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)

A retrospective clinical study was performed to determine the clinical impact of neutropenic enterocolitis (NE) in adult patients with acute leukemia and non-Hodgkin's lymphoma treated with cytosine arabinoside (Ara-C)-containing regimens. The diagnosis of NE was restricted to conditions with clinical signs of peritonitis, ileus, or intestinal hemorrhage. Forty episodes of NE were noted during 461 Ara-C-containing courses (8.6%) in 36 of 211 patients (17%) over a 6-year period. Clinically, 18 cases of ileus, 16 cases of peritonitis, and 6 cases of intestinal hemorrhage were recognized as the most important presentation of NE. NE started about 2 weeks after the initiation of the chemotherapy and lasted for an average of 1 week. All patients had a profound neutropenia. The incidence of septicemia was higher during courses complicated by NE (p less than 0.001). All cases of NE were treated with conservative measures. The mortality was 22.5% and represented one third of all therapy-related deaths during the pancytopenic period. The incidence of NE was significantly higher in courses consisting of high-dose Ara-C for 6 consecutive days when the drug was combined with amsacrine for 3 consecutive days (p less than 0.0001).
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PMID:Neutropenic enterocolitis following treatment with cytosine arabinoside-containing regimens for hematological malignancies: a potentiating role for amsacrine. 203 75

Thirty patients with human immunodeficiency virus (HIV)-associated non-Hodgkin's lymphoma (NHL) receiving chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) were randomized to receive either subcutaneous recombinant human granulocyte-macrophage colony-stimulating factor (rGM-CSF) or no additional therapy. Recombinant rGM-CSF (at a dose of 10-20 micrograms/kg/d) was given on days 1 to 10 (early rGM-CSF) to the first five patients, but was changed to days 4 to 13 (delayed rGM-CSF) of each chemotherapy cycle in subsequent patients. Compared with the control group (N = 10), the delayed rGM-CSF group (N = 11) had higher mean nadirs of the absolute neutrophil count (0.36 v 0.89 x 10(9)/L; P = .009), shorter mean durations of neutropenia (4.9 v 1.3 days; P = .02), fewer chemotherapy cycles complicated by neutropenia and fever (67% v 27%; P = .001), fewer days hospitalized for fever and neutropenia (4.9 v 1.8; P = .004), fewer reductions in chemotherapy dosages, and less frequent delays in chemotherapy administration. No significant differences were observed between patients in the control group and those in the early rGM-CSF group (N = 5). Median levels of serum HIV-1 p24 antigen decreased to 18% and 17% of baseline values in control (N = 4) and rGM-CSF groups (N = 6), respectively, 1 week following administration of the first cycle of chemotherapy. In the third week after chemotherapy, median antigen levels remained below baseline in the control group, but rose to 243% of baseline values in the rGM-CSF group (P = .01), suggesting stimulation of HIV replication. The effect of this change in HIV activity on clinical outcome of treated patients could not be determined, and therefore the clinical significance of this finding remains unclear. Complete response rates of 67%, 70%, and 60% were observed in the control, delayed rGM-CSF, and early rGM-CSF groups, respectively, with corresponding survival times of 9.0, 11.4, and 8.0 months.
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PMID:Clinical and virologic effects of recombinant human granulocyte-macrophage colony-stimulating factor in patients receiving chemotherapy for human immunodeficiency virus-associated non-Hodgkin's lymphoma: results of a randomized trial. 203 29

Data from several clinical trials in patients with solid tumors clearly demonstrate that recombinant human granulocyte-macrophage colony stimulating factor (rhGM-CSF) is able to shorten the time period of neutropenia after chemotherapy and to reduce neutropenia-related morbidity such as infections, time in hospital, etc. A placebo-controlled, double-blind multicenter trial including 81 patients with acute lymphoblastic leukemia and non-Hodgkin's lymphoma demonstrates the efficacy of rhGM-CSF to enhance engraftment (neutrophils greater than 0.5 x 10(3)/mm3) after autologous bone marrow transplantation (p less than 0.001) and to reduce the frequency of bacterial infections (34% vs. 56%). In addition, GM-CSF is able to shift the cell cycle of myeloid leukemic cells from the G0 to S phase in vitro and in vivo, which results in an increased sensitivity to cell-cycling-dependent cytostatic agents. Dose intensification of chemotherapy in patients with soft tissue sarcoma and metastatic breast cancer is possible due to adjuvant treatment with GM-CSF and results in a higher frequency of remissions. Further controlled clinical studies are warranted to support these results.
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PMID:New therapeutic modalities for the clinical use of rhGM-CSF in patients with malignancies. 204 60

