Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q06643 (non-Hodgkin's lymphoma)
 11,307 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Urinary alkalinization with oral sodium bicarbonate has decreased the incidence of acute nephrotoxicity and subsequent myelotoxicity in 18 adults receiving high-dose methotrexate with calcium leucovorin rescue (MTX-LCV) weekly in doses of 1-7.5 g/m2. Close monitoring of 24-hour serum creatinine and MTX levels can predict patients at risk for serious toxicity. By a prompt (24-36 hours) increase in the LCV dose rate, hematologic and biochemical evidence of myelosuppression has been prevented. Kinetic parameters in serum and lumbar cerebrospinal fluid (CSF) were studied in two patients following iv injection of 3 and 7.5 g/m2 respectively. Lumbar CSF MTX concentrations greater than 1 muM are achieved. The half-life of MTX in the CSF (11.95 hours) is twice as long as the serum half-life. In the presence of carcinomatous meningitis, further delay in the clearance of MTX from the CSF was seen. With weekly MTX-LCV, there have been four objective responses in six patients with non-Hodgkin's lymphoma in CNS relapse, including complete regression in two. It is suggested that therapeutic concentrations can be achieved in the central nervous system following MTX-LCV.
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PMID:Weekly methotrexate-calcium leucovorin rescue: effect of alkalinization on nephrotoxicity; pharmacokinetics in the CNS; and use in CNS non-Hodgkin's lymphoma. 1 82

Between 1971 and 1976, 64 patients less than 18 years of age with non-Hodgkin's lymphoma were treated at Boston's Children's Hospital Medical Center-Joint Center for Radiation Therapy. A multimodality approach was used, consisting of radiation therapy (3500--4500 rad), surgery, and chemotherapy. Since 1973, all patients have received a regimen initially comprising Adriamycin, Prednisone, 6-Mercaptopurine, Vincristine, and L-Asparaginase. Methotrexate was substituted for Adriamycin following a cumulative total dose of 450 mg/m2. The 5-year actuarial survival for all patients was 61% while relapse-free survival was 54%. The actuarial and relapse-free survival for patients presenting with localized disease was 75% and 72%, respectively. Median follow-up was 40 months and all relapses occurred within 24 months of initial therapy. A multidisicplinary approach, such as the current regimen, offers a good prognosis for this disease.
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PMID:The role of radiation therapy in the treatment of pediatric non-Hodgkin's lymphomas. 10 19

Methotrexate is now used widely for the treatment of acute leukemia, non-Hodgkin's lymphoma, osteogenic sarcoma, choriocarcinoma, breast carcinoma, pulmonary and epidermoid carcinoma, and intrathecal chemotherapy. It is also useful in bone marrow transplantation, severe psoriasis, rheumatoid arthritis, dermatomyositis, Wegener's granulomatosis and sarcoidosis. The recent dramatic intensification of methotrexate therapy can be attributed in part to advances in our understanding of the clinical pharmacology of the folate antagonists, as well as to the combination of positive results and their effective dissemination to medical oncologists. The review summarizes the pharmacologic findings and illustrates how they are currently being applied to the treatment of malignant disease.
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PMID:The clinical pharmacology of methotrexate: new applications of an old drug. 34 86

High doses of methotrexate (HDMTX), given in pulse infusions of 3 to 30 mg/kg body weight, were studied in 22 children with non-Hodgkin's lymphoma. Sixteen complete and five partial remissions were observed in 21 patients evaluable for remission induction. The dose of MTX was increased stepwise on consecutive treatments until objective tumor response occured. Citrovorum factor rescue (CFR) was used "on demand" when toxicity started to develop, and routinely after 30 mg/kg of MTX. Twelve patients who had no previous chemotherapy were entered in a Phase II study consisting of remission induction with HDMTX and remission maintenance with monthly HDMTX supplemented with one monthly injection of vincristine and Cytoxan and five days of oral 6-mercaptopurine and prednisone. Eleven patients achieved remissions (eight complete and three partial) with HDMTX and one with surgery and radiation followed by HDMTX. The three partial remissions improved to complete remission during remission maintenance. All 12 were given the maintenance cyclic combination chemotherapy. Seven of the 12 patients entered the unmaintained phase of the study. One patient relapsed 6 months after cessation of therapy and died 4 years after diagnosis. Six patients are alive and free of disease 2 1/2 to 5 1/2 years after discountinuing treatment and 4 1/2 to 8 1/3 years after diagnosis. Five of these six patients had advanced (Stage IV) disease.
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PMID:Methotrexate and citrovorum factor rescue in the management of childhood lymphosarcoma and reticulum cell sarcoma (non-Hodgkin's lymphomas): parolonged unmaintained remissions. 78 84

Seventeen patients with recurrent or refractory non-Hodgkin's lymphoma were treated with EMVP (Etoposide 75 mg/m2 i.v. d 1-5, Methotrexate 100mg/m2 i.v. d 1, Vindesine 3 mg/body i.v. d 1, Prednisolone 60 mg/m2 p.o. d 1-5), repeating every 3 weeks. Six complete responses (35%) and five partial responses (30%) were obtained with an overall response rate of 65%. The median duration of response was 26 months (range 8-49+months) for complete response (CR) and 4 months (range 2-6 months) for partial response (PR). The median duration of survival was 31 months for CR, 11 months for PR and 10 months for all patients, respectively. The major toxic effect was myelosuppression. Leukopenia less than 1,000/mm3 and thrombocytopenia less than 25,000/mm3 occurred in 5 and 3 patients, respectively. The other toxicities were alopecia, nausea and mucositis. However, these toxicities were well tolerated and clinically manageable. These results suggested that EMVP therapy was an effective regimen for patients with recurrent or refractory lymphoma.
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PMID:[Salvage therapy for recurrent or refractory non-Hodgkin's lymphoma with etoposide, methotrexate, vindesine and prednisolone (EMVP)]. 146 45

