Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002871 (anemia)
 52,094 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cytogenetic analysis of bone marrow cells revealed an abnormal clone with monosomy 7 and trisomy 21 in a 12-year-old child with Kostmann disease (KD). The patient presented with anemia, thrombocytopenia, and splenomegaly after 5 years of treatment with granulocyte colony-stimulating factor (G-CSF). The bone marrow morphology was consistent with the diagnosis of myelodysplastic syndrome (MDS). Administration of G-CSF was discontinued at this point. Bone marrow studies 2 and 5 months later showed persistence of both myelodysplasia and the abnormal clone with monosomy 7 and trisomy 21. Monosomy 7 was also confirmed by fluorescence in situ hybridization (FISH). After 2 months of follow-up, the patient presented with acute basophilic leukemia, a very rare variant of acute myeloid leukemia (AML), expressing the same bone marrow chromosome abnormalities as observed earlier. This is a rare case of KD with prolonged survival and a cytogenetically abnormal clone evolving to MDS and acute basophilic leukemia. The significance of monosomy 7 and trisomy 21 in KD treated with G-CSF is discussed.
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PMID:An abnormal clone with monosomy 7 and trisomy 21 in the bone marrow of a child with congenital agranulocytosis (Kostmann disease) treated with granulocyte colony-stimulating factor. Evolution towards myelodysplastic syndrome and acute basophilic leukemia. 853 30

Megakaryocyte growth and development factor (MGDF) is a potent inducer of megakaryopoiesis in vitro and thrombopoiesis in vivo. The effects of MGDF appear to be lineage-selective, making this cytokine an ideal candidate for use in alleviating clinically relevant thrombocytopenias. This report describes a murine model of life-threatening thrombocytopenia that results from the combination treatment of carboplatin and sublethal irradiation. Mortality of this regimen is 94% and is associated with widespread internal bleeding. The daily administration of pegylated recombinant human MGDF (PEG-rMGDF) significantly reduced mortality (to < 15%) and ameliorated the depth and duration of thrombocytopenia. The severity of leucopenia and anemia was also reduced, although it was not clear whether these effects were direct. Platelets generated in response to PEG-rMGDF were morphologically indistinguishable from normal platelets. PEG-rMGDF administered in combination with murine granulocyte colony-stimulating factor completely prevented mortality and further reduced leukopenia and thrombocytopenia. These data support the concept that PEG-rMGDF may be useful to treat iatrogenic thrombocytopenias.
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PMID:Pegylated megakaryocyte growth and development factor abrogates the lethal thrombocytopenia associated with carboplatin and irradiation in mice. 854 37

Two patients with severe aplastic anemia received combination therapy consisting of granulocyte colony-stimulating factor (G-CSF) and erythropoietin (EPO) by subcutaneous injection. During the first 8 weeks, we administered only G-CSF, but subsequently we administered EPO with G-CSF. Administration of G-CSF caused rapid increase in neutrophil counts in each case. In the first case, a 23-year-old woman, the first sign of improvement of anemia appeared in the 12th week but 50 more weeks elapsed before improvement of platelet count. In the second case, a 59-year-old woman, marked increase of reticulocytes appeared in the 32nd week, and the RBC count become normal in the 46th week. Minor improvement of platelet count was obtained in the 40th week. After 53 weeks of treatment, we stopped administration of G-CSF and EPO, and all of peripheral blood cell counts decreased. Therefore G-CSF and EPO were given to her again, and she showed the same response as first administration. It showed that she was dependent upon G-CSF and EPO. Finally she obtained normalization of all blood cell counts. In both cases, no serious side effects were observed. Combination therapy consisting of G-CSF and EPO may be beneficial for patients with aplastic anemia.
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PMID:[Two patients with aplastic anemia successfully treated with G-CSF and erythropoietin]. 858 70

