Hematopoietic stem cell transplantation for familial hemophagocytic lymphohistiocytosis and Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis in Japan.

Post-transplant outcomes of hemophagocytic lymphohistiocytosis (HLH) patients were analyzed in Japan where Epstein-Barr virus (EBV)-associated severe forms are problematic. Fifty-seven patients (43 familial HLH [12 FHL2, 11 FHL3, 20 undefined], 14 EBV-HLH) who underwent stem cell transplantation (SCT) between 1995 and 2005 were enrolled based on the nationwide registration. Fifty-seven patients underwent 61 SCTs, including 4 consecutive SCTs. SCTs were employed using allogeneic donors in 93% of cases (allo 53, twin 1, auto 3). Unrelated donor cord blood transplantation (UCBT) was employed in half of cases (21 FHL, 7 EBV-HLH). Reduced intensity conditioning was used in 26% of cases. The 10-year overall survival rates (median +/- SE%) were 65.0 +/- 7.9% in FHL and 85.7 +/- 9.4% in EBV-HLH patients, respectively. The survival of UCBT recipients was >65% in both FHL and EBV-HLH patients. Three out of four patients were alive with successful engraftment after second UCBT. FHL patients showed a poorer outcome due to early treatment-related deaths (<100 days, seven patients) and a higher incidence of sequelae than EBV-HLH patients (P = 0.02). The risk of death for FHL patients having received an unrelated donor bone marrow transplant was marginally higher than that for a related donor SCT (P = 0.05) and that for UCBT (P = 0.07). EBV-HLH patients had a better prognosis after SCT than FHL patients. FHL patients showed either an equal or better outcome even after UCBT compared with the recent reports. UCB might therefore be acceptable as an alternate SCT source for HLH patients, although the optimal conditioning remains to be determined.

Ohga S ，Kudo K ，Ishii E ，Honjo S ，Morimoto A ，Osugi Y ，Sawada A ，Inoue M ，Tabuchi K ，Suzuki N ，Ishida Y ，Imashuku S ，Kato S ，Hara T ... -  《-》

Allogeneic hematopoietic stem cell transplantation for Epstein-Barr virus-associated T/natural killer-cell lymphoproliferative disease in Japan.

Epstein-Barr virus (EBV)-associated T/NK-cell lymphoproliferative disease (LPD) has been linked to several different disorders. Its prognosis is generally poor and a treatment strategy has yet to be established. There are reports, however, that hematopoietic stem cell transplantation (HSCT) can cure this disease. To clarify the current situation regarding allogeneic hematopoietic stem cell transplantation (allo-HSCT) for EBV-associated T/NK-LPD, a nationwide survey was performed in Japan. Data for 74 patients were collected. There were 42 cases of chronic active EBV infection (CAEBV), 10 cases of EBV-associated hemophagocytic lymphohistiocytosis (EBV-HLH), and 22 cases of EBV-associated lymphoma/leukemia (EBV-lymphoma/leukemia). Of those with CAEBV, 54% had the EBV-infected T-cell type and 59% with EBV-lymphoma/leukemia had the EBV-infected NK-cell type. Most patients with EBV-HLH and EBV-lymphoma/leukemia received allo-HSCT within 1 year after onset compared to only 14% of patients with CAEBV. The event-free survival (EFS) rate following allo-HSCT was 0.561 +/- 0.086 for CAEBV, 0.614 +/- 0.186 for EBV-HLH, and 0.309 +/- 0.107 for EBV-lymphoma/leukemia. The EFS of allo-HSCT with conventional conditioning was 0.488 +/- 0.074 and with reduced-intensity conditioning was 0.563 +/- 0.124. Thus, in a substantial number of cases, EBV-associated T/NK-LPD can be cured by either allogeneic conventional stem cell transplantation or reduced-intensity stem cell transplantation.

Sato E ，Ohga S ，Kuroda H ，Yoshiba F ，Nishimura M ，Nagasawa M ，Inoue M ，Kawa K ... -  《-》

Reduced-intensity conditioning in unrelated donor cord blood transplantation for familial hemophagocytic lymphohistiocytosis.

Familial hemophagocytic lymphohistiocytosis (FHL) is a disorder of immune homeostasis characterized by fever, cytopenias, hepatosplenomegaly, and coagulopathy. We studied the outcomes of 13 FHL patients who underwent the first unrelated cord blood transplantation (UCBT) after non-myeloablative conditionings. The major regimen consisted of fludarabine (FLU; n = 12)+melphalan (MEL; n = 11)± low-dose total body irradiation (TBI 2-4 Gy; n = 6). The median age at presentation and period to UCBT were 6 and 5 months, respectively. Central nervous system (CNS) disease developed in one infant at diagnosis, and in two others until UCBT. HLH activity was controlled in all but one at the time of UCBT. Ten patients had early engraftment on median day 21 with no grade >2 treatment-related toxicity and two controllable grade >2 acute GVHD. Two patients with early rejection successfully underwent subsequent UCBT after myeloablative conditioning. Two others had late graft failure following mixed donor chimerism. Two deaths occurred from HLH; early liver failure and late CNS disease. Of 11 FLU+MEL-conditioned patients, the frequency of disease-free complete engraftment was higher for MEL (≥120 mg/m(2) )+TBI, or high-dose MEL (180 mg/m(2) ) than for others (83% vs. 25%, p = 0.036). The FLU+MEL-based non-myeloablative regimen was acceptable for FHL infants undergoing UCBT, although further studies will be needed for confirmation.

Nishi M ，Nishimura R ，Suzuki N ，Sawada A ，Okamura T ，Fujita N ，Kanai R ，Yano J ，Adachi S ，Yasumi T ，Sato E ，Yasutomo K ，Ishii E ，Ohga S ... -  《-》

Longitudinal follow-up of patients with Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis.

Imashuku S ，Teramura T ，Tauchi H ，Ishida Y ，Otoh Y ，Sawada M ，Tanaka H ，Watanabe A ，Tabata Y ，Morimoto A ，Hibi S ，Henter JI ... -  《-》

The outcome of hematopoietic stem cell transplantation in Korean children with hemophagocytic lymphohistiocytosis.

Yoon HS ，Im HJ ，Moon HN ，Lee JH ，Kim HJ ，Yoo KH ，Sung KW ，Koo HH ，Kang HJ ，Shin HY ，Ahn HS ，Cho B ，Kim HK ，Lyu CJ ，Lee MJ ，Kook H ，Hwang TJ ，Seo JJ ... -  《-》