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MRD monitoring may guide risk-based therapy in pediatric ALL
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The sequential monitoring of minimal residual disease levels during remission induction in pediatric patients with acute lymphoblastic leukemia may help guide treatment intensity, according to study results.
“The analysis shows that [minimal residual disease]-directed therapy clearly contributed to the unprecedented high rates of long-term survival that patients in this study achieved,” Ching-Hon Pui, MD, study researcher and chair of the department of oncology at St. Jude Children’s Research Hospital, said in a press release. “[Minimal residual disease] proved to be a powerful way to identify high-risk patients who needed more intensive therapy and helped avoid over-treatment of low-risk patients.”
Ching-Hon Pui
Minimal residual disease (MRD) during remission induction is the most important prognostic indicator among children with ALL, according to study background. Researchers sought to evaluate the association between EFS and the use of sequential MRD measurements to determine treatment plans.
The analysis included 498 patients aged 1 to 18 years who were newly diagnosed with ALL. Pui and colleagues used baseline clinical and laboratory features to provisionally define patients’ risks for relapse as low, standard or high. Researchers measured patients’ MRD levels on days 19 and 46 of remission induction, as well as on week 7 of maintenance treatment, to provide a final risk assessment and establish additional treatment intensity.
All patients received a conventional remission induction regimen. However, patients with MRD levels greater than 1% on day 19 of remission therapy received three additional doses of asparaginase.
All patients received consolidation therapy, the intensity of which varied according to their MRD-defined risk category. Low-risk and standard-risk patients then received risk-directed maintenance therapy for 120 weeks, whereas high-risk patients were offered allogeneic hematopoietic stem cell transplantation when they achieved MRD levels less than 0.01%.
Median follow-up for alive patients in continuous remission was 9.4 years.
Nearly all patients (n = 492) achieved complete remission. Ten-year OS was 91.9% (95% CI, 88.2-95.6) and 10-year EFS was 85.1% (95% CI, 80.2-90).
Researchers detected 1% or higher MRD levels on day 19 in 36 of 280 (13%) patients in the provisional low-risk cohort and in 56 of 198 (28%) patients in the provisional standard-risk cohort (P ˂ .01). A significantly smaller proportion of these patients with higher vs. lower MRD levels achieved 10-year EFS in the provisional low-risk cohort (69.2% vs. 95.5%; P ˂ .001) and the provisional standard-risk cohort (65.1% vs. 82.9%; P = .01). However, conversion from high MRD levels at day 19 to MRD-negative status at day 46 was associated with favorable 10-year EFS (88.9%; 95% CI, 43.3-98.4).
Ten-year EFS was favorable in patients in the provisional low-risk disease cohort who achieved MRD of less than 1% on day 19 (95.5%; 95% CI, 91.7-97.5) and in patients in the standard-risk cohort who achieved negative MRD (83.8%; 95% CI, 72.6-90.7) and MRD between 0.01% and 0.99% (82.1%; 95% CI, 71.2-89.2).
Ten-year EFS outcomes were unfavorable in patients with provisional low-risk ALL (40%; 95% CI, 5.2-75.3) and standard-risk ALL (56.4%; 95% CI, 29.5-76.2) who were reclassified as having high-risk disease based on high MRD levels at day 46.
At the completion of remission induction, 46% of patients were classified as having low-risk disease, 48% as standard-risk and 6% as high-risk based on MRD levels and clinical features. Researchers measured post-remission MRD levels during weeks 7 (n= 465), 17 (n = 450) 48 (n = 437), and 120 (n = 430).
All but one of six patients who displayed post-remission MRD levels during remission induction after achieving MRD-negative disease died despite increased treatment. However, only two of 11 patients who achieved decreasing MRD levels by week 7 of maintenance therapy experienced disease relapse.
“Given the excellent outcome [in low-risk patients with MRD of less than 1% on day 19 of treatment], it will be important to determine if treatment can be further reduced in this subgroup of patients,” Pui said. “The study demonstrates these patients have an extremely low risk of relapse.” – by Cameron Kelsall
Disclosure: Pui reports no relevant financial disclosures. Two researchers report patents pending related to methods for identifying MRD in ALL.
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