The Outcome of Hematopoietic Stem Cell Transplantation in Pediatric Patients with Hemophagocytic Lymphohistiocytosis in Korea.

Objective: Chemoimmunotherapy based treatments improved the survival of patients with hemophagocytic lymphohistiocytosis (HLH), but the outcome is still unsatisfactory. We analyzed the outcome of pediatric patients with HLH after hematopoietic stem cell transplantation (HSCT) in a nation-wide HLH registry.

Methods: Retrospective nation-wide data recruitment for HLH pediatric patients diagnosed between 1996 and 2005 was carried out by Histiocytosis Working Party of the KSH and KSPHO. Sixteen patients who received HSCT among enrolled 129 pediatric patients with HLH were analyzed for transplant related variables and events.

Results: The probability of 3-year survival after HSCT was 81.2% with median follow-up of 27.5 months compared to the 35.2% for patients who were treated with chemoimmunotherapy only (P=0.03). The reasons for HSCT were active disease at 2 months after treatment (n=8), relapsed disease (n=5), and familial HLH (n=3). Eight patients received transplants from matched unrelated donors, 5 from matched siblings and 3 using unrelated cord blood units. Stem cell sources were bone marrow for all the 13 allogeneic transplants other than 3 cord blood transplants. Conditioning regimens were busulphan, cytoxan, and VP-16 with (5) or without (7) antithymocyte globulin (ATG) in 12 patients, fludarabin and melphalan in 3, and other regimen in 1. Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine (CSA) + MTX in 11 patients, CSA +MMF in 2, and others in 2. Twelve patients are alive in complete remission state, 3 patients died of infection and graft failure at early post-transplant period, and 1 patient relapsed at post-transplant 30 days. The relapsed patient developed tuberculous encephalitis after retreatment with chemoimmunotherapy, and alive with supportive care. After HSCT, acute GVHD developed in 5 patients, infection in 5, veno-occlusive disease (VOD) in 2, graft failure in 2, and post-transplant lymphoproliferative disease (PTLD) in 1. Acute lymphoblastic leukemia developed in 1 patient about 2 years after HSCT. Variables such as age at diagnosis, etiology of HLH (familial or secondary), central nervous system (CNS) involvement, disease state after 8 weeks of initial treatment, conditioning regimens, and stem cell sources were not associated with significant difference with regard to 3-year overall survival after HSCT.

Conclusion: HSCT revealed excellent outcome for patients with familial, relapsed, or severe and persistent secondary HLH in Korean nation-wide HLH registry.