UMLS:C0027947 - FACTA Search

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Query: UMLS:C0027947 (neutropenia)
17,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The colony-stimulating factors (CSFs) principally involved in the production of neutrophils and monocytes are granulocyte CSF, granulocyte-macrophage CSF, macrophage CSF, and interleukin 3 (sometimes called multi-CSF). The natural response to inflammation and infection in the immunocompetent host probably involves all of these CSFs. CSFs can be used as pharmacological agents to accelerate the production of neutrophils and monocytes/macrophages and to enhance mechanisms of host defense. Rapidly accumulating evidence appears to justify the use of CSFs for the prevention of fever and infections in several clinical settings, such as chemotherapy-associated neutropenia, bone marrow transplantation, and severe chronic neutropenia. Trials of CSF treatment of infections in settings not including neutropenia are under way.
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PMID:Potential role of colony-stimulating factors in the prevention and treatment of infectious diseases. 814 63

Macrophage colony-stimulating factor (M-CSF) is a homodimeric glycoprotein which stimulates differentiation of progenitor cells to mature monocytes and enhances production of hemopoietic growth factors from mature monocytes such as granulocyte-macrophage CSF, granulocyte CSF and megakaryocyte potentiator, suggesting that M-CSF administration enhances production of monocytes, neutrophils and platelets. Since the commercial availability of M-CSF in 1991, serial M-CSF infusions at a daily dose of 8 million units have been performed in patients with acute myeloid leukemia in complete remission after combination chemotherapy. Although M-CSF infusion reduced the duration of neutropenia in 3 of 5 patients, it reduced the duration of pyrexia over 37 degrees C in all patients, and that over 38 degrees C in 4 of 5 patients. Average durations of pyrexia and parenteral antibiotic injections were significantly shorter in M-CSF than in control courses. Although M-CSF infusion reduced the duration of thrombopenia in 2 of 5 patients, it reduced total platelet units transfused in 4 of 5 patients. The average number of platelet units transfused after combination chemotherapy was significantly lower in M-CSF than in control courses. In mice, M-CSF injection increased the serum concentration of reactive nitrogen intermediates which inhibited the growth of L1210 cells, and increased the survival rate of mice previously injected with them. These results indicate that M-CSF may be a promising agent not for improving patients' quality of life after cancer chemotherapy, but also in cancer immunotherapy.
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PMID:Macrophage colony-stimulating factor for cancer therapy. 819 2

3'-azido-3'-deoxythymidine (AZT), the main antiviral drug used in AIDS treatment, is known to induce anemia and neutropenia. These effects have been attributed to its toxicity to hematopoietic progenitors. In this report, we present a new approach to reduce AZT hematotoxicity by using an inhibitory factor of the hematopoietic stem cells, the tetrapeptide AcSerAspLysPro (AcSDKP, Seraspenide), which has been shown to increase the survival of mice subjected to high doses of chemotherapy and to block reversibly the cycling of human granulocyte-macrophage colony forming unit (CFU-GM) and burst forming unit erythroid (BFU-E) progenitors. Normal bone marrow mononuclear cells (BMMNC) from 14 subjects were incubated with or without AcSDKP (10(-10) M) for 20 h and with or without AZT (100 microM) for another 2 h. After washing, cells were plated in methylcellulose in the presence of interleukin 3 (IL-3), granulocyte-macrophage colony stimulating factor (GM-CSF) and erythropoietin (EPO). Under these conditions, the preincubation of cells with AcSDKP reduced significantly the toxicity of AZT to both BFU-E and CFU-GM at least in 3 out of 8 and 4 out of 10 cases, respectively. A careful statistical analysis of these observations indicates that AcSDKP may be an efficient factor in preserving progenitors against AZT-induced hematopoietic toxicity.
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PMID:The tetrapeptide AcSerAspLysPro (Seraspenide), a hematopoietic inhibitor, may reduce the in vitro toxicity of 3'-azido-3'-deoxythymidine to human hematopoietic progenitors. 824 56

