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
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.
Joel M Kremer, MDSection Editor:James R O’Dell, MDDeputy Editor:Paul L Romain, MD INTRODUCTION
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”.)
Disable hybernation: run powercfg.exe /hibernate off
Delete pagefile.sys in the file explorer
Run c:\dir -h to confirm ‘hyberfil.sys’ and ‘pagefile.sys’ are deleted
Run disk cleanup utility
Clear recycle bin
If ‘not enough space available’ error is found, go to the Event log viewer and find out which file is stuck
Try launching the Event Viewer to see which individual files are blocking the partition shrink.
Once again, attempt to shrink the partition. You should get the “There is not enough space” error. Launch Windows’ Event Viewer application. In Event Viewer, go to Windows Logs > Application. Find and Click a recent log of type Warning. It should have the message, “Error: during volume shrink initiated on volume Windows (C:) we failed to move a movable file extent.” (screenshot) The Diagnostic details will give you the name of the “last unmovable file” Delete this file (Simply send to recycle bin. I did not need a hard delete). Try shrinking your volume again. Repeat steps 2-7 until you successfully shrink your partition. (In my case, I had to do this 3 times, as I had 3 pdf files in my local Google Drive that were for some reason stuck as ‘unmovable’.). Restore your deleted files.