Methotrexate-associated primary hepatic malignant lymphoma following hepatectomy: A case report

Takei, Daisuke; Abe, Tomoyuki; Amano, Hodaka; Hirano, Naomichi; Kobayashi, Tsuyoshi; Ohdan, Hideki; Kondo, Toshinori; Nakahara, Masaaki; Noriyuki, Toshio

doi:10.1016/j.ijscr.2016.12.012

Cited by 16 publications

(4 citation statements)

References 17 publications

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“…Case reports on MTX toxicity have linked MTX to several forms of malignancy, namely pseudolymphoma and lymphomas [58]. However, a research paper published in 1999 could not find a link between MTX treatment and proven oncogenicity due to a lack of solid data [59].…”

Section: Mtx Increases Infection Riskmentioning

confidence: 99%

Overview of Methotrexate Toxicity: A Comprehensive Literature Review

Hamed¹,

Dighriri²,

Baomar³

et al. 2022

Cureus

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Methotrexate (MTX) is significantly more effective than and has a considerable advantage over placebo in patients with severe and persistent rheumatoid arthritis (RA). The drug is used to treat a variety of malignant disorders (leukemia and cancer of the lung, breast, and uterus) and ectopic pregnancy. As its side effects are outweighed by its effectiveness, MTX is a first-line antirheumatic drug in many countries. MTX is found in extracellular compartments, such as the synovium, as well as other organs, such as the kidney and liver. To improve treatment, increase adherence, and decrease mortality in MTX therapy, it is essential to reduce its toxicity and understand its side effects. Therefore, this comprehensive review was conducted to assist physicians and researchers in better understanding the toxicity of MTX and how to deal with this toxicity. MTX is eliminated via the kidneys, which are capable of excretion and reabsorption within the renal tubules. Although higher doses of MTX (known as high-dose MTX (HD-MTX), defined as doses of 500 mg/m 2 or greater) are often more beneficial, they can produce toxicity and side effects such as bone marrow suppression, pulmonary toxicity, nephrotoxicity, hematologic toxicity, and an increased risk of infections. Treatment of severe MTX toxicity has three main goals: clearance of MTX from the bloodstream, folinic acid therapy, and organ treatment. Leucovorin is highly beneficial in preventing myelosuppression, gastric toxicity, and neurotoxic effects after HD-MTX therapy. The preferred antidote for MTX poisoning is folinic acid. Glucarpidase has been licensed for the treatment of high plasma MTX levels of >1 μmol/L in patients with compromised renal function who have delayed MTX elimination. In patients with renal deficiency, a lower initial dose is considered with an estimated glomerular filtration rate (eGFR) between 30 and 59 mL/minute. These patients need to be monitored, and a more gradual dosage increase and a lower weekly maximum should be considered regarding their general health situation. MTX is contraindicated in patients with RA if the eGFR is <30 mL/minute.

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Section: Mtx Increases Infection Riskmentioning

confidence: 99%

Overview of Methotrexate Toxicity: A Comprehensive Literature Review

Hamed¹,

Dighriri²,

Baomar³

et al. 2022

Cureus

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“…Most cases develop after long-term MTX administration. In the 11 previously reported cases of MTX-LPDs of hepatic origin, the average duration of MTX administration was 7.3 (range, 2 -13) years (Table 2) [5][6][7][8][9][10][11][12][13][14][15]. In our case, a primary hepatic OIIA-LPDs-associated tumor rapidly increased in size after an extremely short period of MTX ad-ministration.…”

Section: Discussionmentioning

confidence: 47%

Primary Hepatic Other Iatrogenic Immunodeficiency-Associated Lymphoproliferative Disorders After Methotrexate Therapy

