Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q06643 (non-Hodgkin's lymphoma)
 11,307 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

In this study, 16 eligible patients with intermediate and high-grade non-Hodgkin's lymphoma were treated with a new high-dose DHACT regimen supported by rhG-CSF and peripheral blood stem cell (PBSC) rescue. PBSC were mobilized by rhG-CSF or rhGM-CSF. Single leukapheresis was performed and the PBSC were then frozen in liquid nitrogen. CFU-GM clonogenic assay for mononuclear cells and resuscitated progenitor cells done to calculate how many progenitor cells were alive after freezing. The DHACT chemotherapy was composed of carboplatin 600 mg/m2 on d1, Ara-C 1500 mg/m2 on d2, VM-26 100 mg/m2 on d3, 4, and dexamethasone 40 mg/d, on d1-4. Autologous PBSC was reinfused after 24 to 48 hours of chemotherapy. Recombinant human G-CSF at 300 micrograms administered daily on 2 successive days when the absolute neutrophil count was greater than 1 x 10(9)/L. Other supportive care procedures were standard for the unit. The median amount of PBSC reinfused into a patient was 0.9 x 10(8)/kg. The recovery rate of CFU-GM was 78% after cryopresevation. Within 7 to 9 days after high-dose DHACT chemotherapy, the WBC count and the platlet count arrived nadir, and then rose gradually with rhG-CSF injection. The median time for WBC count from nadir to > or = 1 x 10(9)/L was 4 days, and that for platelet count from nadir to > or = 50 x 10(9)/L was 7 days. Nine patients achieved complete remission and 5 patients achieved partial remission. The median follow-up on survival was 9 months. High-dose DHACT regimen supported by rhG-CSF and PBSC rescue is a safe and effective treatment for patients with advanced intermediate and high-grade non-Hodgkin's lymphoma.
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PMID:[High-dose chemotherapy supported by peripheral blood stem cells to treat intermediate--and high-grade non-Hodgkin's lymphomas]. 938 7

We assessed the concentration of haemopoietic progenitors in peripheral blood in six patients with de novo intermediate grade non-Hodgkin's lymphoma receiving multiple cycles of escalated dose epirubicin and cyclophosphamide on day 1 followed by 5 microg/kg of G-CSF (filgrastim) on days 2-14. Specimens were taken at days 12, 15 and 18 in cycles 1 and 2 and on day 15 for cycles 3-6. Progenitor numbers were maximal on day 15 in cycles 1 and 2. The median number of granulocyte-macrophage colony forming cells (GM-CFC) and CD34+ cells on day 15 of cycles 1 and 2 was 3.8 x 10(4)/ml and 11 x 10(4)/ml, respectively. A 600 ml venesection at this time would contain a median of 36 x 10(4) GM-CFC/kg (range 25-47) and 1.04 x 10(6) CD34+ cells/kg (range 0.73-1.4), based on individual patient weights. Day 15 progenitor numbers were maintained for the first 3 cycles but tended to fall thereafter. The viability of the progenitors collected in whole blood and stored at 4 degrees C for various time intervals was also assessed. The median percent of GM-CFC and erythroid blast forming units (BFU-e) surviving after storage for 48 hrs was 79% and 69% respectively and after 72 hrs was 48% and 63% respectively. Serum collected 2 hrs after the completion of chemotherapy had minimal inhibitory effect on progenitors collected prior to treatment. Our data demonstrate that two weeks after anthracycline-based chemotherapy and G-CSF in previously untreated patients the peripheral blood contains large numbers of progenitors. A 600 ml venesection at this time stored at 4 degrees C, and then reinfused after the next cycle of chemotherapy would contain sufficient viable progenitors to potentially hasten haematological recovery.
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PMID:Viability and quantification of progenitor cells in venesected blood from patients receiving escalated-dose epirubicin and cyclophosphamide with G-CSF for lymphoma: potential role in further increasing dose-intensity. 940 32

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

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

We hypothesized that the conventional ProMACE-CytaBOM regimen could be improved by administering all drugs on d1 with the S-phase agents first in the sequence, prednisone d2-6 only, increasing doxorubicin to 50 mg/m2, and adding G-CSF d2-13 to ameliorate neutropenia. This regimen was tested in a Phase I study of 20 patients (pt) with non-Hodgkin's lymphoma (NHL). The median age was 61 yrs (range, 29-79). Four pt had low grade and 16 intermediate/high NHL. The International Prognostic Index was low in 6 cases, low-intermediate in 12, and high-intermediate in 2. Twelve pt received > or =6 cycles; 4 had 5 cycles, 3 had 4 cycles, and 1 received only 1 cycle. Sixteen pt received subsequent cycles without delay. The response rate was 95% (19/20) with 12 CR and 7 PR; one pt progressed during treatment. After a median follow-up of 30 months, 85% (17/20) remain alive. This higher dose ProMACECytaBOM regimen can be given to older adult patients in an outpatient setting. Phase III studies would be required to determine if it produces a superior overall survival compared to other regimens.
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PMID:A phase I trial of high dose ProMACE-CytaBOM with granulocyte colony stimulating factor for patients with non-Hodgkin's lymphoma. 951 2

