Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026986 (myelodysplastic syndrome)
 14,926 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A combination of cyclosporine (CSA) and methylprednisolone (MP) was used as graft-versus-host disease (GVHD) prophylaxis in 25 patients age 11-47 years (median 27 years) who received HLA-compatible sibling marrow transplants after myeloablative therapy for leukemia, myelodysplasia or lymphoma. CSA was initiated at 3 mg/kg/day in two divided doses, and the dose was adjusted to maintain a trough whole blood h.p.l.c. concentration between 200 and 800 ng/ml. While on i.v. CSA, the dose of CSA was increased for 10 of the 25 patients. The actuarial rate of grades II-IV acute GVHD was 37%. Those patients who developed moderate to severe GVHD had a significantly higher early mortality than those who did not (56% vs 12%, p = 0.02). There was a significant association between the development of acute GVHD and a mean week 2 CSA trough concentration less than 250 ng/ml. Life threatening regimen-related toxicities in the first 100 days included capillary leak syndrome, acute pancreatitis and small bowel perforation. Although the combination of CSA and MP in this dosing schedule was active in preventing acute GVHD, nephrotoxicity remained a problem, and outcome was limited by the inability to achieve the target CSA trough concentration in a substantial proportion of patients.
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PMID:Cyclosporine and methylprednisolone after allogeneic marrow transplantation: association between low cyclosporine concentration and risk of acute graft-versus-host disease. 187 93

Regulation of haemopoiesis in the marrow of patients with myelodysplastic syndromes (MDS) was evaluated by assaying (1) the production of haemopoietic regulators acting upon multipotent and committed progenitors by MDS marrow cells, and (2) the responsiveness of MDS marrow progenitors to stimulation with granulocyte colony-stimulating factor (G-CSF). The levels of multipotent progenitor cell colony-stimulating activity (CFU-GEMMCSA) in 7 d bone marrow-conditioned medium (BMCM) from MDS patients were markedly reduced as compared to controls. MDS BMCM also exhibited reduced levels of burst-promoting activity (BPA) for primitive erythroid (BFU-E) progenitors. Both CFU-GEMMCSA and BPA detected in BMCM were completely neutralized by antibodies directed against interleukin-3. MDS BMCM exhibited markedly reduced levels of murine-active CSA. This activity was partially neutralized by anti-CSF-1 antibodies. Levels of regulators in BMCM of refractory anaemia (RA), sideroblastic anaemia. RA with excess blasts, and chronic myelomonocyte leukaemia were virtually the same. CFU-GEMM and BFU-E growth in MDS marrow (n = 9) was markedly reduced. A 5-fold saturating dose of G-CSF induced an approximately 2-fold increase in CFU-GEMM in four of eight MDS and a 1.5-fold increase of BFU-E in five of nine MDS, but not in control (n = 5) marrow cell cultures. Impaired haemopoiesis in MDS marrow may be related to abnormalities both in regulator production by marrow accessory cells and in regulator responsiveness of multipotent and committed progenitors.
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PMID:Regulatory abnormalities in the marrow of patients with myelodysplastic syndromes. 247 8

There was no overall increase in PB-CFU-GM from normal subjects, or MDS patients, when exogenous CSA (5637-CM) was added to the culture medium. However, there was a sub-group of MDS patients (seven of 35) whose PB-CFU-GM numbers were significantly stimulated by 5637-CM. In addition, there were 11 (out of 48) MDS patients with undetectable PB-CFU-GM in assays without exogenous CSA but only two when 5637-CM was added (p less than 0.01). This sub-group is of particular interest as it is known that those without detectable PB-CFU-GM tend to have significantly shorter survival times than others. The mechanism of the functional abnormality is yet to be determined.
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PMID:Effect of 5637-conditioned medium on peripheral blood granulocyte-macrophage progenitors in normal subjects and patients with the myelodysplastic syndrome. 278 48

Bone-marrow granulocyte-macrophage progenitor cell proliferation and regulatory factor (colony-stimulating activity; CSA) production were assessed at presentation and, if possible, subsequently in twenty-one patients with dysmyelopoiesis and less than 5% bone-marrow blasts. Seven patients underwent acute leukaemic transformation 1-35 months after the first marrow culture. Assay of bone-marrow endogenous CSA proved the most useful prognostic test. The rate of transformation in the seven patients with raised CSA at presentation was significantly greater (five transformed and one died at or before 4 months) than that in the fourteen patients with normal, low, or undetectable CSA (two transformed at 27 and 35 months). In one of the latter an increase in bone-marrow CSA occurred 6 weeks before transformation (serial marrow samples were not available in the other case). No other marrow culture feature measured, including the presence or absence of granulocyte-macrophage colony-forming cells and total clone numbers (colonies and smaller clusters) was as useful.
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PMID:Use of bone-marrow culture in prediction of acute leukaemic transformation in preleukaemia. 613 82

