Methotrexate (MTX)-induced leukoencephalopathy is the most often reported leukoencephalopathy following intrathecal or intravenous administration. A 72-year-old woman developed leukoencephalopathy localized to the cerebellum after treatment with oral MTX at a dose of 15 mg/week for 3 years. She complained of subtle imbalance during walking and reported having fallen. Her symptoms improved after discontinuation of MTX, and the leukoencephalopathy resolved. This is therefore a case report of selective cerebellar reversible leukoencephalopathy associated with oral MTX.
Administration, Intravenous ; Aged ; Cerebellum ; Female ; Humans ; Leukoencephalopathies* ; Methotrexate* ; Walking

Generalized pustular psorissis which is originary described by von Zumbusch in 1910, is the most intense form of the acute exanthematic variant among psoriasis and it is to be occured as a rare disease. We presented a case of generalized pustular psoriasis of a 16 year-old girl, who suddenly developed wide spread pustules during the acute exacerbating course of the psoriasis which had started from the primary plaque on her left anterior chest one month ago. She was free from subjective symptom. As the objective sign, the leukocytosis was only one of the significant laboratory findings. All skin lesions were almost eleared by the oral administration of methotrexate in 3 months.
Administration, Oral ; Adolescent ; Female ; Humans ; Leukocytosis ; Methotrexate ; Psoriasis* ; Rare Diseases ; Skin ; Thorax

OBJECTIVETo develop a novel drug dilivery system based on calcium phosphate cement (CPC) with methotrexate (MTX) as a model drug and to study its drug release in vitro.

METHODSThree MTX mass fractions (0.1%, 0.2%, and 0.5%) were tested after solidification, and the compound of CPC-MTX were put into the simulated body fluid at 37 degrees C. The concentration of MTX was tested by high-performance liquid chromatography at day 2, 5, 10, 16 hours, 1, 2, 3, 5, 8, 10, 15, 20, 25, 30, 35, 40, and 45 days. The drug dilivery curves were drawn and drug dilivery rules were analyzed.

RESULTSMTX was released slowly and stably from the compound of CPC-MTX. Remarked prophase of drug release was noted, which conformed with the Higuchi equation. The drug release rate and concentration was related with the concentration of MTX in compound but not with the thickness and shape of CPC. The releasing time was not affected by the concentration of MTX.

CONCLUSIONA stable drug dilivery system can be developed by loading proper concentration of MTX into CPC.

Calcium Phosphates ; chemistry ; Chromatography, High Pressure Liquid ; Delayed-Action Preparations ; Kinetics ; Methotrexate ; administration & dosage ; analysis

A 40-year-old female visited our clinic for visual disturbance of the right eye, in which a few creamy-yellow retinal lesions and visual field constrictions were noted. She had been treated for primary CNS lymphoma and was in complete remission. After failure to follow-up for three months, she lost vision in the right eye, at which time active panuveitis was seen. Decreased vision and field constriction was observed in the left eye. Her left eye showed a granular pattern and dye leakage from the vessels and disc on fluorescein angiography and small RPE humps were seen in optical coherence tomography (OCT). Diffuse large malignant B-cells with strong immunoreactivities with CD20 immunostaining were seen in the epiretinal membrane biopsy specimen. Intravitreal injections of methotrexate (MTX) (800 microgram/0.1 ml in the right eye, 400 microgram/0.05 ml in the left eye) were performed twice weekly for one month, once weekly for the following month, once every two weeks for the next month, followed by nine monthly injections. Both eyes were free from malignant cells on vitreous biopsy six months later. There was no leakage seen by angiography, but the granular pattern persisted. Visual field constriction was slightly improved, and the small RPE humpsdetachments seen in OCT disappeared. EOG Arden ratio was decreased in both eyes, and b wave amplitude of scotopic ERG was decreased in the left eye. She was free from recurrence until six months later. No ocular complications except minimal opacity of the crystalline lenses were noted in both eyes.
Adult ; Antimetabolites, Antineoplastic/*administration & dosage ; Drug Administration Schedule ; Eye Neoplasms/*drug therapy ; Female ; Humans ; Injections ; Lymphoma/*drug therapy ; Methotrexate/*administration & dosage ; Treatment Outcome ; Vitreous Body

OBJECTIVETo investigate the efficacy and toxicity of methotrexate (MTX) give intravenously in the primary treatment of gestational trophoblastic tumor (GTT).

