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 high-grade malignant non-Hodgkin's lymphomas (hNHL) recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) was evaluated as support to chemotherapy. In a phase III trial, 172 patients (age 18-73 years, stage II-IV) were risk-stratified according to LDH levels and lymphoma size and randomized to receive rhGM-CSF (400 micrograms) (87 patients) or placebo (85 patients) subcutaneously days 8-14 of each cycle of an intensified COP-BLAM regimen. RhGM-CSF significantly reduced the length and nadir of neutropenia, the length of fever episodes, the frequency of all and of severe infections, and of hospitalization and antibiotic requirements. Complete response rates were 63% for all patients and 64% vs. 61% (n.s.) in the rhGM-CSF vs. the control group. Deviations from protocol in applied dosages of myelotoxic drugs and in cycle intervals maintained differed slightly in favor of the rhGM-CSF arm. However, there were no significant differences in overall survival between the GM-CSF treatment and control groups (21 vs. 23 months). Early relapse rates were markedly lower than in the standard-dose COP-BLAM/IMVP-16 regimen. Thus, GM-CSF abates toxic side effects of chemotherapy and may help to maintain dose intensity in high-risk hNHL.
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PMID:Cytokine efficiency in the treatment of high-grade malignant non-Hodgkin's lymphomas: results of a randomized double-blind placebo-controlled study with intensified COP-BLAM +/- rhGM-CSF. 751 44

For patients with advanced-stage or poor-prognosis malignant lymphoma, high-dose therapy with peripheral blood progenitor cell (PBPC) support may become a first-line treatment. The duration of severe cytopenia in this setting is inversely related to the number of PBPCs autografted. In a retrospective analysis, we therefore looked for factors influencing the yield of PBPCs in 61 patients (16 with high-grade and 29 with low-/intermediate-grade non-Hodgkin's lymphoma [NHL], and 16 with Hodgkin's disease) who received cytotoxic chemotherapy and filgrastim (R-metHuG-CSF, 300 micrograms/d; median, 4.2 micrograms/kg/d; range, 2.7 to 6.6 micrograms/kg/d; subcutaneously). Sixteen patients had active disease, while 45 were in partial remission (PR) or complete remission (CR) after conventional therapy. A median of three leukaphereses (range, one to 10) resulted in a median of 5.7 x 10(6) CD34+ cells/kg (range, 0.03 to 31.1 x 10(6)). Previous cytotoxic chemotherapy and irradiation adversely affected the yield of CD34+ cells. Each cycle of chemotherapy is associated with an average decrease of 0.2 x 10(6) CD34+ cells/kg per leukapheresis in nonirradiated patients, while large-field radiotherapy reduces the collection efficiency by an average of 1.8 x 10(6)/kg CD34+ cells. The collection efficiency was also significantly lower in patients with Hodgkin's disease. However, except for one, all had been previously irradiated. In contrast, age, sex, disease status, bone marrow involvement during mobilization, and the time since the last chemotherapy or radiotherapy were not significantly related to the collection efficiency. Following high-dose conditioning therapy, 42 patients were autografted with filgrastim-mobilized PBPCs. Hematological recovery (neutrophils > or = 0.5 x 10(9)/L and an unsupported platelet count > or = 20 x 10(9)/L) within 2 weeks was observed in patients autografted with > or = 2.5 x 10(6) CD34+ cells/kg. In seven patients, the quantity of CD34+ cells reinfused was below this threshold. They required a median of 17 days (range, 11 to 34) and 31 days (range, 13 to 141) for neutrophil and platelet recovery, respectively. If autografting with PBPCs in malignant lymphoma with poor prognosis is being considered, mobilization and harvesting should be planned early after initial diagnosis to avoid exhaustion of hematopoiesis by cumulative toxicity.
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PMID:Patient characteristics associated with successful mobilizing and autografting of peripheral blood progenitor cells in malignant lymphoma. 751 21

Recombinant granulocyte colony-stimulating factor (rhG-CSF) has been shown to hasten granulocyte recovery after autologous BMT. In current protocols, rhG-CSF treatment starts 1 day after BM reinfusion. Our study retrospectively examined the effects on haematological recovery of a day 6 delayed administration. Seventy-eight patients receiving autologous BMT for malignant lymphoma (21 non-Hodgkin's lymphoma and 9 Hodgkin's disease) or solid tumors (33 breast carcinoma and 5 ovarian carcinoma) were split up into three study groups. Two groups receiving a 5 micrograms/kg/day of rhG-CSF starting either 1 day (day +1 group, n = 25 patients) or 6 days (day +6 group, n = 24 patients) after BM reinfusion were compared with 29 historical control patients. Granulocyte recovery to 0.5 x 10(9)/l was 12 days in day +6 and day +1 groups versus 16 days in control group (p < 0.005) without any difference in other hematological parameters, infectious complications or length of hospitalisation between the three groups. The day +6 administration allows elimination of a median of 7 days rhG-CSF. It has been concluded that the day +6 administration gives the same clinical benefit as day +1 administration with consequent cost reductions.
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PMID:Delayed administration of granulocyte colony-stimulating factor after autologous bone marrow transplantation: effect on granulocyte recovery. 753 61

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

Peripheral blood progenitor cells (PBPC) can be mobilized using cytotoxic chemotherapy and cytokines. There is a substantial variability in the yield of hematopoietic progenitor cells between patients. We were looking for predictive parameters indicating a patient's response to a given mobilization regimen. Multiparameter flow-cytometry analysis and clonogenic assays were used to examine the hematopoietic progenitor cells in bone marrow (BM) and peripheral blood (PB) before filgrastim (R-metHuG-CSF; Amgen, Thousand Oaks, CA)-supported chemotherapy and in PB and leukapheresis products (LPs) in the recovery phase. Fifteen patients (four with high-grade non-Hodgkin's lymphoma [NHL], two with low-grade NHL, two with Hodgkin's disease, two with multiple myeloma, three with breast cancer, one with ovarian cancer, and one with germ cell tumor) were included in this study. The comparison of immunofluorescence plots showed a homogenous population of strongly CD34+ cells in steady-state and mobilized PB whereas in steady-state BM, the CD34+ cells ranged from strongly positive with continuous transition to the CD34- population. Consistent with the similarity in CD34 antigen expression, a correlation analysis showed steady-state PB CD34+ cells (r = .81, P < .001) and colony-forming cells (CFCs; r = .69, P < .01) to be a measure of a patient's mobilizable CD34+ cell pool. Individual estimates of progenitor cell yields could be calculated. With a probability of 95%, eg, 0.4 steady-state PB CD34+ cells x 10(6)/L allowed to collect in six LPs 2.5 x 10(6) CD34+ cells/kg, the reported threshold-dose of progenitor cells required for rapid and sustained engraftment after high-dose therapy. For the total steady-state BM CD34+ cell population, a weak correlation (r = .57, P < .05) with the mobilized CD34+ cells only became apparent when an outlier was removed from the analysis. Neither the CD34+ immunologic subgroups defined by the coexpression of the myeloid lineage-associated antigens CD33 or CD45-RA or the phenotypically primitive CD34+/HLA-DR- subset nor the BM CFC count had a predictive value for the mobilization outcome. This may be caused by the additional presence of maturing progenitor cells in BM, which express lower levels of the CD34 antigen and do not circulate. Our results permit us to recognize patients who are at risk to collect low numbers of progenitor cells and those who are likely to achieve sufficient or high progenitor cell yields even before mobilization chemotherapy is administered.
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PMID:Peripheral blood progenitor cell (PBPC) counts during steady-state hematopoiesis allow to estimate the yield of mobilized PBPC after filgrastim (R-metHuG-CSF)-supported cytotoxic chemotherapy. 860 80

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

It has been previously demonstrated that the administration of recombinant human granulocyte-colony stimulating factor (rhG-CSF) ameliorates the decrease of the polymorphonuclear neutrophils (PMNs) count after the cytotoxic chemotherapies, thereby reducing the infection complications associated with neutropenia. In this multi-center study, we studied the prophylaxtic effect of rhG-CSF administration on infection complications in patients with non-Hodgkin malignant lymphoma, who received cytotoxic chemotherapies (CHOP or ProMACE/CytaBOM). rhG-CSF administration reduced the frequency of infection complications, and there was no obvious difference in it's frequency between the CHOP-treated and the ProMACE/CytaBOM-treated groups when administered with rhG-CSF, thereby indicating that third generation therapy for NHL may be safely completed in Japanese in combination with rhG-CSF administration. Furthermore, we investigated both the in vitro and the in vivo effects of rhG-CSF on the function of PMNs in patients with NHL and healthy donors, and revealed that the administration of rhG-CSF for NHL patients receiving cytotoxic chemotherapy brought on an improvement of the production of active oxygen but did not affect serum levels of IFNs, IL-1-beta, and IL-6, inspite of a slight elevation of TNF-alpha. Consistent with these results, in vitro treatment of PMNs with rhG-CSF induced no significant production of these inflammatory cytokines and their mRNA expressions. Furthermore, rhG-CSF administration showed no significant effects in vivo on the expression of CD11a, CD11b and LECAM-1 on PMNs and integrins on platelets.
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PMID:Effects of rhG-CSF on infection complications and impaired function of neutrophils secondary to chemotherapy for non-Hodgkin's lymphoma. Hokkaido Study Group of Malignant Lymphoma, and rhG-CSF, Japan. 754 Apr 62

The phenotypical and functional properties of circulating neutrophils from ten patients suffering from intermediate- and high-grade non-Hodgkin lymphoma were investigated before and after rhG-CSF administration (5 micrograms/kg/day subcutaneously for 5 days). The following parameters were studied: flow cytometry evaluation of surface CD32, CD16, CD11b and CD18 by means of a whole blood method; whole blood phagocytosis by means of a flow cytometric assay; whole blood chemiluminescence using opsonized zymosan as a stimulus. A significant increase in the expression of surface CD32 was detected in all patients, while CD11b expression was found to be increased in only four of them. CD16 and CD18 expression did not change. A significant enhancement of phagocytosis and phagocytosis-associated chemiluminescence was also observed. These results show that rhG-CSF administration can increase both FcRII expression and FcR-related functions.
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PMID:Granulocyte colony-stimulating factor (G-CSF) administration increases PMN CD32 (FcRII) expression and FcR-related functions. 754 71

Mobilization of peripheral blood stem cells (PBSC) can be accomplished with cytokines or rebound from myelo-suppressive chemotherapy. In this study, patients were mobilized with cyclophosphamide (CY) 4 g/m2 either alone or followed by GM-CSF 250 micrograms/m2 or G-CSF 600 micrograms. Colony-stimulating factors were administered subcutaneously. Eligibility included patients with non-Hodgkin's lymphoma (NHL; n = 29), Hodgkin's disease (n 4) and acute lymphoblastic leukemia (n = 2). One patient died from mobilization-related complications. Admission for neutropenic fevers and other complications occurred in 73% of patients receiving CY alone compared with 32% received CY + G-CSF or GM-CSF (P < 0.05). Apheresis was initiated when the white blood count approached 1 x 10(9)/l and continued until approximately 6 x 10(8) mononuclear cells/kg were collected. Mobilization with CY + GM-CSF led to significantly greater numbers of collected CFU-GM than with CY alone. Colony-stimulating factors were not administered after transplantation. collected progenitor cells correlated with the peak cell counts after mobilization. Following transplantation, an ANC > = 500 x 10(6)/l was achieved at 14.5 days and a platelet count > = 50 x 10(6)/l was achieved on day 20. Days to achieve an ANC > = 500 x 10(6)/l did not correlate with any of the analyzed variables. Platelet engraftment correlated with harvested BFU-E, thawed CD34+ cells and peak counts following mobilization. for patients with NHL, CR was obtained in 82% of evaluable cases. Median time to relapse was 343 days. Twenty five per cent of patients remain disease-free at 900+ days of follow-up.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cyclophosphamide-mobilized peripheral blood stem cells in patient with lymphoid malignancies. 759 69

Seventeen consecutive patients with previously untreated poor prognosis Hodgkin's disease (clinical stage II and III with systemic symptoms, and stage IV) received 6 courses of aggressive chemotherapy, with (9 patients) and without (8 patients) the addition of recombinant human granulocyte-macrophage colony stimulating factor (rhGM-CSF). Chemotherapy (MOPP/ABV/CAD regimen) included full doses of nitrogen mustard, lomustine (CCNU), vindesine, melphalan, prednisone, epidoxorubicin, vincristine, procarbazine, vinblastine and bleomycin, and was administered between days 1 and 15 of each course. Course were planned for 28-day intervals. rhGM-CSF was given at a dose of 5 micrograms/kg/day subcutaneously from day 16 to 26 of each course. With cytopenia (i.e. white blood cell, WBC, count < 3.0 x 10(9)/L and/or platelet count < 100 x 10(9)/L) delaying courses was preferred to administering reduced drug dosages. Substantial delays (ranging from 7 to 28 days) in delivering cytostatics were necessary between 70% of courses. The cumulative mean number of days for which the courses had to be delayed before completing the 6 MOPP/ABV/CAD courses was 57. The percentage of planned doses of cytotoxic drugs (nitrogen mustard, melphalan, epidoxorubicin, procarbazine) actually administered was 92%. Causes of treatment delay were presented by leucopenia in 82% and by leuco-thrombocytopenia in 23% of the courses. The WBC nadir was constantly encountered at day 20-21 following completion of courses, and slightly worsened with subsequent courses. The decrease in platelet values was milder than that in WBC counts. There were no differences in any of the above parameters between patients treated with MOPP/ABV/CAD alone or followed by rhGM-CSF.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:MOPP/ABV/CAD chemotherapy with and without recombinant human granulocyte-macrophage colony stimulating factor in untreated, unfavorable prognosis Hodgkin's disease. 768 12


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