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 have previously demonstrated a dose response relationship in Hodgkin's disease for the combination of BCNU, VP16, Ara C and Melphalan, with the superior efficacy of the BEAM regimen requiring haemopoietic support, compared with miniBEAM. To further exploit this, we have attempted to escalate the VP16 dose in BEAM. The standard etoposide dose is 200 mg/m2 IV for four days. Thirty seven patients with refractory lymphoma received 400 mg/m2/day of etoposide, and 13 patients 600 mg/m2/day, in addition to BCNU, cytarabine, and melphalan. Toxicity and outcome parameters were compared in the preceding 40 patients, who received 200 mg/m2/day etoposide. The toxic mortality with 400 mg/m2/day of etoposide (3%) was identical to that for the standard BEAM regimen (5%). Two procedure related deaths occurred in the highest VP16 dose group (15%). The morbidity of the lower etoposide dose regimens was comparable, but 600 mg/m2/day induced significantly greater gastrointestinal toxicity. Twelve of the 13 patients receiving this dose suffered grade II-IV mucositis, with stomatitis, dysphagia and prolonged diarrhoea; 5 haemodynamically significant gastrointestinal haemorrhage, and 1 fatal toxic colitis. Granulocyte colony stimulating factor did not influence the nonhaematological toxicity. The three month response rates were similar (91%) in all dose cohorts. The maximum tolerable etoposide dose within the BEAM regimen is thus 400 mg/m2 for four days.
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PMID:Dose intensification of etoposide in the BEAM ABMT protocol for malignant lymphoma. 858 Jul 95

High-dose chemotherapy with autologous bone marrow transplantation is used in the treatment of relapsed or high-risk Hodgkin's disease. As prospective randomised studies have proved difficult to accrue to, current recommendations are based on the reports of large series of prospectively collected data. We have looked at the outcome of 89 patients treated in this way at a single institution and have developed an index to predict outcome. Of 89 patients, with a median age of 29 years (range 15-51 years), eight patients were in first complete remission/partial remission (CR/PR), 17 in second or later CR, 37 were responding relapses, 13 resistant relapses, 11 primary refractory and three untested relapses. Combinations of melphalan, BCNU and etoposide were given in all cases except in ten patients who received melphalan alone. The median follow-up was 43 months (range 6-77 months). A total of 24 patients were in CR at the time of autologous bone marrow transplantation (ABMT), 33 achieved CR with ABMT, 16 PR, to give a response rate to ABMT of 49/65 = 74% (95% CI 60-83%) with a CR rate of 51% (CI 36-62%). In a Cox's multivariate analysis the most important factors in predicting outcome after ABMT were response to treatment before entry, number of previous treatments and previous chemosensitivity. Using these factors we devised a prognostic index which reliably selects a group of patients (65%) with at least a 70% chance of being progression free from 1 year onwards. Patients who have never achieved a CR and have received three or more chemotherapy regimens do not benefit from high-dose chemotherapy as used in this study.
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PMID:High-dose chemotherapy and autologous bone marrow transplant in relapsed Hodgkin's disease--a pragmatic prognostic index. 863 Feb 92

The present paper is an attempt to assess the efficiency of high-dose cytotoxic therapy followed by autologous bone marrow or peripheral progenitor cell rescue with hematopoietic growth factor support given in a group of 27 patients (16 men, 11 women) at the Department of Hematology of the Mont Godinne University Clinics, mainly in the same interval 1990-1994. The reasons for introducing such a therapy in these patients (6 with Hodgkin's disease, 14 with intermediate or high grade, aggressive non Hodgkin lymphomas and 7 with low grade follicular non Hodgkin lymphomas) were relapse of disease after conventional therapy (11 cases), resistance to initial therapy (5 patients) or because of histologically proven transformation to a more aggressive form (one case); in 10 patients with extended, poor prognosis forms, the procedure was used as part of the first line therapy. The conditioning high dose chemotherapy was given according to various regimens, most of them containing Cyclophosphamide, BCNU and Etoposide, with or without total body irradiation. In 14 patients, bone marrow (BM) graft was used, while peripheral blood progenitor cells (PBPC) were infused in the remaining 13 patients. The number of infused granulocyte-macrophage colony forming units (CFU-GM) ranged between 7,650 and 3,900,000/kg, with a mean value of 461,000/kg. The median time intervals required to reach an absolute neutrophil count > 500/microliter, a platelet count > 50,000/microliter and a hematocrit > 30% were 13 days, 20 days and 23 days respectively. Growth factors (GM-CSF and G-CSF) and PBPC use shortened the time for neutrophil recovery as well as neutropenia-related complications. No procedure-related death was observed and complete remission was achieved in 22 cases (81.4%); after a mean follow-up of 32.6 months, 14 patients (55.5%) are alive and free of disease, while in 7 patients (31% of the complete responders) relapse occurred at an average time interval of 8.2 months since the procedure.
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PMID:High-dose cytotoxic therapy with autologous bone marrow or peripheral blood progenitor cell transplantation in malignant lymphomas. 864 94