Despite major advances in supportive care, neutropenic infections and thrombopenic bleedings remain major lethal treatment- and disease-related complications in patients with malignancy. Moreover, complications of platelet (Plt) and erythrocyte transfusion therapy have become a cause of great concern and shortages of homologous blood products are a constant problem. Suggestions that the application of recombinant human hemopoietins may provide an alternative treatment modality in this patient population is currently being evaluated in clinical trials. Erythropoietin (EPO) has been shown to be effective in the treatment of anemia in patients with bone marrow, infiltrating low-grade non-Hodgkin's lymphoma, multiple myeloma, and in some patients with myelodysplastic syndrome. Preliminary data suggest that subcutaneous administration of EPO results in a higher slope of increasing erythropoietic parameters compared to intravenous administration. Protective effects on normal erythropoiesis have been attributed to EPO in patients receiving chemotherapy. The finding of EPO receptors on megakaryocytes supports the clinical observation of increased Plt production associated with decreased bleeding and transfusion frequencies in a substantial number of patients receiving EPO. Clinical trials with granulocyte-macrophage (GM-CSF) and granulocyte colony stimulating factor (G-CSF) have reached phase III trials. Both factors show high efficacy to shorten or improve neutropenia related to chemotherapy, bone marrow transplant, or underlying disease. Mechanisms responsible for mucosa protection and improved healing of mucositis observed with both factors remain undetermined yet phase I/II evaluation of IL-3 shows multilineage hemopoietic responses including myeloid, erythroid, and megakaryocyte lineages. Possible anti-cancer effects of hemopoietins achieved by direct action or by increased chemotherapy intensity are currently under investigation.
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PMID:Hemopoietins in clinical oncology. 204 61

A girl with non-Hodgkin's lymphoma and immunodeficiency based on absence of the purine salvage pathway enzyme purine nucleoside phosphorylase experienced profound neutropenia while receiving combination chemotherapy with cyclophosphamide, vincristine, methotrexate, and prednisone (COMP). Neutropenia was most severe following courses that included either systemic or intrathecal methotrexate, even in the face of major dose reductions. Delays in the development of neutropenia-during periods of leucovorin administration also implicate methotrexate as the primary responsible agent. This case suggests that certain immunodeficiency states predispose patients to extensive chemotherapy-induced myelosuppression and supports the concept that purine salvage is a clinically important mechanism for modulating methotrexate toxicity.
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PMID:Excessive chemotherapy-related granulocytopenia in a child with non-Hodgkin's lymphoma and a congenital abnormality of purine salvage. 211 61

With the extensive use of Hickman catheters in patients requiring cytotoxic chemotherapy there is now a resurgence of Gram-positive septicaemia among these patients during the neutropenic periods. We are currently running a prospective randomized study of prophylactic teicoplanin during insertion of Hickman catheters to determine if it reduces the incidence of Gram-positive septicaemia. A total of 44 patients have completed the study (23 in the teicoplanin group and 21 in the control group). The diagnoses were: acute myelogenous leukaemia (13), non-Hodgkin's lymphoma (16), Hodgkin's disease (11), chronic granulocytic leukaemia (3) and acute lymphoblastic leukaemia (1). The number of days between insertion of Hickman catheters and the development of neutropenia was: teicoplanin group: mean 14.7, median 11, range 0-53; control group: mean 11.8, median 10, range 0-37. In the treated patients, there were four episodes of line-associated Gram-positive septicaemia and a total of four organisms were isolated. In the control group, 10 organisms were isolated from a total of nine episodes of line-associated Gram-positive septicaemia. The organisms were: coagulase-negative staphylococci (8), Streptococcus B, (1), Strep. faecalis (1), Strep. mitis (1), alpha streptococcus (1), diphtheriods (1) and Staphylococcus aureus (1). All organisms were sensitive to teicoplanin. No adverse reaction was observed in any patient. Prophylactic teicoplanin during insertion of Hickman catheters may therefore reduce the incidence of line-associated Gram-positive septicaemia in neutropenic patients.
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PMID:Prophylactic teicoplanin during insertion of Hickman catheters. 214 48

This paper reports a case of non-Hodgkin's lymphoma concurrent with cyclic neutropenia. A 59-year-old man who exhibited a neutropenia at a periodicity of 14-20 days from July 1986 was diagnosed as having cyclic neutropenia, and was re-admitted to our hospital because of an abdominal tumor in April 1988. Gastroscopy revealed a Borrmann II-like elevated lesion, and abdominal CT scanning showed a low density area in the liver and swelling of the para-aortic lymph nodes. According to histological examination of the stomach and the liver, the patient was diagnosed as having non-Hodgkin's lymphoma (diffuse, medium-cell type). After completion of three courses of COP-BLAM III therapy, which was started on June 7, a partial response was achieved. However, the patient had a relapse and died on May 12, 1989. Cyclic neutropenia in this case was not considered to be due to an immunological abnormality mediated by lymphocytes, but may have been caused by an excessive response of the negative feedback mechanism due to an increase in CIA (Colony-inhibiting activity) of neutrophils. The fact that the patient's EB virus antibody titer became higher than at this initial hospitalization suggests the possible transition from chronic EB virus infection into malignant lymphoma.
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PMID:[Cyclic neutropenia complicated of non-Hodgkin lymphoma]. 216 74

