title: Haematopoietic stem cell transplantation for refractory Langerhans cell histiocytosis: outcome by intensity of conditioning.
abstract: Patients with Langerhans cell histiocytosis (LCH) refractory to conventional chemotherapy have a poor outcome. There are currently two promising treatment strategies for high-risk patients: the first involves the combination of 2-chlorodeoxyadenosine and cytarabine; the other approach is allogeneic haematopoietic stem cell transplantation (HSCT). Here we evaluated 87 patients with high-risk LCH who were transplanted between 1990 and 2013. Prior to the year 2000, most patients underwent HSCT following myeloablative conditioning (MAC): only 5 of 20 patients (25%) survived with a high rate (55%) of transplant-related mortality (TRM). After the year 2000 an increasing number of patients underwent HSCT with reduced intensity conditioning (RIC): 49/67 (73%) patients survived, however, the improved survival was not overtly achieved by the introduction of RIC regimens with similar 3-year probability of survival after MAC (77%) and RIC transplantation (71%). There was no significant difference in TRM by conditioning regimen intensity but relapse rates were higher after RIC compared to MAC regimens (28% vs. 8%, P = 0·02), although most patients relapsing after RIC transplantation could be salvaged with further chemotherapy. HSCT may be a curative approach in 3 out of 4 patients with high risk LCH refractory to chemotherapy: the optimal choice of HSCT conditioning remains uncertain.
authors.affiliation: Great Ormond Street Hospital for Children NHS Trust, London, UK.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Veys
authors.affiliation: Watford General Hospital, Watford, UK.
authors.forename: Vasanta
authors.initials: V
authors.lastname: Nanduri
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
authors.forename: K Scott
authors.initials: KS
authors.lastname: Baker
authors.affiliation: CIBMTR® (Center for International Blood and Marrow Transplant Research), Department of Medicine, Medical College of Wisconsin, Milwaukee, WI, USA.
authors.forename: Wensheng
authors.initials: W
authors.lastname: He
authors.affiliation: Institute of Haematology, St. Orsola University Hospital, Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Bandini
authors.affiliation: Ospedale San Gerardo, Monza, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Biondi
authors.affiliation: EBMT Paediatric Disease Working Party, Paris, France.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Dalissier
authors.affiliation: British Columbia's Children's Hospital, Vancouver, BC, Canada.
authors.forename: Jeffrey H
authors.initials: JH
authors.lastname: Davis
authors.affiliation: Cook Children's Medical Center, Fort Worth, TX, USA.
authors.forename: Gretchen M
authors.initials: GM
authors.lastname: Eames
authors.affiliation: The Hospital for Sick Children, Toronto, ON, Canada.
authors.forename: R Maarten
authors.initials: RM
authors.lastname: Egeler
authors.affiliation: Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
authors.forename: Alexandra H
authors.initials: AH
authors.lastname: Filipovich
authors.affiliation: Hôpital Necker-Enfants malades, Paris, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Fischer
authors.affiliation: Klinik/Poliklinik für Kinderheilkunde, Münster, Germany.
authors.forename: Herbert
authors.initials: H
authors.lastname: Jürgens
authors.affiliation: Section of Hematology-Oncology, Department of Pediatrics, Baylor College of Medicine and the Center for Cell and Gene Therapy, Houston, TX, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Krance
authors.affiliation: Institute G. Gaslini, Genova, Italy.
authors.forename: Edoardo
authors.initials: E
authors.lastname: Lanino
authors.affiliation: St. Jude Children's Research Hospital, Memphis, TN, USA.
authors.forename: Wing H
authors.initials: WH
authors.lastname: Leung
authors.affiliation: St. Anna Kinderspital, Vienna, Austria.
authors.forename: Susanne
authors.initials: S
authors.lastname: Matthes
authors.affiliation: Hôpital d'Enfants de la Timone, Marseille, France.
authors.forename: Gérard
authors.initials: G
authors.lastname: Michel
authors.affiliation: Department of Pediatrics, University of Minnesota Medical Center, Minneapolis, MN, USA.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Orchard
authors.affiliation: Department of Paediatric Oncology, Haematology & HSCT, Poznań, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Pieczonka
authors.affiliation: Division of Therapeutic Immunology, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.|Centre for Allogeneic Stem Cell Transplantation, Stockholm, Sweden.
authors.forename: Olle
authors.initials: O
authors.lastname: Ringdén
authors.affiliation: Department of Paediatric Haematology, Oncology, Paediatric Stem Cell Transplantation Program, University Children's Hospital Wuerzburg, Wuerzburg, Germany.
authors.forename: Paul G
authors.initials: PG
authors.lastname: Schlegel
authors.affiliation: Hôpital Arnaud de Villeneuve, CHRU Montpellier, Montpellier, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Sirvent
authors.affiliation: University of Helsinki, Helsinki, Finland.
authors.forename: Kim
authors.initials: K
authors.lastname: Vettenranta
authors.affiliation: CIBMTR® (Center for International Blood and Marrow Transplant Research), Department of Medicine, Medical College of Wisconsin, Milwaukee, WI, USA.
authors.forename: Mary
authors.initials: M
authors.lastname: Eapen
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology / Q000517:prevention & control; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006646:Histiocytosis, Langerhans-Cell / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D006801:Humans; D007223:Infant; D008297:Male; D012189:Retrospective Studies; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D055815:Young Adult
keywords: Langerhans cell histiocytosis; allogeneic transplantation; conditioning regimen intensity; survival; treatment failure
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