Over an 8-year period we autografted 123 patient with poor-risk lymphoma. Sixty-three patients had Hodgkin's disease (HD) and 60 non-Hodgkin's lymphoma (NHL). Of the patients with HD, 45 had responsive and 18 resistant disease prior to high-dose therapy. Fifty-three patients with NHL had responsive and seven had resistant disease at the time of transplantation. Seventy-seven patients received autologous bone marrow (BM) rescue, 39 autologous peripheral blood progenitor cell (PBPC) rescue, and seven combined BM and PBPC rescue. High-dose chemotherapy was BEM in 67, BEAM in 39, TBI and cyclophosphamide or etoposide or BCNU in 10, etoposide/mitozantrone in six and etoposide/melphalan in one. There was eight (6.5%) deaths due to treatment-related toxicity, within the first 100 days post-transplantation. Of the patients with HD 41 (65%) are alive at a median follow-up of 39 months (range 2-94). Thirty-three (52%) patients remain in CR. The median DFS of the 63 patients with HD is 34 months (95% CI 7-61). The median DFS for patients transplanted with responsive disease was significantly better than for those transplanted with refractory disease (61 vs 21 months P < 0001). Thirty-five (58%) of the patients with NHL are alive, and 20 (33%) remain in CR. The median DFS for patients transplanted with responsive and refractory disease was 11 months (95% CI 3-19) and 4 months (95% CI 0-9; P = NS) respectively. The median DFS for patients transplanted with HD was significantly better than for patients transplanted with NHL (34 vs 8 months, P < 0.002). In both groups there was no significant difference in DFS in patients receiving one, two, three or more lines of therapy prior to transplantation. In summary, in patients with poor-risk lymphoma who have responsive disease high-dose therapy may result in durable CRs. Conversely, only a small proportion of patients with HD or NHL with resistant disease achieve CR after autologous stem cell rescue.
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PMID:High-dose therapy and autologous stem cell rescue for poor risk and refractory lymphoma: a single centre experience of 123 patients. 880 2

Eight consecutive patients with relapsed/refractory non-Hodgkin's lymphoma or Hodgkin's disease received conditioning therapy with BCNU, etoposide, cytosine arabinoside and melphalan (BEAM) followed by autologous blood stem cell transplantation (ABSCT). Cyclosporine was administered from day +1 until day +28 post-ABSCT to induce autologous graft-versus-host disease (GVHD) for a possible antitumor effect. Three patients developed histologically documented grade II GVHD between 22-40 days post-transplant. GVHD resolved with local hydrocortisone 1% application in one patient and after a short course of steroid in the remaining two patients. Further studies are required to document any beneficial antitumor effect of such therapy following ABSCT.
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PMID:Cyclosporine-induced autologous graft-versus-host disease following autologous blood stem cell transplantation for lymphoma. 880 18

Primary nasal T or NK cell lymphoma is rarely seen in the Western population but is more common in the Orientals. Although it often presents with localized disease, the prognosis is generally poor. Long-term remission is seen in only 50% of patients with stage I disease despite aggressive treatment with chemotherapy and radiotherapy, and is invariably fatal if disseminated. Conventional chemotherapy for relapsed disease is usually not successful. Since 1992, three patients with relapsed primary nasal T/NK cell lymphoma have received high-dose chemotherapy with autologous bone marrow rescue at Queen Mary Hospital, Hong Kong. High-dose cyclophosphamide, BCNU and etoposide were used for conditioning. Two of them had a favourable response and remained in complete remission at 12 and 44 months post-transplant. The third patient unfortunately had a systemic relapse 6 months after the transplant. It appears from this experience that, like other aggressive non-Hodgkin's lymphomas, high-dose chemotherapy and autologous bone marrow rescue is an effective treatment for relapsed primary nasal lymphoma following failure of conventional chemotherapy and radiotherapy.
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PMID:Autologous bone marrow transplantation for primary nasal T/NK cell lymphoma. 901 39

