Absolute lymphocyte counts refine minimal residual disease-based risk stratification in childhood acute lymphoblastic leukemia

Abstract

Background: Several studies have demonstrated the prognostic utility of absolute lymphocyte count (ALC) during therapy for a range of malignancies, with low ALC associated with adverse outcome. Here we investigated whether ALC retained independent prognostic significance with respect to minimal residual disease (MRD) status in children with acute lymphoblastic leukemia (ALL).

Procedure: We reviewed 171 cases of pediatric ALL treated on the Children's Oncology Group P9900 series of treatment trials. Variables analyzed included ALC at several time points during Induction, age at diagnosis, cytogenetics, initial white blood cell count, and MRD status at Day 29 of Induction (MRD-29).

Results: We found high ALC at Induction Day 29 (ALC-29) to be an independent, clinically significant predictor of improved relapse-free and overall survival (OS). Patients with ALC-29 >1,500 cells/µl had a superior 6-year relapse-free survival (80 ± 4% vs. 62 ± 8%, P = 0.018) and overall survival (96 ± 2% vs. 74 ± 8%, P = 0.001). Moreover, ALC-29 identified distinct prognostic subgroups within cases stratified by MRD-29. In subjects with >0.01% MRD, ALC-29 > or <1,500 cells/µl had a significant 51% difference in 6-year OS (92 ± 7% vs. 41 ± 16%, P = 0.0001).

Conclusions: ALC, a readily obtainable test, constitutes a significant and independent prognostic factor in childhood ALL that may refine current MRD-based risk stratification algorithms and provide key prognostic information in settings where MRD determination is not feasible.

Conflict of interest statement

Conflict of Interest Statement

The authors have no affiliations or financial disclosures to report.

Copyright © 2011 Wiley Periodicals, Inc.

Figures

Figure 1. The distribution of ALC values approximates a log-normal distribution with sigma of 1/2

Using a Martingale residual analysis, the cut off point for high and low ALC with the most predictive power was determined to be 1,500 cells/μL (approximately the 30th percentile). The median ALC in this population was 2,280 cells/μL, which was also predictive for OS, with a p-value of 0.011.

Figure 2. High ALC at Induction day 29 predicts improved survival

Kaplan-Meier estimates of (A) relapse-free survival (RFS) and (B) overall survival (OS) in patients with ALC-29 ≥ 1,500 cells/μL (solid lines) or ALC-29 <1,500 cells/μL (dashed lines). p-values based on log rank. ALC indicates absolute lymphocyte count.

Figure 3. ALC refines MRD stratification

Kaplan-Meier estimates of (A) relapse-free survival (RFS) and (B) overall survival (OS) in patients with MRDneg (<0.01%) or MRDpos (≥0.01%) and ALChi (ALC-29 ≥1,500 cells/μL) or ALClo (ALC-29 <1,500 cells/μL). p-values based on log rank. ALC indicates absolute lymphocyte count; MRD indicates minimal residual disease.