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) 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 1985–2000, 1457 children aged 0–18 years were treated on four consecutive protocols: 85-01 (1985–7), 87-01 (1987–91), 91-01 (1991–5) and 95-01 (1996–2000). The 10-year event-free survival (EFS) ± standard error 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-ALL patients and 75–78% for adolescents (age 10–18 years). Results of randomized studies revealed that dexrazoxane prevented acute cardiac injury without adversely impacting EFS or OS in high-risk patients and frequently-dosed intrathecal chemotherapy was an effective substitute for cranial radiation in standard-risk patients. Current studies continue to focus on improving efficacy while minimizing acute and late toxicities.

Absence of biallelic TCRγ deletion predicts induction failure and poorer outcomes in childhood T‐cell acute lymphoblastic leukemia

“…Although the use of intensive chemotherapy has enabled patients with T-cell ALL to fare as well as patients with B-cell precursor ALL in some studies, the outcomes are significantly worse for the patients with T-cell ALL in most treatment protocols [3][4][5][6][7][8][9][10][11][12][13][14][15]. Chromosomal alterations, including numbers and translocations, have helped to classify pediatric patients with B-cell precursor ALL and improve treatment outcomes in the past three decades [16].…”

The long-term impact of in vitro drug sensitivity on risk stratification and treatment outcome in acute lymphoblastic leukemia of childhood (CoALL 06-97)

“…[28][29][30][31][32] However, the intensity of treatment protocols has reached a high level, and there has been concern that a substantial proportion of patients is being overtreated due to the lack of a refined risk assignment which relies on traditional risk factors such as initial white blood count, age, immunophenotype and chromosomal translocations. In 1991 the group of Pieters et al 1 demonstrated the prognostic value of an in vitro assay testing the sensitivity of leukemic cells to drugs.…”

The Role of Hematopoietic Stem-Cell Transplantation in First Remission in Pediatric Acute Lymphoblastic Leukemia: A Narrative Review

“…The authors concluded that HSCT should be considered in CR1 due to risk for unsuccessful salvage post-relapse and poor survival rates for HSCT in CR2. Over the years the paradigm appears to have shifted from HSCT in CR1 to more intensive multiagent chemotherapy for previously considered HR patient groups (20)(21)(22)(23). But at the same time, the definition of HR leukemia is changing given recent discoveries with new genomic lesions and continued MRD testing.…”