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

BACKGROUND:The outcome of patients with systemic diffuse large B-cell lymphoma (DLBCL) had improved over the past decade with the addition of monoclonal antibody therapy. Unfortunately, approximately 5% of these patients still developed a secondary central nervous system (CNS) recurrence followed invariably by rapid death. This rate is substantially increased in patients with certain high-risk features. Although prophylaxis against CNS recurrence with either intrathecal or intravenous methotrexate is commonly used for such patients, to the authors' knowledge, there is no standard of care. Retrospectively evaluated was the role of high-dose systemic methotrexate combined with standard cyclophosphamide, doxorubicin, vincristine, and prednisone with rituximab (R-CHOP) chemotherapy to decrease CNS recurrence in high-risk patients. METHODS: A total of 65 patients with DLBCL and CNS risk factors were identified at the study institution between 2000 and 2008 who received intravenous methotrexate as CNS prophylaxis concurrent with standard systemic therapy with curative intent. CNS recurrence rate, progression-free survival, and overall survival were calculated. RESULTS: Patients received a median of 3 cycles of methotrexate at a dose of 3.5 gm/m 2 with leucovorin rescue. The complete response rate was 86%, with 6% partial responses. At a median follow-up of 33 months, there were only 2 CNS recurrences (3%) in this high-risk population. The 3-year progression-free and overall survival rates were 76% and 78%, respectively. Complications associated with methotrexate therapy included transient renal dysfunction in 7 patients and a delay in systemic chemotherapy in 8 patients. CONCLUSIONS: Intravenous methotrexate can be safely administered concurrently with R-CHOP and is associated with a low risk of CNS recurrence in high-risk patients. Cancer 2010;116:4283-90.

Intensified chemotherapy with ACVBP plus rituximab versus standard CHOP plus rituximab for the treatment of diffuse large B-cell lymphoma (LNH03-2B): an open-label randomised phase 3 trial

“…High-dose methotrexate plus calcium folinate rescue is associated with a low risk of CNS relapse in diff use large B-cell lymphoma. 24 Ifosfamide, etoposide, and cytarabine, contained in the consolidation, are the most common drugs used in salvage regimens after relapse subsequent to anthracycline-based treatment. 7 Outcome data in our patients treated with standard R-CHOP are consistent with our initial hypothesis The profi le of toxic eff ects for the R-ACVBP regimen is well characterised.…”

Diffuse large B-cell lymphoma with involvement of the kidney: outcome and risk of central nervous system relapse

“…14,27,28 A recent retrospective study of 65 selected patients with high-risk DLBCL receiving primary chemoimmunotherapy concurrently with intravenous high-dose methotrexate and leucovorin rescue suggests that this strategy may be associated with a lower risk of CNS relapse, 38 but prospective evaluation is necessary. In summary, patients with DLBCL and kidney involvement at diagnosis have a poor prognosis in part due to the high incidence of CNS relapses which occur early.…”

Successful Treatment of Elderly Diffuse Large B-Cell Lymphoma with Central Nervous System Recurrence by Rituximab, Ranimusutine, Ifosfamide, Procarbazine, Dexamethasone, and Etoposide Therapy

“…Some reports have suggested that a high-dose intravenous rituximab infusion or intrathecal rituximab infusion may be an effective treatment option [13], although the clinical safety of such treatments has not been yet been confirmed. In order to prevent CNS recurrence of DLBCL, intrathecal chemotherapy such as MTX and cytarabine is currently performed in many institutions, although its efficacy has been controversial [2,[14][15][16][17][18]. Kim et al described the treatment of 73 DLBCL patients with secondary CNS involvement in 11 institutions in Korea [14].…”