High-Dose Methotrexate-Leucovorin Rescue Therapy: Selected Application in Non-Hodgkin's Lymphoma

Abstract

Methotrexate with leucovorin rescue (HDMTX-LV rescue), has been used to treat solid tumors and non-Hodgkin's lymphomas (NHL). We studied the use of HDMTX-LV rescue in patients with widespread NHL with histologic diagnosis of diffuse poorly differentiated lymphocytic and diffuse histiocytic including involvement of the central nervous system (CNS) and/or bone marrow. The prognosis with conventional chemotherapy is extremely poor. Three patients have bone marrow involvement, 2 patients CNS, and 2 both. These patients were unresponsive to conventional chemotherapy and had a rapid progression of their disease. Therapy with HDMTX-LV rescue induced responses in 5 patients: 2 patients achieved a complete remission and three a partial remission. Regression of CNS involvement was observed in 3 patients; bone marrow toxicity was not observed. Only 1 patient failed to respond. These data suggest that HDMTX-LV rescue may be useful as primary therapy in lymphoma patients with CNS and/or bone marrow involvement.

A randomized comparison of methotrexate dose and the addition of bleomycin to chop therapy for diffuse large cell lymphoma and other non-Hodgkin's lymphomas cancer and leukemia group B study 7851

“…While the low-dose and schedule of bleomycin were not similar to that used in other studies, the consolidation therapy of three weekly courses of high-dose methotrexate was given at a dose and schedule that will result in tumor response when the drug is given as a single agent. [16][17][18]21 Indeed, there appear to be no randomized trials that demonstrate any enhancement of systemic therapeutic effect when methotrexate or bleomycin is added to an otherwise active therapeutic program for lymphoma.…”

Overview of Dual-Acting Drug Methotrexate in Different Neurological Diseases, Autoimmune Pathologies and Cancers

“…MTX application in lymphomas are reported in numerous papers. In this work, we selected the most comprehensive articles on MTX-based lymphoma therapy (Table 2) [124,129,[171][172][173][174][175][176]179,182,240,241]. Primary central nervous system lymphoma (PCNSL) is a malignant disease of the lymphatic system that accounts for about 2% to 5% of all primary intracranial tumours in immunocompetent patients.…”

“…It is an aggressive NHL of B-cell origin and can be located in the brain, meninges, eyes, spinal cord, cerebrospinal fluid and intraocular structures [178,182]. Studies of the use of HDMTX as a single agent followed by LV rescue in patients with widespread NHL have demonstrated the effectiveness of this treatment [171][172][173][174][175][176]. Zhu et al studied the response and adverse effects of intravenous HDMTX administration as a function of age at the time of PCNSL diagnosis [176].…”

Dose-Dependent Disposition of Methotrexate in Abcc2 and Abcc3 Gene Knockout Murine Models

“…Methotrexate (MTX) is a folate antagonist widely used for the treatment of different diseases that require a large therapeutic dose range (Braun and Rau, 2009): low doses for autoimmune diseases such as psoriasis (Hunter, 1962) and rheumatoid arthritis (Weinblatt et al, 1985) and high doses for different types of cancers, such as primary central nervous system lymphoma (Deangelis and Iwamoto, 2006), acute lymphoblastic leukemia (Chessells et al, 1987), and other neoplastic diseases (Rizzoli et al, 1985). On the basis of several in vitro experiments, MTX is a known substrate for numerous membrane transporters, including the multidrug resistance proteins (MRP) ABC subfamily C member 2 (ABCC2/MRP2) and member 3 (ABCC3/MRP3) (Assaraf, 2006).…”