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)

In a retrospective analysis we assessed the data of 46 patients with myelodysplastic syndromes (MDS), who had received more than 50 blood transfusions during the course of disease. The number of units given ranged from 50 to 155 (mean 79). 20 patients (RA n = 4, RARS n = 12, RAEB n = 1, RAEB/T n = 2, CMML n = 1), followed up between 8 and 108 months (mean survival time 39.4 months), developed a secondary hemochromatosis. More than 40% of the patients showed signs of heart failure, in some cases accompanied by cardiac arrhythmias. 11 patients also suffered from hepatopathy and 5 developed diabetes mellitus. Secondary hemochromatosis was particularly common in patients with RARS. Refractory congestive heart failure secondary to hemochromatosis was the cause of death in 14 patients, whereas none died from hepatic insufficiency. We conclude that the risk of secondary hemochromatosis should not be neglected in polytransfused patients with MDS. In some cases, particularly those with favorable prognostic features of MDS, it may shorten life expectancy. The availability of a new oral iron chelator (1,2-dimethyl-3-hydroxypyrid-4-one or L1) offers a promising and practicable approach to prevent this complication.
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PMID:[Secondary hemochromatosis in polytransfused patients with myelodysplastic syndromes]. 128 62

Material from 63 cases with primary myelodysplastic syndromes (P-MDS) (French-American-British [FAB] types: refractory anemia [RA] = 21; RA with ring sideroblasts [RARS] = 8; RA with excess of blasts (RAEB) = 10; RAEB in transformation (RAEBt) = 6; chronic myelomonocytic leukemia [CMML] = 10 and unclassifiable = 8, ie, bone marrow aspiration was inadequate and stringent FAB criteria were not applicable) was analyzed for bone marrow histologic and immunohistochemical patterns. Standard Giemsa, hematoxylin and eosin (H&E) and reticulin stains were used for morphologic assessment. To identify the cell lineage precisely, chloroacetate esterase staining and an indirect immunoperoxidase technique using mouse monoclonal antibodies CD15, CD68, HLA-DR, and rabbit polyclonal CD3 and UEA-1 (lectin) was developed on formalin-fixed paraffin embedded bone marrow biopsies (BMB). The immunohistochemical assessment permitted accurate identification of dysplastic features such as mononuclear and binuclear megakaryocytes, Pelger-Huet neutrophils, and binuclear erythroblasts. Additional bone marrow histologic and immunohistochemical features observed were heterogeneity of immunohistochemical staining in various cell lineages, megakaryocytic emperipolesis, alteration of bone marrow microarchitecture, intravascular clusters of hematopoietic cells, and the types of benign lymphoid aggregates. The nature of abnormally localized immature precursors (ALIP) was discerned. Three types of clusters of immature cells were found that were difficult to distinguish on Giemsa and H&E morphology, these were erythroid aggregates (n = 18); megakaryocytic aggregates (n = 4), and immature granulocytic and monocytic aggregates (n = 32). The bone marrow histologic and immunohistologic patterns permitted the identification of four groups of clinical relevance: Group 1, cases with predominant erythroid hyperplasia and without ALIP (n = 15); group 2, cases with prominent myeloid hyperplasia and presence of ALIP (n = 32); group 3, cases with hypoplastic MDS (n = 10); and group 4, cases with hyperfibrotic MDS (n = 6). Statistical analysis showed a significant difference in survival and leukemic transformation between groups 1, 2, 3, and 4, with cases in group 2 showing the worst prognosis with early death due to increased propensity to leukemic transformation and cytopenia-related complications (P less than .0001). We conclude that immunohistochemistry is feasible on routinely processed BMB and the information obtained is of diagnostic and prognostic importance in P-MDS. The phenotype of ALIP varies with the morphologic and histologic subtypes of MDS and the term should be reserved for cases in whom the clusters in the intertrabecular region are of myeloid (granulocytic and monocytic) lineage on immunohistochemistry.
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PMID:Primary myelodysplastic syndromes: diagnostic and prognostic significance of immunohistochemical assessment of bone marrow biopsies. 137 Feb 3

