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)

The effects of granulocyte-colony stimulating factor (G-CSF) have been studied in several clinical settings. G-CSFs are widely used to stimulate the production of granulocytes and are well known to mobilize peripheral blood stem cells (PBSCs). However, very few studies have examined differences among G-CSFs. The aim of this study was to compare the mobilization of PBSCs induced by a standard dose of two G-CSFs following biweekly cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) therapy. Using a standard dose of G-CSF, we conducted a randomized, crossover trial that compared the efficacy of two kinds of G-CSF, glycosylated [lenograstim (2 micrograms/kg)] and mutated [nartograstim (1 microgram/kg)], on PBSC mobilization in 10 patients with non-Hodgkin's lymphoma after biweekly CHOP chemotherapy. Lenograstim (2 micrograms/kg) was more effective in shortening the duration of neutropenia than nartograstim (1 microgram/kg) (3.8 days vs. 5.0 days, p < 0.05, the number of days for the neutrophil count to reach 5 x 10(9)/l from nadir). The number of CD34+ cells and granulocyte-macrophage colony forming units (GM-CFU) was higher for lenograstim but no statistically significant difference between the two groups was found. Glycosylated G-CSF is more effective than mutated G-CSF in shortening the duration of neutropenia. As for the mobilization of CD34+ cells and the number of CFU-GM, there was a tendency to increase in the lenograstim group but no statistically significant differences were found.
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PMID:Mobilization of peripheral blood stem cells by granulocyte-colony stimulating factors: comparison of a standard dose of glycosylated and mutated granulocyte-colony stimulating factor in non-Hodgkin's lymphoma patients following CHOP therapy. 1076 30

High-dose chemotherapy with autologous hematopoietic stem cell transplantation has been expected to result in a promising outcome in high risk aggressive non-Hodgkin's lymphoma (NHL). However, it remains unknown what type of initial chemotherapy is optimal, especially regarding progenitor cell mobilization. Sixty-three untreated patients with aggressive NHL in a high risk group were randomized to either a biweekly arm with 8 cycles of standard CHOP or 6 cycles of the dose-escalated CHOP arm with cyclophosphamide 1.5 g/m2 and doxorubicin 70 mg/m2. Lenograstim (glycosylated rHuG-CSF 2.0 microg/kg/day) was administered daily from day 3 to patients in both arms. The mobilization effect of the two regimens on circulating CD34+ cells was evaluated. Twenty-seven of 29 patients in the biweekly CHOP arm and 33 of 34 patients in the dose-escalated CHOP were assessable. Dose-escalated CHOP yielded a significantly higher number of circulating CD34+ cells in the first cycle compared with biweekly CHOP (p=0.05). The peak number of circulating CD34+ cells with biweekly CHOP did not significantly change from cycle to cycle; however, in dose-escalated CHOP, the peak number of circulating CD34+ cells mobilized after the fifth and sixth cycle was lower than after the first cycle (p=0.07 and 0.009, respectively). Routine conventional-dose chemotherapy and low-dose G-CSF can mobilize sufficient CD34+ cells in patients with aggressive NHL. The mobilization kinetics of circulating progenitor cells in patients with aggressive NHL is dependent on the dosage and schedule of CHOP.
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PMID:Randomized comparison of mobilization kinetics of circulating CD34+ cells between biweekly CHOP and dose-escalated CHOP with the prophylactic use of lenograstim (glycosylated rHuG-CSF) in aggressive non-Hodgkin's lymphoma. The lenograstim/Lymphoma Study Group. 1095 73

