title: Reduced-intensity conditioning in unrelated donor cord blood transplantation for familial hemophagocytic lymphohistiocytosis.
abstract: 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.
authors.affiliation: Department of Pediatrics, Saga University Hospital, Saga, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Nishi
authors.forename: Ryosei
authors.initials: R
authors.lastname: Nishimura
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Suzuki
authors.forename: Akihisa
authors.initials: A
authors.lastname: Sawada
authors.forename: Takayuki
authors.initials: T
authors.lastname: Okamura
authors.forename: Naoto
authors.initials: N
authors.lastname: Fujita
authors.forename: Rie
authors.initials: R
authors.lastname: Kanai
authors.forename: Jun
authors.initials: J
authors.lastname: Yano
authors.forename: Souichi
authors.initials: S
authors.lastname: Adachi
authors.forename: Takahiro
authors.initials: T
authors.lastname: Yasumi
authors.forename: Emiko
authors.initials: E
authors.lastname: Sato
authors.forename: Koji
authors.initials: K
authors.lastname: Yasutomo
authors.forename: Eiichi
authors.initials: E
authors.lastname: Ishii
authors.forename: Shouichi
authors.initials: S
authors.lastname: Ohga
mesh_terms: D016913:Blood Component Transfusion; D001782:Blood Donors; D002675:Child, Preschool; D003131:Combined Modality Therapy; D036101:Cord Blood Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D018572:Disease-Free Survival; D005260:Female; D006085:Graft Survival; D006086:Graft vs Host Disease; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007564:Japan; D051359:Lymphohistiocytosis, Hemophagocytic / Q000601:surgery* / Q000628:therapy; D008297:Male; D008558:Melphalan / Q000008:administration & dosage; D012086:Reoperation; D012189:Retrospective Studies; D016879:Salvage Therapy; D019172:Transplantation Conditioning / Q000379:methods*; D016896:Treatment Outcome; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives; D014916:Whole-Body Irradiation
chemical_list: D014740:Vidarabine; C024352:fludarabine; D008558:Melphalan