Hatayama,

Sugiyama,

Murakami

et al. 2023

J Med Cases

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Prior reports described cases of lymphoproliferative diseases occurring after methotrexate (MTX) administration, which are called methotrexate-associated lymphoproliferative disorders (MTX-LPDs). It has become clear that these lymphoproliferative diseases also occur following treatment with other immunosuppressive drugs, and they have been termed as other iatrogenic immunodeficiency-associated lymphoproliferative disorders (OIIA-LPDs). In most of these cases, the duration of immunosuppressive drugs is very long, on the order of years. In the present study, we evaluated the development of lymphoproliferative disease despite the short duration of immunosuppressive treatment and determined the tumor doubling time. A 71-year-old woman was diagnosed with adult-onset Still’s disease. The patient was administered prednisone 30 mg per day starting on February 25, 2022 and MTX 6 mg per week starting 2 weeks later. Because she was a hepatitis B virus (HBV) carrier, nucleic acid analog therapy was also started to prevent HBV activation. Eight weeks later, biweekly tocilizumab was started. After 5 months of MTX administration, a solitary liver tumor measuring 37 × 32 mm 2 was detected. Three months later, repeat computed tomography revealed that the liver tumor had grown rapidly to 7 cm in diameter. We considered the possibility of OIIA-LPDs and stopped MTX therapy. Biopsy specimens of the liver tumor exhibited lymphocyte proliferation, which was consistent with OIIA-LPDs. The doubling time for tumor growth was 33 days. Despite withdrawing MTX for 6 weeks, the tumor continued to grow, and thus, the patient was referred to the hematology unit. In previously reported cases of MTX-LPDs of hepatic origin, the average duration of MTX administration was 7.3 (2 - 13) years. This report describes a primary hepatic OIIA-LPDs-associated tumor that rapidly increased in size after an extremely short period of MTX administration.

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“…MTX has been shown to enhance the accumulation of oxidative DNA injuries, which, in turn, have been shown to induce DNA damage in human [ 10,11,12 ]. Case reports on MTX toxicity have linked MTX to several forms of malignancy, namely pseudolymphoma and lymphomas [ 13,14].…”

Section: Discussionmentioning

confidence: 99%

Evaluation of Polytene Chromosome Aberrations Based Genotoxicity Induced by Methotrexate in Drosophila Melanogaster Oregonr

2023

IRJMETS

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Methotrexate (MTX) is a widely used drug for treating many kinds of cancer or severe and resistant forms of autoimmune diseases. However, it faces serious challenges in clinical application due to serious side effects. The objective of our present research work deals with evaluation of clastogenic and cytotoxic effects of MTX using Drosophila melanogaster Oregon R as a model organism. In our experiment exposure of MTX of different concentrations was given to Drosophila melanogaster Oregon R larvae which were sacrificed for temporary squash preparation of polytene chromosome, along with controls. The effect was observed and quantified under microscope. The structural aberration of polytene chromosomes in MTX treated stocks were observed with the incidences of asynapsis, ectopic pairing, inversion, breaks, chromosomal fusion. In control stock spontaneous aberrations were inversion, chromosomal fusion and ectopic pairing, which was significantly less compared to MTX treated groups. Subsequently, statistical analysis was done and it was concluded that MTX induced statistically significant genotoxicity in exposed larvae in comparison to control.

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Methotrexate-associated primary hepatic malignant lymphoma following hepatectomy: A case report

Abstract: HighlightsPrimary hepatic lymphoma is difficult to diagnose preoperatively.MTX use encouraged MTX-related ML.In MTX-related MLs, withdrawing MTX had a therapeutic effect.

Cited by 16 publications

References 17 publications

Overview of Methotrexate Toxicity: A Comprehensive Literature Review

Overview of Methotrexate Toxicity: A Comprehensive Literature Review

Primary Hepatic Other Iatrogenic Immunodeficiency-Associated Lymphoproliferative Disorders After Methotrexate Therapy

Evaluation of Polytene Chromosome Aberrations Based Genotoxicity Induced by Methotrexate in Drosophila Melanogaster Oregonr

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