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)

Masked monosomy 7, i.e. detected by FISH but not by conventional cytogenetics, has been reported in varying frequency in MDS. To establish the prevalence and possible clinical significance of the aberration, we studied the 123 previously karyotyped MDS patients using FISH and a DNA probe specific for chromosome 7. Metaphase cytogenetics revealed ten patients (8%) with monosomy 7 (6 RAEB and 4 RAEB-t). FISH confirmed this result and detected four more cases (4%) with masked monosomy 7 (3 RA and 1 RARS). Thus, masked monosomy 7 is less common than has been suggested, and does not seem to carry the same prognostic weight as monosomy 7 diagnosed by metaphase cytogenetics.
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PMID:Masked monosomy 7 in myelodysplastic syndromes is uncommon and of undetermined clinical significance. 1122 14

The myelodysplastic syndromes (MDS) are clonal hematologic malignancies characterized by pancytopenia, dysplastic hematopoiesis, and a propensity to leukemic transformation. Increased apoptosis has been noted in MDS as a possible explanation for ineffective hematopoiesis, with lower levels in progression to and in de novo acute leukemia. Apoptosis can be measured by binding of Annexin V to exposed membrane phosphatidylserine. We postulated that the apoptotic index would aid in the differential diagnosis of MDS versus other hematopoietic diseases. We examined 33 bone marrow aspirates suspected of hematopoietic malignancy for apoptotic index by Annexin V analysis using a Becton Dickinson FACStar+ flow cytometer. The apoptotic index was expressed as the percentage of Annexin V-positive cells divided by total mononuclear cells in the gate. By standard morphologic analysis, 16 cases were diagnosed as MDS (9 refractory anemia [RA], 2 refractory anemia with ringed sideroblasts [RARS], 1 refractory anemia with excess of blasts [RAEB], 3 chronic myelomonocytic leukemia [CMML], and 1 unclassified), 11 as acute leukemia (AL), 6 as myeloproliferative disorders (MPD). Eight cases (uninvolved marrow of five patients with lymphoproliferative disorders [LPD], one patient with multiple myeloma, and two patients with anemia of chronic disease) served as nonneoplastic controls. A higher degree of apoptosis was observed in MDS (mean = 44.7%; range = 29.5--60%) compared with MPD (mean = 8.2%; range = 2.3--15.4%), AL (mean = 16.1%; range = 5.1--29.4%), and control marrow samples (mean = 11.6%; range = 1.5--21%). Additionally, the apoptotic index was significantly higher in MDS compared with MPD (P < 0.0001). In conclusion, a high apoptotic index occurs in MDS, supporting previous reports and suggesting that Annexin V analysis can be used as an adjunct in the diagnosis of MDS versus MPD. This would be particularly useful for the often-difficult distinction between early MDS and early MPD cases with equivocal morphology.
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PMID:Apoptotic index by Annexin V flow cytometry: adjunct to morphologic and cytogenetic diagnosis of myelodysplastic syndromes. 1124 4

Several prognostic factors for patients with myelodysplastic syndromes (MDS) have been defined in the past. One of these factors appears to be the serum lactate dehydrogenase (LDH) activity. However, the precise predictive value of an elevated LDH level with regard to AML transformation remains uncertain. In this study, the prognostic value of the LDH activity was examined in a cohort of 180 patients with de novo MDS (median age 71 years [27-93]; f/m-ratio 1:1.2; RA: n=53; RARS: n=37; RAEB: n=50; RAEBT: n=19; CMML: n=21). Significant differences in LDH activities were found among FAB groups (P<0.05), and especially among IPSS groups (HIGH: 411+/-574; INT-2: 221+/-90; INT-1: 254+/-145; LOW: 192+/-47 U/l; P<0.05). An LDH level of >/=300 U/l was found to be associated with a significantly shorter median survival (10.3 months) when compared to <300 U/l (33.7 months; P<0.01). Moreover, an LDH activity of >/=300 U/l indicated a reduced AML-free survival in our MDS patients (P<0.01). As assessed by Cox regression, the inclusion of LDH as additional variable into the IPSS system resulted in an improved prediction concerning survival, but not with regard to AML evolution. Together, our data show that a serum LDH activity of >/=300 U/l in MDS is associated with a significantly shorter survival and higher risk to transform to AML. The LDH activity should be considered as an important prognostic factor in MDS.
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PMID:Prognostic value of lactate dehydrogenase activity in myelodysplastic syndromes. 1124 25

