title: Diagnostic cerebrospinal fluid examination in children with acute lymphoblastic leukemia: significance of low leukocyte counts with blasts or traumatic lumbar puncture.
abstract: OBJECTIVE
  To determine the significance of leukemic blasts or traumatic lumbar puncture (TLP) in diagnostic CSF of children enrolled in the Berlin-Frankfurt-Münster (BFM) Acute Lymphoblastic Leukemia-BFM-95 trial.
  
  
  METHODS
  A total of 2,021 patients were retrospectively evaluated according to initial central nervous system (CNS) status. Patients were classified as follows: CNS1 (CNS negative, n = 1,605), CNS2 (< or = 5 WBC/ micro L CSF with blasts, n = 103), CNS3 (CNS positive, n = 58), TLP+ (TLP with blasts, n = 135), or TLP- (TLP without blasts, n = 111). Patients with CNS2 and TLP+ status were eligible for two additional doses of intrathecal (IT) methotrexate (MTX). CNS3 patients received additional IT MTX and cranial irradiation (18 Gy).
  
  
  RESULTS
  CNS2, CNS3, and TLP+ groups contained a higher percentage of patients with unfavorable characteristics. Cox regression analysis identified TLP+ and CNS3 status as prognostically significant (CNS3): risk ratio (RR) = 2.3; 95% confidence interval [CI], 1.4 to 3.6; P =.0005; TLP+: RR = 1.5; 95% CI, 1.02 to 2.2; P =.04. Overall 5-year event-free survival (EFS) is 79%, for CNS1 it is 80%, and for TLP- it is 83%. CNS2 patients have an EFS of 80%, but the cumulative incidence of relapses with CNS involvement is higher compared with CNS1 patients (0.10 v 0.04). TLP+ patients have a significantly reduced EFS (73%, P =.003) because of an increased incidence of CNS relapses. CNS3 patients suffer from more systemic and CNS relapses (EFS 50%).
  
  
  CONCLUSIONS
  CNS2 patients have the same prognosis as patients with CNS1 status, whereas the EFS of TLP+ patients is inferior to CNS1 but superior to CNS3 patients (P =.001). Both subgroups may have benefitted from additional IT MTX.
authors.affiliation: Department of Pediatric Hematology/Oncology, Hannover Medical School, Hannover, Germany. buerger.britta@mh-hannover.de
authors.forename: Britta
authors.initials: B
authors.lastname: Bürger
authors.forename: Martin
authors.initials: M
authors.lastname: Zimmermann
authors.forename: Georg
authors.initials: G
authors.lastname: Mann
authors.forename: Joachim
authors.initials: J
authors.lastname: Kühl
authors.forename: Lutz
authors.initials: L
authors.lastname: Löning
authors.forename: Hansjörg
authors.initials: H
authors.lastname: Riehm
authors.forename: Alfred
authors.initials: A
authors.lastname: Reiter
authors.forename: Martin
authors.initials: M
authors.lastname: Schrappe
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D016543:Central Nervous System Neoplasms / Q000134:cerebrospinal fluid* / Q000188:drug therapy / Q000401:mortality; D002555:Cerebrospinal Fluid / Q000166:cytology; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D016371:Cranial Irradiation; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007278:Injections, Spinal; D007958:Leukocyte Count; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000134:cerebrospinal fluid* / Q000188:drug therapy / Q000401:mortality; D011379:Prognosis; D012189:Retrospective Studies; D012307:Risk Factors; D013129:Spinal Puncture; D016896:Treatment Outcome
chemical_list: D000964:Antimetabolites, Antineoplastic; D008727:Methotrexate