The clinical benefits of the haematopoietic growth factors (HGFs) granulocyte colony stimulating factor (G-CSF) and granulocyte-macrophage colony stimulating factor (GM-CSF) in conjunction with bone marrow transplantation (BMT) have been established from numerous phase II/III clinical trials. Trials with filgrastim (recombinant G-CSF) have shown that it reduces the period of severe neutropenia by about one week, which leads to a reduction in infectious complications and earlier discharge from hospital. Similar clinical effects have been shown in placebo-controlled trials with recombinant GM-CSF. The effect of other HGFs on haematopoietic reconstitution has been investigated in animals and preliminary human studies, however, further data are required before their clinical efficacy can be determined. G-CSF is well tolerated in the BMT setting. GM-CSF also appears to be well tolerated at low doses, but increased toxicity may be seen at higher dosages. Clinical studies have also indicated that the HGFs do not stimulate the proliferation of leukaemic cells, furthermore, graft-versus-host disease (GVHD) is not enhanced by the use of growth factors. Pharmacological purging of the bone marrow may lead to a reduction in the granulocyte-macrophage colony-forming unit (CFU-GM) content of transplanted marrow. An alternative purging approach is the positive selection of CD34+ marrow stem cells. This technique may also be used to select stem cells from the peripheral blood for use in conjunction with or as an alternative to autologous or allogeneic BMT.
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PMID:A review of the efficacy and tolerability of recombinant haematopoietic growth factors in bone marrow transplantation. 833 33

The haematopoietic growth factor (HGF), granulocyte colony stimulating factor (G-CSF; filgrastim) substantially shortens the period of severe neutropenia that follows high-dose chemotherapy and autologous bone marrow infusion by stimulating granulopoiesis. Filgrastim also increases numbers of circulating progenitor cells. We have studied the ability of filgrastim to mobilise peripheral blood progenitor cells (PBPC) and assessed their efficacy when infused after chemotherapy on recovery of neutrophil and platelet counts. Seventeen patients with non-myeloid malignant disorders received filgrastim (12 micrograms/kg daily for six days) by continuous subcutaneous infusion. Numbers of granulocyte-macrophage progenitors in peripheral blood increased a median of 58-fold over pretreatment values, and numbers of erythroid progenitors increased a median of 24-fold. Three leukapheresis procedures collected a mean total of 33 (SEM 5.7) x 10(4) granulocyte-macrophage progenitors per kg body weight. After high-dose chemotherapy in 14 of the patients (busulphan and cyclophosphamide), these cells were used to augment autologous bone marrow rescue and post-transplant filgrastim treatment. Platelet recovery was significantly faster in these patients than in controls who received the same treatment apart from the infusion of peripheral blood progenitors; the platelet count reached 50 x 10(9)/L a median of 15 days after infusion of haematopoietic cells in the study patients compared with 39 days in controls (p = 0.0006). The accelerated neutrophil recovery associated with filgrastim treatment after chemotherapy was maintained. Subsequently, 10 patients received filgrastim-mobilised PBPC without marrow after high-dose chemotherapy. The rate of platelet and neutrophil recovery in these patients was at least equal to that observed in the patients receiving PBPC and bone marrow.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of peripheral blood progenitor cells mobilised by filgrastim (G-CSF) on platelet recovery after high-dose chemotherapy. 833 35

