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)

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

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

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

Phase II-III trials of oral VP 16-213 (VP 16) were conducted in non-Hodgkin lymphoma (NHL) and small cell lung cancer (SCLC). Of 29 heavily pretreated patients (pts) with NHL treated VP 16 at a dose of 200 mg/d days 1-5 q 3w, there were 3 CRs and 6 PRs (CR + PR : 31%) lasting 16 (7-185) weeks. Of 19 pts with NHL in stages III-IV treated by a non-cross alternating regimen consisting of AVCP (ADM, VCR, CPM, PDN)/EMLP (VP 16, MTX, L-ASP PDN), there were 4 CRs (21%) and 14 PRs (74%) lasting a median duration of 4.5 months. A combination consisting of VCR. VP 16 and CPM (VEC) was administered to a total of 29 pts with SCLC. Nine out of 10 pts with LD and 10 out of 19 pts with ED were attained CR after 2 cycles of VEC and subsequent irradiation to primary tumor. A median survival time of CR (LD + ED) exceeded one year while that of PR was 7+ months. These results indicated that oral VP 16 has significant activity for NHL and SCLC and lack of cross resistance to conventional drugs used for NHL.
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PMID:[VP 16-213]. 387 41

High-dose methotrexate (HDMTX) with citrovorum factor (CF) was used to treat non-Hodgkin's lymphomas either as a single agent in those patients who had previously failed to respond to conventional chemotherapy or in previously untreated patients in combination with bleomycin, Adriamycin, cytoxan, and vincristine. Twenty-five patients who had been previously treated and were refractory to cytotoxic chemotherapy were treated with HDMTX ranging between 1 and 7.5 g/m2 as an iv infusion over 20 to 40 minutes. CF rescue was begun at 24 hours and was maintained orally every 6 hours at 10 mg/m2 for a total of 72 hours. In instances where the 24-hour serum level of MTX was in excess of 1 X 10(-7) M, the dose of CF was increased to 100 mg/m2 every 3 hours until the serum MTX level fell into the appropriate range. Of the 25 patients, 13 (52%) responded. Response duration was brief, lasting a median of 2 months. Three patients had prolonged control lasting 13, 16, and 21 months respectively. Five of the six patients with central nervous system (CNS) involvement have demonstrated marked clearing of spinal fluid abnormalities and reversion of brain scans toward normal. Fifty-four previously untreated patients with diffuse histiocytic or undifferentiated lymphoma have been treated with combination chemotherapy including MTX given at the level of 3 g/m2 on day 14 of a cycle. Bleomycin, Adriamycin, cyclophosphamide, and vincristine are given on Day 1 of the cycle. Dexamethasone 6 mg/m2 is given orally on Days 1 through 5. The cycle is repeated on Day 21, and patients are treated with 10 such cycles for a total of 30 weeks. Of our 42 patients who are evaluable for response and who have completed chemotherapy, 33 (78%) achieved a complete remission (CR). A total of seven patients have relapsed. Only one patient in the CR group has relapsed in the CNS after the cessation of chemotherapy.
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PMID:Methotrexate as a single agent and in combination chemotherapy for the treatment of non-Hodgkin's lymphoma of unfavorable histology. 617 18

Since 1979 in a cooperative study (COALL-80) 110 children with acute lymphoblastic leukemia (ALL) and 13 children with high grade malignant non Hodgkin's lymphoma (NHL) have been treated with a less aggressive modification of the Westberlin Study Program BFM 76/79. Asparaginase has been delayed from the initial 4 drugs regimen and interposed in between induction therapy and treatment of central nervous system (CNS). Induction therapy that way was well tolerated and realized mostly on an outpatient basis. The expected 2 1/2 years disease free survival rate for ALL is 86% and no worse than the results of the original BFM study. We were able to define by age (greater than 2, less than 7 years), initial blast count (less than 25000/mm3) and immunological typing (cALL Ag+) a great group of patients (52%) which has remained in continuous remission as a whole. For this group further reduction of therapy intensity is planned (omission of cyclophosphamide during CNS-phase and use of intermediate dose methotrexate (MTX-mHD) instead of CNS-irradiation).
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PMID:[Therapy of acute lymphoblastic leukemia in childhood. Multicenter prospective therapy study COALL-80]. 634 10

Nineteen patients with malignant lymphomas were treated with 52 courses of high dose methotrexate with leucovorin rescue (HDMTX-LCV): 17 non-Hodgkin's lymphoma (11 nodal primary, and 6 Waldeyer's ring), 1 Hodgkin's disease, and 1 Burkitt's lymphoma; 10 No prior chemotherapy, 9 prior chemotherapy; Median age 50 years (18-67); Sex M 13:F 6. MTX was given according to Frei III et al's regimen(1975). In brief, alkalinization of the urine was achieved by administration of NaHCO3 both by oral and by intravenous route. Hydration with at least 3 liters of fluid per day was maintained throughout each course. MTX was administered as a six-hour infusion at an initial dose of 0.5-1.0 g/m2 with gradual escalation to 3-5 g/m2. Thirty minutes before the infusion of MTX, 1.4 mg/m2 of vincristine (VCR) (maximum dose 2 mg) was given intravenously in each course. MTX levels were not monitored. The overall response rate was 63% with 7 partial responses and 5 complete responses. Five of 10 previously untreated patients and 7 of 9 patients with prior chemotherapy achieved an objective response. Our excellent result may be contributed in part by VCR. Although, in general, during this study HDMTX-LCV was well-tolerated, a 67 year-old male had severe and unpredictable toxicity which resulted in shock condition, leukopenia and thrombocytopenia. Accordingly, we feel that HDMTX-LCV is dangerous without monitoring plasma MTX level. In other side effects, peripheral neuropathy and constipation possibly due to VCR occurred especially in elderly patients.
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PMID:[High dose methotrexate with leucovorin rescue in the treatment of malignant lymphoma]. 698 94