Eighteen patients with metastatic non-small cell lung cancer were treated with a combination of intravenous vinorelbine (Navelbine; Burroughs Wellcome Co, Research Triangle Park, NC; Pierre Fabre Medicament, Paris, France) 25 mg/m2 on days 1 and 8 and intravenous paclitaxel 175 mg/m2 on day 2 every 3 weeks. All patients were given granulocyte colony-stimulating factor 5 micrograms/kg/d subcutaneously on days 3 through 7 and 9 through 17 or until the absolute neutrophil count reached 10 x 10(9)/L or higher. One patient was enrolled in this study too recently to be assessed. The mean age of the remaining 17 patients was 59 years (age range, 33 to 75 years); all but one patient had refractory disease, mostly to cisplatin-containing regimens. Four patients were ineligible (two because of poor performance status and two because of previous exposure to vinblastine). Three partial responses were observed, with durations of 46, 64, and 140+ days. Four patients had stable disease and four had progressive disease. The most common side effect was neutropenia (five grade 4 and one grade 3); two patients died of leukopenic sepsis in the first cycle. Peripheral neuropathy was also common (four grade 1 and one grade 2 sensory neuropathy). Other toxic effects were anemia and nausea and vomiting. The median survival was 153 days in all patients and 179 days in eligible patients. The preliminary results in this ongoing study of combination vinorelbine and paclitaxel as second-line therapy for metastatic non-small cell lung cancer are promising, and using this regimen as first-line therapy is warranted.
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PMID:Pilot study of vinorelbine (navelbine) and paclitaxel in patients with refractory non-small cell lung cancer. 861 Feb 31

We performed a dose-escalation study to evaluate the maximum tolerated dose (MTD) of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) plus a fixed dose of epirubicin. Epirubicin was administered as a 90 mg/m2 bolus immediately followed by a 3-hour infusion of paclitaxel starting at 135 mg/m2 and escalating by 20mg/m2 for each triplet of patients as long as no dose-limiting toxicity had occurred; courses were repeated every 3 weeks. The MTD was defined as that at which any of the following toxicities occurred in at least two of six patients: absolute neutrophil count less than 500/microliter for more that 7 days or less than 100/microliter for more than 3 days; any episode of febrile neutropenia requiring intravenous antibiotics and hospitalization; grade 4 thrombocytopenia requiring platelet transfusion; failure to recover absolute neutrophil count to > or = 1,500/microliter and/or platelets to > or = 100,000/microliter by day 28; and any grade > or = 3 nonhematologic toxicity. Two MTDs were defined: the first without granulocyte colony-stimulating factor (MTD 1) and the second with granulocyte colony-stimulating factor given either to accelerate recovery of grade 4 neutropenia lasting more than 72 hours or immediately in case of febrile neutropenia (MTD 2); granulocyte colony-stimulating factor was never used prophylactically. To date, 22 patients have been entered into the study; the median patient age was 55 years (age range, 30 to 66 years). Nineteen (86%) patients had received adjuvant chemotherapy that included anthracyclines in 12 cases (55%). The viscera were the dominant sites of disease in 55% of patients. Median baseline ventricular ejection fraction was 58% (range, 53% to 67%). Short-lasting grade 4 neutropenia occurred in 61% of courses; however, only four episodes of febrile neutropenia were recorded. Grade 4 thrombocytopenia was reported in 8% and grade 3 anemia in 3% of courses; four patients experienced peripheral neuropathy (three patients grade 1, one patient grade 2); complete alopecia was universal. The cardiac effects of the combination were surprisingly low: median ejection fraction at study entry was 58%, and after a cumulative dose 1,080 mg/m2 it was 56%. Three complete responses and 12 partial responses have been documented for an overall response rate of 83.3% (95% confidence interval, 58% to 96%). In conclusion, neutropenia is the most frequent toxicity of this novel combination. However, the MTD has not yet been reached. The combination of epirubicin plus paclitaxel is highly active, and no signs of cumulative myocardiopathy have been observed.
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PMID:Activity and safety of epirubicin plus paclitaxel in advanced breast cancer. 862 33