One hundred nineteen patients with relapsed or refractory Hodgkin's disease (HD) received high-dose therapy followed by autologous hematopoietic progenitor cell transplantation. Three preparatory regimens, selected on the basis of prior therapy and pulmonary status, were employed. Twenty-six patients without a history of prior chest or pelvic irradiation were treated with fractionated total body irradiation, etoposide (VP) 60 mg/kg and cyclophosphamide (Cy) 100 mg/kg. Seventy-four patients received BCNU 15 mg/kg with identical doses of VP and Cy. A group of 19 patients with a limited diffusing capacity or history of pneumonitis received a novel high-dose regimen consisting of CCNU 15 mg/kg, VP 60 mg/kg and Cy 100 mg/kg. Twenty-nine patients (24%) had failed induction therapy and 35 (29%) had progressive HD within 1 year of initial chemotherapy. At 4 years actuarial survival was 52%, event-free survival was 48% and freedom from progression (FFP) was 62%. No significant differences were seen in survival data with the three preparatory regimens. Six patients died within 100 days of transplantation and 5 died at a later date of transplant-related complications. Secondary malignancies have developed in 6 patients, including myelodysplasia/leukemia in four patients and solid tumors in two patients. Regression analysis identified systemic symptoms at relapse, disseminated pulmonary or bone marrow disease at relapse and more than minimal disease at the time of transplantation as significant prognostic factors for overall and event-free survival and FFP. Patients with none of these factors enjoyed an 85% FFP at 4 years compared with 41% for patients with one or more unfavorable prognostic factors (P = .0001). Our results confirm the efficacy of high-dose therapy and autografting in recurrent or refractory HD. Although longer follow-up is necessary to address ultimate cure rates and toxicity, our data indicate that a desire to reduce late effects should drive future research efforts in favorable patients whereas new initiatives are needed for those with less favorable prognoses.
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PMID:High-dose therapy and autologous hematopoietic progenitor cell transplantation for recurrent or refractory Hodgkin's disease: analysis of the Stanford University results and prognostic indices. 902 11

High-dose chemotherapy followed by autologous peripheral blood progenitor cell transplantation (PBPCT) is increasingly applied in patients with relapsed, poor risk malignant lymphomas. Different strategies for progenitor cell mobilization using cytoreductive chemotherapy, hematopoietic growth factors, or both have been described. We studied the safety and efficacy of a modified DexaBEAM regimen (dexamethasone, BCNU [carmustine], etoposide, ara-C, melphalan) followed by granulocyte-colony stimulating factor (G-CSF) that was administered in order to minimize any residual disease and to obtain a sufficient amount of progenitor cells in the autografts. Until now, 16 patients at poor risk (8 with Hodgkin's disease, 8 with non-Hodgkin's lymphoma) entered the study. All the 12 patients with measurable disease at study entry responded to DexaBEAM. Median time of subsequent leukopenia (leukocytes < 1.000/microL) was 6 days (range 5-8 days). Peak numbers of CD34+ hematopoietic progenitor cells appeared in the peripheral blood after a median of 20 days (range 18-22 days) after onset of therapy. At that time, peripheral mononuclear cells were collected for autografting. Thereafter, the leukapheresis products were frozen until the day of transplantation, either unpurged in the case of Hodgkin's disease or purged with the ether lipid edelfosine in cases of non-Hodgkin's lymphoma. After high-dose chemotherapy with the CBV regimen (cyclophosphamide, BCNU, etoposide) the patients received their autografts, followed again by G-CSF treatment. A stable hematopoietic recovery was reached with granulocytes > 2.000/muL within 11 days (range 8-17 days), and platelets > 50.000/microL within 15 days (range 10-31 days), respectively, without significant differences between the purged and unpurged transplants. After a median follow-up of 28 months (range 1-40 months) 7 patients are alive without signs of recurrent disease, while 1 patient has died due to acute treatment related toxicity. Three patients had refractory disease, and 5 have relapsed of whom 4 have died. In summary, the DexaBEAM/G-CSF/CBV strategy appears to be safe and effective for salvage treatment in patients with poor risk malignant lymphomas.
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PMID:Peripheral blood progenitor cell mobilization with Dexa-Beam/G-CSF, ether lipid purging, and autologous transplantation after high-dose CBV treatment: a safe and effective regimen in patients with poor risk malignant lymphomas. 903 Nov 11

