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)

In order to determine whether high-dose combination chemotherapy was active in chemotherapy resistant patients, 19 patients, (9 with small cell bronchogenic carcinoma, 6 with embryonal cell carcinoma, 2 with diffuse histiocytic lymphoma, 1 with Hodgkin's disease and 1 with chondrosarcoma), 18 of whom had had extensive prior chemotherapy and failed, received 23 courses of high-dose chemotherapy with autologous bone marrow infusion (ABMT). Three patients received four courses of cytoxan (2-6 g/m2) and VP-16 (500-600 mg/m2) and 16 patients received 19 courses of cytoxan and VP-16 in these doses plus BCNU (300 mg/m2). Activity was observed in 6 of 8 evaluable small cell bronchogenic carcinoma patients (1 complete response (CR), 4 partial responses (PR), 1 less than PR), in 6 embryonal cell carcinoma patients (3 CR, 2 PR, 1 less than PR), in both patients with diffuse histiocytic lymphoma (1 CR, 1 less than PR), in the patient with Hodgkin's disease (1 PR); and in the patient with chondrosarcoma (stable). Only 2 patients who had received prior cytoxan and VP-16 extensively showed resistance to these programs. The median response duration was 11 weeks (range = 4-55 + weeks). Major toxicity consisted of bacterial infections. Two patients died from treatment related causes. Neutrophils recovered to levels of greater than or equal to 1.5 x 10(9)/liter by days 20-42 (median, day 27) and platelets to levels of greater than 100 x 10(9)/liter by days 21-56 (median, day 32) without any delayed BCNU toxicity. High-dose combination chemotherapy with ABMT causes acceptable toxicity and high response rates of relatively short duration in tumors refractory to conventional chemotherapy.
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PMID:High-dose combination chemotherapy with autologous bone marrow transplantation in adult solid tumors. 699 70

In a randomized study, the effect of single agent therapy, with CCNU was compared with that of BCNU in previously treated patients with advanced Hodgkin's disease. The dosage of CCNU was 100 mg/m2 p.o. q. 6 weeks and of BCNU, 200 mg/m2, p. 6 weeks with dose modification adjusted to individual tolerance. For 60 evaluable patients the response rate (complete and partial was 60 for CCNU and 28% for BCNU (p = 0.025); median duration of response was 4.5 months and 2.0 months, respectively (P = 0.26). Median survival for responders was 11.0 months and for non-responders 5.0 months. No major difference was observed in hematologic toxicity between the two compounds. Used as single agents in equitoxic dosages, CCNU is superior to BCNU for the treatment of previously treated advanced Hodgkin's disease, and CCNU has the additional advantage of oral administration.
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PMID:The superiority of CCNU in the treatment of advanced Hodgkin's disease: Cancer and Leukemia Group B Study. 700 89

Between 1972 and 1981, the Eastern Cooperative Oncology Group completed two major studies of advanced Hodgkin's disease. The first trial EST 2472, demonstrated that the five-drug combination of carmustine (BCNU), cyclophosphamide, vinblastine, procarbazine, and prednisone (BCVPP) is an effective alternative to mechlorethamine, vincristine, prednisone, and procarbazine (MOPP) chemotherapy. Although the complete remission (CR) rate for BCVPP (77%) was similar to that for MOPP (73%) in this randomized trial, the choice of induction chemotherapy significantly influenced CR duration. Patients achieving CR with BCVPP had a significantly greater disease-free survival than those who achieved CR with MOPP (65% vs 50%, respectively, at 5 years, P = 0.02). Overall survival is not different at this time between patients who received BCVPP and those who received MOPP. BCVPP produced significantly less gastrointestinal toxicity and neurotoxicity than MOPP. There was no influence on CR duration or survival with maintenance chemotherapy or BCG immunotherapy when compared to no further treatment. In the second trial, EST 1476, there was only a 58% CR rate with six cycles of low-dose bleomycin-MOPP induction chemotherapy. Complete responders and continuing partial responders were then randomized to receive either non-cross-resistant chemotherapy with doxorubicin, bleomycin, vinblastine, and DTIC (dacarbazine) (ABVD) or low-dose radiotherapy to all sites of pretreatment involvement except bone marrow. Fifty percent of the partial responses were converted to CR with either ABVD or radiotherapy consolidation. The overall CR rate at the end of consolidation was 68%. At the present time, there is no significant difference in disease-free or overall survival between ABVD and radiotherapy.
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PMID:Treatment of advanced Hodgkin's disease: 10-year experience in the Eastern Cooperative Oncology group. 704 87

