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)

Methotrexate with leucovorin rescue (HDMTX-LV rescue), has been used to treat solid tumors and non-Hodgkin's lymphomas (NHL). We studied the use of HDMTX-LV rescue in patients with widespread NHL with histologic diagnosis of diffuse poorly differentiated lymphocytic and diffuse histiocytic including involvement of the central nervous system (CNS) and/or bone marrow. The prognosis with conventional chemotherapy is extremely poor. Three patients have bone marrow involvement, 2 patients CNS, and 2 both. These patients were unresponsive to conventional chemotherapy and had a rapid progression of their disease. Therapy with HDMTX-LV rescue induced responses in 5 patients: 2 patients achieved a complete remission and three a partial remission. Regression of CNS involvement was observed in 3 patients; bone marrow toxicity was not observed. Only 1 patient failed to respond. These data suggest that HDMTX-LV rescue may be useful as primary therapy in lymphoma patients with CNS and/or bone marrow involvement.
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PMID:High-dose methotrexate-leucovorin rescue therapy: selected application in non-Hodgkin's lymphoma. 387 36

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

Diffuse histiocytic lymphomas (Rappaport) are extranodal lesions frequently formed in the digestive tract. They are clinically different from lymphomas of nodal origin and are no longer considered to arise from histiocytes. They comprise from one-third to one-half of non Hodgkin's lymphomas and chiefly involve the stomach and duodenum. Identification of these tumors and their place in current systems of classification, at present, depends on sophisticated immunologic, histochemical and ultramicroscopic procedures not always suitable for clinical prognosis. Staging laparotomy, useful in Hodgkin's disease, does not always correlate with the prognosis of non Hodgkin's lesions. Radical removal of the affected organ may be curative. Nonresectable lesions may be treated with radiation and chemotherapy. Methotrexate, cyclophosphamide, vincristine, prednisone, nitrogen mustard, Adriamycin, bleomycin and other substances have been used in various combinations to obtain remission of the disease. While results have been favorable, the ideal therapeutic agent has not been found.
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PMID:Diffuse histiocytic lymphomas of the gastrointestinal tract in the adult. 635 9

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

Modern combination chemotherapy cures about one third of patients with non-Hodgkin's lymphomas (NHL) [3]. Attempts to increase this proportion by more intensive chemotherapeutic regimens have failed so far in randomized trials [4, 5]. Dose intensity has been reported to be important for cure [8]--a factor which can be enhanced by hematopoietic growth factors--but addition of recombinant human granulocyte colony-stimulating factor (rhG-CSF) to intensive chemotherapy did not improve response on survival in a controlled study published recently [10]. Therefore, we tried to design a regimen which might be more appropriate for combination with growth factors, using pulse chemotherapy rather than continuous treatment and employing drugs of low stem-cell toxicity. Ifosfamide (Ifo) appeared to be ideal because it is effective even in some resistant cases [1] and might act synergistically with anthracyclines by reducing intracellular glutathione levels [9]. Epirubicin (Epi) was favored because of its low hemato- and cardiotoxicity [2]. These drugs, together with etoposide (VP-16) had been found to be very effective in relapsed cases [7]. Methotrexate (Mtx) was added because it penetrates the spinal fluid. Moreover, we chose granulocyte/macrophage colony-stimulating factor (rhGM-CSF) as an adjunct cytokine because this not only enhances neutrophil regeneration [6] but might also have antitumor effects, as suggested by an uncontrolled study in sarcomas [11]. This report summarizes our experiences regarding feasibility, toxicity, and responses with this new regimen obtained in a pilot study.
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PMID:IEVM chemotherapy with rhGM-CSF support for aggressive non-Hodgkin's lymphomas: a pilot study. 847 59

In cancer chemotherapy, routine monitoring of drug concentrations has been practical only for methotrexate (MTX). The primary setting for pharmacokinetic monitoring of MTX is its use in high doses (HDMTX) for adjuvant therapy of osteosarcoma, for single-agent treatment of intracranial lymphomas, and in combination therapy of childhood leukemia as well as adult and pediatric non-Hodgkin lymphomas. Typically, HDMTX is infused in doses of 3-15 g/m2 over a period of 6-24 h. Precautions must be taken to ensure a high urine flow and an alkaline urine pH, so as to prevent precipitation of MTX in urine. Patients with decreased renal function, advanced in age, and taking nonsteroidal anti-inflammatory drugs or nephrotoxic agents are at increased risk of developing renal dysfunction during MTX infusion, thus being placed at high risk for toxicity. At the end of HDMTX infusion, and periodically thereafter for 24-48 h, drug concentrations are measured to assure that the disappearance rate of MTX from plasma is occurring at a normal rate. Also, at the end of HDMTX infusion, the patient is given leucovorin (5-formyl-tetrahydrofolic acid; LV), which replenishes intracellular stores of reduced folate and attenuates the toxicity secondary to HDMTX. In the presence of inappropriately high concentrations of MTX, routine doses of LV will be ineffective; the dose of LV required must be increased in proportion to the MTX concentration it faces in plasma. In practice, routine monitoring of plasma MTX concentrations allows early detection of abnormal clearance, as well as institution of early and effective countermeasures, including the use of increased and prolonged LV rescue.
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PMID:Concepts in use of high-dose methotrexate therapy. 869 6

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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