Central nervous system relapse prevention in 1165 standard-risk children with acute lymphoblastic leukemia in five BFM trials.
In treatment of childhood ALL, prevention of CNS relapse by cranial irradiation is followed by considerable long-term sequelae. In the three ALL-BFM (Berlin-Frankfurt-Münster) trials 70, 76, and 79, employing radiotherapy (8.5 Gy craniospinal, 18 or 24 Gy cranial irradiation) in all arms, the incidence of CNS relapses (isolated and combined) in standard-risk patients (SR, 60% of all children) was consistently less than 6%. A risk factor (RF) calculated from absolute blast number, liver, and spleen size at diagnosis was used to stratify patients in the subsequent trials ALL-BFM 81 and 83. In ALL-BFM 81, SR patients (RF less than 1.2) were randomized to receive 18 Gy cranial irradiation or intermediate-dose i.v. methotrexate (ID-MTX) (4 x 0.5 g/m2). In ALL-BFM 83, the SR group was further subdivided into group SR low (SR-L, RF less than 0.8) and group SR high (SR-H, RF 0.8 - less than 1.2). SR-L patients received no irradiation, and were tested by randomization for the effectiveness of an intensive reinduction regimen (protocol III). SR-H patients were randomized for 12 or 18 Gy. The results were as follows: In patients of both trials with RF less than 0.8, radiotherapy could be replaced by ID-MTX plus protocol III. Without protocol III, relapses increased from 15.7% to 31.7%. Concomitantly, the fraction of relapses with CNS involvement increased from 26.7% to 36.4%. However, SR patients with RF between 0.8 and 1.2 could not be protected by reinduction alone (isolated/overall CNS relapse rate with irradiation, 4%/5%; without irradiation, 11%/22%). Dosages of 12 and 18 Gy were found to be equally protective.
Bührer
C
C
Departments of Pediatric, Hannover Medical School, FRG.
Henze
G
G
Hofmann
J
J
Reiter
A
A
Schellong
G
G
Riehm
H
H
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000453:epidemiology / Q000517:prevention & control*; D002648:Child; D003131:Combined Modality Therapy; D005860:Germany, West / Q000453:epidemiology; D006801:Humans; D007278:Injections, Spinal; D008727:Methotrexate / Q000008:administration & dosage; D015337:Multicenter Studies as Topic; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000628:therapy*; D011879:Radiotherapy Dosage; D016032:Randomized Controlled Trials as Topic; D012189:Retrospective Studies; D012306:Risk; D013120:Spinal Cord Neoplasms / Q000453:epidemiology / Q000517:prevention & control*
D008727:Methotrexate