The Southeastern Cancer Study Group has explored a variety of approaches to the management of advanced Hodgkin's disease. These have largely involved the use of nitrosoureas, especially BCNU (carmustine), alone or in combination with other agents. Initial phase II trials of BCNU as a single agent in patients refractory to mechlorethamine demonstrated considerable antitumor activity. Exploratory experiments with BCNU in combination with alkylating agents, vinca alkaloids, and corticosteroids resulted in the development of the combination BVCPP (BCNU, vinblastine, cyclophosphamide, procarbazine, and prednisone). BVCPP, given only once monthly, produces at least a 65% complete response rate with minimal to moderate toxicity, making it an effective alternative to other regimens such as MOPP. Alternating BVCPP with a non-cross-resistant combination (doxorubicin, DTIc [dacarbazine], and bleomycin) offered no advantage in response rate or survival. Continued research with new agents and/or combined modality approaches is necessary in view of continued primary and secondary treatment failure with all regimens used for the management of advanced Hodgkin's disease.
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PMID:Chemotherapy for advanced Hodgkin's disease: conclusions from the Southeastern Cancer Study Group. 704 89

The purpose of this trial was to evaluate the efficacy and the tolerance of high-dose therapy with autologous stem cell transplantation as part of front-line therapy in Hodgkin's disease for patients with both adverse prognostic factors: high tumor burden at presentation and slow response to initial chemotherapy. In a prospective one-center study, 20 consecutive patients with slow response (tumor reduction < 75%) (16 pts) or refractory (4 pts) to 3-4 courses of conventional HD chemotherapy received high-dose therapy followed with autologous bone marrow (14 pts) or peripheral blood stem cell (6 pts) transplantation. They were 13 males, 7 females, median age 26 years (8-45). At the time of initial diagnosis, all but one of the patients had B symptoms, all had high-risk HD defined as Ann Arbor stage IV (7 pts) or large mediastinal involvement (LMI = tumor/thorax > 0.45 at T5-T6) (6 pts) or both stage IV+LMI (7 pts). Median time between diagnosis and autotransplantation was 5 months. Intensive therapy consisted of either CBV (cyclophosphamide 1.5 g/m2 x 4, BCNU 300 mg/m2, etoposide 200 mg/m2 x 3) (12 pts) or cyclophosphamide 120 mg/kg + 12 Gy total body irradiation for 8 patients with diffuse bone or lung involvement. For pts treated with CBV, 40 Gy involved field radio-therapy was performed after hematological recovery. Median duration of neutropenia was 16 days (9-21). Neither veno-occlusive disease, nor interstitial pneumonitis nor toxic death were observed. Seventeen pts are alive with no progression of the disease (16/16 in partial response after initial chemotherapy, 1/4 with refractory disease).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Early intensive therapy with autotransplantation for high-risk Hodgkin's disease. 751 54

Sixty-two patients with a variety of malignant diseases including 44 with breast cancer, seven with sarcomas, five with germ cell tumours, four with Hodgkin's disease and two with multiple myeloma received short duration, high dose chemotherapy, with non-cryporeserved peripheral blood progenitor cell rescue as treatment for malignancy. Limited, (one or two) peripheral blood precursor cell collections were performed following either cyclophosphamide, cyclophosphamide+GCSF or GCSF priming. Total nucleated cell and CD34+ cell yields were significantly higher with either of the two GCSF priming regimens as compared to cyclophosphamide only priming. Cell viability at the time or reinfusion was also enhanced by GCSF priming. Chemotherapy regimens included either high dose cyclophosphamide, mitoxantrone and VP16 (HD-CNV); high dose melphelan plus VP16; high dose BCNU, cyclophosphamide and VP16 (BCV); or high carboplatin, cyclophosphamide and VP16 (PCV) all given over 8-12 h. Non-cryopreserved blood progenitor cells, stored at 4 degrees C, were reinfused 24 h after completion of chemotherapy. Sixty-one of 62 patients showed hematologic recovery. Median time to hematologic recovery was significantly shorter for patients receiving GCSF primed cell collections. There was also significantly less hospitalization and antibiotic usage for patients receiving GCSF primed precursor cell collections. The addition of post chemotherapy GCSF did not, however, appear to enhance the rate of hematologic recovery. This study shows that simplified schedules for high dose chemotherapy administration together with simple precursor cell collection procedures provide safe and effective methods for administering myeloablative chemotherapy treatment.
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PMID:Non-cryopreserved, limited number (1 or 2) peripheral blood progenitor cell (PBPC) collections following GCSF administration provide adequate hematologic support for high dose chemotherapy. 752 46

