Favorable Outcome with Durable Chimerism after Allogeneic Hematopoietic Cell Transplantation Using Busulfan and Fludarabine-Based Reduced-Intensity Conditioning for Children with Hemophagocytic Lymphohistiocytosis

Abstract

Purpose Hematopoietic Stem Cell Transplantation (HSCT) is the only curative treatment for patients with familial, relapsing, or persistent hemophagocytic lymphohistiocytosis (HLH). Here, we present a single center experience of using busulfan (Bu) and fludarabine (Flu) based reduced intensity conditioning regimen (RIC) for treatment of HLH. Methods Medical records of pediatric patients with HLH, who received HSCT using Bu/Flu based RIC regimen.from January 2008 to December 2017, were reviewed retrospectively. HSCT outcomes including engraftment, survival, and GVHD were analyzed. Results Nine patients were received HSCT using Bu/Flu based RIC regimen. Three patients received HSCT after diagnosis of familial HLH and the other 6 received after reactivation. All 3 patients with familial HLH had UNC13D mutations. Median 8.35 × 106 /kg (range, 2.84-10.05 × 106) CD34 positive cells were infused. All patients achieved WBC and PLT engraftment at median 11 days (range, 10-21) and 19 days (range, 13-32) from HSCT with full donor chimerism which sustained until last visit. Cyclosporine and mycophenolate mofetil were applied as GVHD prophylaxis except one patient who received HSCT from syngeneic sibling. Three patients (33%) experienced acute graft-versus-host disease (GVHD) of grade 2 which was well controlled after conventional steroid treatment. Two patients (22%) underwent chronic GVHD, and one of them died. One patient (11%) had reactivation 4 months after HSCT from syngeneic sibling donor, and died. The 5-year overall survival was 78%. Two patients died; one died of disease and the other died of treatment related mortality (TRM). No TRM other than chronic GVHD was existed. Conclusion Our experience suggests that Bu/Flu based RIC regimen can be effective option for pediatric patients with HLH who need HSCT showing durable chimerism and long-term survival with decreased toxicity.