Relapse is the major cause of death after allogeneic bone marrow transplantation (BMT). This study tested the hypothesis that the numbers of donor mononuclear cells, lymphocytes, and CD34(+) cells influence relapse and event-free survival (EFS) after BMT. The study population consisted of 113 consecutive patients with hematologic malignancies who underwent non-T-cell-depleted BMT from HLA-matched siblings. Sixty-four patients had low-risk diagnoses (ALL/AML CR1, MDS RA/RARS, and CML CP1); 49 patients had high-risk diagnoses (all others). CD34(+) cells, T cells, B cells, natural killer cells, monocytes, and a rare population of CD3(-), CD4(bright) cells in the allografts were measured by flow cytometry. The CD3(-), CD4(bright) cells in bone marrow had the same frequency and phenotype as CD123(bright) type 2 dendritic cell (DC) progenitors, and they differentiated into typical DCs after short-term culture. Cox regression analyses evaluated risk strata, age, gender, and the numbers of nucleated cells, CD3(+) T cells, CD34(+) hematopoietic cells, and CD4(bright) cells as covariates for EFS, relapse, and nonrelapse mortality. Recipients of larger numbers of CD4(bright) cells had significantly lower EFS, a lower incidence of chronic graft-versus-host disease (cGVHD), and an increased incidence of relapse. Recipients of larger numbers of CD34(+) cells had improved EFS; recipients of fewer CD34(+) cells had delayed hematopoietic engraftment and increased death from infections. In conclusion, the content of donor CD4(bright) cells was associated with decreased cGVHD and graft-versus-leukemia effects in recipients of allogeneic bone marrow transplantation, consistent with a role for donor DCs in determining immune responses after allogeneic BMT.
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PMID:Larger numbers of CD4(bright) dendritic cells in donor bone marrow are associated with increased relapse after allogeneic bone marrow transplantation. 1134 16

Amifostine is a cytoprotective agent mainly used in cancer therapies, in order to ameliorate the toxic effects of anticancer chemotherapy and radiotherapy. In the past years an intriguing number of applications of amifostine have been identified; one of these is bone marrow cells protection and stimulation. Amifostine was administered in seven patients with myelodysplastic syndromes, four males and 3 females aged between 67 and 78 years old, in order to estimate its efficacy in reducing the need for red blood cells transfusions. Two patients had RAEB, four RA and one RARS. The drug was administered in an outpatient basis in a dose of 300 mgr/m2, three times weekly for at least four weeks. We administered at the same time erythropoietin 10.000 U subcutaneously. All patients received daily supplementation of oral ferrum sulfate and folic acid. Three patients, a woman with RA and two men, one with RA and another with RAEB improved the levels of Hb beyond 12,0 gr/dl and did not receive blood transfusions after the second week of treatment. The drug was well tollerated without any side effects in all of the patients.
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PMID:Preliminary results of amifostine administration in combination with recombinant human erythropoietin in patients with myelodysplastic syndromes. 1137 Aug 27

A number of prognostic scoring systems for patients with myelodysplastic syndromes (MDS) have been introduced in the past. In the present study, survival and AML evolution were analyzed retrospectively in a total of 180 patients with de novo MDS (observation period: 1989-1999; median age: 71; range 27-93; f/m ratio: 1/1.2). Diagnoses were established according to FAB criteria (RARS, n=37; RA, n=53; RAEB, n=50; RAEB-t, n=19; CMML, n=21). Six different multiparameter scoring systems (the Mufti, Aul, Sanz, Morel, and Toyama scores, and the international prognostic scoring system [IPSS]) were applied. The Aul, Sanz, and Mufti scores were applied to all 180 patients, Morel and Toyama scores to 109 patients, and the IPSS to 102. As assessed by multivariate analysis, the percentage of bm-blasts, hemoglobin, platelet count, neutrophil count, LDH, and karyotype were found to be independent single variables for survival, and bm-blasts, neutrophil count, platelet count, and karyotype for AML evolution. All prognostic scoring systems applied appeared to be highly predictive for survival and AML development (P<0.001). The highest predictive values were found for the Aul, Sanz, and Toyama scores for overall survival, and the IPSS, Toyama, and Morel scores for AML-free survival. In summary, our data show that scoring systems are useful for predicting overall and AML-free survival in patients with MDS. Karyotype-based multiparameter systems appear to be particularly effective in defining MDS patients who are at high risk of transforming to leukemia.
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PMID:Survival analysis and AML development in patients with de novo myelodysplastic syndromes: comparison of six different prognostic scoring systems. 1144 29

Considering the recently stated suggestion of neovascularization being implicated in myelodysplastic syndromes (MDS) pathogenesis, we evaluated multiple morphometric microvascular characteristics in MDS, in relation to clinicopathologic factors and prognosis. Trephines from 50 newly diagnosed MDS patients were immunostained for factor VIII and compared to those from 20 controls, 10 chronic myelomonocytic leukemia (CMML) and 12 acute myeloid leukemia (AML) patients. Quantitation of microvessel density (MVD), area, total vascular area (TVA), major and minor axis length, perimeter, compactness, shape factor, Feret diameter, and the number of branching vessels was performed by image analysis. Overall, the MDS group had significantly higher MVD, TVA, minor axis and shape factor values and significantly lower compactness than the control group. AML was characterized by increased vascularity compared to MDS and CMML, as well as by the presence of flattened microvessels (lower values of shape factor). Hypercellular MDS showed higher MVD. RA/RARS displayed larger caliber vessels than RAEB, which explains the favorable prognostic effect of increased size-related parameters on progression and/or survival. Moreover, decreased compactness and MVD were independent predictors of longer progression-free survival. It is concluded that angiogenesis is involved in the conversion of normal marrow to MDS and ultimately to AML and that disease progression within MDS is accompanied by qualitative alterations of the microvascular network. Furthermore, size-related parameters affect survival, while shape-related parameters and MVD are more influential with regard to progression-free survival.
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PMID:Prognostic evaluation of the microvascular network in myelodysplastic syndromes. 1151 97