METHODSA total of 37 patients with low-risk GTT was primarily treated by single MTX in Women's Hospital, School of Medicine, Zhejiang University. Data on the patients' age, clinical stage, WHO classification criteria, antecedent pregnancy, presenting level of human chorionic gonadotropin, courses of chemotherapy required to achieve complete remission, and toxicity related to chemotherapy treatments were collected.

RESULTSThirty-seven patients with low-risk GTT totally received 137 cycles of MTX between Oct. 1999 and Sep. 2002, 34 patients (91.9%) achieved complete remission. Twenty-nine patients received multiple courses of MTX, complete remission was induced in 26 patients (89.7%). The complete response rates of I stage and III stage were 100.0% and 70.0% (P = 0.03) respectively in patients who were received multiple courses of MTX. However, eight patients received single course of chemotherapy, 7 patients achieved complete remission, and 1 achieved complete remission after another additional course of MTX was conducted. Grade III side effects (WHO criteria) only appeared in 7 courses (5.1%) during MTX treatment. Follow-up data showed that only one patient with single course of chemotherapy relapsed after 6 months.

CONCLUSIONSingle MTX chemotherapy may be effective and well tolerated for low-risk GTT.

Adolescent ; Adult ; Antimetabolites, Antineoplastic ; administration & dosage ; Choriocarcinoma ; drug therapy ; Drug Administration Schedule ; Female ; Gestational Trophoblastic Disease ; drug therapy ; Humans ; Methotrexate ; administration & dosage ; Pregnancy ; Uterine Neoplasms ; drug therapy

BACKGROUNDMagnetic targeting therapy may be a new method for the treatment of malignent tumors. The purpose of this study was to investigate the localization and distribution of ferrofluid microsphere of human serum albumin methotrexate (FM-HSA-MTX) carriers in the brain and to explore the magnetic targeting chemotherapy for malignant brain tumor.

METHODSNinety SD rats were divided into three groups: targeting group, non-magnetic targeting group, and control group. Synthesized FM-HSA-MTX carriers (MTX 25 mg/kg) were injected into the systemic circulation via the caudal vein (magnetic targeting group, n = 30). A 0.6 T magnetic field was placed around the right hemisphere. The non-magnetic targeting group (n = 30) was administered with FM-HSA-MTX without external magnetic field, meanwhile the control group (n = 30) was treated with MTX and a magnetic field. Random serial sacrifices (n = 10) were conducted at 15, 30 and 45 minutes after drug administration. Bilateral hemispheres were collected respectively, and analyzed for total MTX content.

RESULTSMTX content in the right hemisphere of the magnetic targeting group was significantly higher than that in the other two groups at 15, 30 and 45 minutes after drug administration (P < 0.05) No difference was seen between the non-targeting group and control group. In the magnetic targeting group, MTX returned to the peak level [(0.564 +/- 0.018) mg/g, q15-45 = 32.252, P < 0.05] 45 minutes after the injection but it deceased in the other two groups [non-magnetic targeting group: (0.060 +/- 0.015) mg/g, q15-45 = 9.245, P < 0.05, control group: (0.074 +/- 0.045) mg/g, q15-45 = 6.299, P < 0.05]. In the magnetic targeting group, the concentration of MTX in the right hemisphere was significantly higher than that in the left hemisphere (t45min = 21.135, P = 0.000) but no difference was observed between bilateral hemispheres in the other two groups (non-magnetic targeting group: t45min = 0.434, P = 0.670; control group: t45min = 0.533, P = 0.600).

CONCLUSIONIn the presence of the external magnetic field, FM-HSA-MTX can distribute successfully in the targeting areas of the brain.

Animals ; Antineoplastic Agents ; administration & dosage ; Brain ; metabolism ; Drug Carriers ; Magnetics ; Methotrexate ; administration & dosage ; pharmacokinetics ; Microspheres ; Rats ; Rats, Sprague-Dawley ; Serum Albumin ; administration & dosage ; pharmacokinetics

OBJECTIVETo compare the efficacy and toxicity of the chemotherapeutic regimen containing pirarubicin and mitoxantrone on the treatment of relapsed or refractory acute myeloid leukemia (AML) in adults.