In order to investigate, whether heme would induce a response in myelodysplastic syndromes (MDS), 14 symptomatic patients (4 RA, 3 RARS and 7 RAEB) were treated with infusions of heme arginate 3 mg/kg body weight on 4 consecutive days, mostly for six cycles at 2-week intervals. Three of 14 patients (21%) showed an improvement in anemia (97-152, 79-120 and 92-114 g/l) within a few weeks, and 1 showed a milder increase in hemoglobin level (102-118 g/l). Of the 2 responders with marked thrombocytopenia, 1 showed an improvement in the platelet count (7-37 x 10(9)/l) and her regular need for red cell and platelet transfusions ceased. Some regression in bone marrow (BM) cytology was seen in all 3 responders. One of the responders is still in remission 41 months after cessation of the treatment, while in the other 2 the response lasted for 26 and 5 months. Four patients progressed during the treatment: 1 RA to RAEB, 1 RAEB to RAEBt and 2 RAEB, both with very complex chromosomal abnormalities at the beginning of the therapy, to acute erythroleukemia (AML-M6). Pretreatment delta-aminolevulinic acid synthase and heme synthase activities were generally low. Five patients had mild thrombophlebitis, but not after the infusion procedure was changed. No other side-effects common to growth factors occurred. In conclusion, it is likely that heme arginate has a therapeutic effect on some MDS patients, obviously by stimulating erythropoiesis. The response may be long-lasting.
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PMID:Therapeutic effect of heme arginate in myelodysplastic syndromes. 834 47

In a retrospective study, 45 (19.4%) out of 232 patients with MDS revealed myelosclerosis (MS) in bone marrow biopsy (BMB). Histological classification according to FAB criteria showed the following distribution: RA 21 (47%), RARS 1 (2%), RAEB 9 (20%), RAEB-T 3 (7%), and CMMol 11 (24%). Sclerosis occurred in all subtypes of MDS, but with a higher incidence in CMMol. Clinical data showed lower values of hemoglobin and lower platelet counts in MDS.MS. Life expectancy was reduced to 7.8 months, compared with 15.0 months in MDS without MS (p = 0.0026). In RA, the survival times were 9.7 months in MDS.MS, compared to 27.9 months in MDS without MS (p = 0.0035). 21 (47%) of the patients with MDS.MS experienced a transformation into ANLL. Myelosclerosis therefore seems to herald a bad prognosis.
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PMID:[Myelosclerosis in myelodysplastic syndromes (MDS). Retrospective analysis of 232 patients with MDS]. 170 73

More than 1300 MDS cases with clonal cytogenetic abnormalities, 200 of them secondary MDS, have been reported. The most common aberrations in primary MDS are del(5q) (27%), trisomy 8 (19%), monosomy 7 (15%), der(11q) (7%), -5, der(12p) and -Y (5%), del(7q) (4%), and t(1;7), der(3q), del(13q), i(17q) and del(20q) in 2% or less. The 5q- is mostly, but not always, a del(5)(q13q33); it is the cytogenetic hall-mark of the "5q- syndrome" and is frequently found as the sole abnormality. The frequency of the aberrations varies among MDS subgroups: 5q- is most frequent in RA, -5, -7, and der(12p) are more common in CMML and especially in RAEB, and +8 and der(11q) are more often found in RARS. The most common aberrations in secondary MDS are -7 (41%), del(5q) (28%), -5 (11%), der(21q) (9%), 7q-, +8 and der(12p) (8%), t(1;7) and -12 (7%), der(17p) (6%), der(3p) and der(6p) (5%), and der(3q), der(11q), -17, -18 and der(19q) (4%). The average number of abnormalities per case is 5.3, compared with 2.9 in unspecified MDS. The frequency of cytogenetically unrelated clones is 5.7% in secondary and 4.3% in primary MDS. When the literature data are broken down by type of genotoxic exposure, it turns out that -5, -7, and der(17p) are over-represented in patients who have received chemotherapy, whereas 5q- is associated with no exposure or preceding radiotherapy only. The karyotypic profile is prognostically important: patients with -7 or complex karyotypes have a higher risk of progression to acute leukemia and shorter survival.
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PMID:Cytogenetic findings in primary and secondary MDS. 173 69

