title: Improved treatment results in childhood B-cell neoplasms with tailored intensification of therapy: A report of the Berlin-Frankfurt-Münster Group Trial NHL-BFM 90.
abstract: In study NHL-BFM 90, we investigated whether the serum lactate dehydrogenase (LDH) concentration and early response are useful markers for stratification of therapy for childhood B-cell neoplasms in addition to stage, if the outcome of patients with abdominal stage III and LDH >/=500 U/L can be improved by high-dose (HD) methotrexate (MTX) at 5 g/m(2) instead of intermediate-dose (ID) MTX at 500 mg/m(2) in the preceding study 86; whether 2 therapy courses are enough for patients with complete resection; and whether combined systemic and intraventricular chemotherapy is efficacious for central nervous system-positive (CNS(+)) patients. After a cytoreductive prephase, treatment was stratified into 3 risk groups: patients in R1 (completely resected) received 2 5-day courses (ID-MTX, dexamethasone, oxazaphorins, etoposide, cytarabine, doxorubicin, and intrathecal therapy), patients in R2 (extra-abdominal primary only or abdominal tumor and LDH <500 U/L) received 4 courses containing HD-MTX, and patients in R3 (abdominal primary and LDH >/=500 U/L or bone marrow/CNS/multilocal bone disease) received 6 courses. Incomplete responders after 2 courses received an intensification containing HD-cytarabine/etoposide. Patients with no or necrotic tumor thereafter received 3 more courses; 6 patients with viable tumor received autologous bone marrow transplantation. From April 1990 through March 1995, 413 evaluable patients were enrolled (R1, 17%; R2, 40%; and R3, 43%). The 6-year event-free survival (pEFS) was 89% +/- 2% for all and 100%, 96% +/-2%, and 78% +/- 3% in R1, R2, and R3, respectively. The pEFS of patients with abdominal stage III and LDH >/=500 U/L was 81% +/- 4% as compared with 43% +/- 10% in study 86. Of 26 CNS(+) patients, 5 died early, but only 3 relapsed.
authors.affiliation: Department of Pediatric Hematology and Oncology, Medizinische Hochschule, Hannover, Germany. alfred.reiter@paediat.med.uni-giessen.de
authors.forename: A
authors.initials: A
authors.lastname: Reiter
authors.forename: M
authors.initials: M
authors.lastname: Schrappe
authors.forename: M
authors.initials: M
authors.lastname: Tiemann
authors.forename: W D
authors.initials: WD
authors.lastname: Ludwig
authors.forename: E
authors.initials: E
authors.lastname: Yakisan
authors.forename: M
authors.initials: M
authors.lastname: Zimmermann
authors.forename: G
authors.initials: G
authors.lastname: Mann
authors.forename: A
authors.initials: A
authors.lastname: Chott
authors.forename: W
authors.initials: W
authors.lastname: Ebell
authors.forename: T
authors.initials: T
authors.lastname: Klingebiel
authors.forename: N
authors.initials: N
authors.lastname: Graf
authors.forename: B
authors.initials: B
authors.lastname: Kremens
authors.forename: S
authors.initials: S
authors.lastname: Müller-Weihrich
authors.forename: H J
authors.initials: HJ
authors.lastname: Plüss
authors.forename: F
authors.initials: F
authors.lastname: Zintl
authors.forename: G
authors.initials: G
authors.lastname: Henze
authors.forename: H
authors.initials: H
authors.lastname: Riehm
mesh_terms: D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism; D002051:Burkitt Lymphoma / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology / Q000601:surgery; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage; D003561:Cytarabine / Q000008:administration & dosage; D003907:Dexamethasone / Q000008:administration & dosage; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage; D007223:Infant; D007770:L-Lactate Dehydrogenase / Q000378:metabolism*; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology / Q000601:surgery; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D009367:Neoplasm Staging; D011239:Prednisolone / Q000008:administration & dosage; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D014408:Biomarkers, Tumor; D003561:Cytarabine; D014750:Vincristine; D005047:Etoposide; D003907:Dexamethasone; D004317:Doxorubicin; D003520:Cyclophosphamide; D011239:Prednisolone; D007770:L-Lactate Dehydrogenase; D007069:Ifosfamide; D008727:Methotrexate