Improved treatment results in childhood B-cell neoplasms with tailored intensification of therapy: A report of the Berlin-Frankfurt-Munster group trial NHL-BFM 90

In study NHL-BFM 90, we investigated whether the serum lactate dehydrogenas e (LDH) concentration and early response are useful markers for stratificat ion of therapy for childhood B-cell neoplasms in addition to stage, if the outcome of patients with abdominal stage III and LDH greater than or equal to 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 stud y 86; whether 2 therapy courses are enough for patients with complete resec tion; and whether combined systemic and intraventricular chemotherapy is ef ficacious for central nervous system-positive (CNS+) patients. After a cyto reductive prephase, treatment was stratified into 3 risk groups: patients i n 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 (abdomina l primary and LDH greater than or equal to 500 U/L or bone marrow/CNS/multi local bone disease) received 6 courses. Incomplete responders after 2 cours es received an intensification containing HD-cytarabine/etoposide. Patients with no or necrotic tumor thereafter received 3 more courses; 6 patients w ith viable tumor received autologous bone marrow transplantation. From Apri l 1990 through March 1995, 413 evaluable patients were enrolled (R1, 17%; R 2, 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, respectivel y. The pEFS of patients with abdominal stage III and LDH greater than or eq ual to 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. (C) 1999 by The Americ an Society of Hematology.