To evaluate the incidence of second malignant tumors in a cohort of subjects previously treated for childhood cancer, we analyzed data from the Off-Therapy Registry (OTR) of the Italian Association of Pediatric Hematology/Oncology, which collects information on children treated for Hodgkin's disease, non-Hodgkin's lymphoma, Wilms' tumor, acute lymphoblastic leukemia (ALL) and acute non-lymphatic leukemia and who had been removed from treatment in the absence of clinical signs of disease, i.e. the off-therapy stage. Second malignant tumors (SMT), diagnosed before December 31, 1988, were identified through a special enquiry to the 36 institutions cooperating in the registry. Observed cases were compared to expected numbers estimated from age- and sex-specific incidence rates derived from the Cancer Registry of the Province of Varese. In a total of 3,310 study subjects, 27 SMTs have been registered. The Cumulative Risk (CR) of SMT was 2.9% 15 years after the end of treatment and the Standard Incidence Ratio (SIR) was 10.8. The ALL sub-cohort had the highest risk of SMT (SIR 13.6) and 9 cases of CNS tumor occurred in this group (SIR 58.9). All 9 had received prophylactic cranial radiotherapy (CRT) and 5 had been treated on one protocol, characterized by low-dose intrathecal methotrexate (IT MTX) given monthly for 2 years after CRT. The Off-Therapy Registry has unique criteria for inclusion; direct comparisons with similar studies are therefore somewhat problematic. However, our data suggest that the risk of SMT in childhood ALL cancer survivors may be greater than previously reported, and that CNS tumors are the most common SMT in this group. The administration schedule of IT MTX may be an important risk factor.
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PMID:Second malignant tumors after elective end of therapy for a first cancer in childhood: a multicenter study in Italy. 796 Feb 10

The influence of the intrathecal methotrexate (IT MTX) prophylaxis on frequency and intensity of lymphomatous infiltrates within the leptomeninges and spinal roots in adults with non-Hodgkin's lymphomas (HGNHL) of high grade malignancy was evaluated. The effect of selected risk factors on the central nervous system (CNS) involvement by infiltrates was also analysed. Based on the results, indications for the prophylactic management were discussed. The post-mortem neuropathological investigations have been performed on 42 deceased patients having the NHL of high grade malignancy, treated and suffered in the Department of Haematology of the Pomeranian Medical Academy between 1980-1994. In all patients, neither apparent neurological complications nor changes in the cerebrospinal fluid during the disease were noted. Generally, lymphomatous infiltrates within the leptomeninges and spinal roots were observed in 64 per cent of cases. They were usually observed as variously sized foci: from single small to large, diffused in many regions. The study group of 21 patients subjected to IT MTX prophylaxis were compared with 21 patients without "CNS prophylaxis" (control group). Frequency and intensity of lymphomatous infiltrates decreased significantly after more than 3 IT MTX injections (Tab. 1) within spinal leptomeninges only (Tab. 2, 3). No benefits of this kind of treatment within cerebellar leptomeninges were noted. A poor penetration of the MTX (given by lumbar injection) into this region, could be a possible explanation of such result. It was disclosed that high white blood cells (WBC) count was the most important risk factor of the CNS involvement by lymphomatous infiltrates. Frequency of lymphomatous infiltrates diminished after IT MTX prophylaxis only in patients with WBC count less than 50 G/1 during the disease (Tab. 4). It was also found that lymphomatous infiltrates within the leptomeninges and spinal roots occurred in high percentage in both groups, and were independent of histological type of the HGNHL (Tab. 5) as well as of patients' age. From the neuropathological point of view, IT MTX prophylaxis seems to be ineffective in patients with the HGNHL, who did not reach a complete heamatological remission. A complete elimination of lymphomatous cells from the intracranial leptomeninges is particularly difficult to achieve. Considering the fact that it is hard to foresee response to polychemotherapy, especially at the beginning of the treatment, and--as present study shows--the lymphomatous infiltrates in the CNS are frequently found soon after the onset of the disease, "CNS prophylaxis" should be initiated simultaneously with the induction of remission. However, the continuation of the prophylaxis without haematological control of the disease seems to be aimless.
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PMID:[Neuropathologic evaluation of intrathecal prophylaxis results in adults with high grade non-Hodgkin's lymphomas]. 947 16


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