Jeanette Pullen

PURPOSE: To define more uniform criteria for risk-based treatment assignment for children with acute lymphoblastic leukemia (ALL), the Cancer Therapy Evaluation Program (CTEP) of the National Cancer Institute (NCI) sponsored a workshop in September 1993. Participants included representatives from the Childrens Cancer Group (CCG), Pediatric Oncology Group (POG), Dana-Farber Cancer Institute (DFCI), St Jude Children's Research Hospital (SJCRH), and the CTEP. METHODS: Workshop participants presented and reviewed data from ALL clinical trials, using weighted averages to combine outcome data from different groups. RESULTS: For patients with B-precursor (ie, non-T, non-B) ALL, the standard-risk category (4-year event-free survival [EFS] rate, approximately 80%) will include patients 1 to 9 years of age with a WBC count at diagnosis less than 50,000/microL. The remaining patients will be classified as having high-risk ALL (4-year EFS rate, approximately 65%). For patients with T-cell ALL, different treatment strategies have yielded different conclusions concerning the prognostic significance of T-cell immunophenotype. Therefore, some groups/institutions will classify patients with T-cell ALL as high risk, while others will assign risk for patients with T-cell ALL based on the uniform age/WBC count criteria. Workshop participants agreed that the risk category of a patient may be modified by prognostic factors in addition to age and WBC count criteria, and that a common set of prognostic factors should be uniformly obtained, including DNA index (DI), cytogenetics, early response to treatment (eg, day-14 bone marrow), immunophenotype, and CNS status. CONCLUSIONS: The more uniform approach to risk-based treatment assignment and to collection of specific prognostic factors should increase the efficiency of future ALL clinical research.

BACKGROUND: Children with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph-positive ALL) have a poor prognosis, and there is no consensus on the optimal treatment for this variant of ALL. METHODS: We reviewed the medical records of patients with Ph-positive ALL who were treated with intensive chemotherapy, with or without bone marrow transplantation, by 10 study groups or large single institutions from 1986 to 1996. Data on 326 children and young adults, who ranged in age from 0.4 to 19.9 years (median, 8.1), were analyzed to determine the rate of complete remission and the probability of event-free, disease-free and overall survival according to standard prognostic factors and type of treatment. RESULTS: The 267 patients who achieved a complete remission after induction chemotherapy (82 percent) were stratified into three subgroups according to the age and leukocyte count at the time of diagnosis: those with the best prognosis (a leukocyte count of less than 50,000 per cubic millimeter and an age of less than 10 years; 95 patients); those with an intermediate prognosis (intermediate-risk features; 92 patients); and those with the worst prognosis (a leukocyte count of more than 100,000 per cubic millimeter; 80 patients). The estimates of disease-free survival at five years (+/-SE) were 49+/-5 percent) for patients with the best prognosis), 30+/-5 percent (for those with an intermediate prognosis), and 20+/-5 percent (for those with the worst prognosis) (P<0.001 for the overall comparison). We also found that transplantation of bone marrow from an HLA-matched related donor offered significantly greater benefit than intensive chemotherapy alone in terms of protecting patients from relapse or other adverse events (relative risk, 0.3; 95 percent confidence interval, 0.2 to 0.5; P<0.001). This finding was consistent in all three groups. CONCLUSIONS: Unlike the usual type of all, Ph-positive ALL is associated with a poor prognosis. Nevertheless, in some patients with favorable prognosis features, the disease can be be controlled by intensive chemotherapy. Transplantation of bone marrow from an HLA-matched related donor is superior to other types of transplantation and to intensive chemotherapy alone in prolonging initial complete remissions.