A 45-year-old male with acute lymphoblastic leukemia in first remission was successfully transplanted with G-CSF (filgrastim)-mobilized syngeneic PBPC (peripheral blood progenitor cells). Conditioning regimen consisted of high-dose etoposide, cyclophosphamide and total body irradiation. For PBPC mobilization the patient's healthy syngeneic brother was subcutaneously stimulated with 16 micrograms/kg/day G-CSF for 5 consecutive days. Only mild adverse effects (myalgia, transient changes of laboratory test) were observed. PBPC-apheresis was performed three times without complications on days 4, 5 and 6 after the start of G-CSF application. The unmanipulated PBPC (total 5.75 x 10(8)/kg mononucleated cells) were transfused immediately after each collection. Engraftment under administration of G-CSF (5 micrograms/kg/day subcutaneously) from day 0 to +12 was very rapid. Neutrophils exceeded 1.0 x 10(9)/l on day +9, platelet counts reached 50 x 10(9)/l on day +13. On day +27 the patient was discharged from the hospital with normal blood counts except mild anemia (Hb 9.5 g%). Bone marrow aspiration was repeatedly normocellular with normal differential count and no leukemia. We demonstrate that G-CSF-mobilized syngeneic PBPC transplantation after myeloblative chemoradiotherapy results in rapid and so far stable hematologic reconstitution with an actual follow-up of more than 15 months. This experience may be of relevance for future allogeneic G-CSF-mobilized PBPC transplantation.
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PMID:[Successful syngeneic transplantation using G-CSF-stimulated peripheral hematopoietic progenitor cells combined with post-transplant administration of G-CSF in a patient with acute lymphatic leukemia]. 870 Dec 54

This report examines the effect of filgrastim (granulocyte colony-stimulating factor, [G-CSF] in 12 patients with neutropenia [absolute neutrophil count [ANC] < 1,000/mm3]) caused by Fanconi anemia (FA). Two of 14 patients who were evaluated for study entry were ineligible because of unsuspected cytogenetic abnormalities in their bone marrow (BM). G-CSF was started at 5 micrograms/kg/d. All patients had an increase in their ANC at week 8 (mean increase = 15,664/mm3). The median ANC during therapy was 5,030/mm3. Eight of 10 patients who completed 40 weeks on study maintained an ANC > 1,500/mm3 on G-CSF given every-otherday. Four patients had an increase in their platelet count by week 8 without transfusion (maximum increase = 23,000 to 45,000/mm3); however, platelet counts fell toward baseline levels as the G-CSF dose was reduced. BM CFU-MK were increased at week 8 in three of four evaluable patients. Four patients who did not receive red blood cell transfusions had an increase in their hemoglobin level of at least 2.0 g/dL. A fifth patient had a red blood cell transfusion in week 2 and then had a similar increase in hemoglobin level without subsequent transfusion. Eight of 10 patients who completed 40 weeks of treatment showed increases in the percentage of BM CD34+ cells measured by flow cytometry. The same proportion showed increases in peripheral blood CD34+ cells. Increased BM cellularity and myeloid hyperplasia were constant findings and were associated with increased expression of the proliferating cell nuclear antigen. Adverse experiences were mild fever (1 patient) and a new BM cytogenetic abnormality at week 40 (1 patient). This study shows that prolonged administration of G-CSF exerts a stimulatory effect on the BM of FA patients and may be used to maintain a clinically adequate ANC in these patients. G-CSF has beneficial effects on multiple hematopoietic lineages in some patients and may be a good candidate for use in combination cytokine protocols for FA patients with progressive aplastic anemia. G-CSF use results in an increase in circulating CD34+ cells, a finding with important implications for future gene transfer protocols.
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PMID:Prolonged administration of granulocyte colony-stimulating factor (filgrastim) to patients with Fanconi anemia: a pilot study. 878 14