METHODSIn this open prospective multicentre study, we randomly assigned patients with relapsed or refractory AML to receive TAE regimen (pirarubicin+cytarabine+etoposide) versus MAE regimen (mitoxantrone + cytarabine + etoposide). The efficacy and toxicity were compared between the two groups.

RESULTS56 patients entered this clinical trial. The complete remission (CR) rate on TAE arm was 79.0% versus 55.6% on MAE arm with the overall response (OR) rates of 86.8% versus 88.9%, respectively. The CR was higher on TAE arm (P=0.035) but with no significant difference between the two groups regarding the overall response (OR) rate. The regimens were well tolerated in both groups. Hematologic and non-hematologic toxicity were similar except relatively lower the mean dosage of G-CSF, red blood cells and platelets transfusion on TAE arm. No significant differences were seen between the two groups regarding the overall survival and relapse free survival rates.

CONCLUSIONTAE regimen might be an effective salvage therapy in patients with relapsed or refractory AML.

Adult ; Antineoplastic Combined Chemotherapy Protocols ; administration & dosage ; therapeutic use ; Dactinomycin ; administration & dosage ; Doxorubicin ; administration & dosage ; analogs & derivatives ; Etoposide ; administration & dosage ; Granulocyte Colony-Stimulating Factor ; administration & dosage ; Humans ; Leukemia, Myeloid, Acute ; drug therapy ; Methotrexate ; administration & dosage ; Prospective Studies ; Recurrence ; Remission Induction

Most reports on serious MTX toxicity have focused on hepatic abnormalities, while other effects, including hematologic reactions, have not been emphasized. We experienced a case of pancytopenia secondary to MTX therapy in a patient with RA and renal insufficiency. A 67-year-old woman with a 12-year history of active seropositive RA that was a response to non-steroidal anti-inflammatory drugs, hydroxychloroquinine and intra-articular steroid injections, had been followed up and was diagnosed as early chronic renal failure in October, 1993. Recently, because of significant morning stiffness and polyarthralgia, the decision was made to institute MTX treatment. This was begun as a single oral dose of 5mg/week. After 2 doses, the patient was admitted to the hospital with general weakness. Laboratory tests showed a hemoglobin level of 7.9 g/dl, WBC count 1800/mm3 and platelet count of 64000/mm3. The serum creatinine level was 6.1 mEq/dl and the BUN level was 82 mEq/dl. Liver function test results were normal, but the serum albumin level was 2.7 g/dl. The patient subsequently developed fever and blood transfusions, granulocyte colony stimulating factor (G-CSF) and intravenous prophylactic antibiotic therapy were required. Her condition was improved. In summary, Low-dose MTX-related adverse hematologic side effects, including fatal pancytopenia, are rare but are a cause of increasing concern in patients with RA and renal insufficiency. Close monitoring of associated risk factors, particularly impaired renal function, should be mandatory for all patients who are receiving MTX therapy.
Aged ; Antirheumatic Agents/adverse effects* ; Antirheumatic Agents/administration & dosage ; Arthritis, Rheumatoid/drug therapy ; Arthritis, Rheumatoid/complications ; Case Report ; Female ; Human ; Kidney Failure, Chronic/complications ; Methotrexate/adverse effects* ; Methotrexate/administration & dosage ; Pancytopenia/chemically induced* ; Risk Factors

Acute Kidney Injury ; chemically induced ; Child ; Humans ; Male ; Methotrexate ; administration & dosage ; adverse effects ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; drug therapy

A 13-year-old male and a 15-year-old female presented with optic disc edema associated with chronic recurrent uveitis. While the ocular inflammation responded to high doses of oral prednisolone, the disc edema showed little improvement. After oral administration of methotrexate, the disc edema and ocular inflammation were resolved, and the dose of oral corticosteroid could be reduced.
Administration, Oral ; Adolescent ; Chronic Disease ; Female ; Glucocorticoids/administration & dosage ; Humans ; Immunosuppressive Agents/administration & dosage ; Male ; Methotrexate/administration & dosage ; Papilledema/drug therapy/*etiology ; Prednisolone/administration & dosage ; Recurrence ; Uveitis/*complications/drug therapy