The role of intrathecal chemotherapy prophylaxis in patients with diffuse large B-cell lymphoma

Relapse in the central nervous system (CNS) following initial treatment of diffuse large B-cell lymphoma (DLBCL) is an uncommon but serious complication. This single centre retrospective study investigated the rate of CNS relapse in patients with DLBCL who received standardised intrathecal (IT) chemoprophylaxis.

A total of 259 patients were newly diagnosed and treated for DLBCL from October 1996 to May 2005 and retrospectively analysed for incidence of CNS relapse. Our institutional policy for patients at risk for CNS relapse was for IT chemoprophylaxis to be administered concurrently with systemic treatment. Defined at-risk patients were those with lymphoma involvement at the following sites: bone marrow, testis, nasal/paranasal sinuses, orbits, bone/vertebrae and peripheral blood.

Of 259 patients with DLBCL, a total of 51 patients (19.7%) received IT chemoprophylaxis. Forty-four patients received single agent IT methotrexate (MTX) 12.5 mg (median 3 doses, range 1-7); 27 patients (53%) received 1-3 doses and 17 patients (33.3%) 4-7 doses of MTX. Seven patients (13.7%) received a combination of IT MTX plus cytarabine. Three patients (1.1%) subsequently developed CNS relapse. One of these patients had IT chemoprophylaxis, the other two did not meet the Royal Marsden Hospital (RMH) criteria for IT chemoprophylaxis. The median time from diagnosis of DLBCL to CNS relapse was 31.8 months (range 27.3-34.1 months).

The CNS relapse rate in this cohort of patients with primary DLBCL was low at 1.1%. This retrospective analysis demonstrates in a homogeneous group of DLBCL patients that a relatively low-intensity IT chemoprophylaxis regimen given according to site-based risk can be associated with a low risk of CNS relapse.