Tolerability and efficacy of high-dose methotrexate was studied in 70 pediatric patients with lymphoblastic tumors (acute lymphoblastic leukemia and non-Hodgkin's lymphoma). Methotrexate was given by 24-hour infusion of 500-1000 mg/m2 (total dose-700-3000 mg) after remission had been achieved. An antidote--calcium folinate--was administered 24 hours postinfusion. Major adverse side-effects involved were stomatitis, hepatotoxicity and fever. Survival in the study group was higher than in controls.
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PMID:[High methotrexate doses in the treatment program for acute lymphoblastic leukemia and lymphosarcoma in children]. 225 13

Methotrexate (MTX) is frequently used as an antifolics agent in many malignant neoplasms such as leukemia, lymphoma and osteosarcoma. The major side effects of MTX are liver and renal damages, bone marrow suppression and so on. But careful management and citrovorum factor rescue could decrease the incidence and degree of these side effects. In this report, we described a patient with non-Hodgkin's lymphoma who developed and died of fulminant hepatic failure soon after the administration of intermediate dose MTX. Serological tests for HB virus were not changed throughout, and lymphocyte stimulation test for MTX was strongly positive. His autopsy revealed no inflammatory cell infiltration into the liver, but marked biliary congestion which is a distinctive feature of drug induced hepatitis. From above results, it was suggested that nature of this fulminant hepatic failure was an allergic reaction to MTX. There is no previous report which is concerning about MTX and fetal drug related hepatic failure.
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PMID:[Fulminant hepatic failure induced by intermediate dose methotrexate in a case of non-Hodgkin's lymphoma]. 228 73

Five children, ages 2.5 to 12 years (mean 6.2 years), with acute lymphoblastic leukemia or non-Hodgkin's lymphoma were given 22 courses of high-dose methotrexate (HD-MTX) therapy (6-8 g/m2/24 h). No serious clinical complications were encountered, but stomatitis occurred after three (14%) of the courses. First-phase elimination half-lives (t1/2(alpha)) of MTX and 7-hydroxy-methotrexate (7-OH-MTX) after 21 infusions were 2.7 +/- 0.4 h and 6.5 +/- 1.8 h (mean +/- SD). In one course (4.5%) there was delayed systemic MTX elimination, with first-phase elimination half-lives (t1/2(alpha] for MTX and 7-OH-MTX of 4.2 and 9.9 h, respectively, and second-phase elimination half-lives (t1/2(beta)) of 43 and 58 h. Significant decreases in white blood cell count, increases in serum creatinine, and increases in alanine aminotransferase and/or aspartate aminotransferase during the first 2-6 days were present in five (23%), three (14%), and six (27%) of the courses, respectively. The regimen was tolerated well by the children.
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PMID:High-dose methotrexate therapy (6-8 g/m2) in childhood malignancies: clinical tolerability and pharmacokinetics. 315 11

Twenty-three children with refractory or relapsed non-Hodgkin's lymphoma (NHL) received high-dose methotrexate (HD-MTX), and 9 received Ara-C by continuous intravenous infusion, as phase II studies. They all had previously received a protocol including vincristine, adriamycin, cyclophosphamide, IV push Ara-C, asparaginase, intrathecal MTX, and cranial irradiation, and had failed to respond or had relapsed. HD-MTX was given at the dose of 6 g/m2 or more with leucovorin rescue, Ara-C at the dose of 100 mg/m2/day by continuous infusion over 10 days. Among the 22 evaluable patients receiving HD-MTX, 10 responses (7 CR; 3 PR) were observed. Among the 9 patients receiving Ara-C, 4 responded (1 CR; 3 PR). Toxicity in those previously heavily treated patients was acceptable. These two drugs are now successfully included in childhood NHL treatment protocols.
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PMID:High-dose methotrexate and continuous infusion Ara-C in children's non-Hodgkin's lymphoma: phase II studies and their use in further protocols. 315 14

An autopsy case of disseminated necrotizing leukoencephalopathy in non-Hodgkin's lymphoma associated with high-dose methotrexate (HD-MTX) is reported. The patient was a 5-year-old girl, who was admitted to Hamamatsu University School of Medicine because of an abdominal mass in April, 1984. She was diagnosed as having diffuse lymphoma, medium cell type, according to the LSG classification of a biopsied specimen of the liver mass and great omental lymph nodes. Chemotherapy containing HD-MTX was given until the first bone marrow relapse occurred in September, 1985. Subsequently, the physical and CT findings were normal except for decrement of deep tendon reflex, though slight gait disturbance was apparent. In serial spectral EEG analysis, the alpha/s ratio showed slowing activity upon administration of HD-MTX, and it became irreversible. In June, 1986, second bone marrow relapse occurred, and the patient died in July, 1986. At necropsy, multifocal necroses and extensive spongiosis in the white matter of the parietal and occipital lobes were revealed in the bilateral hemispheres of the cerebrum and cerebellum. Irregular confluent demyelination and necroses were also present in the brain stem, especially the pons. Therefore, serial EEG analysis might be a means of achieving early detection of leukoencephalopathy in HD-MTX-treated patients.
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PMID:[Serial spectral EEG analysis in a patient with non-Hodgkin's lymphoma complicated by leukoencephalopathy induced by high-dose methotrexate]. 335 88


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