title: Reduced-intensity conditioning significantly improves survival of patients with hemophagocytic lymphohistiocytosis undergoing allogeneic hematopoietic cell transplantation.
abstract: Recent experience suggests that reduced-intensity conditioning (RIC) regimens can improve the outcomes of patients with hemophagocytic lymphohistiocytosis (HLH) undergoing allogeneic hematopoietic cell transplantation (HCT). However, studies directly comparing RIC to myeloablative conditioning (MAC) regimens are lacking. Forty patients with HLH underwent allogeneic HCT between 2003-2009 at Cincinnati Children's Hospital. Fourteen patients received MAC consisting of busulfan, cyclophosphamide, and antithymocyte globulin plus or minus etoposide. Twenty-six patients received RIC consisting of fludarabine, melphalan, and alemtuzumab. All patients engrafted. Acute graft-versus-host disease grades II to III occurred in 14% of MAC patients and 8% of RIC patients (P = .3171). Posttransplantation mixed donor/recipient chimerism developed in 18% of MAC patients and 65% of RIC patients (P = .0110). The majority of patients with mixed chimerism received intervention with reduction of immune suppression plus or minus donor lymphocyte infusion or stem cell boost, which stabilized or increased donor contribution to hematopoiesis and prevented relapse of HLH in all but 1 patient. Grade II to III graft-versus-host disease occurred in 5 of 14 RIC patients after donor lymphocyte infusion. The overall estimated 3-year survival after HCT was 43% (confidence interval = ± 26%) for MAC patients and 92% (confidence interval = ± 11%) for RIC patients (P = .0001). We conclude that RIC significantly improves the outcome of patients with HLH undergoing allogeneic HCT.
authors.affiliation: Division of Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA. rebecca.marsh@cchmc.org
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Marsh
authors.forename: Gretchen
authors.initials: G
authors.lastname: Vaughn
authors.forename: Mi-Ok
authors.initials: MO
authors.lastname: Kim
authors.forename: Dandan
authors.initials: D
authors.lastname: Li
authors.forename: Sonata
authors.initials: S
authors.lastname: Jodele
authors.forename: Sarita
authors.initials: S
authors.lastname: Joshi
authors.forename: Parinda A
authors.initials: PA
authors.lastname: Mehta
authors.forename: Stella M
authors.initials: SM
authors.lastname: Davies
authors.forename: Michael B
authors.initials: MB
authors.lastname: Jordan
authors.forename: Jack J
authors.initials: JJ
authors.lastname: Bleesing
authors.forename: Alexandra H
authors.initials: AH
authors.lastname: Filipovich
mesh_terms: D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D005260:Female; D006086:Graft vs Host Disease / Q000401:mortality* / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D051359:Lymphohistiocytosis, Hemophagocytic / Q000401:mortality* / Q000628:therapy*; D008297:Male; D012074:Remission Induction; D012189:Retrospective Studies; D015996:Survival Rate; D019172:Transplantation Conditioning; D016896:Treatment Outcome; D055815:Young Adult