Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019829 (Hodgkin's disease)
 30,247 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A pregnant woman in the 17th week of gestation with Hodgkin's disease was treated with 50 mg Methotrexate i.v. on the 3 days preceeding therapeutic abortion. Cytogenetic studies on blood, brain, skin and lung of the fetus were performed. Slight structural aberrations such as gaps, chromatid breaks and accentric fragments were found in an average of 8,5% of the counted metaphases. The following drastic structural chromosome aberrations were found in 24,8% of all observed metaphases: 1) mitoses with stretched chromosomes, comparable with special segments (9,9%). 2) clumping of chromosomes in varying degrees (5,4%). 3) combinations of 1) and 2) (0,4%). 4) nuclear fragments (7,4%). 5) pulverized chromosomes (1,7%). Endoreduplications were found in 2%. The modal number was 46 with a rate of 50,1%, hypodiploids 46,3%, hyperdiploids and polyploids 3,6%. Karyotype: 46, XX.
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PMID:[Effects of Methotrexat on the chromosomes of a human fetus in vivo (author's transl)]. 121 66

We investigated the effect of high dose methotrexate (HDMTX) therapy on plasma hypoxanthine (Hx) and uridine (UR) concentrations in 12 children with acute lymphoblastic leukemia (ALL) or non-Hodgkin lymphoma (NHL). The initial plasma Hx level before the first administration of HDMTX (1 g/m2) was significantly higher in patients (25.5 +/- 17.5 microM) than that in healthy adult controls (4.0 +/- 1.4 microM). By 48 or 72 hours after the beginning of MTX infusion, the Hx concentration had decreased to 7.9 +/- 7.7 microM and 4.7 +/- 4.1 microM, respectively. This decrease of plasma Hx concentration after MTX infusion was also observed with the second course of HDMTX (3 g/m2) therapy. On the other hand, the plasma UR level did not change significantly. The in vitro treatment with 2 microM MTX of hypoxanthine-guanine phosphoribosyltransferase (HGPRT)-deficient mutant cells selected from HL-60 lowered the excretion of Hx into the culture medium. These data suggest a possible new explanation of the synergism of HDMTX and 6-thiopurines, for example 6-mercaptopurine and 6-thioguanine, since plasma Hx is considered to counteract 6-thiopurine toxicity through competition at the level of HGPRT.
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PMID:Effect of high-dose methotrexate on plasma hypoxanthine and uridine levels in patients with acute leukemia or non-Hodgkin lymphoma in childhood. 143 5

Between October 1985 and October 1989, 75 previously untreated patients with stage III and IV non Hodgkin's lymphoma, large cell type, were treated with an alternating weekly chemotherapy regimen including the following drugs: week 1: Doxorubicin, vincristine, cyclophosphamide, bleomycin, and intrathecal (i.th.) methotrexate and cytarabine; week 2: Methotrexate with leucovorin rescue; week 3: Doxorubicin, ifosfamide with mesna, etoposide, and i.th. methotrexate and cytarabine; week 4: Methotrexate with leucovorin rescue. Complete responders after three cycles according to this schedule (12 weeks) were given 18 gys cranial irradiation and randomized between one additional cycle or three monthly CHOP (consolidation treatment). Among 66 evaluable patients, 53 achieved a complete remission (CR 80 per cent) and seven a partial remission (11 per cent). There were six failures, and nine early deaths during the initial phase, mostly due to septic problems. Forty-one of the 53 CR patients (77.3 per cent) have remained free of disease with a median follow-up of 15 months (1-49). Eight of the 12 relapses occurred during the first year, the four others at 13, 14, 16 and 38 months respectively. The 2-year survival was 63 per cent for the whole group, and 77 per cent for the CR group. No difference has been observed up until now between the two groups with different consolidation treatment. Therefore, this protocol seems to be able to produce a high rate of complete and durable remission. The analysis of prognostic factors suggests that some high-risk patients should be considered for intensification therapy with the support of autologous bone marrow transplantation.
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PMID:Multicentre combined chemotherapy protocol for large cell advanced non Hodgkin's lymphoma. 172 Jul 59

