IMPROVED OUTCOME IN ADULT B-CELL ACUTE LYMPHOBLASTIC-LEUKEMIA

A total of 68 adult patients with B-cell acute lymphoblastic leukemia (B-ALL) were treated in three consecutive adult multicenter ALL studie s. The diagnosis of B-ALL was confirmed by L3 morphology and/or by sur face immunoglobulin (SIg) expression with >25% blast cell infiltration in the bone marrow (BM). They were characterized by male predominance (78%) and a median age of 34 years (15 to 65y) with only 9% adolescen ts (15 to 20y), but 28% elderly patients (50 to 65y). The patients rec eived either a conventional (N = 9) ALL treatment regimen (ALL study 0 1/81) or protocols adapted from childhood B-ALL with six short, intens ive 5-day cycles, alternately A and B. In study B-NHL83 (N = 24) cycle A consisted of fractionated doses of cyclophosphamide 200 mg/m(2) for 5 days, intermediate-dose methotrexate (IdM) 500 mg/m(2) (24 hours), in addition to cytarabine (AraC), teniposide (VM26) and prednisone. Cy cle B was similar except that AraC and VM26 were replaced by doxorubic in. Major changes in study B-NHL86 (N = 35) were replacement of cyclop hosphamide by ifosphamide 800 mg/m(2) for 5 days, an increase of IdM t o high-dose, 1,500 mg/m(2) (HdM) and the addition of vincristine. A cy toreductive pretreatment with cyclophosphamide 200 mg/m(2), and predni sone 60 mg/m(2), each for 5 days was recommended in study B-NHL83 for patients with high white blood cell (WBC) count (>2,500/m(2)) or large tumor burden and was obligatory for all patients in study B-NHL86. Ce ntral nervous system (CNS) prophylaxis/treatment consisted of intrathe cal methotrexate (MTX) therapy, later extended to the triple combinati on of MTX, AraC, and dexamethasone, and a CNS irradiation (24 Gy) afte r the second cycle. Compared with the ALL 01/81 study where all the pa tients died, results obtained with the pediatric protocols B-NHL83 and B-NHL86 were greatly improved. The complete remission (CR) rates incr eased from 44% to 63% and 74%, the probability of leukemia free surviv al (LFS) from 0% to 50% and 71% (P = .04), and the overall survival ra tes from 0% to 49% and 51% (P = .001). Toxicity, mostly hematotoxicity and mucositis, was severe but manageable. In both studies B-NHL83 and B-NHL86, almost all relapses occurred within 1 year. The time to rela pse was different for BM, 92 days, and for isolated CNS and combined B M and CNS relapses, 190 days (P = .08). The overall CNS relapses chang ed from 50% to 57% and 17%, most probably attributable to the high-dos e MTX and the triple intrathecal therapy. LFS in studies B-NHL83 and B -NHL86 was significantly influenced by the initial WBC count < or >50, 000/mu L, LFS 71% versus 29% (P = .003) and hemoglobin value > or <8 g /dL, LFS 67% versus 27% (P = .02). Initial CNS involvement had no adve rse impact on the outcome. Elderly B-ALL patients (>50 years) also ben efited from this treatment with a CR rate of 56% and a LFS of 56%. It is concluded that this short intensive therapy with six cycles is effe ctive in adult B-ALL. HdM and fractionated higher doses of cyclophosph amide or ifosphamide seem the two major components of treatment. (C) 1 996 by The American Society of Hematology.