Involved-field radiotherapy and intra-Ommaya methotrexate/cytarabine in patients with AIDS-related lymphomatous meningitis.

Abstract

PURPOSE To evaluate combined limited-field radiotherapy and concentration times time (C X T) intra-CSF chemotherapy in patients with AIDS-related lymphomatous meningitis (LM). PATIENTS AND METHODS Fourteen men and one woman with AIDS had cytologically documented LM. Eleven patients had systemic non-Hodgkin's lymphoma (NHL) (all B-cell histology, including six immunoblastic, four large cell, one small cell) with leptomeningeal metastases and four patients had primary CNS lymphoma (PCNSL) (all B-cell histology, including two immunoblastic, two large cell) with CSF dissemination. Presenting neurologic examinations included cranial neuropathies (n = 7), normal (n = 4), abulia (n = 2), paraparesis (n = 2), ataxia (n = 1), hemiparesis (n = 1), and aphasia (n = 1). Standardized pretreatment evaluations included contrast cranial magnetic resonance/computed tomography (MR/CT), placement of an intraventricular reservoir, CT myelogram/contrast spine MR, ophthalmologic examination, and indium 111-pentetic acid (DTPA) CSF flow studies. Regions of bulky or symptomatic disease were treated with limited-field radiation therapy, which included whole brain in 10 patients combined with spinal cord irradiation in five patients. Concurrent systemic chemotherapy was administered in 12 patients. All patients were scheduled to receive intraventricular methotrexate (MTX) 2 mg/d for 5 consecutive days biweekly for 8 weeks (induction), followed in cytologically responding patients by MTX administered in a similar manner every 4 weeks (maintenance). In MTX-responsive and consenting patients with cytologic relapse, intraventricular cytarabine (ara-C) was administered, 25 mg/d for 3 consecutive days weekly for 4 weeks (induction), followed by ara-C administered in a similar manner every 4 weeks (maintenance). CSF cytology and neurologic examinations were performed biweekly. RESULTS In 13 assessable patients (two patients refused CNS directed therapy following standardized pretreatment evaluations), median time to tumor progression was 60 days (range, 3 to 260) and median survival duration was 125 days (range, 44 to 260). Response rate, determined clinically (four of 13 patients) and cytologically (nine of 13), was 69%. Complications included reservoir infection (n = 2) and myelosuppression (n = 11); the latter was felt to be a consequence of coadministered systemic chemotherapy. CONCLUSION There were no treatment-related deaths. We conclude that involved-field irradiation and intraventricular MTX/ara-C is effective palliative treatment of AIDS-related LM.