The improved outcome of acquired aplastic anemia (AA) has revealed later complications, such as myelodysplastic syndrome (MDS) and acute myelogenous leukemia (AML). We retrospectively analyzed 167 children with severe acquired AA. Eleven of 50 children treated with cyclosporin (CSA) and recombinant human granulocyte colony-stimulating factor (rhG-CSF) developed MDS/AML; 8 of these were within 36 months of the diagnosis of AA, much earlier than previous reports. Six of the 11 children received rhG-CSF exceeding 10 microg/kg/d, and 9 received rhG-CSF therapy for over 1 year. Ten children showed monosomy 7 at diagnosis of MDS. All of the 11 children were administered both CSA and rhG-CSF. There was no development of MDS/AML among 41 children treated with either CSA or rhG-CSF or among 48 children who underwent bone marrow transplantation. A well-controlled clinical trial is warranted to determine whether therapeutic modalities affect the development of MDS/AML in children with severe acquired AA.
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PMID:Myelodysplastic syndrome and acute myelogenous leukemia as a late clonal complication in children with acquired aplastic anemia. 924 30

To explore the feasibility and potential advantages of PBSC in allogeneic transplantation, we grafted 24 patients (age 16-57, median 37) with different hematologic diseases (ALL = 10, AML = 5, MM = 4, NHL = 2, CML = 1, MDS = 1, AA = 1), 23 HLA-identical to their siblings and 1 partially matched. Cells were collected from donors by apheresis after G-CSF 10 to 16 mg/kg/day for 4 to 5 days, and stored at 4 degrees C until infusion. The patients were conditioned with chemotherapy regimens including busulfan and cyclophosphamide in the majority of cases and received GVHD prophylaxis with CSA-MTX in all but two. The graft consisted of PBSC alone, with a median of 143.5 (range 18.1-358.9) x 10(4)/kg CFU-GM, 9.0 (range 3.3-18.0) x 10(6)/kg CD34+ cells and 2.8 (range 1.2 to 8.6) x 10(8)/kg CD3+ and cells. An ANC >0.0.5 x 10(9)/L was recovered on (median) day 13 (range 11-17), and a platelet count >50 x 10(9)/L on (median) day 13 (range 12-55) post graft. There was no correlation between CD34+ cells or CFU-GM number in the inoculum and time to hematologic reconstitution. Acute GVHD (grade II-IV) occurred in 10 out of 22 (45%), chronic GVHD in 10 out of 18 evaluable (55%) patients. We found no relationship between occurrence of acute or chronic GVHD and number of CD3+ cells in the graft. Four patients relapsed and 7 died after transplantation. Fifteen patients are currently alive and disease-free 67 to 710 (median 286) days from the graft. Allogeneic transplantation with unmanipulated PBSC ensures a fast and stable engraftment. Acute GVHD incidence and severity seems comparable to that of bone marrow transplantation, but there may be an increase in chronic GVHD, mainly of the extensive form.
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PMID:Transplantation of unmanipulated allogeneic PBSC: preliminary report on 24 patients. 957 Jun 80

Myelodysplastic syndrome (MDS) and T-cell large granular lymphocytic disease (T-LGL) are bone marrow failure disorders. Successful use of immunosuppressive agents to treat cytopenia in MDS and LGL suggests a common pathophysiology for the two conditions. Of 100 patients with initial diagnoses of either MDS or T-LGL referred to the National Institutes of Health for immunosuppressive treatment of cytopenia, nine had characteristics of both T-LGL and MDS (T-LGL/MDS). Fifteen patients with T-LGL received cyclosporin (CSA) (10 responses). Eight out of nine patients with T-LGL/MDS received CSA (two responses) and one patient received ATG (one response). Of 76 patients with MDS, eight received CSA (one response) and 68 received ATG (21 responses). The response to immunosuppression was significantly lower in patients with T-LGL/MDS and MDS than in patients with T-LGL disease alone (28% vs. 66%, P = 0.01). The proportion of T-helper cells and T-suppressor cells with an activated phenotype (HLA-DR(+)) was increased in patients with T-LGL, T-LGL/MDS and MDS, but the increase in activated T-suppressor cells in patients with T-LGL/MDS was not statistically significant. Autoreactive T cells may suppress haematopoiesis and contribute to the cytopenia in T-LGL and some patients with MDS, leading to T-LGL/MDS. The lower response rate of MDS or T-LGL/MDS to immunosuppression, compared with T-LGL alone, may reflect the older age and intrinsic stem cell abnormalities in MDS and T-LGL/MDS patients.
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PMID:Coincident myelodysplastic syndrome and T-cell large granular lymphocytic disease: clinical and pathophysiological features. 1116 2

