Intravenous methotrexate as central nervous system (CNS) prophylaxis is associated with a low risk of CNS recurrence in high-risk patients with diffuse large B-cell lymphoma

Abstract

We read with interest the article by Abramson et al.1 describing their results incorporating high-dose intravenous methotrexate (HD MTX) with a rituximab-cyclophosphamide, hydroxydaunorubicin (doxorubicin or Adriamycin), vincristine (Oncovin), and prednisone combination (R-CHOP) to prevent central nervous system (CNS) recurrence in diffuse large B-cell lymphoma (DLBCL) patients at risk of this complication. We have used a similar approach for CNS prophylaxis in at-risk DLBCL patients at our institution and found comparably low rates of CNS relapse. Similar to Abramson et al.,1 patients were deemed at high risk of CNS recurrence when their lymphomas met previously published criteria2 or occurred in “at risk” sites. However, unlike Abramson et al.,1 we scheduled HD MTX after completion of R-CHOP as follows: R-CHOP x6 with 4-6 doses of intrathecal (IT) MTX (12 mg IT day 1 R-CHOP) followed by 2 doses of HD MTX (3 gm/m2 days 1 and 15) . Since 2003, 32 consecutive at-risk DLBCL patients have been treated with R-CHOP and IT and HD MTX for CNS prophylaxis at our institution. Median age of patients was 63 years (range, 26-79 years), with a majority (29 of 32 patients) suffering advanced stage and high-intermediate or high-risk International prognostic index (IPI, 24 of 32). Patients were assigned as high risk of CNS recurrence when they had a combination of elevated lactate dehydrogenase (LDH) and involvement of ≥2 extranodal sites (56% and 44% of patients, respectively) due to involvement of an at-risk site. Overall response to R-CHOP plus IT and HD MTX was 97%, with 94% complete response (CR). At a median follow-up of 22 months (range, 2.4-71 months), 2-year overall and relapse-free survival rates were 91% and 92%, respectively. Systemic relapse occurred in 2 patients, 1 of whom subsequently suffered a CNS relapse. HD MTX was well tolerated and was delivered on an outpatient basis to 75% of patients. The major complication was transient reversible elevation in creatinine in 34% of patients, necessitating dose reduction of the second HD MTX treatment in 19% of patients. We fully agree with Abramson et al.1 that use of HD MTX in addition to R-CHOP chemotherapy offers effective prophylaxis of CNS recurrence in at-risk DLBCL patients and think our data supports the effectiveness and safety of this therapy.