Primed peripheral blood progenitor cells (PBPC) with hematopoietic growth factors enhance marrow engraftment after autologous bone marrow transplantation (BMT). G-CSF and GM-CSF stimulate the production of PBPC; both cytokines alone also stimulate neutrophil recovery after autologous BMT. Little data exist comparing these two cytokines. We prospectively studied G-CSF and GM-CSF in autologous BMT. Forty-four consecutive patients with either Hodgkin's disease or non-Hodgkin's lymphoma underwent autologous BMT using both PBPC and autologous marrow. The autologous BMT preparative regimen was CBV (VP-16 2400 mg/m2, CY 1800 mg/m2 i.v. four times daily for 4 days, BCNU 600 mg/m2). Sixteen patients received G-CSF 5 micrograms/kg sc daily for 8 days for mobilization of PBPC and received G-CSF 16 micrograms/kg i.v. four times daily after autologous BMT. Twenty-eight patients received GM-CSF to mobilize PBPC (14 patients received 250 micrograms/m2 sc daily for 8 days; 14 patients received 125 micrograms/m2 sc twice daily for 8 days) and GM-CSF (250 micrograms/m2 i.v. four times daily) after autologous BMT. Patients underwent three to five pheresis procedures to harvest at least 3 x 10(8) nucleated cells/kg. Patients receiving G-CSF had higher peripheral WBC counts than did those receiving GM-CSF. Total numbers of mononuclear cells, total CD34+ cells and total CD34+/33-negative cells were similar in the two treatment groups. The patients receiving G-CSF after autologous BMT experienced a more rapid engraftment of both neutrophils (9 days vs 13 days, p = 0.0001) and platelets (14 days vs 18 days, p = 0.027) than did patients receiving GM-CSF after transplant.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Comparison of G-CSF with GM-CSF for mobilizing peripheral blood progenitor cells and for enhancing marrow recovery after autologous bone marrow transplant. 753 72

In 54 patients with malignant lymphoma, haematopoietic recovery after high-dose chemotherapy and autologous bone marrow transplantation (BMT) was compared between patients randomised to receive 10 or 30 micrograms/kg/day of r-metHuG-CSF (filgrastim) or no growth factor. After standard high-dose chemotherapy with cyclophosphamide, etoposide and BCNU (CVB regimen for patients with Hodgkin's disease) or BCNU, etoposide, cytosine arabinoside and melphalan (BEAM regimen for patients suffering from non-Hodgkin's lymphoma) followed by autologous BMT, r-metHuG-CSF was administered by continuous intravenous infusion from the first day after autologous BMT until neutrophil recovery. When the r-metHuG-CSF groups were compared with the control group the major findings were: the median time to reach an absolute neutrophil count (ANC) > or = 0.5 x 10(9)/L was 20 days in the control group and 12 and 14 days, respectively, in the r-metHuG-CSF groups (P = 0.0004). The duration of neutropenia (ANC < 0.5 x 10(9)/L) was reduced from 27 days in the control group to 11 and 13 days in the r-metHuG-CSF groups (P = 0.0001). In addition, fewer days of febrile neutropenia were observed in the r-metHuG-CSF groups (5 and 6 days) than in the control group (10 days; P = 0.036). No significant effects of r-metHuG-CSF administration on the number of days with fever, the use of intravenous antibiotics and hospitalisation were detected. R-metHuG-CSF was well tolerated without any serious side-effects.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Results of a randomised, controlled, multicentre study of recombinant human granulocyte colony-stimulating factor (filgrastim) in patients with Hodgkin's disease and non-Hodgkin's lymphoma undergoing autologous bone marrow transplantation. 753 68

