2002; 100:2367-2372).  In light of the highly proinflammatory cytokine environment that characterizes HLH, alemtuzumab for profound lymphocyte depletion in concert with conditioning for pediatric SCT is becoming increasingly common, with an impact on rates of acute GvHD and mixed chimerism reported.  (Marsh. Blood 2010;116:5824-5831; Marsh. Pediatr Blood Cancer 2013;60:101-109).  To assess current practices and outcomes in adults, we performed a retrospective review using the CIBMTR database of all subjects over 18 years of age receiving allogeneic SCT for histiocytic conditions between 2001 and 2012.  Results: 47 subjects were identified, 16 of whom were transplanted in 2011 or 2012. Median age was 25 (18-67).  Underlying diagnoses were familial HLH (47%), secondary HLH (32%), malignant histiocytosis (15%), and histiocytic disorders not otherwise specified (6%).  31 subjects (66%) received transplants from unrelated donors.  26 subjects (55%) received PBSCs.  The remaining subjects received bone marrow, except for one who received umbilical cord blood.  26 subjects (56%) received myeloablative conditioning, primarily cytoxan-TBI-based or cytoxan and busulfan.  21 subjects underwent reduced-intensity or non-myeloablative conditioning with fludarabine-based regimens.  18 subjects (38%) underwent conditioning in combination with alemtuzumab.  Kaplan-Meier survival rate estimates for the entire cohort were 93% at 100 days (95% CI, 71-93), 60% at one year (95% CI, 45-75) and 57% at 2 years (95% CI, 40-72).  Conclusions: Adults with histiocytic disorders, primarily HLH, have survival rates after allogeneic SCT similar to those seen in the pediatric literature.  Inclusion of alemtuzumab prior to or in concert with conditioning is common in adults.  Allogeneic SCT regimens for HLH merit prospective studies in adults as well as children.  We encourage participation in the BMT-CTN 1204 study, a phase II study of reduced-Intensity conditioning for children and adults with hemophagocytic syndromes or selected primary immune deficiencies preceded by alemtuzumab therapy.