Low platelet counts after induction therapy for childhood acute lymphoblastic leukemia are strongly associated with poor early response to treatment as measured by minimal residual disease and are prognostic for treatment outcome

Abstract

Background: Numerous reports have been published on the association between kinetics of leukemic cells during early treatment of childhood acute lymphoblastic leukemia and therapeutic outcome. In contrast, little is known about the prognostic relevance of normal blood counts in this setting.

Design and methods: Normal hematopoiesis during and after induction treatment (days 8, 15 and 33) was correlated with therapeutic outcome in a cohort of 256 children with acute lymphoblastic leukemia treated in one of three consecutive ALL-BFM trials at a single institute. Replication analysis of positive findings was performed in an independent cohort of 475 patients from the ALL-BFM 2000 multicenter trial.

Results: A platelet count in the first quartile on treatment day 33 and a neutrophil count above the median on day 8 were significantly associated with treatment outcome, conferring multivariate risk ratios for an event of 3.27 (95% confidence interval 1.60-6.69) and 2.26 (95% confidence interval 1.23-4.29), respectively. Replication analysis confirmed the prognostic effect of platelet count on treatment day 33 and demonstrated a strong association with minimal residual disease-based risk group distribution (P<0.00001).

Conclusions: Platelet counts after induction treatment may improve treatment stratification for patients with childhood acute lymphoblastic leukemia and be of particular interest in non-minimal residual disease-based trials. (ALL-BFM 2000 is registered at: ClinicalTrials.gov: NCT00430118. National Cancer Institute: Protocol ID 68529).

Figures

Figure 1

Kaplan-Meier estimates of 8-year event-free survival (EFS) and cumulative incidences of relapse (CI) of all evaluable patients with childhood ALL treated on trials ALL-BFM 90, 95 and 2000 at Hannover Medical School; SE, standard error; quartiles based on cut-points shown in Table 3. (A) EFS according to quartiles of platelet count at treatment day 33; Log-rank test: quartile 1 versus quartiles 2 to 4, P=0.0002, the probability of EFS at 8 years is given in the rows at the bottom of the figure directly after the respective quartile. (B) CI according to quartiles of platelet count at treatment day 33; Gray’s test: quartile 1 versus quartiles 2 to 4, P=0.0002; the incidences at 8 years are given in the rows at the bottom of the figure directly after the respective quartile. (C) EFS according to quartiles of neutrophil count at treatment day 8; Log-rank test: quartiles 1 and 2 versus quartiles 3 and 4, P=0.0001; the probability of EFS at 8 years is given in the rows at the bottom of the figure directly after the respective quartile. (D) CI according to quartiles of neutrophil count at treatment day 8; Gray’s test: quartiles 1 and 2 versus quartiles 3 and 4, P=0.0001; the incidences at 8 years are given in the rows at the bottom of the figure directly after the respective quartile.

Figure 2

Kaplan-Meier estimates of 8-year event-free survival (EFS) of patients with childhood ALL from the replication cohort treated in trial ALL-BFM 2000; SE, standard error; quartiles based on the cut-points shown in Table 3. (A) EFS according to quartiles of platelet count at treatment day 33; Log-rank test: quartile 1 versus quartiles 2 to 4, P=0.0002, the probability of EFS at 8 years is given in the rows at the bottom of the figure directly after the respective quartile. (B) EFS according to quartiles of neutrophil count at treatment day 8; Log-rank test: quartiles 1 and 2 versus quartiles 3 and 4, P=0.18; the probability of EFS at 8 years is given in the rows at the bottom of the figure directly after the respective quartile.