The ability of an infusion of ex vivo expanded hematopoietic cells to ameliorate cytopenia following transplantation of hematopoietic stem cells (HSCs) is controversial. To address this issue, we measured the recovery of circulating leukocytes, erythrocytes, and platelets in lethally irradiated mice transplanted with 10(3) enriched HSCs, with or without their expanded equivalent (EE) generated after 7 days of culture in interleukin-3 (IL-3), IL-6, granulocyte colony-stimulating factor and Steel Factor. Two HSC populations differing in their content of short-term repopulating progenitors were evaluated. Thy-1loLIN-Sca-1+ (TLS) bone marrow (BM) is enriched in colony-forming cells (CFCs), day 8 and day 12 spleen colony-forming units (CFU-S) (435 +/- 19, 170 +/- 30, and 740 +/- 70 per 10(3) cells, respectively), and stem cells with competitive long-term repopulating potential (> or = 1 per 43 cells). Thy-1loSca-1+H-2Khl cells (TSHFU) isolated from BM 1 day after treatment of donor mice with 5-fluorouracil (5-FU) are also highly enriched in competitive repopulating units (CRU, > or = 1 per 55 cells), but are depleted of CFCs, day 8 and day 12 CFU-S (171 +/- 8, 0 and 15 +/- 4 per 10(3) cells, respectively). Recipients of 10(3) TLS cells transiently recovered leukocytes to > or = 2,000/microL in 12 days, but sustained engraftment required 25 days. Platelets recovered to > or = 200,000/microL in 15 days, and erythrocytes never decreased below 50% of normal. Mice transplanted with 10(3) TSHFU cells recovered leukocytes in 15 days, and platelets and erythrocytes in 18 days. Recipients of unseparated normal or 5-FU-treated BM cells (containing 10(3) TLS or TSHFU cells) recovered safe levels of blood cells in 9 to 12 days, suggesting that unseparated marrow contains early engrafting cells that were depleted by sorting. Upon ex vivo expansion, total cells, CFCs and day 12 CFU-S were amplified 2,062-,83- and 13-fold, respectively, from TLS cells; and 1,279-, 259- and 708-fold, respectively, from TSHFU cells. Expanded cells could regenerate the majority of lymphocytes and granulocytes in primary (17 weeks) and secondary (26 weeks) hosts and were only moderately impaired compared to fresh HSCs. The EE of TSHFU cells was more potent than that of TLS cells, suggesting that more highly enriched HSCs are more desirable starting populations for this application. When mice were transplanted with 10(3) TSHFU cells and their EE, the duration of thrombocytopenia was shortened from 18 to 12 days, and anemia was abolished. Leukocytes were also elevated on days 9 to 12, although sustained recovery was not accelerated. Anemia was also abrogated in recipients of 10(3) TLS cells and their EE. Early platelet counts were slightly higher than with TLS cells alone, but leukocyte recovery was not improved. These data confirm that TLS cells contribute to early and sustained hematopoiesis, and demonstrate a benefit of ex vivo expanded cells in accelerating engraftment of more primitive TSHFU stem cells depleted of progenitors.
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PMID:Partially differentiated ex vivo expanded cells accelerate hematologic recovery in myeloablated mice transplanted with highly enriched long-term repopulating stem cells. 889 35

The recent production of recombinant human growth factors has expanded the neonatal clinician's armamentarium for treating sepsis and anemia of prematurity (AOP). Agents that may prove useful in the premature neonate include recombinant human erythropoietin (rh-EPO), granulocyte colony-stimulating factor (rhG-CSF), and CSF). Within the neonatal population, research utilizing these agents is still relatively new. Appropriate clinical trials are still needed to elucidate the optimal dosing regimen for both rhG-CSF and rh-EPO, as are studies to address the issue of long-term safety. Use of rhG-CSF in sepsis and of rh-EPO for AOP is still considered experimental, but in instances where conventional treatments are not proving beneficial, these agents may provide a therapeutic alternative. Their potential for improving care of the premature neonate must also be assessed.
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PMID:Hematopoietic growth factors: Part I. 893 67

Administration of large doses of recombinant granulocyte colony-stimulating factor (rG-CSF) to mice results in diminished erythropoiesis. Hyporegenerative anemia does not occur in adult humans as a consequence of treatment with rG-CSF, but it is not clear whether this will be a problem in neonates. Because rG-CSF is currently being tested as a treatment for neutropenia in neonates, we assessed the possibility that such treatment will diminish their erythropoiesis. To do this, we added rG-CSF, in vitro, to clonogenic cultures of hematopoietic progenitors obtained from the bone marrow and liver of seven human fetuses and from the umbilical cord blood of five term and five preterm infants. The range of rG-CSF concentrations tested (0.1-10.0 ng/mL) included the peak concentrations measured in the blood of neonates receiving rG-CSF treatment on experimental protocols. Inclusion of rG-CSF in the cultures did not diminish clonal maturation of fetal erythroid (erythroid colony-forming and burst-forming unit) progenitors, nor did it reduce the number of normoblasts generated per erythroid progenitor cell colony. On the basis of these studies we predict that administration of rG-CSF to neonates will not result in down-modulation of erythropoiesis.
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PMID:Effect of recombinant granulocyte colony-stimulating factor on erythropoiesis in the human fetus and neonate. 894 65


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