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Query: UMLS:C0026986 (myelodysplastic syndrome)
 14,926 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We evaluated the effects of recombinant human granulocyte colony stimulating factor (rhG-CSF) and granulocyte-monocyte colony stimulating factor (rhGM-CSF) on the in vitro proliferative, differentiative, and regenerative responsiveness of marrow cells from myelodysplastic syndrome patients (MDS) in comparison to those from normal individuals. Our studies showed decreased primary clonogenicity of myeloid (CFU-GM) and erythroid (BFU-E) hemopoietic progenitor cells from the MDS patients. rhGM-CSF had more potent stimulatory effects than rhG-CSF for MDS marrow CFU-GM growth; no enhanced cellular proliferation in the MDS patients was observed in liquid culture with either rhGM-CSF or rhG-CSF. Decreased myeloid clonal cell self-generation and/or recruitment occurred in the MDS patients upon exposure to either rhG-CSF or rhGM-CSF. rhG-CSF demonstrated more potent granulocytic differentiation effects than rhGM-CSF both for normals and MDS patients using marrow enriched for immature myeloid cells with lesser differentiation noted for MDS. Cytogenetic abnormalities, present with or without additional normal karyotypes in native marrow of four MDS patients, persisted after culture with rhG-CSF, indicating induced differentiation of both normal and abnormal clones. Although proliferative and differentiative effects were seen with both factors these data show MDS marrow cells in vitro to have predominantly differentiative responsiveness to rhG-CSF and proliferative responsiveness to rhGM-CSF.
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PMID:Effects of recombinant human granulocyte colony stimulating factor and granulocyte-monocyte colony stimulating factor on in vitro hemopoiesis in the myelodysplastic syndromes. 169 Mar 18

We present a patient with refractory anemia (RA) who developed Sweet's syndrome during the treatment of recombinant human granulocyte colony-stimulating factor (rhG-CSF). A 30-year-old man was admitted to the hospital for evaluation of anemia. He was diagnosed as MDS (RA). As a phase II study in MDS, rhG-CSF therapy was begun. Fever associated with cutaneous lesion developed over the left shoulder. Antibiotics showed no effects. Skin biopsy revealed Sweet's syndrome. This skin lesion disappeared thoroughly with discontinuance of G-CSF and administration of prednisolone. To examine whether Sweet's syndrome was related to the G-CSF therapy, we analyzed the effect of G-CSF on the function of patient's neutrophils. However, the function of patient's neutrophils was not activated by G-CSF administration.
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PMID:[Sweet's syndrome in patient with refractory anemia during recombinant human granulocyte colony stimulating factor therapy]. 169 95

In order to obtain more insight into the nature of the abnormal in vitro colony formation in myelodysplastic syndromes (MDS), we investigated the kinetics of the colony formation of 23 MDS cases in response to recombinant human interleukin-3 (IL-3), Granulocyte-macrophage colony-stimulating factor (GM-CSF), granulocyte colony-stimulating Factor (G-CSF), and giant cell tumor cell line conditioned medium (GCT-CM). The kinetics of GCT-CM-induced colony formation were comparable to that of G-CSF-induced colony growth, both in MDS and in normal bone marrow cultures. Colony formation was found to be delayed in MDS. The delay in colony formation was most apparent in the GCT-CM (G-CSF) responsive progenitor cell compartment. In MDS cases with clinical features of high risk disease, this delay was more pronounced as compared with low risk cases (7 and 3 days, respectively, in response to GCT-CM). The delay in colony formation was found to be caused by an increase in the time interval before progenitor cells had begun to divide. These results suggest that a prolongation of the time spent in G0 of myeloid progenitor cells in MDS may be the cause of the indolent in vitro colony formation observed in this disease.
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PMID:The effects of interleukin-3, GM-CSF, and G-CSF on the growth kinetics of colony-forming cells in myelodysplastic syndromes. 169 40

Based on pre-clinical and in vitro studies demonstrating enhanced granulocytic proliferation and differentiation induced by granulocyte-monocyte and granulocyte-colony stimulating factors (GM-CSF and G-CSF), these recombinant human hormones have been used to treat cytopenic patients with preleukemia [i.e., myelodysplastic syndromes (MDS)]. To date, five studies have been reported using GM-CSF short-term (generally 7-14 days, x 1-5 courses). Thirty-eight of 45 treated patients had improvements in neutrophil counts, 14 had increased reticulocyte counts with three of these individuals having decreased RBC transfusion requirements, and eight had transient increases in platelets. In 12 patients an increase in marrow and/or peripheral blood blasts was noted. Seven patients progressed to acute myeloid leukemia (AML), particularly patients with greater than 15% marrow blasts. In a longer term study, five patients received GM-CSF for 2 to 9 weeks, although only one individual maintained increased neutrophil counts, one developed antibodies to GM-CSF and one evolved into AML. Eighteen patients have been treated for 2 months with G-CSF, 16 of whom had normalization of neutrophil counts with improved marrow maturation, five had increased reticulocyte counts with three having decreased transfusion requirements, no substantial changes in platelet counts were noted. Eleven patients have received maintenance therapy with G-CSF for 6-16 months, ten had persistent increases in neutrophil counts with enhanced marrow myeloid maturation and five had increased reticulocytes. Decreased infectious episodes were notedat times of neutrophil improvements. Four of the 18 individuals have subsequently developed AML after 6-16 months.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of CSFs in preleukemia. 169 91

