Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027947 (neutropenia)
 17,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The pharmacokinetics of methotrexate (MTX) in the proliferating and the maturing myeloid compartments of the bone marrow and in the neutrophils of the peripheral blood was investigated in four patients with malignant non-Hodgkin's lymphoma after treatment with 24-h MTX infusions (500-790 mg/m2) followed by leukovorin rescue. The myeloid bone marrow cells were separated into two fractions, using a two-step discontinuous Percoll gradient with densities of 1.076 and 1.095 g/ml. The upper fraction consisted predominantly of immature bone marrow cells plus lymphocytes, and the lower fraction contained the mature myeloid bone marrow cells. Cells in the proliferating (immature) myeloid compartment took up and retained MTX to a much greater extent than the mature myeloid cells and the neutrophils. Two days after the MTX infusion no MTX was detected in the neutrophils in spite of a general rise in the total neutrophil count. MTX reappeared in the neutrophils on day 8 in concentrations not related to the concentrations in the proliferating myeloid cells during the MTX infusion. The time of reappearance of MTX in the neutrophils was in accordance with the time it takes for cells in the proliferating pool of the bone marrow to mature and be released into the circulation. No neutropenia was seen after the MTX infusions.
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PMID:Methotrexate kinetics in myeloid bone marrow cells and peripheral neutrophils. 381 25

Twenty-two patients with non-Hodgkin's lymphoma were treated with a four-drug combination of mitoxantrone, etoposide, cisplatin and prednisolone (MEPP) after their disease had failed to respond to, or had relapsed after, induction chemotherapy consisting of cyclophosphamide, adriamycin, vincristine and prednisolone with/without bleomycin (CHOP/CHOP-bleo). Of 18 evaluable patients, four (22%) achieved complete remission and six (33%) responded partially. The median duration of response was 29 weeks (range, 9 to 54 weeks). The median survival time was 45 weeks for responders and 22 weeks for non-responders. Gastrointestinal toxicity was common, but well tolerated. Myelosuppression was the major dose-limiting toxicity: 11 patients (61%) experienced a febrile episode during periods of neutropenia and two patients, both of whom had massive bone marrow involvement of the disease, succumbed to infection. Despite the moderate to severe myelotoxicity, these results provide evidence that MEPP is an effective regimen for non-Hodgkin's lymphoma resistant to CHOP or CHOP-bleo.
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PMID:[Salvage chemotherapy of non-Hodgkin's lymphoma with a four-drug combination of mitoxantrone, etoposide, cisplatin and prednisolone (MEPP)]. 382 58

Forty evaluable patients with malignant lymphoma (ML) were treated with bisantrene at a dose of 260 mg/m2 every 3 weeks (18 patients) or 208 mg/m2 every 3 weeks (22 patients). The initial dose rate was determined on the basis of expected myelosuppression. Patients were heavily pretreated and had advanced disease (92% had stage IV). The overall response rate was 10% and included 1 partial response (PR) in 17 patients with Hodgkin's disease (HD), 1 PR and 1 complete response (CR) in 5 patients with favorable histology in non-Hodgkin's lymphoma (NHL), and 1 PR in 18 patients with unfavorable histology in NHL. Neutropenia (WBC less than or equal to 3000 cells/microliter) was the most common toxicity, occurring in 50% of patients. Phlebitis was a common side effect in patients treated with bisantrene administered by way of peripheral veins. Bisantrene has limited activity in heavily pretreated patients with HD or unfavorable histology in NHL. The role of bisantrene for treatment of NHL with favorable histology or for treatment at an earlier point in the natural history of ML is unknown.
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PMID:A phase II study of bisantrene in malignant lymphomas. A Southwest Oncology Group Study. 394 Feb 22