Previous study has shown that the combination of mitoxantrone (Novantrone, NO) and Ara-C (AC) (NOAC) was active in refractory non-Hodgkin's lymphoma (NHL) but myelosuppression was dose-limiting. In a pilot study, we investigated the effects of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) after NOAC chemotherapy in patients with refractory NHL. NO was applied at a dosage of 10 mg/m2/day on days 2 and 3 and AC at 3 g/m2/12h on days 1 and 2. RhGM-CSF was administered at 250 ug/m2/day as a continuous i.v. infusion from day 6 until the neutrophils were greater than 3.0/nl for 3 consecutive days. Twenty-three patients from five of the nine participating centers were treated with NOAC chemotherapy plus rhGM-CSF, whereas 14 patients from the other four centers received chemotherapy alone. With rhGM-CSF, the median duration of severe neutropenia (less than 0.5/nl) after NOAC was 8 days versus a median of 13 days without rhGM-CSF (P = 0.0058), and that of thrombocytopenia (less than 20.0/nl), 3 days versus 7 days (P greater than 0.4, NS). The rates of infections and stomatitis were 25% and 17%, respectively, for patients treated with rhGM-CSF as compared to 53% (P = 0.0547, NS) and 60% (P = 0.0078), respectively, without rhGM-CSF. The following side effects were associated with the administration of rhGM-CSF: pleural and/or pericardial effusions in five patients, thrombosis in two patients, bone pain in two patients, and respiratory distress syndrome in one patient. A complete remission was achieved in nine of the 23 patients treated with NOAC plus rhGM-CSF, and in two of the 14 patients treated with chemotherapy alone. The median survival of patients treated with rhGM-CSF was not reached at 400 days and seemed to be longer than that of patients treated with chemotherapy alone (median, 109 days; P = 0.036). RhGM-CSF after chemotherapy can be applied safely to patients with NHL, shorten the period of severe cytopenia, reduce the rates of stomatitis, and did not seem to cause adverse effects on response.
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PMID:Mitoxantrone/high-dose Ara-C and recombinant human GM-CSF in the treatment of refractory non-Hodgkin's lymphoma. A pilot study. 219 41

Fifty-five patients, initially diagnosed as having advanced high grade non-Hodgkin's lymphoma (NHL) or Hodgkin's disease (HD) refractory to first-line treatment or in relapse, were treated with ifosfamide 6 g/m2, infused over 48 h, followed by mitoxantrone 12 mg/m2. The regimen repeated at three-weekly intervals. Of 32 patients with NHL evaluable for response, 10 (31 per cent) achieved complete remission and five partial remission, giving an overall response rate of 47 per cent. Two patients subsequently went on to bone marrow transplant (BMT)--one allogeneic and the other autologous. Of 17 patients with HD evaluable for response, six (35 per cent) achieved complete remission and six partial remission, giving an overall response rate of 71 per cent. Two of this group also went on to BMT (both autografts). The principal toxicity was neutropenia, though central nervous system changes were observed in 10 patients. Given the need to offer alternative treatment of patients in these categories, this combination (I-M) is clearly of value in relapsed patients especially where therapeutic options are limited because of previous multi-drug treatment.
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PMID:Ifosfamide and mitoxantrone (I-M) in relapsed and refractory high grade non-Hodgkin's lymphoma and Hodgkin's disease. 221 Jun 89

In a clinical phase II study, the antitumor activity of the recently introduced combination of prednimustine and mitoxantrone (PmM) was evaluated in 17 patients with advanced low-grade non-Hodgkin's lymphoma after failure with or relapse after standard chemotherapy. The PmM regimen consisted of prednimustine 100 mg/m2/d orally on days 1 to 5, and mitoxantrone 8 mg/m2/d intravenously on days 1 and 2, giving a total dose of 16 mg/m2. Treatment was repeated every 4 to 6 weeks to a maximum of 6 cycles. Patients achieving complete remission (CR) or partial remission (PR) received two additional courses for consolidation, followed by interferon (IFN) alpha-2b 5 x 10(6) U subcutaneously three times a week until progression or relapse. Twelve of the 17 patients (71%) responded (CR, 4 and PR, 8). Side effects consisted mainly of neutropenia, which required dose reduction in 48% of treatment cycles. All 12 responders subsequently received IFN alpha-2b maintenance treatment. At present, remission duration ranges from 4.5+ to 17.5+ months (median 14.5 months). In comparison to unmaintained first remission prior to receiving PmM/IFN alpha-2b, a clear tendency towards a longer period of freedom from progression emerged in the 12 patients receiving IFN alpha-2b maintenance treatment during a second PR or CR. These data indicate a high antitumor activity of PmM in low-grade non-Hodgkin's lymphoma and suggest a beneficial effect of IFN alpha-2b maintenance. Present findings, however, will require confirmation in future investigations.
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PMID:Treatment of low-grade non-Hodgkin's lymphoma by cytoreductive chemotherapy with prednimustine/mitoxantrone followed by interferon alpha-2b maintenance: results of a clinical phase II study. 225 19


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