Chromosomes of bone marrow cells obtained from nine patients with myelodysplastic syndrome (MDS) were assessed after in vitro co-culture (48 hours culture) with recombinant human granulocyte colony-stimulating factor (rhG-CSF), recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF), or recombinant human erythropoietin. Three of the nine MDS cases showed no cytogenetic abnormalities with or without any recombinant human hematopoietic growth factors; one MDS patient with a t(3;4) did not show any change in the proportion of cells with this cytogenetic change. The remaining five cases exhibited changes in the frequency of subclones after the treatment. An increasing number of metaphase cells with less complex chromosome abnormalities was observed in two of the five cases by treatment with rhG-CSF; one of them also showed an increasing number of cells with normal karyotypes. After rhGM-CSF treatment, cells with nonclonal hyperdiploid abnormalities appeared in one MDS patient. After erythropoietin treatment, an increasing number of cells with a prototypic change was observed in one MDS patient, whereas one patient showed an increasing number of cells with an additional chromosome abnormality. These observations indicate that hematopoietic growth factors possibly modify the constitution of marrow cells with multiple chromosome abnormalities and the degree is different in each MDS patient. Furthermore, a chromosome analysis using an in vitro culture system with human recombinant hematopoietic growth factors may be able to detect metaphase cells with additional chromosome abnormalities in some MDS patients.
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PMID:In vitro cytogenetic effects of recombinant human hematopoietic growth factors on cells derived from myelodysplastic syndromes. 169 82

Marrow cells from 36 patients with myelodysplastic syndromes (MDS) (13 refractory anemia [RA], 14 refractory anemia with excess of blasts [RAEB], 9 RAEB in transformation [RAEB-T]) were evaluated for their in vitro proliferative and differentiative responsiveness to recombinant human granulocyte colony-stimulating factor (G-CSF) or granulocyte-monocyte CSF (GM-CSF). GM-CSF exerted a stronger proliferative stimulus than G-CSF for marrow myeloid clonal growth (CFU-GM) in these patients (44 v 12 colonies per 10(5) nonadherent buoyant bone marrow cells [NAB], respectively, P less than .025). GM-CSF stimulated increased CFU-GM growth in the 16 patients with abnormal marrow cytogenetics in comparison with the 20 patients who had normal cytogenetics (52 and 30 colonies per 10(5) NAB, respectively, P less than .05), whereas no such difference could be demonstrated with G-CSF (11 and 16 colonies per 10(5) NAB, respectively). In contrast, granulocytic differentiation of marrow cells was induced in liquid culture by G-CSF in 15 of 32 (47% patients), while GM-CSF did so in only 4 of 18 (22%) patients (P less than .025) including, for RAEB/RAEB-T patients: 9 of 18 versus 0 of 9, respectively (P less than .025). For MDS patients with normal cytogenetics, G-CSF- and GM-CSF-induced marrow cell granulocytic differentiation in 12 of 18 (67%) versus 3 of 11 (27%), respectively (P less than .025), contrasted with granulocytic induction in only 3 of 14 (21%) and 1 of 7 (14%) patients with abnormal cytogenetics, respectively. We conclude that G-CSF has greater granulocytic differentiative and less proliferative activity for MDS marrow cells than GM-CSF in vitro, particularly for RAEB/RAEB-T patients and those with normal cytogenetics.
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PMID:Impact of marrow cytogenetics and morphology on in vitro hematopoiesis in the myelodysplastic syndromes: comparison between recombinant human granulocyte colony-stimulating factor (CSF) and granulocyte-monocyte CSF. 169 77

