In pediatric patients with B-cell precursor acute lymphoblastic leukemia (B-ALL), minimal residual disease (MRD) from peripheral blood (PB) was found to correlate with clinical outcomes and risk parameters but lacked prognostic significance of sufficient strength to substitute for monitoring MRD in bone marrow (BM). These findings, published in Pediatric Blood and Cancer, come from the completed, phase 3 AIEOP-BFM ALL 2000 trial (ClinicalTrials.gov identifier: NCT00430118), which assessed whether various regimens of combination chemotherapy were more efficacious at treating ALL in pediatric patients.

Flow cytometric monitoring of MRD in BM during induction therapy in pediatric patients with ALL is commonly used for prognostication and stratification of treatments. Here, researchers assessed whether monitoring from PB yielded comparable results, as PB is easier to obtain than BM.

This analysis examined samples from 288 pediatric patients with ALL enrolled in the AIEOP-BFM ALL 2000 trial. Of the samples, 1303 were collected from PB on days 0, 8, 15, 33, and 52, and 285 were collected from BM on day 15.

In patients with B-ALL only, MRD measures from PB at early time points (days 8 and 15) were associated with relapse incidence (CIR) and were used to separate patients into cohorts with higher and lower risk of relapse. The best separation occurred at a threshold of less than 1 blast/uL from PB samples at day 8 (5-year CIR, 0.02 ± 0.02 vs 0.12 ± 0.03; P =.044).

In patients with T-cell precursor ALL (38 patients), there were only 5 relapses, and no MRD time point had the power to separate these patients into low- and high-risk cohorts.

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Though patients with the highest risk of relapse were not distinguishable as a third stratum, PB-MRD positivity at days 33 and 52 was associated with response to prednisone and postinduction BM-MRD by PCR (P <.001). However, in multivariate analysis that included 15-day BM-MRD, PB-MRD measurements no longer had statistical power.

The researchers suggested that PB-MRD could hold value in treatment regimens that do not use multifaceted risk stratification with other MRD measurements. They concluded by stating the PB-MRD at day 8 in particular warrants a prospective study for its potential ability to stratify patients early and spare some patients from unnecessarily intensive therapeutic regimens.

Reference

1. Schumich A, Maurer-Granofszky M, Attarbaschi A, et al. Flow-cytometric minimal residual disease monitoring in blood predicts relapse risk in pediatric B-cell precursor acute lymphoblastic leukemia in trial AIEOP-BFM-ALL 2000 [published online December 18, 2018]. Pediatr Blood Cancer. doi: 10.1002/pbc.27590.