Navelbine (NVB) is a new semi-synthetic Vinca alkaloid selected on the basis of its affinity for tubulin. NVB inhibits the polymerisation of tubulin and it has significant antitumor activity on P388 and L1210 leukemias and some other experimental tumors. In the present study, 20 patients (9 carcinomas, 10 lymphomas and 1 blastic crisis of chronic myeloid leukemia) received a median of 4 weekly i.v. doses of NVB. Two patients at least received each dose level: 3.6 mg/m2 (1/10 of the LD10 dose/kg in BDF1 mice), 7.2, 12, 18, 32.4, 35 and 43 mg/m2 per week. A total of 89 doses were administered. All patients had been first heavily pretreated and 17 of them had received a Vinca alkaloid. Leukopenia (neutropenia) was the dose-limiting toxicity. There was no thrombocytopenia. Leukopenia was dose-related and first seen at 32.4 mg/m2 per week. The maximal tolerated dose appears to be about 43 mg/m2. At that dose, 2 out of 3 patients developed severe leukopenia and neutropenia. One localized allergic reaction, one case of transient hepatic dysfunction, and 2 reversible peripheral neuropathies were seen. Pharmacokinetics, studied with a radioimmunoassay (RIA) method, suggested an elimination half-life of 30 h and a plasma clearance of 75 l/h. Four patients with Hodgkin's disease and two patients with non-Hodgkin's lymphoma, all of them refractory to vincristine (VCR) and/or vinblastine (VBL), showed minor responses lasting 2-8 weeks. They had received between 4 and 12 doses of 30 and 43 mg/m2. We recommend for phase 11 trials the dose of 40 mg/m2 per week.
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PMID:Phase I pharmacologic study of a new Vinca alkaloid: navelbine. 401 23

A phase II study of vindesine in 41 evaluable patients demonstrated the drug to be active in heavily pretreated patients with breast cancer, non-Hodgkin's lymphoma, and other tumors. There were two partial responses in 11 patients with breast cancer (18%) and five partial responses and one complete response in 11 patients with non-Hodgkin's lymphoma (40%). Other responses were seen in small cell carcinoma of the lung, ovarian carcinoma, and Hodgkin's disease. Prior vinca exposure did not adversely affect the response rate. Neutropenia was dose-limiting. Neurotoxic effects occurred in 10% of the patients. A high incidence of local tissue reactions at the injection site (27%) could be reduced by a careful administration technique. Vindesine should be studied further in combination with other agents.
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PMID:Phase II trial of vindesine in the treatment of lymphomas, breast cancer, and other solid tumors. 744 18

Increased numbers of bone marrow mast cells were found in 45 (2.2%) of 2,000 bone marrow specimens obtained from patients who had hematologic disorders. Mast cells were most frequently seen in the marrows of patients who had preleukemic syndromes, lymphoproliferative disorders, and acute leukemia. The 16 patients who had preleukemic syndromes included those with refractory sideroblastic and megaloblastic anemia (with or without an excess of blasts), idiopathic pancytopenia or pure erythrocytic aplasia, paroxysmal nocturnal hemoglobinuria, idiopathic refractory neutropenia, agranulocytosis or thrombocytopenia, and persistent eosinophilia. Five of the seven patients who had acute leukemia had nonlymphoblastic leukemia; two had blastic crisis of chronic granulocytic leukemia. Of the 13 patients who had lymphoproliferative disorders, eight had chronic lymphocytic leukemia, three had macroglobulinemia, and two had non-Hodgkin's lymphoma. Three patients who had chronic renal failure associated with severe anemia and two who had chronic liver disease, splenomegaly, or hypersplenism were also encountered. In this study there appeared to be a consistent relationship between the presence of increased numbers of mast cells and the lymphocyte and plasma cell counts in the bone marrow. The significance of the presence of secondary mastocytosis in premalignant lesions, neoplasia, and, in particular, lympho- and myeloproliferative disorders, is still unclear.
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PMID:Increased bone marrow mast cells in preleukemic syndromes, acute leukemia, and lymphoproliferative disorders. 745 27