While CHOP therapy is effective for malignant lymphoma, the optimum schedule for elderly patients remains controversial. The present study investigated the usefulness of reduced-dose CHOP therapy for elderly patients. Previously untreated patients aged 65 years or older with intermediate to high-grade non-Hodgkin's lymphoma were given up to 6 courses of reduced-dose CHOP therapy at 3-week intervals. Group A patients were given (5/6) of the standard dose and Group B received 7/12 of the standard dose. Filgrastim was administered when the white blood cell count fell below 2,000/microL. Fifty-seven patients were evaluable and the scheduled therapy was completed in 37. For patients aged from 65 to 79 years and for patients older than 80 years, the complete response rate was 79.5% and 46.2%, overall 3-year survival was 58.2% and 30.4%, and event-free 3-year survival was 49.3% and 44.4%, respectively. Major toxicities (> or = grade 3) included leukopenia in 42 patients and documented infection in 7 patients. Grade 3 cardiac plus renal failure, grade 3 peritonitis due to small bowel perforation, and grade 3 liver dysfunction occurred in 1 patient each. One patient died of toxicity (grade 4 hematological toxicity and pneumonia). In conclusion, it seems that in the elderly patients with non-Hodgkin's lymphoma, response to reduced-dose ((5/6) dose) CHOP therapy is comparable to that for standard CHOP in younger adults, mainly because of improved dose-intensity.
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PMID:Reduced-dose chop therapy for elderly patients with non-Hodgkin's lymphoma. 1137 49

Filgrastim (r-metHuG-CSF) was approved in the United States in 1991 for use in decreasing the incidence of infection, as manifested by febrile neutropenia, in patients with nonmyeloid malignancies treated with myelosuppressive chemotherapy. Colony-stimulating factors such as filgrastim are a significant advance in the supportive care of patients with cancer. However, because of its short half-life, filgrastim requires daily dosing by injection to maintain its effects on the bone marrow. Pegfilgrastim (Neulasta; Amgen, Thousand Oaks, CA) is a longer-acting, self-regulating form of filgrastim created by the covalent linkage of a 20-kd polyethylene glycol molecule to the N-terminal of the filgrastim molecule. The molecular characteristics of pegfilgrastim result in a longer terminal half-life, making once-per-chemotherapy-cycle administration possible. The results from two randomized double-blind phase III clinical trials in patients with breast cancer treated with myelosuppressive chemotherapy showed that a single dose of pegfilgrastim provides neutrophil support comparable with that provided by an average of 11 daily injections of filgrastim. Pegfilgrastim has also been shown to be comparable to filgrastim in reducing neutropenic complications in patients treated with chemotherapy for lymphoma. Data from three clinical trials have been presented: a randomized controlled trial in elderly patients treated with CHOP (cyclophosphamide/doxorubicin/vincristine/prednisone) for relapsed or refractory non-Hodgkin's lymphoma; a randomized controlled trial in patients treated with ESHAP (etoposide/methylprednisolone/cisplatin/cytarabine) for relapsed or refractory lymphoma; and a study in patients with newly diagnosed non-Hodgkin's lymphoma. The safety profile of pegfilgrastim is comparable to that of filgrastim in the clinical settings studied to date. The once-per-cycle administration of pegfilgrastim may improve patient quality of life because it is less disruptive to patients and caregivers, and increase adherence because no doses are missed, thus further advancing the management of chemotherapy-induced neutropenia and its consequences.
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PMID:Once-per-cycle pegfilgrastim (Neulasta) for the management of chemotherapy-induced neutropenia. 1450 17

A high incidence of nonrelapse mortality (NRM) has limited the use of allogeneic transplantation for poor prognosis non-Hodgkin's lymphoma (NHL). We sought to improve the outcome of allografting by utilizing Filgrastim-mobilized peripheral blood stem cells (PBSC) in combination with either standard ablative or reduced-intensity conditioning. A total of 21 patients with intermediate/high-grade lymphoma and seven patients with low-grade histology were enrolled on protocols using PBSC. All patients were considered high risk for recurrence and/or NRM because of age >50 (n=16), refractory disease (n=17), failed autologous transplant (n=11) and abnormal organ function (n=2). In all, 17 patients received ablative regimens and 11 received modified conditioning including fludarabine, intravenous busulfan and ATG. Tacrolimus and mini-dose methotrexate were used for graft-versus-host-disease (GVHD) prophylaxis. Median follow-up was 38 months. Disease-free and overall survival were 57 and 58%. Seven of the 11 patients who relapsed after a previous transplant remain disease free. Four of the 10 patients with recurrent/persistent disease post transplant responded to additional therapy including withdrawal of immunosuppression+/-DLI. These results support a potent graft-versus-lymphoma effect and suggest that patients who relapse after an autologous transplant can be salvaged with an allogeneic transplant.
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PMID:Allogeneic peripheral blood stem cell transplantation for high-risk non-Hodgkin's lymphoma. 1452 Apr 19