The prognostic value of the FAB classification, bone marrow histology, Bournemouth score, and chromosome findings was studied in 88 patients with primary myelodysplastic syndromes. The median survival for the whole group of patients was 22 months (RA 61.7 months, RARS 31.6 months, CMML 15.7 months, RAEB 10.3 months, and RAEBt 8.2 months). Chromosomal abnormalities were found in 37 of the 70 patients investigated (52%). Only the differences in survival between patients with complex versus normal karyotype were statistically significant (p = 0.02). The presence of small blastic cells, located away from the endosteal surface (abnormal localization of immature blasts or ALIP) appears to be a major prognostic factor in predicting the duration of survival and progression to ANLL, especially in the FAB subgroups RA and RARS. Median survival for the 22 ALIP- cases with RA/RARS was 65 months, compared with 31 months for the ALIP+ cases (p = 0.0006). Nine ALIP+ patients (53%) developed ANLL in contrast to 3 (13%) of the ALIP- cases (p = 0.008). By redefining ALIP and evaluating the number and characteristics of the accompanying cells, histological subtypes were distinguished correlating largely with the FAB subgroups. Our findings demonstrate the prognostic importance of bone marrow biopsy and quantifying the complexity of bone marrow chromosome changes. It should be helpful in evaluating current attempts to find effective treatment for patients with MDS.
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PMID:Update on the prognostic implication of morphology, histology, and karyotype in primary myelodysplastic syndromes. 179 66

We analyzed the prognostic value of clinical, hematologic and bone marrow (BM) histologic findings at presentation in 94 patients with myelodysplastic syndromes (MDS) (28 RA; 2 RARS; 34 RAEB; 6 CMML; 24 RAEB-t). With survival as the dependent variable, stepwise multivariate analysis indicated as the prognostically most important factors among the MDS taken as a whole: latency from the first symptoms to diagnosis, age, and percentage of BM blasts. In each main MDS group the most unfavorable initial characteristics were: 1) low Hb, no macro-megaloblastosis, male sex for RA/RARS; 2) low Hb and low platelet levels for RAEB/CMML; 3) granuloblastic hyperplasia and high BM blastosis for RAEB-t. Of the BM histologic parameters, only the percentage of blasts had significant prognostic value. Histologic assessment of BM blastosis, however, did not differ statistically from that based on cytologic examination of BM smears, so that marrow histology seemed not essential for initial prognostic assessment in MDS patients. The finding of abnormal localization of immature precursors (ALIP) in BM biopsies was associated with a negative trend without reaching statistical significance. Using four objective parameters of proven significance (age, Hb, platelets, and BM blasts) we devised a staging system of immediate clinical utility for prognostic stratification and risk-adapted therapeutic choices.
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PMID:Risk assessment in myelodysplastic syndromes: value of clinical, hematologic and bone marrow histologic findings at presentation. 220 26

We report on 37 adults aged 50 years or less with de novo myelodysplastic syndrome (MDS) (excluding cases secondary to chemo or radiotherapy), who represented 6.7% of our total cases of adult MDS. Median age was 42 (range 18-50). At diagnosis, there were 9 RA, 6 RAEB, 13 RAEB-T, 9 CMML but no RARS. Five patients had a familial history of MDS, and 3 a history of occupational exposure to potential carcinogens. Twenty-one patients received intensive chemotherapy (at diagnosis or during the evolution) but only 8 (38%) achieved complete remission (CR), and median CR duration was 10 months. Five patients were allografted (3 of them as first line therapy): 2 remained disease free after 12 and 10 months, and 3 died of transplant related complications. Median actuarial survival of the 37 patients was 21 months. Significantly shorter survival was seen in patients who had circulating blasts, Bournemouth score greater than 1 or 2, abnormal karyotype (especially monosomy 7) and RAEB or CMML. When compared with our MDS aged more than 50, our MDS aged 50 or less were characterized by more familial cases, more cases of RAEB-T and less cases of RAEB and RARS, more frequent abnormal karyotype and monosomy 7, more frequent progression to AML, identical overall survival but longer survival in RAEB-T and shorter survival in CMML. MDS in younger adults seem relatively often familiar or associated to occupational exposure. They have a poor prognosis with conventional therapeutic approaches and therefore require allografting, whenever possible.
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PMID:de novo myelodysplastic syndromes in adults aged 50 or less. A report on 37 cases. 228 Jun 3

