What determines the outcomes for adolescents and young adults with acute lymphoblastic leukemia treated on cooperative group protocols? A comparison of Children's Cancer Group and Cancer and Leukemia Group B studies

Abstract

We performed a retrospective comparison of presenting features, planned treatment, complete remission (CR) rate, and outcome of 321 adolescents and young adults (AYAs) ages 16 to 20 years with newly diagnosed acute lymphoblastic leukemia (ALL) who were treated on consecutive trials in either the Children's Cancer Group (CCG) or the Cancer and Leukemia Group B (CALGB) from 1988 to 2001. CR rates were identical, 90% for both CALGB and CCG AYAs. CCG AYAs had a 63% event-free survival (EFS) and 67% overall survival (OS) at 7 years in contrast to the CALGB AYAs, in which 7-year EFS was only 34% (P < .001; relative hazard rate [RHR] = 2.2) and OS was 46% (P < .001; RHR = 1.9). While CALGB AYAs aged 16 to 17 years achieved similar outcomes to all CCG AYAs with a 7-year EFS of 55%, the EFS for 18- to 20-year-old CALGB patients was only 29%. Comparison of the regimens showed that CCG AYAs received earlier and more intensive central nervous system prophylaxis and higher cumulative doses of nonmyelosuppressive agents. There were no differences in outcomes of those who reached maintenance therapy on time compared with those who were delayed. Based on these observations, a prospective study for AYAs with ALL using the more successful approach of the CCG has been initiated.

Figures

Figure 1

Comparison of EFS and OS. (A) Comparison of EFS among CALGB (gray line) and CCG (black line) patients. The 7-year RHR for CALGB patients was 2.2 (CI, 1.6-3.0; P < .001). (B) Comparison of OS among CALGB (gray line) and CCG (black line) patients. The 7-year relative hazard ratio (RHR) for death in CALGB patients was 1.9 (CI, 1.3-2.7; P < .001).

Figure 2

Estimated incidence of isolated CNS relapses. The 7-year estimated incidence of isolated CNS relapses (ICNS) of 11% for CALGB patients (9 events) was significantly higher than the ICNS rate of 1.4% (2 events) for CCG patients (P < .001); RIR, 9.2 (CI, 2.0-42.7).

Figure 3

Age effect on outcome. CALGB patients aged 16 to 17 years had a 7-year EFS of 55%, which was similar to a 64% EFS for 16- to 17-year-old CCG patients (P = .49). CALGB patients aged 18 to 20 years old had a 7-year EFS of 29%, which was significantly worse than that for the younger CALGB patients and the 57% EFS for 18- to 20-year-olds on CCG trials (P = .01; RHR, 2.1 [CI, 1.2-3.8]).