Reduced-intensity therapy effective for children with very low-risk ALL
Children with very low-risk acute lymphoblastic leukemia can be treated successfully with reduced-intensity therapy, according to results of a study published in Blood.
This approach should be considered in settings where treatment-related mortality hinders cure rates and where effective but less complex therapy is needed, researchers noted. Further studies are needed to better address the management of cases where detectable minimal residual disease (MRD) levels are less than 0.01% at early time points, they added.
“Our results corroborate and expand those of a previous study that used the same stratification criteria and treatment approach,” Iman Sidhom, MD, senior consultant of pediatric oncology at Children’s Cancer Hospital Egypt, and colleagues wrote. “The concern that reducing the treatment intensity would increase the relapse rate and offset the potential beneficial effect on survival was not substantiated.”
OS rates of children with ALL who receive contemporary therapy now exceed 90% because of the adoption of risk-adapted chemotherapy intensification combined with improved supportive care, according to study background. However, long-term follow-up of childhood cancer survivors, including survivors of ALL, has shown a range of treatment-related late effects.
Low-intensity treatment has produced excellent outcomes for patients with ALL selected based on a combination of presenting features and an MRD level of less than 0.01% on day 19 of induction therapy.
Sidhom and colleagues examined the effect of residual disease early in remission induction on outcomes of children with very low-risk ALL who received low-intensity therapy.
The study included 200 consecutive patients with B-precursor ALL, favorable clinicopathologic features and MRD levels less than 0.01%, as assessed by flow cytometry in the bone marrow on day 19 and at the end of induction therapy, who received reduced-intensity therapy between October 2011 and September 2015.
Median age at diagnosis was 4 years (range, 1.3-9.8; 53.5% male), and patients had a median leukocyte count of 5.75 × 109/L (range, 0.3 × 109/L to 48.7 × 109/L).
Results showed 5-year rates of 89.5% (standard error, ± 2.2%) for EFS, 95.5% (± 1.5%) for OS and 7% (95% CI, 4-11) for cumulative incidence of relapse.
Twenty-nine patients had detectable MRD levels between 0.001% and less than 0.01% on day 19. These patients demonstrated a 5-year cumulative incidence of relapse significantly higher than that of those with undetectable residual leukemia (17.2% ± 7.2% vs. 5.3% ± 1.7%; P = .02).
“The results of our study also have important implications for treating ALL in low- to middle-income countries,” Sidhom and colleagues wrote. “Intensification of ALL therapy, which is associated with the high cure rates seen in high-income countries, has had minimal impact on outcomes of ALL in these countries because of treatment-related mortality.”