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Outcome Of CNS Disease At Diagnosis in Disseminated Small Noncleaved-Cell Lymphoma and B-Cell Leukemia: A Children’s Cancer Group Study

From the Memorial Sloan-Kettering Cancer Center and New York University Medical Center, New York, NY; Children’s Cancer Group Operations Center, Arcadia, CA; Lombardi Cancer Center, Washington, DC; and Children’s Hospital of Philadelphia, Philadelphia, PA.

Address reprint requests to Sridharan Gururangan, MRCP(UK), Children’s Cancer Group, PO Box 60012, Arcadia, CA 91066-6012; email gururooz{at}mc.duke.edu

PURPOSE: To examine the impact of initial CNS involvement on outcome and patterns of failure in patients with disseminated small noncleaved-cell lymphoma and B-cell leukemia who were treated in four successive Children’s Cancer Group trials.

PATIENTS AND METHODS: Of 462 patients with disseminated disease, 49 (10.6%) had CNS disease at diagnosis (CNS+). CNS disease included meningeal disease or CNS parenchymal masses with or without cranial neuropathies (CSF+/Mass; CNPs) in 36 patients and isolated CNPs in 13. Of the CNS+ patients, 28 had M2 (5% to 25% blasts) or M3 (> 25% blasts) bone marrow involvement. All patients received protocol-based systemic and intrathecal chemotherapy. Thirty-six patients also received CNS irradiation.

RESULTS: Relapses occurred in 21 (43%) of 49 patients, predominantly in the CNS (71%) and bone marrow (52%). The 3-year event-free survival ± SE for all patients with CNS+ disease was 45% ± 7%. Patients with CSF+/Mass had a nominally higher treatment failure rate compared with patients with CNS- after adjusting for marrow status and lactate dehydrogenase (LDH) diagnosis, with a relative failure rate (RFR) of 1.52 (95% confidence interval [CI], 0.88 to 2.6; P = .15). In comparison, the RFRs for patients with M2 or M3 marrow and for those with LDH levels greater than 500 IU/L after adjusting for CNS disease were 1.4 (95% CI, 0.96 to 2.0; P = .029) and 2.2 (95% CI, 1.5 to 3.0; P < .001), respectively. The RFR for patients with isolated CNPs was 0.87 (95% CI, 0.36 to 2.1; P = .76).

CONCLUSION: We conclude that, with the treatments used during the period covered by these studies, the presence of CSF+/Mass CNS disease at diagnosis was associated with a nominally worse outcome independent of initial bone marrow status and LDH level, but the effect was not statistically significant.

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