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 (>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 × 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.