In order to evaluate the potential clinical and economic benefits of granulocyte colony-stimulating factor (G-CSF, filgrastim) following peripheral blood progenitor cells (PBPC) rescue after high-dose chemotherapy (HDCT), 23 consecutive patients aged less than 60 years with poor-prognosis, high-grade non-Hodgkin's lymphoma (NHL) were entered into a prospective randomized trial between May 1993 and September 1995. Patients were randomized to receive either PBPC alone (n = 12) or PBPC+G-CSF (n = 11) after HDCT with busulphan and cyclophosphamide. G-CSF (300 microg day[-1]) was given from day +5 until recovery of granulocyte count to greater than 1.0 x 10(9) l(-1) for 2 consecutive days. The mean time to achieve a granulocyte count > 0.5 x 10(9) l(-1) was significantly shorter in the G-CSF arm (9.7 vs 13.2 days; P<0.0001) as was the median duration of hospital stay (12 vs 15 days; P = 0.001). In addition the recovery periods (range 9-12 vs 11-17 days to achieve a count of 1.0 x 10(9) l[-1]) and hospital stays (range 11-14 vs 13-22 days) were significantly less variable in patients receiving G-CSF in whom the values clustered around the median. There were no statistically significant differences between the study arms in terms of days of fever, documented episodes of bacteraemia, antimicrobial drug usage and platelet/red cell transfusion requirements. Taking into account the costs of total occupied-bed days, drugs, growth factor usage and haematological support, the mean expenditure per inpatient stay was pound sterling 6500 (range pound sterling 5465-pound sterling 8101) in the G-CSF group compared with pound sterling 8316 (range pound sterling 5953-pound sterling 15,801) in the group not receiving G-CSF, with an observed mean saving of 1816 per patient (or 22% of the total cost) in the G-CSF group. This study suggests that after HDCT and PBPC rescue, the use of G-CSF leads to more rapid haematological recovery periods and is associated with a more predictable and shorter hospital stay. Furthermore, and despite the additional costs for G-CSF, these clinical benefits are not translated into increased health care expenditure.
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PMID:Recombinant human granulocyte colony-stimulating factor (filgrastim) following high-dose chemotherapy and peripheral blood progenitor cell rescue in high-grade non-Hodgkin's lymphoma: clinical benefits at no extra cost. 957 36

Many centers use CY and G-CSF to mobilize PBPC. In this study we explored whether a standard chemotherapy regimen consisting of mitoguazon, ifosfamide, MTX and etoposide (MIME) combined with G-CSF was capable of mobilizing PBPC in lymphoma patients. Twelve patients with Hodgkin's disease (HD) and 38 patients with non-Hodgkin's lymphoma (NHL) were mobilized with MIME/G-CSF. Most patients were heavily treated with different chemotherapy regimens receiving a median of 11 cycles (range 3 to 20) of chemotherapy prior to mobilization. It was found that the optimal time of PBPC harvest was at days 12 and 13 after initiating the mobilization regimen. The median number of collected CD34+ cells per kg body weight was 7.1 x 10(6) (range 0.5-26.2). More than 2.0 x 10(6) CD34+ cells/kg were achieved in 69% of the patients after one apheresis. When additional cycles of apheresis were done, only 6% failed to harvest this number of CD34+ cells. There was a statistically significant inverse correlation between the number of prior chemotherapy cycles and CD34+ cell yield (P = 0.003). No such association was found between CD34+ cell yield and prior radiotherapy. When MIME/G-CSF was compared with Dexa-BEAM/G-CSF, it was found that MIME/G-CSF tended to be more efficient in mobilizing PBPC in spite of being less myelotoxic. All patients transplanted with MIME/G-CSF mobilized PBPC had fast and sustained engraftment. These results demonstrate that an ordinary salvage chemotherapy regimen, such as MIME combined with G-CSF can be successfully used to mobilize PBPC.
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PMID:Combination chemotherapy with mitoguazon, ifosfamide, MTX, etoposide (MIME) and G-CSF can efficiently mobilize PBPC in patients with Hodgkin's and non-Hodgkin's lymphoma. 961 78


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