MRD-Stratified Treatments in Children With ALL

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Allogeneic transplantation was found not to improve overall outcome, in particular for patients who achieved MRD-negative status after induction.

Undergoing allogeneic transplantation did not provide significant improvements to overall outcomes for pediatric patients with newly diagnosed hypodiploid acute lymphoblastic leukemia (ALL), according to a study published in Journal of Clinical Oncology.

After adjustment for waiting time and exclusion of patients with high hypodiploidy, the 5-year survival rate for patients who underwent transplant was 59% compared with 51.5% for those who received chemotherapy alone. No significant differences in outcome were noted between the two groups, especially among those patients who achieved minimal residual disease negative status after induction chemotherapy.

“This study confirms our earlier observation that patients with hypodiploid ALL who have no evidence of minimal residual disease after remission induction therapy should not be transplanted,” first and corresponding author Ching-Hon Pui, MD., chair of the St. Jude Department of Oncology, said in a press release. “We recommend continued treatment with intensive chemotherapy.”

In the retrospective study, Pui and colleagues used data from 306 patients with hypodiploid ALL enrolled in 16 cooperative study groups of institutions from 1997–2013. Of these, 272 were eligible for this study. Patient ages ranged from .6–19.5.

At the end of induction, 99% of patients had achieved complete remission of their disease; 59% of patients were MRD-negative. Ninety patients had disease relapse.

The 5-year event-free survival was 55.1% with an overall survival rate of 61.2%. At 8 years, these decreased to 53.8% and 57.5%, respectively. However, some groups had improved event-free survival. Among patients with negative MRD at the end of induction, high hypodiploidy with 44 chromosomes, and treatment with MRD-stratified protocols the 5-year event-free survival was 75%, 74%, and 62%, respectively.

According to the study, transplant is not currently offered to patients with high hypodiploidy with 44 chromosomes. Once these patients were excluded, 42 of the 228 patients underwent transplant. After adjustment, the 5-year disease-free survival rate was 53.0% for chemotherapy alone compared with 59.8% for transplantation. No difference was found for 5-year overall survival between the two groups, with rates of 57.7% for chemotherapy alone compared with 68.9% for transplantation.

“Because no new effective therapies have been developed recently for hypodiploid ALL, increased event-free survival in our current cohort may be partly attributed to MRD-stratified treatments which, by avoiding transplantation in patients with good response to chemotherapy or undertreatment of those with poor response to chemotherapy, has been shown to improve outcome in other subtypes of ALL,” the researchers wrote. “If all patients had received MRD-stratified treatment, the overall event-free survival rate likely would have been higher.”

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