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Diagnostic Cerebrospinal Fluid Examination in Children With Acute Lymphoblastic Leukemia: Significance of Low Leukocyte Counts With Blasts or Traumatic Lumbar Puncture

Britta Bürger, Martin Zimmermann, Georg Mann, Joachim Kühl, Lutz Löning, Hansjörg Riehm, Alfred Reiter, Martin Schrappe

From the Department of Pediatric Hematology/Oncology, Hannover Medical School, Hannover; University Children’s Hospital, Würzburg; Children’s Hospital, Klinikum Oldenburg; Department of Pediatric Hematology/Oncology, University of Giessen, Germany; and St. Anna Children’s Hospital, Vienna, Austria.

Address reprint requests to Britta Bürger, MD, Department of Pediatric Hematology/Oncology, Hannover Medical School, Carl-Neuberg-Str 1, 30625 Hannover, Germany; email: buerger.britta{at}mh-hannover.de.

Purpose: 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.

Patients and 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 ( 5 WBC/µL 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%).

Conclusion: 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.

Supported by grants from the Deutsche Krebshilfe.

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