Chemotherapy-induced myelosuppression is the most common dose-limiting side effect of cancer chemotherapy. Neutropenia is a serious risk with chemotherapy, associated with infectious complications, use of intravenous antibiotics, hospitalization, and even death. The occurrence of febrile neutropenia can lead to dose reductions and delay in subsequent cycles of chemotherapy that may have a detrimental affect on overall survival and disease-free survival. Granulocyte colony-stimulating factors (G-CSF) can reduce the duration of severe neutropenia, the incidence of febrile neutropenia, and allow planned dosing and timing of chemotherapy. Filgrastim is a G-CSF that has demonstrated benefit for the treatment and prophylaxis of chemotherapy-induced neutropenia (CIN), but its short half-life requires repeated daily subcutaneous injection. Pegfilgrastim is a recombinant G-CSF created by attaching a polyethylene glycol (PEG) molecule to the filgrastim protein. Once-per-cycle dosing of pegfilgrastim has been evaluated in clinical trials using myelosuppressive chemotherapy in breast cancer, Hodgkin's lymphoma, and non-Hodgkin's lymphoma. Trials have demonstrated that pegfilgrastim is comparable in safety and efficacy to filgrastim for decreasing the duration of severe neutropenia after chemotherapy in patients with nonmyeloid malignancy. This review will summarize recent clinical trial results and novel uses of pegfilgrastim.
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PMID:Pegfilgrastim use during chemotherapy: current and future applications. 1549 75

Dose densification and dose escalation of cytotoxic chemotherapy may be important in improving the cure rates of chemotherapy-responsive cancers. We conducted two phase I studies, in non-small cell lung cancer (NSCLC) and in lymphoma, to explore the possibility of intensifying chemotherapy by compressing the delivery of and escalating the dose of standard combination chemotherapy. One study used etoposide and cisplatin chemotherapy in patients with unresectable stage III or IV NSCLC, intensifying chemotherapy by reducing the cycle length. The second study used cyclophosphamide, doxorubicin, vincristine, and prednisone, CHOP chemotherapy, in the treatment of stage II-IV intermediate or immunoblastic high-grade lymphoma, intensifying chemotherapy first by reducing the cycle length and then by escalating the dosages of cyclophosphamide and doxorubicin. Filgrastim support was used during dose intensification. Fifty-five patients with NSCLC and 49 with non-Hodgkin's lymphoma (NHL) were enrolled and treated in successive cohorts. At standard dosages and intervals of chemotherapy, filgrastim support resulted in incidences of grade 3 and 4 neutropenia that were between 62% and 77% lower than those in the no-filgrastim control; the mean duration of neutropenia was, likewise, more than 80% lower. Absolute neutrophil counts were >/=2 x 10(9)/l at day 14 in virtually 100% of patients receiving filgrastim. In the NSCLC trial, etoposide and cisplatin were intensified by >50%, and in the lymphoma trial, cyclophosphamide was intensified by 270% and doxorubicin was intensified by 87%. Chemotherapy reductions or delays for neutropenia were rare in the groups receiving filgrastim; but at higher chemotherapy intensities, dose-limiting thrombocytopenia was encountered. We conclude that the delivery of myelosuppressive chemotherapy in both a dose-intense and a dose-dense manner is feasible with filgrastim support.
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PMID:Increasing chemotherapy dose density and intensity: phase I trials in non-small cell lung cancer and non-Hodgkin's lymphoma. 1570 16


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