title: Treosulfan-based conditioning regimen for children and adolescents with hemophagocytic lymphohistiocytosis.
abstract: In hematopoietic stem cell transplantation for hemophagocytic lymphohistiocytosis, high transplant-related mortality after busulfan-based myeloablative regimens has been observed. Conditioning regimens with reduced toxicity based on melphalan or treosulfan are promising alternatives. We retrospectively analyzed hematopoietic stem cell transplantations in 19 hemophagocytic lymphohistiocytosis patients after conditioning with fludarabine, treosulfan, alemtuzumab, with or without thiotepa. Overall and disease-free survivals were 100% (follow up 7-31 months). Two patients required second transplant (1 after haploidentical transplantation). In 6 patients, overall donor chimerism dropped below 75% and prompted donor lymphocyte infusions. Administration of donor lymphocytes or second transplantation were significantly more frequent after transplantation from a human leukocyte antigen mismatched (9/10) versus matched (10/10) donor (P=0.018). The toxicity profile was favorable, with one veno-occlusive disease, one grade 3 graft-versus-host disease after donor lymphocyte infusion, and 2 severe viral infections (1 influenza, 1 Epstein Barr virus). In conclusion, the treosulfan-based regimen in hemophagocytic lymphohistiocytosis is effective with low toxicity and gives excellent overall and disease-free survival rates. In the future, the incidence of mixed chimerism, particularly after human leukocyte antigen mismatched donor transplants, needs to be addressed.
authors.affiliation: k.lehmberg@uke.de.
authors.forename: Kai
authors.initials: K
authors.lastname: Lehmberg
authors.forename: Michael H
authors.initials: MH
authors.lastname: Albert
authors.forename: Rita
authors.initials: R
authors.lastname: Beier
authors.forename: Karin
authors.initials: K
authors.lastname: Beutel
authors.forename: Bernd
authors.initials: B
authors.lastname: Gruhn
authors.forename: Nicolaus
authors.initials: N
authors.lastname: Kröger
authors.forename: Roland
authors.initials: R
authors.lastname: Meisel
authors.forename: Ansgar
authors.initials: A
authors.lastname: Schulz
authors.forename: Daniel
authors.initials: D
authors.lastname: Stachel
authors.forename: Wilhelm
authors.initials: W
authors.lastname: Woessmann
authors.forename: Gritta
authors.initials: G
authors.lastname: Janka
authors.forename: Ingo
authors.initials: I
authors.lastname: Müller
mesh_terms: D000293:Adolescent; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage*; D002066:Busulfan / Q000008:administration & dosage / Q000031:analogs & derivatives*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000209:etiology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D007223:Infant; D051359:Lymphohistiocytosis, Hemophagocytic / Q000235:genetics / Q000401:mortality / Q000628:therapy*; D008297:Male; D012189:Retrospective Studies; D012307:Risk Factors; D018183:Transplantation Chimera; D019172:Transplantation Conditioning; D016896:Treatment Outcome; D014777:Virus Diseases / Q000209:etiology; D055815:Young Adult
chemical_list: D018906:Antineoplastic Agents, Alkylating; C018404:treosulfan; D002066:Busulfan