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)

Peripheral blood progenitor cell (PBPC) mobilization was evaluated in 53 patients receiving the high-dose sequential (HDS) regimen: 27 had non-Hodgkin's lymphoma or Hodgkin's disease, primary refractory or at first relapse, 26 had non-Hodgkin's lymphoma at diagnosis. Mobilization was assessed following either 7 g/m2 cyclophosphamide (48 patients) or 2 g/m2 etoposide, both followed by G-CSF (filgrastim) at 5 microg/kg/d. PBPC mobilization was significantly higher in patients at diagnosis compared to refractory/relapsed patients (median peak values of circulating CFU-GM: 25,209/ml v 4270/ml, P < 0.0001 and CD34+ cells: 286/microl v 47/microl, P < 0.0001). All patients receiving HDS as up-front treatment mobilized enough PBPC for an autograft, often requiring a single leukapheresis; whereas only 15 patients under salvage treatment with HDS were able to complete PBPC autograft. Bone marrow (BM) cells, alone or with PBPC, were needed in six patients, and autograft could not be performed in six patients. Among refractory/relapsed patients, those having a high PBPC mobilization experienced a significantly longer EFS compared to those who had not; autograft completion also significantly enhanced EFS. Thus, the use of an effective mobilizing protocol does not ensure adequate PBPC mobilization in moderately pretreated patients; low mobilization must be considered as an early sign of poor outcome in patients receiving a high-dose salvage programme.
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PMID:Peripheral blood progenitor cell mobilization in patients with primary refractory lymphoma or at first relapse: comparison with patients at diagnosis and impact on clinical outcome. 935

Autologous transplantation for non-Hodgkins lymphoma and Hodgkin's disease is widely used as standard therapy for those with high-risk or relapsed tumor. Peripheral blood stem cell (PBSC) collections have nearly completely replaced bone marrow stem cell (BMSC) harvests because of the perceived advantages of more rapid engraftment, less tumor contamination in the inoculum, and better survival after therapy. The advantage of PBSC, however, may derive from the hematopoietic stimulating cytokines used for PBSC mobilization. Therefore, we tested a randomized comparison of GM-CSF vs. G-CSF used to prime either BMSC or PBSC before collection for use in autologous transplantation. Sixty-two patients receiving transplants (31 PBSC; 31 BMSC) for non-Hodgkin's lymphoma (n = 51) or Hodgkin's disease (n = 11) were treated. All patients received 6 days of randomly assigned cytokine. Those with cellular marrow in morphologic remission underwent BMSC harvest, while those with hypocellular marrow or microscopic marrow tumor involvement had PBSC collected. Neutrophil recovery was similarly rapid in all groups (median 14 days; range 10-23 days), though two patients had delayed neutrophil recovery using GM-CSF primed PBSC (p = 0.01). Red cell and platelet recovery were significantly quicker after BMSC mobilized with GM-CSF or PBSC mobilized with G-CSF. This speedier hematologic recovery resulted in earlier hospital discharge as well. However, in multivariate analysis, neither the stem cell source nor randomly assigned G-CSF vs. GM-CSF was independently associated with earlier multilineage hematologic recovery or shorter hospital stay. Relapse-free survival was not independently affected by either the assigned stem cell source or the randomly assigned priming cytokine, though malignant relapse was more frequent in those assigned to PBSC (RR of relapse 3.15, p = 0.03). These data document that BMSC, when collected following cytokine priming, can yield a similarly rapid hematologic recovery and short hospital stay compared with cytokine-primed PBSC. Using primed BMSC, no difference in malignant relapse or relapse-free survival was observed. These findings suggest that despite widespread use of PBSC for transplantation, BMSC, when collected following hematopoietically stimulating cytokines, may remain a satisfactory source of stem cells for autologous transplantation. G-CSF and GM-CSF are both effective in priming autologous PBSC or BMSC for collection.
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PMID:Cytokine-primed bone marrow stem cells vs. peripheral blood stem cells for autologous transplantation: a randomized comparison of GM-CSF vs. G-CSF. 936 Jul 84