We have examined the effects of recombinant human interleukin-11 (rhIL-11) on the recovery of peripheral blood cell counts and proliferation of progenitors and hematopoietic stem cells (day 12 colony-forming units-spleen-CFU-S12) in vivo using a mouse bone marrow (BM) and spleen cell transplantation model. Recovery of leukocytes was accelerated in animals receiving daily administration of rhIL-11 (100 micrograms/kg/d) and reached normal levels by day 14 posttransplantation. This increased total leukocyte count reflected mainly an increase in neutrophils. Neutropenia (absolute neutrophil count [ANC] < 1,500) was present in control transplant mice for 14 to 15 days, while in the rhIL-11-treated group, neutrophils recovered to normal by days 8 to 10 and continued to increase until day 19. Animals treated with rhIL-11 had only 1 day with ANC demonstrated < 500. Correspondingly, rhIL-11 treatment increased granulocyte-macrophage progenitors (CFU-GM) derived from both spleen and BM cells. Higher doses of IL-11 increased CFU-GM nearly threefold and CFU-Mix fourfold to fivefold, while increasing burst-forming units-erythroid to a lesser degree. BM and spleen cellularity were both increased in IL-11-treated mice, but no increase in CFU-S12 was noted. In addition, in vivo daily administration of IL-11 increased peripheral platelet counts by threefold over control transplant mice at day 10 posttransplantation during the post-irradiation platelet nadir. Further treatment led to platelet counts higher than normal 18 days posttransplantation when control animals had just attained normal platelet counts. IL-11 can accelerate the recovery of the peripheral blood leukocytes, mainly neutrophils, and platelets in transplant mice, effects that may be clinically useful in future applications for BM transplantation and chemotherapy-related cytopenias.
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PMID:Effects of recombinant human interleukin-11 on hematopoietic reconstitution in transplant mice: acceleration of recovery of peripheral blood neutrophils and platelets. 841 98

Marrow graft failure is a significant cause of morbidity following bone marrow transplantation. A case is reported of marrow graft failure due to neutrophil antibodies. A 13-year-old girl with a large granular lymphocytosis and chronic neutropenia was treated with granulocyte transfusions prior to undergoing a transplant with bone marrow from a partially matched, unrelated donor. Following the transplant, a bone marrow biopsy showed engraftment of donor myeloid cells, but the recipient remained neutropenic. Testing of the serum for neutrophil antibodies found that the recipient's serum had a high-titer neutrophil antibody. Immunoprecipitation studies using the marrow recipient's serum and 125I surface-labeled neutrophils showed that the antibody reacted to the neutrophil-specific antigen NB1. Phenotyping of neutrophils from the marrow donor found that they expressed NB1 antigen, and, in a crossmatch assay, the recipient's serum reacted with donor neutrophils. Despite treatment with granulocyte-macrophage--colony-stimulating factor, the marrow transplant recipient remained neutropenic and died of polymicrobial sepsis and aspergillosis 38 days after the transplant. The presence of high-titer antibodies to neutrophil-specific antigen NB1 in this patient following transplant likely prevented the recovery of her peripheral blood neutrophils and contributed to her death.
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PMID:Prolonged neutropenia resulting from antibodies to neutrophil-specific antigen NB1 following marrow transplantation. 843 Apr 56

The synthetic cytokine (Synthokine) SC-55494 is a high-affinity interleukin-3 (IL-3) receptor ligand that stimulates greater in vitro multilineage hematopoietic activity than native IL-3, while inducing no significant increase in inflammatory activity relative to native IL-3. The aim of this study was to investigate the in vivo hematopoietic response of rhesus monkeys receiving Synthokine after radiation-induced marrow aplasia. Administration schedule and dose of Synthokine were evaluated. All animals were total-body irradiated (TBI) with 700 cGy 60Co gamma radiation on day 0. Beginning on day 1, cohorts of animals (n = 5) received Synthokine subcutaneously (SC) twice daily with 25 micrograms/kg/d or 100 micrograms/kg/d for 23 days or 100 micrograms/kg/d for 14 days. Control animals (n = 9) received human serum albumin SC once daily at 15 micrograms/kg/d for 23 days. Complete blood counts were monitored for 60 days postirradiation and the durations of neutropenia (NEUT; absolute neutrophil count [ANC] < 500/microL) and thrombocytopenia (THROM; platelet count < 20,000/microL) were assessed. Synthokine significantly (P < .05) reduced the duration of THROM versus the HSA-treated animals regardless of dose or protocol length. The most striking reduction was obtained in the animals receiving 100 micrograms/kg/d for 23 days (THROM = 3.5 v 12.5 days in HSA control animals). Although the duration of NEUT was not significantly altered, the depth of the nadir was significantly lessened in all animal cohorts treated with Synthokine regardless of dose versus schedule length. Bone marrow progenitor cell cultures indicated a beneficial effect of Synthokine on the recovery of granulocyte-macrophage colony-forming units that was significantly higher at day 24 post-TBI in both cohorts treated at 25 and 100 micrograms/kg/d for 23 days relative to the control animals. Plasma pharmacokinetic parameters were evaluated in both normal and irradiated animals. Pharmacokinetic analysis performed in irradiated animals after 1 week of treatment suggests an effect of repetitive Synthokine schedule and/or TBI on distribution and/or elimination of Synthokine. These data show that the Synthokine, SC55 94, administered therapeutically post-TBI, significantly enhanced platelet recovery and modulated neutrophil nadir and may be clinically useful in the treatment of the myeloablated host.
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PMID:Acceleration of hematopoietic reconstitution with a synthetic cytokine (SC-55494) after radiation-induced bone marrow aplasia. 855 80

