Long-term results of Dana-Farber Cancer Institute ALL Consortium protocols for children with newly diagnosed acute lymphoblastic leukemia (1985-2000)

Abstract

The Dana-Farber Cancer Institute (DFCI) acute lymphoblastic leukemia (ALL) Consortium has been conducting multi-institutional clinical trials in childhood ALL since 1981. The treatment backbone has included 20-30 consecutive weeks of asparaginase during intensification and frequent vincristine/corticosteroid pulses during the continuation phase. Between 1985 and 2000, 1457 children aged 0-18 years were treated on four consecutive protocols: 85-01 (1985-1987), 87-01 (1987-1991), 91-01 (1991-1955) and 95-01 (1996-2000). The 10-year event-free survival (EFS)+/-s.e. by protocol was 77.9+/-2.8% (85-01), 74.2+/-2.3% (87-01), 80.8+/-2.1% (91-01) and 80.5+/-1.8% (95-01). Approximately 82% of patients treated in the 1980s and 88% treated in the 1990s were long-term survivors. Both EFS and overall survival (OS) rates were significantly higher for patients treated in the 1990s compared with the 1980s (P=0.05 and 0.01, respectively). On the two protocols conducted in the 1990s, EFS was 79-85% for T-cell ALL patients and 75-78% for adolescents (age 10-18 years). Results of randomized studies revealed that dexrazoxane prevented acute cardiac injury without adversely affecting EFS or OS in high-risk (HR) patients, and frequently dosed intrathecal chemotherapy was an effective substitute for cranial radiation in standard-risk (SR) patients. Current studies continue to focus on improving efficacy while minimizing acute and late toxicities.

Figure 1

Event-Free Survival (EFS) by Decade. The EFS of protocols conducted in the 1990s (91-01 and 95-01) was superior to that of protocols conducted in the 1980s (85-01 and 87-01), p=0.05.

Figure 2

Overall Survival (OS) by Decade. The OS of protocols conducted in the 1990s (91-01 and 95-01) was superior to that of protocols conducted in the 1980s (85-01 and 87-01), p=0.01.

Figure 3

Event-free survival and Cumulative Incidence of isolated or any CNS relapse for 220 patients treated on Protocol 85-01 (1985–7). Median follow-up was 13.8 years.

Figure 4

Event-free survival and Cumulative Incidence of isolated or any CNS relapse for 369 patients treated on Protocol 87-01 (1987–91). Median follow-up was 13.3 years.

Figure 5

Event-free survival and Cumulative Incidence of isolated or any CNS relapse for 377 patients treated on Protocol 91-01 (1991–5). Median follow-up was 12.5 years.

Figure 6

Event-free survival and Cumulative Incidence of isolated or any CNS relapse for 491 patients treated on Protocol 95-01 (1996–2000). Median follow-up was 8.6 years.