Sera were obtained from two groups of patients. Group A included 7 patients with low-grade non-Hodgkin's lymphoma treated with three or more cycles of standard-dose chemotherapy and recombinant human granulocyte-colony stimulating factor (rhG-CSF). The cytokine was administered to half the patients after the first chemotherapy cycle and to the other half after the second according to a randomized design and then to all patients from the third chemotherapy cycle on, until documented hemopoietic reconstitution. Group B included 3 patients with high-grade non-Hodgkin's lymphoma, 1 patient with resistant Hodgkin's disease, and 1 patient with multiple myeloma who received high-dose chemotherapy and rhG-CSF. Anti-G-CSF antibodies were detected in the sera of 4 patients. Both immunoglobulin IgM and IgG antibodies were detected at low levels in pretreatment sera from one group A patient. IgG antibody titers increased markedly during the first and second periods of G-CSF administration. IgG class antibodies developed in 3 groups B patients during the first course of rhG-CSF administration. Circulating anti-G-CSF antibodies did not seem to affect hematological recovery. Low levels of anti-G-CSF antibodies were also detected in sera (15/135) from different healthy adults and in sera (5/40) from umbilical cord blood. Saturable antibody binding and competition enzyme-linked immunosorbent assay (ELISA) and immunoblotting confirmed antibody specificity.
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PMID:Naturally occurring and therapy-induced antibodies to human granulocyte colony-stimulating factor (G-CSF) in human serum. 936 26

The optimal time for starting G-CSF application after autologous peripheral stem cell transplantation (APSCT) still remains undetermined. All previous studies used 'fixed' days (0 or +1 vs +5 or +7 post-transplant) for this purpose. As many other drugs have individual, patient-dependent criteria (eg antibiotics, blood products, etc), and the discontinuation of G-CSF also has strict patient-dependent criteria (surprisingly absent when starting the drug) we suppose that attempts to find general criteria suitable for every patient may not be successful. In order to also take the patients' individual predispositions into account we designed a randomized clinical trial to compare 'immediate' administration of G-CSF (day +1: group A) vs 'delayed, patient-dependent' (first day when absolute neutrophil count (ANC) was below 0.5 x 10[9]/1: group B) therapy with G-CSF (both groups received 10 microg/kg/day i.v.). A total of 70 patients after APSCT suffering from non-Hodgkin's lymphoma (NHL) and Hodgkin's disease (HD) conditioned with BEAM, or from multiple myeloma (MM) after melphalan (L-PAM: 200 mg/m2) were enrolled in this study (35 in each group). Both groups were comparable with regard to age, sex, disease stage and previous therapy as well as the number of CD34+ cells transplanted. In group B, G-CSF administration began on day +4 post-transplant (+2 - +5). There were no detectable differences seen in the hematopoietic recovery (time to reach ANC more than 0.5 x 10(9)/l: 12 days vs 13 days; time to platelet recovery, more than 50 x 10(9)/l: 24 days in both groups), use of blood products or antibiotics, infections, or days of hospitalization. Delayed G-CSF application led to significant cost saving in terms of APSCT (approximately US$1341 for each patient). We suggest that 'patient-dependent' criteria for starting G-CSF are reasonable especially in patients conditioned with protocols only slowly inducing neutropenia: eg NHL and HD patients after BEAM, MM after L-PAM or patients after busulphan and cyclophosphamide (BUCY2).
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PMID:Individual criteria could be optimal for starting G-CSF application after autologous stem cell transplantation. 938 26

