TREATMENT OF PATIENTS WITH ACUTE LYMPHOBLASTIC-LEUKEMIA WITH BULKY EXTRAMEDULLARY DISEASE AND T-CELL PHENOTYPE OR OTHER POOR PROGNOSTIC FEATURES - RANDOMIZED CONTROLLED TRIAL FROM THE CHILDRENS CANCER GROUP

BACKGROUND. Children with acute lymphoblastic leukemia with multiple p oor prognostic factors and who have a lymphomatous mass at diagnosis, whether of T-or non-T-immunophenotype, are at increased risk of short term remission and extramedullary recurrence, and are in need of bette r therapies. METHODS. Six hundred and ninety-four eligible patients ra nging in age from 1-20 years were entered on the study. Sixty-five per cent of the patients had T-cell immunophenotype. Of these, 678 were ra ndomized to one of four regimens: Regimen A: Berlin-Frankfurt-Munster (BFM) 76/79; Regimen B: LSA(2)-L-2 with cranial irradiation; Regimen C : LSA(2)-L-2 without cranial irradiation; and Regimen D: the New York (NY) regimen. RESULTS. Complete remission was induced in 97% of patien ts. The overall event free survival (EFS) +/- the standard deviation w as 60 +/- 4% 6 years after diagnosis, in contrast to 36 +/- 6% in a co mparable historic group. The EFS of the 371 T-cell patients was 62 +/- 7%. EFS was best on the NY (67 +/-: 7%) and the BFM (67 +/- 6%) arms. These were significantly better than the EFS on the 2 LSA(2)-L-2, reg imens, with an EFS of 53 +/- 8% (Regimen B) and 42 +/- 11% (Regimen C) (P = 0.03 and 0.0003 for NY vs. Regimen B and NY vs. Regimen C; P = 0 .01 and 0.0001 for BFM vs. Regimen B and BFM vs. Regimen C). Regimen C had a 3-fold greater central nervous system (CNS) recurrence rate tha n the identical chemotherapy Regimen B (16 +/- 5% vs. 6 +/- 4%; P = 0. 02), although the difference in overall EFS did not reach the required level for significance. Testicular recurrence varied from 2-8% in com parison with 20% in the historic group. EFS was not influenced by age, gender, CNS disease at diagnosis, morphology, or immunophenotype. In addition to treatment regimen and early response rate, initial leukocy te count, hemoglobin level, liver, spleen, and lymph node enlargement, and the presence of a mediastinal mass had univariate prognostic infl uence on EFS. In multivariate analysis, only the kinetics of response, leukocyte count (unfavorably, P < 0.0001), and mediastinal mass statu s (favorably, P = 0.01) were prognostic. CONCLUSIONS. The adverse prog nostic implications of lymphomatous ALL can be minimized by the NY and BFM regimens. Cranial irradiation resulted in better CNS disease cont rol when added to the LSA(2)-L-2, regimen, but did not improve the ove rall disease free survival. With improved systemic chemotherapy, there was no excess of lymph node, testicular, or other local recurrence wi thout prophylactic irradiation to sites of initial bulk disease or to the testes.