title: Therapy prolongation improves outcome in multisystem Langerhans cell histiocytosis.
abstract: Langerhans cell histiocytosis (LCH)-III tested risk-adjusted, intensified, longer treatment of multisystem LCH (MS-LCH), for which optimal therapy has been elusive. Stratified by risk organ involvement (high [RO+] or low [RO-] risk groups), > 400 patients were randomized. RO+ patients received 1 to 2 six-week courses of vinblastine+prednisone (Arm A) or vinblastine + prednisone + methotrexate (Arm B). Response triggered milder continuation therapy with the same combinations, plus 6-mercaptopurine, for 12 months total treatment. 6/12-week response rates (mean, 71%) and 5-year survival (84%) and reactivation rates (27%) were similar in both arms. Notably, historical comparisons revealed survival superior to that of identically stratified RO+ patients treated for 6 months in predecessor trials LCH-I (62%) or LCH-II (69%, P < .001), and lower 5-year reactivation rates than in LCH-I (55%) or LCH-II (44%, P < .001). RO- patients received vinblastine+prednisone throughout. Response by 6 weeks triggered randomization to 6 or 12 months total treatment. Significantly lower 5-year reactivation rates characterized the 12-month Arm D (37%) compared with 6-month Arm C (54%, P = .03) or to 6-month schedules in LCH-I (52%) and LCH-II (48%, P < .001). Thus, prolonging treatment decreased RO- patient reactivations in LCH-III, and although methotrexate added no benefit, RO+ patient survival and reactivation rates have substantially improved in the 3 sequential trials. (Trial No. NCT00276757 www.ClinicalTrials.gov).
authors.affiliation: Children's Cancer Research Institute and St. Anna Children's Hospital, Vienna, Austria. helmut.gadner@ccri.at
authors.forename: Helmut
authors.initials: H
authors.lastname: Gadner
authors.forename: Milen
authors.initials: M
authors.lastname: Minkov
authors.forename: Nicole
authors.initials: N
authors.lastname: Grois
authors.forename: Ulrike
authors.initials: U
authors.lastname: Pötschger
authors.forename: Elfriede
authors.initials: E
authors.lastname: Thiem
authors.forename: Maurizio
authors.initials: M
authors.lastname: Aricò
authors.forename: Itziar
authors.initials: I
authors.lastname: Astigarraga
authors.forename: Jorge
authors.initials: J
authors.lastname: Braier
authors.forename: Jean
authors.initials: J
authors.lastname: Donadieu
authors.forename: Jan-Inge
authors.initials: JI
authors.lastname: Henter
authors.forename: Gritta
authors.initials: G
authors.lastname: Janka-Schaub
authors.forename: Kenneth L
authors.initials: KL
authors.lastname: McClain
authors.forename: Sheila
authors.initials: S
authors.lastname: Weitzman
authors.forename: Kevin
authors.initials: K
authors.lastname: Windebank
authors.forename: Stephan
authors.initials: S
authors.lastname: Ladisch
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D004359:Drug Therapy, Combination; D005260:Female; D006646:Histiocytosis, Langerhans-Cell / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D007223:Infant; D007231:Infant, Newborn; D053208:Kaplan-Meier Estimate; D008297:Male; D015122:Mercaptopurine / Q000008:administration & dosage; D008727:Methotrexate / Q000008:administration & dosage*; D011241:Prednisone / Q000008:administration & dosage*; D012008:Recurrence; D014747:Vinblastine / Q000008:administration & dosage*
chemical_list: D007166:Immunosuppressive Agents; D014747:Vinblastine; D015122:Mercaptopurine; D011241:Prednisone; D008727:Methotrexate