Extensive pretreatment has been identified as a significant risk factor for failure of sufficient PBSC mobilization. From published data and our own experience we defined pretreatment variables which render patients at risk for not collecting at least 2.5 x 10(6) CD34-positive cells per kg bodyweight (BW). These variables were previous unsuccessful PBSC mobilization trial, previous large field radiotherapy, four or more cycles of myelosuppressive chemotherapy regimens, and combinations of extended field radiotherapy plus chemotherapy. Based on these inclusion criteria we treated 19 patients with disease-specific conventional-dose chemotherapy followed by sequential subcutaneous administration of IL-3 (5 microg/kg BW) for 5 consecutive days and G-CSF (10 microg/kg) until PBSC collection or neutrophil recovery. Patients were 10 males and nine females with a median age of 43 years. Diagnoses were non-Hodgkin's lymphoma n = 5, Hodgkin's disease n = 2, multiple myeloma n = 2, CML n = 4, AML n = 4 and testicular cancer n = 2. Twelve patients had prior unsuccessful trial of PBSC mobilization with chemotherapy followed by G-CSF. Except for mobilization chemotherapy-related neutropenic fever, no major toxicities (WHO grade > or = 2) were observed. Growth factors were well tolerated. Collection of at least 2.5 x 10(6) CD34-positive cells per kg BW was possible in 11 out of 19 patients (58%). In five out of 12 patients with a previous unsuccessful trial of PBSC mobilization, the study regimen mobilized sufficient CD34-positive cells. Nine patients went on to high-dose chemotherapy followed by autologous PBSC transplantation. Prompt hematologic recovery was seen in all of them. In conclusion, the sequential administration of IL-3 followed by G-CSF after conventional-dose chemotherapy allows successful PBSC collection in the majority of extensively pretreated patients.
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PMID:Peripheral blood stem cell (PBSC) mobilization with chemotherapy followed by sequential IL-3 and G-CSF administration in extensively pretreated patients. 946 74

We studied platelet recovery in relation to graft content in CFUs and CD34+ cells in 31 patients with multiple myeloma (21) or non-Hodgkin lymphoma (10) receiving marrow-ablative therapy followed by autologous transplantation with G-CSF mobilized CD34+ cells purified from leukapheresis products. Twelve patients had prolonged post-transplantation thrombopenia (> or = 14 days): their graft contents in CD34+ cells, CFU-GM and BFU-E were significantly inferior to those of patients with rapid platelet recovery. Although numbers of infused CD34+ cells and CFU-GM or BFU-E were well correlated, the graft content in CD34+ cells was the only parameter predictive of platelet recovery (r = -0.38, p = 0.04), with a threshold of 2.5 x 10(6) CD34+ cells/kg. However, because rapid platelet reconstitution was obtained for 4 of 16 patients re-infused with < 2.5 x 10(6) CD34+ cells/kg, we investigated whether the graft CFU-MK content might be a better predictor of platelet reconstitution than the CD34+ cell content. Eighteen CD34 grafts were studied for CFU-MK content: CD34 and CFU-MK contents were weakly correlated (r = 0.52, p = 0.03), but there was no correlation between numbers of infused CFU-MK and time to platelet recovery. We conclude that, for autologous CD34 grafts, CFU-MK assays, like CFU-GM or BFU-E assays, cannot be used to predict platelet recovery. A CD34+ cell content > or = 2.5 x 10(6)/kg remains the only reliable indicator of the platelet reconstitution capacity of a CD34 graft.
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PMID:Analysis of platelet recovery after autologous transplantation with G-CSF mobilized CD34+ cells purified from leukapheresis products. 949 91

G-CSF is given after autologous progenitor cell transplantation to accelerate neutrophil engraftment. Historically, G-CSF has been started on the day of progenitor cell infusion. To study the timing of the initiation of G-CSF after autologous peripheral blood progenitor cell (PBPC) transplantation, we conducted a prospective, randomized trial comparing the initiation of G-CSF therapy on day 0, day +3 or day +5 after autologous PBPC transplantation. Seventy patients with diagnoses of breast cancer, non-Hodgkin's lymphoma, Hodgkin's disease, or multiple myeloma were prospectively randomized to one of the three treatment arms. All patients were treated with a chemotherapy (only) preparative regimen. The source of hematopoietic reconstitution was PBPC alone (without autologous marrow), and all patients yielded a minimum of 2 x 10(6) CD34+ cells per kilogram. Times to neutrophil engraftment and platelet engraftment were identical in the three treatment groups, with neutrophil engraftment occurring at a median of 10, 11 and 11 days when starting G-CSF on day 0, day 3 or day 5, respectively. Time to platelet transfusion independence was 14, 11 and 14 days by treatment group. We conclude that delaying the initiation of G-CSF from day 0 to day +5 does not affect engraftment and results in cost savings.
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PMID:Delayed G-CSF after autologous progenitor cell transplantation: a prospective randomized trial. 982 88

