title: Central nervous system prophylaxis with combined intravenous and intrathecal methotrexate in diffuse lymphoma of aggressive histologic type.
abstract: With the use of a multivariate regression model, 21 patients with diffuse lymphoma were identified as having greater than 15% risk of experiencing relapse in the central nervous system (CNS). The efficacy of a combination of sequential intravenous methotrexate (MTX) (1 g/m2) and intrathecal MTX in preventing relapse in the CNS and improving survival times was assessed. A comparable historical control group of patients with similar risk of CNS relapse and who did not receive any CNS prophylaxis was used. The CNS relapse-free survival rate (RFS) was improved in patients who received CNS prophylaxis (95% versus 59% at 2 years; P = 0.01). Pretreatment serum lactic dehydrogenase (LDH) levels correlated with the incidence of relapse in the CNS in the control group (P = 0.01). In patients with high pretreatment serum LDH levels (greater than 225 U/L), CNS RFS was improved in those who received CNS prophylaxis (RFS at 2 years: 91% versus 46%; P = 0.02). Both CNS RFS (100% versus 38% at 2 years; P = 0.03) and survival rates (100% versus 38% at 2 years; P = 0.02) were improved in six patients with histologic type other than large cell. In 15 patients with large cell lymphoma, no significant differences in CNS RFS (93% versus 75% at 2 years; P = 0.29) and survival rates (43% versus 44% at 2 years; P = 0.56) were observed. Cerebrospinal fluid MTX levels were above the therapeutic level of 1 X 10(-6) M for at least 20 hours in 90% of courses of combined MTX. The MTX combination used is an effective and non-neurotoxic CNS prophylaxis method. Because the comparison between different methods of CNS prophylaxis is difficult to make without a precise idea of the expected CNS relapse rate, use of the multivariate regression technique is recommended.
mesh_terms: D000328:Adult; D000367:Age Factors; D001853:Bone Marrow / Q000473:pathology; D006801:Humans; D007275:Injections, Intravenous; D007278:Injections, Spinal / Q000009:adverse effects; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008223:Lymphoma / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D008727:Methotrexate / Q000009:adverse effects / Q000134:cerebrospinal fluid / Q000627:therapeutic use*; D008954:Models, Biological; D009423:Nervous System Neoplasms / Q000517:prevention & control*; D012306:Risk
chemical_list: D007770:L-Lactate Dehydrogenase; D008727:Methotrexate