Hematopoietic growth factors, including granulocyte colony-stimulating factor (G-CSF), are being increasingly used to prevent chemotherapy-induced neutropenia. We report a patient with aggressive non-Hodgkin's lymphoma who was successfully supported with G-CSF through a weekly VACOP-B chemotherapy regimen. The patient had become severely neutropenic at week 3, requiring a one-week delay. For the remainder of the treatment, G-CSF at a dose of 4 micrograms/kg/day was administered daily over 4 days after week 4, then over 3 days thereafter, beginning the day after the non-myelosuppressive weeks (vincristine/bleomycin). A total of 5 such G-CSF courses were given, with no further neutropenia despite administration of full chemotherapy doses on schedule. This case suggests that, at least with the VACOP-B regimen, chemotherapy-induced neutropenia can be prevented using much lower quantities of G-CSF than has been reported using other regimens.
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PMID:Prevention of chemotherapy-induced neutropenia using G-CSF with VACOP-B--a case report. 751 Jan 92

We report the safety and efficacy of autologous bone marrow transplantation (ABMT) in 30 patients with high-grade non-Hodgkin's lymphoma (NHL) in first complete remission (CR1) following remission induction chemotherapy. Two patients relapsed prior to ABMT. All patients were conditioned with high-dose melphalan. In Addition, ten received fractionated total body irradiation, one hemi-body irradiation and four high-dose etoposide. Unmanipulated non-cryopreserved autologous marrow was reinfused within 56 h of harvesting. Engraftment occurred in all patients with a median of 11 days of neutropenia (< 0.5 x 10(9) l-1), a median requirement for platelet transfusion of 3 days and packed red cell transfusion of 2 units, with a median hospital stay of 18 days post transplant. There was no procedure-related mortality and only minor morbidity was observed. Two patients relapsed at 1 and 2 months post transplantation, and one patient died of carcinoma of the lung 33 months after transplantation. The remaining 25 patients remain alive, well and in CR1 with a median follow-up of 44 months. The event-free survival at 3 years for all patients considered for ABMT was 83%. We conclude that ABMT for high-grade NHL in CR1 with non-cryopreserved marrow results in rapid haematological recovery without growth factor support. It is safe and is associated with high survival when used as consolidation of CR in high-risk patients.
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PMID:Autologous bone marrow transplantation in poor-risk high-grade non-Hodgkin's lymphoma in first complete remission. Newcastle and Northern Lymphoma Group. 752 62

The clinical effects of COP-BLAM III combination chemotherapy and recombinant human granulocyte colony-stimulating factor (rhG-CSF) were examined in 60 patients with intermediate or high-grade non-Hodgkin's lymphoma (NHL). The patients consisted of 37 men and 23 women with a median age of 53 years. The modified COP-BLAM III regimen based on the method of Boyd et al. consisted of six cycles of 6 weeks duration each. The complete remission rate for all patients was 83.3% (50 of 60 patients). With the median observation duration of 47.5 months, the overall median survival time for all patients was 86 months or more. The disease-free survival rate for the 50 CR patients was 88.2% at 86 months. The incidence of infections was significantly reduced by the concomitant use of rhG-CSF. The most common adverse effect was neutropenia (< or = 1000/microliters). The percent diffusing capacity for carbon monoxide in the lung (%DLCO) was reduced in 12 of the 60 patients (20.0%). We conclude that COP-BLAM III is a useful regimen for intermediate and high-grade NHL. However, caution is required since some elderly patients had reduced pulmonary function.
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PMID:Combination chemotherapy with COP-BLAM III for intermediate and high-grade non-Hodgkin's lymphoma. 752 16

The clinical usefulness of Recombinant Human Granulocyte Colony Stimulating Factor (rhG-CSF, Filgrastim, GRAN) was evaluated in patients with leukopenia and neutropenia following chemotherapy for non-Hodgkin's lymphoma, lung cancer and breast cancer. During chemotherapy when patients' leukocyte count (WBC) fell below 4.0 x 10(9)/L.rhG-CSF(GRAN) at a dose of 75 micrograms/body.day was given subcutaneously 48 hours after the termination of chemotherapy. The results indicated that rhG-CSF(GRAN) could elevate nadirs of WBC and significantly shortened leukopenic period with WBC below 4.0 x 10(9)/L and expedited the recovery of WBC. rhG-CSF (GRAN)'s side effects were mild.
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PMID:[Clinical study of recombinant human granulocyte colony stimulating factor (rhG-CSF) on leukopenia induced by chemotherapy in cancer patients]. 752 73


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