Autologous peripheral blood stem cell transplantation (APBSCT) is a method used analogically to autologous bone marrow transplantation (ABMT) to obtain hematological reconstitution following myeloablative therapy in patients with hematological malignancies. We have now applied this procedure in two patients with recurrent high risk Hodgkin's disease. Collection of circulating stem cells mobilised with cyclophosphamide/G-CSF was performed by several leukaphereses on Fenwal 3000, with access through inferior vena cava. Nucleated cells were separated by dextran sedimentation, cryopreserved, and stored at (-) 196 degrees C. Additional marrow collection was performed in one patient. Conditioning regimen consisted of BCNU, etoposide and cyclophosphamide delivered at days -3 and -2. Collected material containing on average 3.6 x 10(8)/kg nucleated cells and 8.0 x 10(6)/kg CD34(+) cells was transfused at day 0. G-CSF was administered following transplantation to one patient to hasten the recovery. Hematological recovery was relatively quick. Neither serious adverse events nor signs of relapse were observed following transplantation. Our results supported by other's reports indicate, that APBSCT enables hematological recovery similarly to ABMT in Hodgkin's disease. The advantage of APBSCT is a possibility to collect material in patients with marrow involvement, hypoplasia or fibrosis. Outcomes obtained following APBSCT are at least as good as following ABMT. High-dose chemotherapy followed by APBSCT or ABMT should be considered in all patients with recurrent Hodgkin's disease sensitive to chemotherapy.
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PMID:[Autologous peripheral blood stem cell transplantation as an effective treatment for recurrent Hodgkin's disease]. 953 61

This second part of the review looks at change seen in the bone marrow haemostasis and malignancies found in HIV infection. Examination of bone marrow is requested in the presence of cytopaenias, splenomegaly, lymphomas and myelodysplasia. The findings include marrow hypocellularity, myelodysplasia and poor marrow recovery. Dysmegakaryocytpoiesis is found in 88% while dyserythropoeisis in 83% of cases. Mechanisms leading to these pertubations include direct HIV effect on marrow progenitor cells, effect of drugs and other infective diseases. Altered levels and functions of growth modifies IL6 and G-CSF are also to contribute. Haemostatic disorder frequently noted is bleeding due to thrombocytopaenia. Non-Hodgkin's lymphomas with aggressive characteristics and Kaposi's sarcoma are the commonly associated malignancies. Currently IL6 is being linked with the causation of KS and NHL. While standard approaches to the management of these malignancies tend to be the practices, adjustments are usually necessary in most patients.
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PMID:Haematological changes in human immunodeficiency virus infection. Part II. 955 50

Thirty-five aggressive non-Hodgkin's lymphomas (NHL) with marrow involvement received high-dose cyclophosphamide (7 g/m2) and G-CSF in order to collect peripheral blood progenitor cells (PBPC). Fourteen patients were in partial remission, 16 patients were in relapse ("sensitive", 12; "resistant", 4) and 5 patients were in refractory to conventional treatment. A good yield of PBPC was obtained in 30 patients, while a low number of CD34+ cells and of CFU-GM was seen in two cases. Two patients entered progression and one patient died. Thirty patients underwent PBPC autografting. Twenty-nine out of 35 (83%) patients entered complete remission (CR). Two patients died in CR of infection following marrow aplasia 3 and 6 months after autografting. At 3 years the probability of survival and disease-free survival (DFS) are of 62% and 51% respectively.
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PMID:Mobilization/transplantation of peripheral blood progenitor cells for aggressive non-Hodgkin's lymphoma with marrow involvement. 957 Jun 84


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