R-CHOP + and High-Dose Methotrexate (HM)

Article 1: CHOP-R and High-Dose Methotrexate In The Primary CNS Lymphoma Revisited. 10-Year Experience and 92 Patients From a Single Institution (2013)

Article 2: Patient Selection for High-Dose Methotrexate As Central Nervous System Prophylaxis in Diffuse Large B-Cell Lymphoma in Australia: Are We Getting It Right?

Conclusions: HDMTX was well-tolerated by patients, therefore can safely be administered as CNS prophylaxis under current hospital protocols. Application of the DSHNHL prognostic model identifies a different population of candidates for CNS prophylaxis compared to historical risk factors and may lead to better patient selection for this intervention

Article 3: Addition of high-dose methotrexate to standard treatment for patients with high-risk diffuse large B-cell lymphoma contributes to improved freedom from progression and survival but does not prevent central nervous system relapse

Combination of rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) is regarded as standard care for diffuse large B-cell lymphoma (DLBCL) and upfront intensification of therapy is still controversial. The current study aimed to dertermine whether the addition of high-dose methotrexate (HDMTX) affects long-term outcomes and could also prevent central nervous system (CNS) relapse. Medical records of 480 patients with DLBCL treated between 1994 and 2013 at Rambam and Hadassah medical centers in Israel were reviewed; 130 (27%) had received HDMTX. Patients receiving HDMTX generally had higher International Prognostic Index (IPI) and CNS-IPI scores. HDMTX addition significantly improved progression free and overall survival (p = .001) and this advantage was maintained in multivariate analysis (HR for OS 0.3; 95% CI 0.19-0.47; p < .0001). Thirty-one (6.5%) patients had CNS relapse and in these cases high CNS-IPI, but not HDMTX treatment, was independently associated with CNS relapse (HR 1.2; 95% CI 1.2-11.5; p = .02). In conclusion, the addition of HDMTX to CHOP/RCHOP independently and significantly improved prognosis of patients with high-risk DLBCL, irrespective of their risk for CNS relapse.


Side effects needing medical attention
Black, tarry stools; bloody vomit; diarrhea; sores in mouth or on lips; stomach pain; fever; chills; sore throat; unusual bleeding or bruising; blood in urine or dark urine; blurred vision; confusion; convulsions or seizures; cough; dizziness; drowsiness; headache; joint pain; shortness of breath; rash; swelling of feet or lower legs; unusual tiredness or weakness; yellowing of eyes and skin; loss of appetite; nausea or vomiting. The above side effects may be more likely to occur in very young and very old patients.

Side effects needing medical attention after stopping this medication
Blurred vision; convulsions or seizures; dizziness; drowsiness; headache; confusion; unusual tiredness or weakness.

Major side effects of low-dose methotrexate

Joel M Kremer, MDSection Editor:James R O’Dell, MDDeputy Editor:Paul L Romain, MD

Methotrexate (MTX) use can be associated with a variety of adverse effects over a wide range of severity; the risk of most side effects is influenced by the MTX dose and treatment regimen. In rheumatoid arthritis (RA) and other disorders, MTX is administered as long-term, low-dose therapy, usually 7.5 to 25 mg weekly, unlike its use for treatment of malignant disease, where it is may be administered in a cyclic fashion in doses of 1 gram or more.
The most commonly observed side effects of MTX at doses typically used for the treatment of RA are rarely life-threatening, in contrast with the high doses used in the treatment of malignancies. Nevertheless, they may become clinically significant if they result in premature discontinuation or dose alteration of a drug that is the best therapeutic alternative for a given individual.

Potentially life-threatening hepatotoxicity, pulmonary damage, and myelosuppression may be seen with use of MTX as either high- or low-dose therapy, while nephrotoxicity is a manifestation of high-dose therapy that occurs rarely, if ever, with low-dose MTX treatment.

The major side effects of low-dose MTX are reviewed here. The use of low-dose MTX in patients with RA and other rheumatic diseases and the clinical use and adverse effects of high-dose MTX and related adverse effects are described separately. (See “Use of methotrexate in the treatment of rheumatoid arthritis” and “Therapeutic use and toxicity of high-dose methotrexate”.)

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