Patients with Hodgkin's disease (HD) who fail to enter a complete remission after an initial course of combination chemotherapy are usually considered to have an induction failure (IF); this subset of patients has an extremely poor outcome with further conventional therapy. Since 1985, we have entered 30 IF patients into protocols using conditioning with high-dose cyclophosphamide, carmustine (BCNU), and etoposide (VP16-213) with or without cisplatin (CBV +/- P) followed by autologous stem cell transplantation (ASCT) with bone marrow (19 patients), peripheral blood stem cells (PBSCs; 8 patients), or both (3 patients). All except 2 patients had previously received chemotherapy regimens for HD that contained at least 7 drugs, and 9 had received prior radiotherapy (RT). After documentation of IF, the majority of patients received some cytoreductive therapy as specified by protocol (local RT in 9, two cycles of conventional chemotherapy in 2, both modalities in 2, or high-dose cyclophosphamide to enhance PBSC collection in 11) before CBV +/- P. Five treatment-related deaths occurred, all before day 150 posttransplant. Eleven patients have had progressive HD at a median of 6 months (range, 0.1 to 45 months) after ASCT. The actuarial progression-free survival (PFS) at a median follow-up of 3.6 years (range, 0.2 to 8.2 years) is 42% (95% confidence intervals, 21% to 61%). The statistical analysis identified only prior clinical bleomycin lung toxicity as an adverse risk factor for PFS, mainly because of the increased nonrelapse mortality seen in these patients. CBV +/- P and ASCT can produce durable remission in a substantial proportion of IF HD patients who otherwise have a poor survival, and we believed ASCT approaches represent the best therapy currently available for these patients. Additional measures are needed to reduce the primary problem of disease progression despite high-dose chemotherapy and stem cell transplantation.
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PMID:High-dose cyclophosphamide, carmustine (BCNU), and etoposide (VP16-213) with or without cisplatin (CBV +/- P) and autologous transplantation for patients with Hodgkin's disease who fail to enter a complete remission after combination chemotherapy. 754 61

Agents with stem cell-toxic potential are frequently used for salvage therapy of Hodgkin's disease (HD) and high-grade non-Hodgkin's lymphoma (NHL). Because many patients with relapsed or refractory lymphoma are candidates for autologous progenitor cell transplantation, possible toxic effects of salvage chemotherapy on progenitor cells must be taken into account. In a retrospective study, we have analyzed the influence of a salvage regimen containing the stem cell-toxic drugs BCNU and melphalan (Dexa-BEAM) on subsequently harvested bone marrow (BM)- and peripheral blood-derived progenitor cell grafts (PBPC) and compared it with other factors. Progenitor cells were collected from 96 patients with HD or high-grade NHL. Seventy-nine grafts were reinfused (35 PBPC and 44 BM) after high-dose chemotherapy. Compared with patients autografted with BM, hematopoietic recovery was significantly accelerated in recipients of PBPC. For PBPC, the number of Dexa-BEAM cycles ( > or = v > 1) was the predominate prognostic factor affecting colony-forming unit-granulocyte-macrophage (CFU-GM) yield (66 v 6.8 x 10(4)/kg, P = .0001), CD34+ cell yield (6.6 v 1.6 x 10(6)/kg, P = .0001), neutrophil recovery to > 0.5 x 10(9)/L (9 v. 11 days, P = .0086), platelet recovery to > 20 x 10(9)/L (10 v 15.5 days, P = .0002), and platelet count on day +100 after transplantation (190 v 107 x 10(9)/L, P = .031) using univariate analysis. Previous radiotherapy was associated with significantly lower CFU-GM and CD34+ cell yields but had no influence on engraftment. Patient age, patient sex, disease activity, or chemotherapy other than Dexa-BEAM did not have any prognostic impact. Multivariate analysis confirmed that Dexa-BEAM chemotherapy was the overriding factor adversely influencing CFU-GM yield (P < .0001), CD34+ cell yield (P < .0001), and platelet engraftment (P < .0001). BM grafts were not significantly affected by previous Dexa-BEAM chemotherapy or any other variable tested. However, prognostic factors favoring the use of BM instead of PBPC were not identified using joint regression models involving interaction terms between the graft type (PBPC or BM) and the explanatory variables investigated. We conclude that, in contrast to previous radiotherapy or other chemotherapy, exposure to salvage regimens containing stem cell-toxic drugs, such as BCNU and melphalan, is a critical factor adversely affecting yields and performance of PBPC grafts. Marrow progenitor cells appear to be less sensitive to stem cell-toxic chemotherapy. PBPC should be harvested before repeated courses of salvage chemotherapy involving stem cell-toxic drugs to preserve the favorable repopulation kinetics of PBPC in comparison with BM.
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PMID:Autologous progenitor cell transplantation: prior exposure to stem cell-toxic drugs determines yield and engraftment of peripheral blood progenitor cell but not of bone marrow grafts. 757 68


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