title: High cure rates and reduced long-term toxicity in pediatric Hodgkin's disease: the German-Austrian multicenter trial DAL-HD-90. The German-Austrian Pediatric Hodgkin's Disease Study Group.
abstract: OBJECTIVE
  To further reduce therapy-related late effects in patients with pediatric Hodgkin's disease (HD) while maintaining the high cure rates achieved with vincristine, prednisone, procarbazine, and doxorubicin (OPPA) or OPPA/cyclophosphamide, vincristine, prednisone, and procarbazine (COPP) chemotherapy and involved-field radiotherapy. The risk of testicular dysfunction was addressed by substituting etoposide for procarbazine (OEPA) in the induction therapy for boys. Radiation doses and fields were further reduced.
  
  
  METHODS
  Three hundred nineteen boys and 259 girls younger than 18 years with previously untreated HD, enrolled onto the study between 1990 and 1995, were allocated to treatment group (TG)1 (early stages), TG2 (intermediate stages), or TG3 (advanced stages). All groups underwent two cycles of OEPA (boys) or OPPA (girls) for induction chemotherapy. TG2 and TG3 continued on additional two or four cycles, respectively, of COPP. Low-dose radiotherapy was given to the initially involved sites, ie, reduced involved fields.
  
  
  RESULTS
  Initial response to OPPA or OEPA induction was virtually identical. Eight of 578 patients experienced early progression of HD. Thirty-seven relapses, three secondary tumors, and no secondary leukemias have been recorded, with a median follow-up duration of 5.1 years (maximum, 8.1 years). Thirteen of 578 patients died. The probability of 5-year event-free survival/overall survival is 91%/98% in the total group, 94%/97% with OPPA, and 89%/98% with OEPA induction therapy. Risk factor analysis showed two significant prognostic factors: histologic subtype NS2 and "B" symptoms. OEPA induction therapy, large mediastinal tumor, and age were not significant. Preliminary studies of testicular function indicate a lower risk of germ cell damage than previously documented with OPPA.
  
  
  CONCLUSIONS
  OEPA is a satisfactory alternative to OPPA. Radiotherapy can be confined to involved sites when combined with appropriate chemotherapy. The DAL-HD-90 regimen represents a comprehensive treatment program for all stages of pediatric HD and offers a favorable benefit/risk ratio, combining excellent disease control, moderate acute toxicity, and reduced long-term toxicity.
authors.affiliation: Department of Pediatric Hematology and Oncology, University Children's Hospital, Germany. schellon@uni-muenster.de
authors.forename: G
authors.initials: G
authors.lastname: Schellong
authors.forename: R
authors.initials: R
authors.lastname: Pötter
authors.forename: J
authors.initials: J
authors.lastname: Brämswig
authors.forename: W
authors.initials: W
authors.lastname: Wagner
authors.forename: F J
authors.initials: FJ
authors.lastname: Prott
authors.forename: W
authors.initials: W
authors.lastname: Dörffel
authors.forename: D
authors.initials: D
authors.lastname: Körholz
authors.forename: G
authors.initials: G
authors.lastname: Mann
authors.forename: B
authors.initials: B
authors.lastname: Rath
authors.forename: A
authors.initials: A
authors.lastname: Reiter
authors.forename: G
authors.initials: G
authors.lastname: Weissbach
authors.forename: M
authors.initials: M
authors.lastname: Riepenhausen
authors.forename: M
authors.initials: M
authors.lastname: Thiemann
authors.forename: E W
authors.initials: EW
authors.lastname: Schwarze
mesh_terms: D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001317:Austria; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D005858:Germany; D006689:Hodgkin Disease / Q000188:drug therapy* / Q000532:radiotherapy; D006801:Humans; D008297:Male; D011241:Prednisone / Q000008:administration & dosage; D011344:Procarbazine / Q000008:administration & dosage; D011829:Radiation Dosage; D012307:Risk Factors; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D011344:Procarbazine; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone