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)

The toxicity and feasibility of a high-dose sequential (HDS) chemotherapy programme delivered with growth factor support were evaluated in patients with intermediate and high-grade non-Hodgkin's lymphoma (NHL) or with progressive Hodgkin's disease. The scheme includes the sequential administration of single cytotoxic drugs at very high doses followed by intensified treatment with circulating progenitor autograft. In some instances, the original HDS scheme, initially designed at the Milan Cancer Center, was partially modified and intensified with a preliminary debulking phase. The use of G-CSF (filgrastim) made toxicity in the high-dose phase acceptable and allowed good harvests of peripheral blood progenitor cells (PBPC); the use of PBPC in the final autografting phase resulted in low haematological toxicity. Of 71 patients with NHL treated at our institution with either the original or the intensified HDS version, the overall toxicity-related mortality was 5.6%, thus comparable to lethal toxicity commonly associated with conventional chemotherapy. Adequate PBPC harvests are crucial for good tolerability of the programme. Optimal harvests are generally obtained in patients without neoplastic marrow infiltration while patients with marrow disease often have a poorer mobilisation. However, an optimally time-spaced chemotherapy debulking might also restore sufficient mobilisation in these latter patients. In terms of therapeutic efficacy, HDS had produced promising results since the initial experience in relapsed patients. More recently, HDS was evaluated as first-line treatment in a series of 22 consecutive patients, presenting with advanced-stage, intermediate-grade NHL other than diffuse large cell subtype. A CR rate of 82% was obtained following HDS, with a projected survival of 86% at five years. Thus, delivery of an intensive high-dose chemotherapy programme with haematopoietic growth factor support was found to be feasible and reasonably safe. The high anti-tumour efficacy of such a scheme makes it suitable for wider applicability in all those chemosensitive tumours where a dose increase might enhance the chance of cure.
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PMID:Haematological support of high-dose sequential chemotherapy: clinical evidence for reduction of toxicity and high response rates in poor risk lymphomas. 875 Jan 37

Luminol-enhanced whole blood chemiluminescence of human neutrophils was studied using opsonized zymosan as a stimulus. Heparinized blood (0.5 microliters) was used, and the chemiluminescence signals were recorded by a very sensitive, automated, and computer-assisted luminometer (LB 950, Berthold, Wildbad, Germany). The following parameters were provided: integral values over the total measuring time, peak values, the time to reach maximum value, and the time to reach half maximum value. Normal subjects, neutropenic patients, subjects with total or partial myeloperoxidase deficiency, patients with recurrent infections, phagocytic defects, thrombocythemic patients and those with non-Hodgkin's lymphomas undergoing therapy with recombinant human granulocyte colony-stimulating factor were studied. The integral response of chemiluminescence and the time of reach half maximal value were useful indicators of chemiluminescence defects; the assay, was able to detect chemiluminescence responses in neutropenic subjects with neutrophil levels as low as 0.6 x 10(9)/l; differences between cellular and plasma defects could be identified; the quenching effect exerted by erythrocytes was negligible.
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PMID:Luminol-enhanced, whole blood chemiluminescence of human neutrophils evaluated by means of an automated, computer-assisted, and high-sensitivity luminescence analyzer. 878 51

Six patients with human immunodeficiency virus (HIV)-associated non-Hodgkin lymphoma receiving chemotherapy (CT) with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) plus granulocyte colony-stimulating factor were sequentially monitored to study the effects of these treatments on their immunologic status (CD4 and CD8 cell counts) and on HIV plasma viremia. We show that mean CD4 cell counts declined significantly after the third cycle of CT (187 +/- 117/microliters before CT versus 92.4 +/- 60/microliters; p = 0.04) and remained significantly reduced 4 months after completion of CT. Modifications of CD8 cell counts were not statistically significant. The effects of CT on plasma viremia, as measured by a competitive polymerase chain reaction technique, were delayed until the fourth cycle, when an increase of viral load ranging from 0.6 to 2 logs (p = 0.027) was observed. After this point, viremia returned to baseline levels, with the exception of two patients who later developed opportunistic infections and one who underwent disease progression. These results suggest that, contrary to CD4 cell counts, plasma viremia could be a faithful surrogate marker for monitoring of HIV disease progression in patients undergoing CT.
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PMID:The effects of antineoplastic chemotherapy on HIV disease. 895 47

It was the aim of our study to determine the collection efficiency and yield of CD34+ cells in 88 cancer patients (pts, 44 males/44 females) who underwent 154 large-volume leukaphereses (LV-LPs). The diagnoses were as follows: 18 patients had Non-Hodgkin's lymphoma, 9 Hodgkin's disease, 24 multiple myeloma, 6 acute leukemia, 27 breast cancer, and 4 patients had solid tumors of different types. During the course of LV-LPs, 20 liters (1) of blood were processed at a median flow-rate of 85 ml/min (CS 3000 Baxter) and 130 ml/min (COBE Spectra), respectively. Peripheral blood stem cells (PBSC) were collected following granulocyte colony-stimulating factor (G-CSF)-supported cytotoxic chemotherapy. A 31% and 21% mean decrease in the platelet and white blood count was noted at the end of the LV-LPs when compared with the pre-leukapheresis values. The aphereses were well tolerated without adverse effects. The level of circulating CD34+ cells was closely related to the number of CD34+ cells contained in the respective leukapheresis product (R = 0.89, P < 0.001). Compared with 270 patients who underwent 838 regular 10 1 LPs, the yield of CD34+ cells/kg was almost two-fold greater (4.84 +/- 0.63 x 10(6) [Mean +/- SEM] vs. 2.60 +/- 0.16 x 10(6), P < 0.001). The antigenic profile of CD34+ cells was assessed in 54 separate products collected on the occasion of 27 LV-LPs following the processing of 10 1 and 20 1, respectively. The intra-individual comparison included differentiation- as well as lineage-associated markers (CD38, Thy-1, c-kit, CD33, CD45RA). No difference in the subset composition was observed between the first and second product, arguing against a preferential release of particular CD34+ cell subsets during the procedure. As shown by molecular biological or immunocytochemical examination, the likelihood of harvesting malignant cells using large-volume aphereses was not increased in comparison with regular leukaphereses. Single harvests of > or = 2.5 x 10(6) CD34+ cells/kg could be obtained in 74% of the patients, compared with 52% in case of regular LPs. As the majority of patients were autografted with more than 2.5 x 10(6) CD34+ cells/kg following high-dose therapy, hematological recovery in general was rapid and not related to the type of apheresis product used. Considering patient comfort and savings in resource utilization, large-volume leukaphereses have become the standard procedure for PBSC collection in our center.
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PMID:Successful collection and transplantation of peripheral blood stem cells in cancer patients using large-volume leukaphereses. 898 64

Although a large amount of data is available on the effects of filgrastim (granulocyte colony-stimulating factor [G-CSF]) on the mobilization of stem cells in the circulation, data concerning its effects on bone marrow (BM) harvesting is scarce and controversial. We have designed a randomized trial comparing filgrastim-mobilized peripheral blood stem cell (PBSC) transplantation with filgrastim-primed autologous bone marrow transplantation (ABMT). Fifty-five patients affected by non-Hodgkin's (n = 38) or Hodgkin's (n = 17) lymphoma, selected for autologous transplantation over a 12-month period in a single institution, were randomized 2:1 to undergo BM or PB harvest/collection after priming for 3 days with filgrastim, 16 microg/kg body weight daily subcutaneously. BM priming with G-CSF allowed the harvest of a significantly higher number of mononuclear cells (MNC) (0.53 x 10(8)/kg, range, 0.32 to 1.40), as compared with a historical control of unprimed BM harvests (0.43 x 10(8) MNC/kg, range, 0.15 to 0.72, P = .001). After high-dose ablative therapy, median time to neutrophil recovery above 0.5 x 10(9)/L was 12 days for BM and 11 days for PB (P = .219); median time to platelet recovery above 20 x 10(9)/L was 13 days for BM and 11 days for PB (P = .242). The same number of red blood cells, platelet transfusions, and posttransplant G-CSF doses were required in the two groups of patients. Less patients (50% v 70%) became febrile in the group transplanted with mobilized PB, but days of fever/patient and days on antibiotics were overlapping. The median time spent in the hospital after reinfusion was 16.5 and 15.5 days after primed BM and primed PB, respectively (P = .134). These data suggest that in patients with lymphoma submitted to autologous transplantation, the reinfusion of filgrastim-primed BM or filgrastim-mobilized PB leads to similar results, with an advantage of only 1 day in the neutrophil recovery and 1 day on the time spent in the hospital in favor of primed PB. Either option can be chosen on the basis of the availability of a surgery room or cell separator facilities and considering the patients' characteristics and wishes.
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PMID:Randomized trial of autologous filgrastim-primed bone marrow transplantation versus filgrastim-mobilized peripheral blood stem cell transplantation in lymphoma patients. 978 99

A prospective study was undertaken to compare the mononuclear cell, CD34+ cell, and CFU-GM yields of the Haemonetics MCS-3P and the Cobe Spectra cell separators in ten patients (nine multiple myeloma and one non-Hodgkin lymphoma) on two consecutive days after mobilization with high-dose filgrastim (12-16 micrograms/k) for 4 days. All patients were harvested once on each machine, five starting on each machine. The target duration of the procedure on the Spectra was 160 minutes, and the target blood volume processed on the MCS-3P was 60-70 ml/kg body weight. Both machines were operating on the 1995 software versions supplied by the respective manufacturers. The time taken for the procedure was significantly longer with the Haemonetics machine. The volumes of blood processed and the product collected were significantly higher with the Spectra, as were the absolute mononuclear and CD34+ cell yields, and yields per unit time. Mononuclear and CD34+ cell yields per unit volume of blood processed were comparable for both machines. The differences in CFU-GM yields were not significant, largely because of wide interpatient variations. The extent of platelet depletion as a result of the procedure was greater with the Spectra because of the higher blood volume being processed. We conclude that the Cobe Spectra is a significantly faster machine than the Haemonetics MCS-3P; and consequently, its use is associated with higher mononuclear and CD34+ cell yields.
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PMID:Prospective, concurrent comparison of the Cobe Spectra and Haemonetics MCS-3P cell separators for leukapheresis after high-dose filgrastim in patients with hematologic malignancies. 926 12

A multicenter phase I/II clinical trial was conducted to evaluate the safety of a device (Isolex System; Baxter Health Corporation, Irvine, Calif., USA) using the immunomagnetic bead method to purify CD34+ stem cells from peripheral blood and to assess the efficacy and toxicity of high-dose chemoradiotherapy with peripheral blood stem-cell transplantation (PBSCT) using purified CD34+ stem cells in patients with refractory hematological malignancies. Patients eligible for the study included those who had T-cell acute lymphoblastic leukemia (T-ALL), lymphoblastic lymphoma (LBL), mantle-cell lymphoma (MCL), high-risk aggressive non-Hodgkin's lymphoma (NHL), and adult T-cell leukemia/lymphoma (ATLL) in first complete remission (CR) and those who had standard-risk aggressive NHL, indolent lymphoma, Hodgkin's disease, or acute promyelocytic leukemia (APL) in second CR or first partial remission (PR) after the completion of first-line chemotherapy and were chemosensitive to salvage chemotherapy, in whom tumor contamination of harvested peripheral blood stem cells (PBSCs) was possible due to bone marrow or peripheral blood involvement. Lack of CD34 expression by tumor cells was an important selection factor. Eight patients with hematological malignancies (six NHL patients, one ATLL patients, and one APL patient) were enrolled; their median age was 41 years (range 26-49 years). After consolidation and mobilization chemotherapy, two or three courses of apheresis were performed in each patient. After high-dose chemo(radio)therapy, in each patient a median of 1.8 x 10(6) cells/kg (range 8.2 x 10(5)-5.1 x 10(6) cells/kg) purified CD34+ PBSCs were infused; granulocyte colony-stimulating factor was given from day 1. Median times to hematopoietic recovery were as follows: WBC of > or = 1,000/microliter, day 11; platelet count of > or = 50,000/microliter, day 19; and reticulocyte count of > or = 10/1000, day 15. Two NHL patients relapsed at 23 and 9 months after PBSCT, respectively; the remaining six patients are alive and in CR. No severe toxicity was observed in any patient. Tumor contamination as measured using a polymerase chain reaction-mediated RNase protection assay at the 10-4 level was detected in the CD34(+)-purified fractions of 2 of the 5 samples analyzed; however, a reduction in contaminating lymphoma cells from the autograft of at least 1,000 to 10,000 orders of magnitude was achieved by CD34+ selection using the immunomagnetic bead method. High-dose chemoradiotherapy with transplantation of CD34+ PBSCs purified by the immunomagnetic bead method was thus shown to be an active and safe therapy for refractory hematological malignancies with bone marrow or peripheral blood involvement. However, it is too early for evaluation of the long-term survival benefit.
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PMID:Phase I/II trial of cure-oriented high-dose chemoradiotherapy with transplantation of CD34+ peripheral blood stem cells purified by the immunomagnetic bead method for refractory hematological malignancies. Nagoya CD34+ PBSCT Study Group. 927 35

Several clinical trials have demonstrated that high-dose chemotherapy (HDC) with autologous hematopoietic stem-cell transplantation is more effective than conventional-dose chemotherapy in some subsets of patients with malignant lymphoma, such as relapsed aggressive lymphoma patients showing a response to salvage chemotherapy and those with Hodgkin's disease who fail primary initial chemotherapy. This paper summarizes recent findings and the following issues remaining to be resolved: (1) whether HDC is superior to conventional-dose chemotherapy as initial therapy for aggressive lymphoma in unfavorable risk groups, (2) whether single HDC or multiple semi-HDC is better, (3) whether HDC has curative potential in indolent lymphoma or mantle-cell lymphoma, and (4) the HDC regimen that is most useful. To clarify these controversial issues, well-designed clinical trials are needed. To evaluate whether the concept "the more chemotherapy, the better in malignant lymphoma" is valid, the Lymphoma Study Group of the Japan Clinical Oncology Group is conducting two kinds of clinical trials in high- and high-intermediate-risk aggressive lymphoma patients, focusing on the dose intensity of key agents. One is a randomized phase II trial of dose-escalated cyclophosphamide, doxorubicin, vincristine, and prednisolone (high CHOP) versus shortened CHOP (biweekly CHOP) with prophylactic use of granulocyte colony-stimulating factor. The other is a phase II trial of HDC with peripheral blood stem-cell transplantation as a part of the initial therapy. If promising results are obtained from these trials a randomized phase III trial will be considered to compare the best dose-intensive regimen with standard CHOP.
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PMID:Chemotherapy: the more, the better in malignant lymphoma? 927 45

The main objective of this study was to assess to what extent filgrastim (G-CSF, Amgen-Roche) can facilitate administration of the full dose intensity of MOPP/ABVD chemotherapy to patients with Hodgkin's disease. Sixteen patients with Hodgkin's disease were treated with MOPP/ABVD and filgrastim support between January 1992 and March 1994. Twenty-five patients treated with MOPP/ABVD 1987-1991 served as historical controls. The two groups were well matched for age, gender, stage, performance status and histological subgroups, but in the study group more patients had B-symptoms (p < 0.05). Dose intensity (DI) was calculated in mg/m2/week and the intended average dose was designated as 1. The planned average DI was reached by 8/16 patients in the study group but by only 1/25 in the control group (p < 0.001). The reasons for decreased DI in the study group were neutropenia (n = 5), thrombocytopenia (2 pts) and neurotoxicity (n = 1). In the control group the reason for decreased DI was neutropenia (n = 24). In the study group 15/16 patients achieved Complete Response (CR), 2/15 relapsed and 15/16 were surviving after a median follow-up 31 (6-48) months. In the control group 25/25 patients attained CR, 5/25 relapsed and 20/25 were surviving after a median follow up 67 (12-100) months. No severe toxicity was observed during filgrastim therapy. To conclude, the dose intensity during MOPP/ABVD therapy was significantly higher if filgrastim was administered, but the additional benefit that this confers remains to be determined. A large scale, retrospective analyses of treatment response and actual dose-intensity should help answer this question and give guidance as to if and when hematopoietic growth factors should be administered to patients with Hodgkin's disease.
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PMID:G-CSF (filgrastim) as an adjunct to MOPP/ABVD therapy in Hodgkin's disease. 929 44

The combination of cyclophosphamide (CY) and etoposide is synergistic, spares bone marrow stem cells and can be given repeatedly in high doses without stem cell support. Thirteen patients with non-Hodgkin's lymphoma (n = 8) or Hodgkin's disease (n = 5), received high-dose chemotherapy (HDC). Median age was 32 years (24-52). Male to female ratio was 10:3. All the patients were in advanced-stage. Karnofsky score prior to HDC was 60% (range 40-90). Six patients showed primary refractoriness and 7 had resistant relapse. HDC consisted of CY 1,500 mg/m2/day and etoposide 300 mg/m2/day, both for 4 days. rhG-CSF was started 24 h after the last dose of chemotherapy as a continuous intravenous infusion at a dose of 0.01 mg/kg/day and stopped when the leukocyte count reached 1 x 10(9)/1 on 3 consecutive days. Overall, 69% (9/13) of patients responded to HDC. Four achieved CR and 5 achieved PR. Two of the patients showed disease progression. The other 2 died during the early period of HDC. Neutrophil and platelet recovery after HDC were 8 (6-16) and 10 (4-14) days, respectively. The major nonhematological toxicities were nausea-vomiting (100%) and diarrhea (61%). The median follow-up was 204 (7-600) days. Two patients relapsed 48 and 185 days after HDC. Eight patients are still alive, 7 progression free. The progression-free survival is 220 (40-285) days. In conclusion, HDC + granulocyte colony-stimulating factor (G-CSF), without stem cell support seems to be promising in refractory or resistant relapse lymphoma patients bringing the need for randomized studies to show the cost effectiveness of HDC + G-CSF compared to HDC + autologous stem cell support.
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PMID:Use of high-dose chemotherapy plus granulocyte colony-stimulating factor for the salvage of refractory or resistant-relapse lymphoma patients without stem cell support. 935 43


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