A clinical study of rhG-CSF (KRN8601) in patients with myelodysplastic syndrome (MDS) was performed to investigate the hematopoietic effects and the increase of neutrophils. The rhG-CSF was administered daily by intravenous infusion over 30 min. to 21 patients with MDS (PARA = 11, RAEB = 4, RAEB in T = 6). The dose was escalated stepwise from 50 to 400 microgram/m2 every week. Within one week to 26 days after commencement of rhG-CSF administration, the increases of absolute neutrophil counts in peripheral blood were observed in all patients. Treatment with rhG-CSF enhanced normal marrow myeloid cell differentiation and maturation in 3 of 9 PARA patients and in 3 of 4 RAEB patients. None of patients changed to acute leukemia attributable to rhG-CSF, but one of RAEB patient and two of RAEB in T patients progressed to leukemic phase in 21 days or two months after treatment. Minor side effects or abnormal laboratory findings were observed in 3 patients (14.3%). These results suggested that treatment with rhG-CSF was well tolerated and effective for improving the neutropenia between 50 to 400 micrograms/m2 in patients with MDS.
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PMID:[Clinical study of rhG-CSF (KRN8601) in patients with myelodysplastic syndrome]. 169 7

The effects of four recombinant hemopoietic growth factors (HGF) and of the impure factor HTB9 on proliferation and maturation of marrow myeloid (CFU-GM) and erythroid (BFU-E) progenitor cells were studied in 22 cases of myelodysplastic syndromes (MDS). In most cases, IL-3, GM-CSF and G-CSF increased significantly the number of myeloid colonies, the best combination being IL-3 + GM-CSF. A significant increase in the myeloid colony/cluster ratio was also noted, but cytological examination of colony cells showed little maturation. The analysis of myeloid colony surface markers with four monoclonal antibodies (to CD13, CD15, CD33 and CD34) showed minor modifications with an increase of CD13 and CD15 in about one third of cases when compared to control without HGF. Erythroid colonies were obtained in one case with erythropoietin alone, and in 19 cases with the addition of GM-CSF and/or IL-3. In short-term liquid cultures, IL-3, GM-CSF and G-CSF increased 3H-thymidine incorporation. We conclude that progenitor cells of most MDS are able to proliferate in the presence of HGF, with wide case-to-case variations. However, the pattern of growth remains abnormal when compared to normal marrow. Although the combination of IL-3 and GM-CSF is the most efficient, there is a large overlap in the stimulating effects of all factors studied.
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PMID:In vitro effects of recombinant hemopoietic growth factors on progenitor cells from patients with myelodysplastic syndromes. 170 6

Hematopoietic growth factors have now been purified, cloned, and produced in bacteria and yeast. Those that are currently in clinical study include erythropoietin, GM-CSF, G-CSF, M-CSF (also called CSF-1), and multi-CSF (also called interleukin 3). Growth factor appear likely to enhance the recovery and function of circulating white cells after standard-dose cancer therapy and high-bone-dose cancer therapy with marrow transplant and to restore leukocyte numbers and competence in the acquired immune deficiency syndromes and myelodysplastic syndromes. Phase I, II trials in AIDS, in cancer patients receiving chemotherapy, in cases of myeloproliferative disease, and after bone marrow transplant have been published. The results of phase III studies are just becoming available.
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PMID:G-CSF and GM-CSF in clinical trials. 170 37

The regulation of haemopoiesis in myelodysplastic syndromes (MDS) was evaluated by measuring and comparing the in vitro response of marrow progenitors from 18 MDS patients to stimulation with recombinant haemopoietic growth factors (HGFs), granulocyte-macrophage colony-stimulating factor (GM-CSF), granulocyte CSF (G-CSF) and interleukin-3 (IL-3). A similar pattern of colony growth was detected with all three HGFs in most MDS patients, exhibiting subnormal growth of GM-CFU and markedly poor to absent growth of BFU-E and CFU-GEMM. A common severe impairment in the growth of all colony types with all three HGFs was observed in five patients, four of whom presented with pancytopenia. The stimulation of MDS marrow progenitors with a five-fold higher than control saturating dose of HGFs induced a significant increase in the frequency of one, two, or all three colony types in cultures of 14 patients, whereas colony numbers in control (n = 8) marrow cell cultures were not significantly changed. All four of the non-responders were pancytopenic and three exhibited markedly impaired colony growth. Supersaturating GM-CSF, G-CSF and IL-3 increased GM-CFU numbers in six, three, and three patients, respectively. The values for BFU-E were three, six, and seven and for CFU-GEMM two, one, and five. The enhancement of MDS marrow colony numbers by supersaturating HGFs which exert their effects directly or via the action of marrow accessory cells, suggests that the progenitor cell growth abnormalities in these disorders may involve a defect in the capacity of accessory and/or progenitor cells to respond to stimulation with specific haemopoietic growth regulators.
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PMID:Impaired response of myelodysplastic marrow progenitors to stimulation with recombinant haemopoietic growth factors. 170 45


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