Granulocyte colony stimulating factors (G-CSF) has a wide spectrum of action: it stimulates proliferation and differentiation of granulocyte-macrophage progenitors, it promotes the chemotactic activity of monocytes and granulocytes and it develops the antibody-dependent cytotoxicity of neutrophils. In vivo G-CSF induces leucocytosis and it hastens the granulocyte recovery after chemio-radiotherapy. So it has been used in many pathologies: aplastic anaemia, AIDS in treatment with antiviral drugs, myelodysplastic syndromes, acute leukemias and solid tumors. If G-CSF is administered after chemotherapy, both in acute leukemias and in solid tumors, it reduces the duration of neutropenia and the number of febrile episodes so that it is possible to give the whole therapy at the planned dosage with no delay. However G-CSF does not modify the incidence of complete remissions and the overall survival. G-CSF allowed the increase of dose-intensity in chemoresistent neoplasms even if this therapy is always complicated by a heavy extrahaematological toxicity. Moreover G-CSF shortens the total duration of neutropenia after autologous or allogenic bone marrow and peripheral stem cell transplantation even if the appearance of the first neutrophil is not accelerated.
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PMID:[Biologic aspects and clinical use of granulocyte growth factor]. 858 87

This is a double-blind randomized placebo-controlled trial to evaluate the efficacy and safety of granulocyte-macrophage colony-stimulating-factor (GM-CSF) after dose-intensive cyclophosphamide, etoposide, and cisplatin (DICEP). Fifty-six patients with lymphoma or breast carcinoma were randomized to receive GM-CSF 250 microg/m2 or placebo subcutaneously (SC) every 12 hr after each course of DICEP until recovery of absolute neutrophil count (ANC) of 1.5 x 10(9)/L. Each patient was to receive three courses of DICEP. There were 28 patients in each group. The median duration of ANC below 0.5 x 10(9)/L was 10 versus 12 days for Course 1 (P = 0.010), 10 versus 12 days for Course 2 (P = 0.248), and 16.5 versus 15 days for Course 3 (P = 0.126); platelet counts below 20 x 10(9)/L was 4 versus 4 days for Course 1 (P = 0.586), 8.5 versus 7 days for Course 2 (P = 0.013), and 23.5 versus 10.5 days for Course 3 (P = 0.104); hospitalization for patients readmitted with cytopenic fever were 4 versus 8 days for Course 1 (P = 0.035); 7 versus 6 days for Course 2 (P = 0.692); and 8 versus 12 days for Course 3 (P = 0.884) in the GM-CSF and placebo group, respectively. GM-CSF significantly shortens the duration of neutropenia and readmission only during the first course of DICEP. There was a delay in platelet recovery and an increase in transfusion requirement during subsequent courses in the GM-CSF group. The result cautions the routine use of lineage specific hematopoietic growth factors in supporting repeated cycles of dose-intensive chemotherapy.
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PMID:Randomized placebo-controlled trial of granulocyte-macrophage colony-stimulating-factor support for dose-intensive cyclophosphamide, etoposide, and cisplatin. 860 29

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