Results of Recent Clinical Trials in Acute Lymphoblastic Leukemia by the Cancer and Leukemia Group B

Abstract

Since 1988, the CALGB has enrolled 598 adults with untreated acute lymphoblastic leukemia (ALL) onto 4 clinical trials using intensive multi-agent therapy. The median age was 35 years (range, 16-81 years); 15% were >60 years old. Seventy-one percent were B/BMy and 19% were T/TMy by immun -ophenotyping. Of 334 studied, 28% were Philadelphia chromosome positive or BCR/ABL positive; 8% had t(4;11). Overall, complete remission (CR) was achieved in 85%. The median disease-free survival (DFS) was 2.1 years (95% confidence interval (CI), 1.7-2.4 years), and the median survival was 2.2 years (95% CI, 1.9-3.0 years). At 3 years, 41% (95% CI, 37-46%) remained in continuous CR, and 45% (95% CI, 41-50%) were alive. In CALGB study 9111, filgrastim (G-CSF) was shown to reduce the median time to recover 1000 neutrophils/ml during treatment from 22 days to 16 days (p 60 years old improved from 55% to 81%. In CALGB study 9311, B-lineage ALL patients received two postremission courses of anti-B4-blocked ricin, an antiCD19 immunotoxin, over 7 days each. Toxicity was minimal, but neither clinical outcome nor molecular monitoring for unique antigen receptor genes suggested efficacy. T-cell ALL patients received high-dose cyta-rabine consolidation. CALGB study 9511 explored the pharmacokinetics of PEG-asparaginase. One dose (2000 U/m2) resulted in asparagine depletion for 14 days in the majority of patients. An additional 24 patients with Burkitt-type ALL-L3 were enrolled on CALGB study 9251, a 17-week intensive regimen that included cranial irradiation. The median age for these patients was 45 years (range, 20-71 years); 21% were >60 years old. The CR rate was 75%. The median DFS was >1.7 years, and the median survival was 2.1 years. At 3 years, 53% (95% CI, 29-76%) remained in continuous CR, and 44% (95% CI, 25-65%) were alive. The current study for adult ALL (CALGB 19802) evaluates higher doses of daunorubicin during induction and higher doses of cytarabine and methotrexate during consolidation in lieu of cranial irradiation. Patients with relapsed or refractory T-cell ALL are enrolled on a phase 2 trial (CALGB 19801) evaluating GW506U78, the prodrug for 9-D-arabinofuranosylguanine (ara-G). Our risk-adapted strategy recommends allogeneic stem cell transplantation in first remission for patients with t(9;22) or t(4;11).