Treatment of Biologically Determined Subsets of Acute Lymphoblastic Leukemia in Adults: Cancer and Leukemia Group B Studies

Abstract

The Cancer and Leukemia Group B (CALGB) has conducted a series of prospective clinical trials in adults with acute lymphoblastic leukemia (ALL). The impact of certain clinical and biological characteristics on the outcome of intensive chemotherapy has been investigated. In this report, the prognostic features of 379 patients entered onto two sequential trials (CALGB 8811 and 9111) are described. A total of 325 (86%) patients achieved a complete remission (CR). A higher CR rate was observed in younger patients (93% for those <30 years old, 86% for those 30-59 years old, and 64% for those ≥60 years old; p<0.001), and in those who had a mediastinal mass (98%) or blasts with a T-cell immunophenotype. A total of 83% of Blineage and 94% of T-cell ALL patients achieved a CR (p = 0.04). Co-expression of myeloid antigens did not affect the CR rate or remission duration. Of those with cytogenetic or molecular evidence of the Philadelphia (Ph) chromosome, 76% and 87% of those without such evidence achieved a CR (p = 0.08). The median survival for all patients is 28 months, and 47% (95% confidence interval, CI, 40%–54%) of all patients are estimated to be alive at 3 years. The median remission duration for the 325 CR patients is also 28 months. Favourable pretreatment characteristics relative to remission duration or survival are younger age, the presence of a mediastinal mass, white blood cell (WBC) count <30000/µl, T or TMy immunophenotype, and the absence of the Ph chromosome. The estimates for the proportion surviving at 3 years are 66% for patients < 30 years old, 36% for those 30–59 years old, 84% for those with a mediastinal mass, 54% with WBC <30000/µl, 65% with T or TMy antigen expression, and 52% for those who lack the Ph chromosome. Twenty-two patients (6%) had no unfavourable prognostic features and have an estimated probability of survival at 3 years of 91% (95% CI, 66%-98%). Patients with high-risk features are now being selected for additional therapy.