Diagnostic cerebrospinal fluid examination in children with acute lymphoblastic leukemia: significance of low leukocyte counts with blasts or traumatic lumbar puncture.
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.
Bürger
Britta
B
Department of Pediatric Hematology/Oncology, Hannover Medical School, Hannover, Germany. buerger.britta@mh-hannover.de
Zimmermann
Martin
M
Mann
Georg
G
Kühl
Joachim
J
Löning
Lutz
L
Riehm
Hansjörg
H
Reiter
Alfred
A
Schrappe
Martin
M
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
D000964:Antimetabolites, Antineoplastic; D008727:Methotrexate