Immunosuppression with antithymocyte globulin (ATG) or cyclosporine (CSA) can be used to treat the cytopenia associated with myelodysplastic syndrome (MDS). Previously, we identified HLA-DR15, younger age, and shorter duration of red cell transfusion dependence as pretreatment variables that correlate significantly with a response. Using these pretreatment variables we have devised a simple method to prospectively identify patients with low or high probabilities of response to immunosuppression. The ability of this system to predict response was confirmed in a separate cohort of 23 patients with MDS treated with immunosuppression.
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PMID:A simple method to predict response to immunosuppressive therapy in patients with myelodysplastic syndrome. 1282 3

This study was purposed to explore the efficacy of hematopoietic reconstitution and survival of patients with myelodysplastic syndrome (MDS) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Allo-HSCT without T lymphocyte depletion was used in 6 patients with MDS from November 1999 to June 2007. 4 cases out of them received allo-PBSCT from HLA matched sibling donors with conditioning regimen of cyclophosphamide (CTX) and Bu. Graft versus host disease (GVHD) was prevented by the administration of immunosuppressive drugs of cyclosporine A (CsA) and short-course MTX. 2 patients received haploidentical allogeneic bone marrow transplantation (hi-alloBMT) after preconditioning with cytosine arabinoside (Ara-C), CTX and total body irradiation (TBI) with a linear accelerator. GVHD was prevented by the administration of immunosuppressive drugs including CSA, short-course MTX, MMF, anti-CD25 monoclonal antibody and ATG. The results showed that all of the patients were engrafted successfully. The median time of granulocyte recovery exceeding 0.5 x 10(9)/L and platelets exceeding 20 x 10(9)/L were days 15 and 20.3 respectively, and 100% donor hematological cells were detected by cytogenetic analysis. All patients did not experience serious acute graft-versus-host disease (aGVHD). During 18 - 108 months of following-up, 2 cases died of pulmonary complication and of relapse; the other 4 cases survive in a disease-free situation. In conclusion, allo-HSCT was an effective approach for the treatment of MDS.
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PMID:[Allogeneic hematopoietic stem cell transplantation in 6 patients with myelodysplastic syndrome]. 1954 94

To improve diagnosis and therapy for aplastic anaemia (AA) in Shanghai, clinical and laboratory data for patients with AA (n = 142) and hypocellular myelodysplastic syndrome (MDS; n = 22) were comparatively analysed (follow-up 2 - 6 years). Red blood cell distribution width and absolute lymphocyte and reticulocyte counts were significantly different between the two groups. AA was diagnosed in 54.2% of patients using a single bone marrow aspirate smear plus peripheral haemogram results, and in 95.1% using an additional bone marrow biopsy; 4.9% required multiple-site bone marrow examination. Clonal chromosomal abnormalities occurred in 3.9% and 31.8% of patients with AA and MDS, respectively. In patients with severe AA, 12.0% received antithymocyte globulin (ATG) + cyclosporin A (CSA; effectiveness rate 77.8%; 5-year survival 74.1%), 45.3% received CSA + androgen therapy (effectiveness rate 58.8%; 5-year survival 76.5%) and 26.7% received androgen monotherapy (effectiveness rate 25.0%). Multivariate analysis of prognostic factors indicated that therapy regimen and blood platelet count affected survival. Peripheral blood smears, bone marrow spicule classification and biopsy are important diagnostic factors. Standardization of evidence-based therapy and promotion of ATG + CSA would improve general therapeutic effects in AA.
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PMID:Diagnosis and treatment of acquired aplastic anaemia in adults: 142 cases from a multicentre, prospective cohort study in Shanghai, China. 2211 4


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