The risk of idiopathic pneumonia syndrome (IPS) in patients with Hodgkin's disease (HD) undergoing high-dose chemotherapy (HDC) is significant, and once developed IPS is potentially fatal. The aim of this study was to quantify this risk accurately and determine prognostic factors for its development and course. Using a computerized database, all patients with HD treated with BCNU (carmustine) containing HDC and haematopoietic support at The Royal Marsden between November 1985 and March 1994 were identified. Patient characteristics, previous treatments, disease status at HDC, dose of BCNU, incidence and severity of IPS and survival were all determined and analysed. During the study period, 94 patients received HDC, of whom 26 (28%) had a first episode of IPS within a year of HDC and 23 within 6 months. The median time to presentation after HDC was 93 days (range 12-336 days). The only factors that significantly increased the risk of developing IPS on multivariate analysis were dose of BCNU (P for trend = 0.03) and female sex (P = 0.04). Of these 26 patients, 14 had complete resolution of all symptoms, three had persisting pulmonary symptoms at 6 months and the remaining nine died of IPS at a median of 74 days (19-418 days). All the patients who died from IPS had the first symptoms within 6 months of HDC and all received doses of BCNU > 475 mg m(-2) (P for trend = 0.001). For women receiving > 475 mg m(-2) the risk of death was significantly higher than for men (P = 0.035) but not for those receiving < 475 mg m(-2). Previous lung disease, persisting residual disease before HDC, previous bleomycin or previous mantle radiotherapy did not increase either the incidence of IPS or risk of a fatal outcome. We conclude that the main avoidable risk factor for fatal IPS after HDC is dose of BCNU, and this is especially true for women. If < 475 mg m(-2) is given, even patients with previous mantle radiotherapy and/or previous bleomycin have a very low risk of developing fatal lung toxicity if lung function tests are normal.
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PMID:Idiopathic pneumonia syndrome after high-dose chemotherapy for relapsed Hodgkin's disease. 908 41

In the present paper, we evaluate tolerability, outcome and prognostic factors in patients with poor prognosis non-Hodgkin's lymphoma (NHL) and Hodgkin's disease (HD) when uniformly treated with BCNU, etoposide, cytarabine and melphalan (BEAM) and autologous stem cell transplant (ASCT). On hundred and forty-eight patients with NHL (n = 112) or HD (n = 36) received BEAM followed by infusion of bone marrow (n = 55), peripheral blood stem cells (n = 79) or both (n = 14). Twenty-eight patients had low-grade lymphoma (LGL), 68 intermediate- and 16 high-grade lymphoma (IGL). Within the NHL group, 21 patients were in 2nd or subsequent complete remission (CR) at transplant, 34 had sensitive disease and 11 resistant disease; 46 patients were transplanted in 1st CR due to the presence of > or = 2 adverse prognostic features at diagnosis or to a slow CR. Of the HD patients at transplant 17 had active disease, 16 were in > or = 2 CR and three in 1st CR. The overall percentage of toxic deaths was 5.4%, while in the group of patients transplanted with PBSC it was only 1.3%. NHL patients: 78% were in CR following ASCT, including 25 out of 45 patients (56%) who were transplanted with active disease. Only two of the 11 patients transplanted with resistant disease achieved CR. Incidence of overall survival (OS) and disease-free survival (DFS) at 3 years was 65 and 75%, respectively. As far as histology was concerned, OS was significantly better for patients with LGL in comparison with IGL (88 vs 56%) (P = 0.002). DFS was significantly higher for patients transplanted in first CR or first partial remission (PR) than it was for those transplanted in a later CR or PR (86 vs 53%) (P = 0.02). Multivariate analysis for OS showed that histology, bulky disease, poor performance status at transplant and achievement of CR were independent prognostic factors. In addition, a high number of infused MNC was associated with poor DFS. HD patients: 30 (83%) were in CR after transplantation, with 25 maintaining CR at the end of the study. Only one of the four patients transplanted with resistant disease reached CR. Incidence of OS and DFS at 3 years was 78 and 81%. DFS was similar for patients transplanted with early or late relapse (95 and 93%). With multivariate analysis, the only independent variable for OS was CR after transplant. In conclusion, the present results demonstrate the efficacy and low toxicity of the BEAM regimen in high-risk lymphoma patients with sensitive disease. Other strategies should be investigated for patients with refractory lymphoma.
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PMID:BEAM chemotherapy followed by autologous stem cell support in lymphoma patients: analysis of efficacy, toxicity and prognostic factors. 931 77


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