Methotrexate (MTX) is now widely used for the treatment of acute leukemia and non-Hodgkin lymphoma in the pediatric oncology field and is thought to be one of the key drugs for this treatment. A regimen utilizing high dose MTX (HD-MTX) with leucovorin rescue is being investigated as effective chemotherapy in the patients with these kinds of cancer. Relatively large amounts of MTX (225 mg/m2) are given to such outpatients by intravenous push as a course of maintenance therapy. It is said that those amounts will infuse safely. However, we experienced two serious cases-patients T.H. and M.Y.--which developed into severe side effects after this treatment. Both patients showed acute renal failure, severe myelosuppression, erosion around the oral and anal region, and continuous diarrhea. Judging from the serum concentration of MTX, patient T. H. was exposed to more than the maximum allowance serum MTX level for 9.6 days, patient M. Y. for 6.5 days. This suggests physicians must pay attention to the clinical symptoms even after treatment using MTX without HD-MTX.
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PMID:[Clinical evaluation of severe toxicity in two patients with acute lymphoblastic leukemia receiving outpatient methotrexate therapy]. 175 61

A retrospective analysis of 22 patients with central nervous system (CNS) non-Hodgkin's lymphomas seen from 1978 to 1989 at Hamamatsu University Hospital was carried out. These were corresponding to 16% (22/137) of non-Hodgkin's lymphomas treated by irradiation during the same period. Six patients had primary intracranial involvement, six had secondary one, five had leptomeningeal involvement and five had spinal cord compression. Median survival of these groups 29 months, 7 months, 6 months and 4 months, respectively. On the case primary intracranial involvement, neurological signs and symptoms and performance status (PS) were improved in most patients. Whole brain irradiation with a dose of 45 Gy to 50 Gy followed by systemic chemotherapy was considered as effective treatment modalities. On the other hands, for the secondary intracranial lymphomas, clinical symptoms and PS were excellently improved by radiation therapy, however these were not reflected to survival. The conditions having primary site on gastrointestinal tract and relapse as systemic dissemination were considerable risk factors for the control of CNS involvement. For these patients, prophylactic chemotherapy should be necessary. Improvement of PS on patients with leptomeningeal lymphomas was obtained in only 3 of 5 cases. These were treated by irradiation on whole spine or neuroaxis and intrathecal MTX injection. We observed 2 cases dying from cerebrovascular accident and one case from leukoencephalopathy. This showed that such combination therapy should be carefully attempted. Five patients having spinal cord compression suffered from paraplegia and none of them had been improved on their symptoms.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Radiation therapy of CNS lymphoma]. 227 18

Procarbazine hydrochloride (PCZ), a chemotherapeutic agent used extensively to treat Hodgkins disease and other tumors, induces leukemia, lymphoma, mammary gland and other solid tumors in rodents and non-human primates and is strongly implicated as a leukemogen in humans. Lipotrope (choline and methionine) deficiency is a powerful potentiator of chemical carcinogenesis in liver and, under some conditions, in other tissues in rodents. Methotrexate (MTX), another commonly used chemotherapeutic agent, interferes with one-carbon metabolism and limits availability of lipotropes. Studies of PCZ carcinogenesis in lipotrope-deficient or MTX-treated male rats are reported, showing that both deficiency and MTX increased PCZ carcinogenicity in the mammary gland. In addition, PCZ was found to induce abnormalities of hepatic choline metabolism. Weanling male Sprague-Dawley rats were fed control (C) or lipotrope-deficient (D) diet. After 3 weeks, C and D rats were given PCZ, MTX, the two drugs together or 0.9% saline by i.p. injection. Doses were 0.2 or 0.5 mg MTX/kg or 25 mg PCZ/kg, given 2 or 3 days per week for 5 or 14 weeks. After 5 weeks of drug treatment livers were assayed for choline, phosphatidylcholine, phosphocholine (PCho), glycerophosphocholine and betaine. PCZ perturbed choline metabolism, increasing hepatic choline and PCho in deficient or MTX-treated rats and, to a smaller extent, in rats fed control diet. MTX markedly enhanced the effect of PCZ on choline metabolism. PCZ-induced mammary tumor incidence was increased 50-70% by lipotrope deficiency or by MTX. In PCZ-treated rats, cumulative probability of bearing a mammary tumor was significantly increased by lipotrope deficiency (P = 0.05), and was increased similarly but not significantly by MTX (P = 0.1). Cumulative tumor numbers per group in PCZ-treated rats were significantly greater in both deficient and MTX-treated rats compared to rats fed control diet (P less than 0.005). Incidences of leukemia, lymphoma and Zymbal's gland tumors induced by PCZ were not significantly altered by diet or MTX.
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PMID:Procarbazine carcinogenicity in methotrexate-treated or lipotrope-deficient male rats. 240 Oct 40

