title: 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).
  
  
  METHODS
  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.
authors.affiliation: Division of Pediatric Hematology/Oncology, Texas Children's Cancer Center, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Karen R
authors.initials: KR
authors.lastname: Rabin
authors.forename: M Monica
authors.initials: MM
authors.lastname: Gramatges
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Borowitz
authors.forename: Shana L
authors.initials: SL
authors.lastname: Palla
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Shi
authors.forename: Judith F
authors.initials: JF
authors.lastname: Margolin
authors.forename: Patrick A
authors.initials: PA
authors.lastname: Zweidler-McKay
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007223:Infant; D018655:Lymphocyte Count; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis* / Q000401:mortality; D011379:Prognosis; D012008:Recurrence; D012074:Remission Induction; D012306:Risk; D016896:Treatment Outcome
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