An antimetabolite-based regimen with low myelosuppressive activity may be capable of eradicating a subset of pediatric B-cell acute lymphoblastic leukemia, according to results of a prospective study published in Blood.
“In limited-resource countries, attempts to increase treatment intensity for children with ALL have not translated into improved outcomes,” Francisco Pedrosa, MD, clinical researcher in the department of pediatric oncology at Real Hospital Português in Brazil, and colleagues wrote. “Socioeconomic and cultural barriers and a lack of hospital infrastructure have resulted in high rates of treatment-related mortality and treatment abandonment. In this context, there is a strong rationale for identifying a subset of patients with ALL who can be treated with a reduced-intensity regimen.”
A previous study testing standard-intensity regimens among children with ALL showed those with minimal residual disease levels below 0.01% early in remission induction had very low rates of relapse.
Pedrosa and colleagues sought to test their hypothesis that children with highly drug-sensitive ALL who received a low-intensity regimen would demonstrate low rates of toxic death and high rates of DFS.
The researchers used a simplified flow-cytometric assay to identify 101 children (median age, 4 years; range, 1.2-9.8; 52.5% male; 65.3% mixed race) with very-low-risk B-cell ALL (B-ALL), criteria for which included white blood cell count of less than 50 x 109/L, lack of extramedullary leukemia, and minimal residual disease levels of less than 0.01% on remission induction day 19.
The children, treated in a low-resource center in Recife, Brazil, received two doses of daunorubicin and a combination of drugs with a comparatively low myelotoxicity profile, such as corticosteroids, vincristine, L-asparaginase, methotrexate and 6-mercaptopurine.
Researchers observed no cases of toxic death or treatment abandonment during remission induction.
Median follow-up was 6.6 years (range, 3.4-13.1).
Results showed estimated 5-year EFS rates of 92% ± 3.9% and OS rates of 96% ± 2.8%.
Five-year cumulative risk for relapse was 4.24% ± 2%.
Eight major adverse events occurred, including six relapses, one treatment-related death from septicemia during remission and one case of secondary myeloid leukemia.
“The impetus for implementing a low-intensity regimen for patients with ALL in Recife came from the observation that a simplified flow-cytometric assay revealed a subset of patients with B-ALL who had an exceedingly low cumulative risk for relapse when treated with standard chemotherapy regimens,” Pedrosa and colleagues wrote. “The survival rates for our patients with very-low-risk ALL were comparable with those for patients with low-risk B-ALL treated with much more intensive regimens. These observations suggest that by using a simple selection procedure, approximately 25% of children with B-ALL can be treated with a relatively nontoxic regimen.” – by John DeRosier
Disclosures: The authors report no relevant financial disclosures.