From September 1983 to October 1988, 13 undifferentiated non-Hodgkin's lymphomas (NHL) of Burkitt's or non-Burkitt's type and 3 B cell acute lymphoblastic leukemias were treated with various multiagent chemotherapy regimens containing modest to high dose methotrexate (HDMTX) infusions. All were children between the ages 2 years 8 months and 14 years 1 month. The group included 13 boys and 3 girls. The lymphomas were located primarily in the head and neck, 5; abdomen, 7; and lymph nodes, 1. The clinical stages at diagnosis were stage I, 1; stage II, 6; stage III, 3; and stage IV, 3. The MTX infusion dosage ranged from 300 to 4,285 mg/M2, and the total cumulative dose per patient ranged from 750 to 30,168 mg/M2. Citrovorum Factor Rescue was given following all MTX infusions, except for 62 of the 300 mg/M2 infusions. The serum MTX levels were monitored following all HDMTX. The chemotherapy related toxicities were graded and analysed. The clinical characteristics, which might predispose to HDMTX-related toxicities, were identified and are discussed. Our data reveals the inpatient and interpatient variations in the kinetics of MTX. There were no drug-related deaths, and the overall outcome of the patients was satisfactory. We conclude that MTX infusion continues to play an important role in the current management of childhood B cell malignancies; however, obstacles still remain, especially for those with widespread B cell disease.
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PMID:Evaluation of methotrexate containing chemotherapeutic regimens in the treatment of childhood undifferentiated non-Hodgkin's lymphoma and B cell acute lymphoblastic leukemia. 269 90

Mitoxantrone is similar to Adriblastin in its mechanism of action and antitumor activity. Objective remissions were obtained in 20-30% pretreated patients and in 23-44% of untreated patients by single-drug treatment of patients suffering from metastatic breast cancer. The objective response rates to Mitoxantrone in combination with CTX, 5-FU, MTX, VCR, MMC. Prednimustine or Vindesine were 16-46% in treatment and 38-89% in primary treatment. Randomized studies comparing Mitoxantrone with Adriblastin in single-drug and combination treatment did not show any significant differences in efficacy. However, Mitoxantrone was significantly less toxic. Remission rates of between 24 and 54% were achieved by single-drug treatment in pretreated patients suffering from non-Hodgkin lymphoma. Mitoxantrone appears to be active in ovarian cancer, lung cancer and hepatocellular carcinoma.
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PMID:Mitoxantrone: mechanism of action, antitumor activity, pharmacokinetics, efficacy in the treatment of solid tumors and lymphomas, and toxicity. 332 53

Diffuse non-Hodgkin lymphoma of B-cell origin has been established as a serially transplantable xenograft line in artificially immunesuppressed mice. The take rate and growth rate increased with repeated passages compared to the first transplant generation. However the xenografted tumor preserved many of its characteristics, including morphology, cell surface markers and DNA index. Chromosome analysis proved the human origin of tumors grown in mice and revealed translocation 8,14. Cyclophosphamide, Methotrexate and Vincristine produced substantial inhibition of tumor growth, while Dianhydrogalactitol and Adriamycin were less effective. Human alpha interferon also produced a delay in tumor growth.
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PMID:Transplantable human non-Hodgkin lymphoma line in artificially immunesuppressed mice. 359 31

Four men and four women, aged 16 to 43, developed dural sinus thrombosis, five patients with acute lymphoblastic leukemia (L.A.L.) and three with non Hodgkin malignant lymphoma (N.H.M.L.). All the cases of L.A.L. were F.A.B.-2 subtype without any unusual hematological features. In 6 cases, the disorders occurred during the phase of therapeutical induction (E.O.R.T.C.-A.L.L.-H.R. protocol) at D5, D10, D15, D26, D30, D38, and in 2 cases during maintenance after a period of remission. All patients had received Vincristine and Prednisone, intrathecal Methotrexate in 5 cases, encephalic irradiation in 3 cases and L-Asparaginase in one case. Three women were taking contraceptive drugs. The neurological symptoms and signs were headache due to intracranial hypertension in 6 cases, Grand Mal seizures in 5 cases, focal seizures in 2 cases, a regressive hemiparesis in 4 cases, stupor in 3 cases. CT scan was abnormal in 4 cases, displaying oedema in 3 cases and an hemorrhagic infarction in 1 case. Angiography showed in all cases occlusion of the superior sagittal sinus in 7 cases and of the transverse sinus on 1 case. Six patients received anticoagulant therapy. Outcome was fatal in 3 cases: in 2 cases of L.A.L., the condition worsened rapidly after the onset and death was related to a tentorial herniation; in 1 case of N.H.M.L. death resulted from an intercurrent infection.
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PMID:[Dural venous sinus occlusions in hemopathies]. 385 30


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