Fifty-four patients with myelodysplastic syndrome (MDS) (35 men and 19 women aged 34-92 years) were studied cytogenetically. Bone marrow cell culture and chromosome preparation were performed according to four different protocols used in parallel: methotrexate (MTX)-synchronized or thymidine (TdR)-unsynchronized techniques, and presence or absence of 5637 conditioned medium (CM). Some patients responded better to MTX; others had better results with TdR exposure only. Use of 5637 CM generally improved quantity and quality of metaphases. A cytogenetic result was obtained in 53 cases. 60% of the patients had a chromosome abnormality. Percentage of abnormality varied from one French-American-British (FAB) subtype to the other: 62% in refractory anemia with ringed sideroblasts (RARS, 8/13), 50% in refractory anemia (RA, 6/12), 60% in refractory anemia with excess of blasts (RAEB, 3/5), 77% in refractory anemia with excess of blasts in transformation (RAEB-T, 7/9), and 57% in chronic myelomonocytic leukemia (CMMoL, 8/14). Chromosome defects were subdivided into three categories: single, two, and complex defects. The most frequent chromosome abnormalities, either single or one of two or complex defects were del(5q) or monosomy 5 (13 cases), trisomy or rearrangement of chromosome 8 (eight cases), total or partial monosomy or rearrangement of chromosome 7 (eight cases), Y loss (seven cases), and del(20q) (two cases). With the exception of del(5q) in macrocytic RA, this study confirms the absence of chromosome defects specific to each FAB category of MDS. Recurrent defects in MDS are relatively limited, however, in terms of chromosomes involved and type of abnormality. Consequently, these defects, mostly of deleted type, are assumed to play a specific role in the genesis of myelodysplasia.
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PMID:Cytogenetic analysis of 54 cases of myelodysplastic syndrome. 234 Apr 87

A series of 116 patients with MDS consisted of 74 cases of RA, 10 cases of RARS, 14 cases of RAEB, 9 cases of RAEB-T and 9 cases of CMML, were studied on the quantity and morphological abnormalities of megakaryocytes in relation to over all survival and leukemic change. The amount of megakaryocytes was graded into four groups; marked hypoplasia (O), moderate hypoplasia (L), normoplasia (N) and hyperplasia (H), RA cases showed heterogeneous pattern; containing 14 cases (18.9%) of group (O), 18 cases (24.3%) of group (L), 31 cases (41.9%) of group (N) and 11 cases (14.9%) of group (H). RARS, RAEB, RAEB-T and CMML cases were classified into group (N) or group (H). The heterogeneous pattern of RA did not relate to leukemic change, but over all survival tended to be shorter in group (N) cases. A significant number of young female cases of RA were involved in group (O). Morphological abnormalities of MDS megakaryocytes were classified into five types; I, mononuclear micromegakaryocytes, II, binuclear micromegakaryocytes, III, mononuclear small megakaryocytes, IV, multiseparated-nuclear megakaryocytes and V, megakaryocytes with bizzare nuclei. RAEB and RAEB-T cases uniformly showed marked dysmegakaryopoiesis ranging from type I to V. whereas RA, RARS and CMML cases showed mild dysmegakaryopoiesis. Only five cases (6.4%) of RA cases had type I micromegakaryocytes. Eight RA cases with type I on diagnosis or obtaining it during the clinical course tended to develop acute myeloid leukemia (5 cases) or to transform to RAEB sooner or later. In two cases of RAEB in which hematological improvement was obtained with low dose cytosine arabinoside regimen, disappearance of type I micromegakaryocytes was noted. A female case with 5q-anomaly surviving more than 10 years showed marked megakaryocyte hyperplasia and almost exclusively type III and IV megakaryocytes. These findings indicated that pattern of dysmegakaryopoiesis, especially appearance of type I, was closely related to leukemic change in MDS. Thus quantitative and qualitative evaluations of MDS megakaryocytopoiesis seemed important to understand the further heterogeneity of pathophysiology in MDS subtypes.
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PMID:[Study on pathophysiology of the myelodysplastic syndromes (MDS)--pattern of dysmegakaryopoiesis related to leukemic transformation]. 259 45


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