There is accumulating evidence that the marrow-failure of myelodysplastic syndrome (MDS) is immune-mediated. We studied patients with MDS to look for oligoclonal or clonal expansion in T cells indicative of an autoimmune process. We used a PCR-based technique (spectratyping) to characterize the T cell repertoire in MDS (n=15; 9 RA, 4 RARS, 2 RAEB) and compared results with age-matched healthy donors (n=20) and transfusion-dependent (TD) patients with hemoglobinopathy (n=5). We found a significantly higher number of skewed Vbeta profiles in the MDS patients compared with controls. In peripheral blood T cells, 60/345 Vbeta profiles examined were skewed in MDS patients compared with 3/115 Vbeta profiles in TD controls (P<0.0001), and 58/460 Vbeta profiles in age-matched controls (P=0.05). A study of Jbeta region within the skewed Vbeta profiles revealed preferential usage of Jbeta 2.1 in MDS in contrast with a wide distribution over the entire Jbeta spectrum in controls, consistent with non-random T cell clonal expansion in MDS. These findings provide further evidence that T cell mediated immune processes are a feature of MDS.
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PMID:Oligoclonal T cell expansion in myelodysplastic syndrome: evidence for an autoimmune process. 1168 79

In 1999 a working group of the World Health Organization (WHO) published a revised classification for myelodysplastic syndromes (MDS): RA, RARS, refractory cytopenia with multilineage dysplasia (RC+Dys), RAEB I and II, del (5q) syndrome, and MDS unclassifiable. Chronic myelomonocytic leukemia (CMML) and RAEB-t were excluded. Standard French-American-British (FAB) and new WHO classifications have been compared in a series of patients (n = 431) from a single center, analyzing morphologic, clinical, and cytogenetic data. According to the WHO findings, dysgranulocytopoiesis or dysmegakaryocytopoiesis only were found in 26% of patients with less than 5% medullary blasts. These patients are thus unclassified and should remain in the subgroups RA and RARS. Splitting of heterogeneous RAEB into 2 subgroups according to blast count was supported by a trend to a statistically significant difference in the single-center study population. Patients with CMML whose white blood cell counts are above 13 000/microL may be excluded from the MDS classification, as warranted by WHO, but a redistribution of patients with dysplastic CMML according to medullary blast count leads to more heterogeneity in other WHO subgroups. Although the natural courses of RAEB-T and acute myeloid leukemia (AML) with dysplasia are different, comparable median survival durations after treatment in patients with RAEB-T and AML were in favor of the proposed 20% medullary blast threshold for AML. The homogeneity of subgroups was studied by evaluating prognostic scores. A significant shift into lower IPSS risk groups was evident in the new classification. These data cannot provide evidence for the new WHO proposal, which should not be adopted for routine clinical use at present. Some of its aspects can provide a starting point for further studies involving refined cytogenetics and clinical results.
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PMID:Myelodysplastic syndromes, from French-American-British to World Health Organization: comparison of classifications on 431 unselected patients from a single institution. 1201 69

Intensity and specificity of leukocyte endothelial interaction may differ in various subtypes of myelodysplastic syndromes. To assess endothelial activation, plasma levels of endothelial adhesion molecules (E-selectin, VCAM-1 and ICAM-1) were analyzed in 65 patients with MDS using commercially available immunoassays. In MDS patients, high levels of sVCAM-1 were closely related to circulation of monocytic cells in the peripheral blood and splenic enlargement. Patients with CMML showed the highest sE-selectin, sICAM-1 and sVCAM-1 levels, whereas receptor levels in low-risk MDS (RA, RARS) were not significantly different from those in high-risk MDS (RAEB, RAEB-t). Similar receptor concentrations were measured in bone marrow aspirations and samples from peripheral blood. Based on levels of circulating endothelial adhesion molecules there is no clear-cut evidence for a general endothelial cell activation in MDS. Furthermore, levels of circulating endothelial adhesion molecules had no prognostic significance in MDS. Concerning MDS subtypes, patients with CMML demonstrate the highest endothelial activation based on cCAM levels obtained. Thus, increased leukocyte endothelial interaction may account for the higher incidence of extramedullary infiltrations in this MDS subtype.
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PMID:Levels of circulating endothelial adhesion molecules in patients with myelodysplastic syndromes. 1174 59


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