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)

Current prognostic models for myelodysplastic syndromes (MDS) do not allow the identification of patients with lower risk disease and poor prognosis that may benefit from early therapeutic intervention. We evaluated the characteristics of 856 patients with low or intermediate-1 disease by the International Prognostic Scoring System. Mean follow-up was 19.6 months (range 1-262). Of these patients, 87 (10%) transformed to acute myelogenous leukemia, and 429 (50%) had died. By multivariate analysis, characteristics associated with worse survival (P<0.01) were low platelets, anemia, older age, higher percent of marrow blasts and poor-risk cytogenetics. Although not included in the model, higher ferritin (P=0.007) and beta2-microglobulin (P<0.001) levels were associated with worse prognosis. This allowed the development of a scoring system in which patients could be grouped in three categories: category 1 (n=182, 21%) with a median survival of 80.3 months (95% CI 68-NA); category 2 (n=408, 48%) with a median survival of 26.6 months (95% CI 22-32) and category 3 (n=265, 31%) with a median survival of 14.2 months (95% CI 13-18). In summary, this analysis indicates that it is possible to identify patients with lower risk MDS and poor prognosis who may benefit from early intervention.
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PMID:A prognostic score for patients with lower risk myelodysplastic syndrome. 1854 98

Allogeneic hematopoietic stem cell transplantation (SCT) has the potential to cure patients with acute leukemia or myelodysplastic syndromes (MDS), but a number of prognostic factors can influence the outcome of transplantation. At present, no transplantation-specific risk score exists for this patient population. We propose a simple scoring system for patients with acute myelogenous leukemia (AML), acute lymphoblastic leukemia (ALL), or MDS, based on a retrospective analysis of 445 patients undergoing SCT at our institution (divided into training and validation subsets). The score depends on 5 variables: age, disease, stage at transplantation, cytogenetics, and pretransplantation ferritin. It divides patients into 3 groups of comparable size, with 5-year overall survival (OS) of 56% (low risk), 22% (intermediate risk), and 5% (high risk). This prognostic score could be useful in making treatment decisions for individual patients, in stratifying patients entering clinical trials, and in adjusting transplantation outcomes across centers under the new federal reporting rules.
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PMID:A prognostic score for patients with acute leukemia or myelodysplastic syndromes undergoing allogeneic stem cell transplantation. 1815 58

Myelodysplastic syndromes (MDS) are a group of disorders characterized by ineffective hematopoiesis that leads to peripheral cytopenias. Iron overload results from high transfusion requirements and retrospective studies have shown it to be associated with relatively poor survival in a subset of the low risk patients. Recent discoveries have led to the identification of hepcidin as a key regulator of iron metabolism and to the association of non-transferrin bound iron moieties, such as labile plasma iron, with the end organ damage in iron overload states. Currently, there is limited data in evaluating the role of iron chelators in MDS and data from studies in Thalassemia and hemachromostosis have been used to predict ferritin levels above 1000 - 2500 ng/mL and history of 20 blood transfusions as clinical end points for considering iron chelation in MDS. Deferoxamine and deferasirox, the two iron chelators approved for use in the US, have shown efficacy in reducing iron overload in MDS in retrospective studies are now being evaluated for effects on overall survival in prospective studies. On the basis of retrospective data, it is reasonable to offer iron chelation to the lower risk MDS patients requiring frequent transfusions, while monitoring for specific adverse affects in patients on treatment.
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PMID:Iron overload in myelodysplastic syndromes. 1829 18

Anemia can result from deficient erythropoiesis [aplastic anemia, myelodysplastic syndromes (MDS), iron deficiency anemia, anemia of chronic disease (ACD), thalassemia, megaloblastic anemia, chronic renal failure, hematological malignancies, etc.], excessive RBC destruction [hereditary spherocytosis, inherited enzyme deficiency, hemoglobinopathies, autoimmune hemolytic anemia (AIHA), paroxysmal nocturnal hemoglobinuria (PNH), etc.], and blood loss. Based on the measured red cell size(MCV), anemia is classified as microcytic, normocytic, or macrocytic. Iron parameters (serum iron, serum ferritin, etc.), reticulocyte count, bone marrow examination, Coombs test, serum vitamin B12 level, and Ham test are also useful in the differential diagnosis of anemia. Novel treatment of anemia includes lenalidomide for 5q(-)MDS, azacitidine for high-risk MDS, and eculizumab for PNH. Oral iron chelator(deferasirox) developed for the treatment of transfusional iron overload is also very useful for the management of patients with bone marrow failure syndromes.
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PMID:[Pathophysiology, diagnosis and treatment of anemia]. 1832 12

Thirty-five adult myelodysplastic syndrome (MDS) patients were included in this study: 11 refractory anemia (RA), 4 RA with ring sideroblasts (RARS), 9 RA with excess of blasts (RAEB), 10 RAEB in transformation (RAEB-T) and 1 chronic myelomonocytic leukemia (CMML). The ranges of survival were 4-51 months, 40-59 months, 7-38 months, 5-24 months and 5 days, respectively. Three patients died and 3 showed disease progression during the course of the study. A composite analysis of proliferative indices, cytogenetics, immunophenotype and other conventional/novel prognostic parameters in the context of Indian MDS patients was performed. The proliferative indices (AgNOR and Ki 67 positivity), immunophenotypic markers, serum LDH and ferritin levels revealed wide variations and great overlap among different FAB subtypes. The scoring systems (Bournemouth, Dusseldorf and Goasguen) did not correlate with the prognosis and survival (p > 0.05). Clonal cytogenetic abnormalities were detected in 24/35 (68.57%) patients, +8, -5 and -7 being observed commonly. Cytogenetic abnormalities were more frequent in RAEB (88.8%), RAEB-T (80.0%) and RA (63.6%) subtypes of MDS. By Using Mufti's prognostic system and International prognostic scoring system (IPSS), a good positive correlation was found between low risk category and RARS with better survival as compared to other risk categories/FAB subtypes (p < 0.01). However, rest of the FAB subtypes were assigned into high, intermediate and low risk categories without any correlation with the survival and/or leukemic transformation. RARS subtype revealed itself as the better prognostic category according to the cytogenetic findings as well as Mufti's grading system. This was possible due to the longer follow up available for these patients (40-59 months).
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PMID:Proliferative indices, cytogenetics, immunophenotye and other prognostic parameters in myelodysplastic syndromes. 1841 75

In a retrospective study of 126 adult patients with French-American-British-defined refractory anemia with ringed sideroblasts (RARS), staging by the International Prognostic Scoring System was highly predictive of survival outcome (P < 0.0001). In addition, red blood cell (RBC) transfusion requirement at diagnosis (P = 0.001), but not the number of RBC units transfused during the disease course (P = 0.17), was independently associated with inferior survival. There were no correlations between survival and serum ferritin level, measured either at diagnosis (median 567 ng/mL, range 16-3,475; P = 0.24) or during follow-up (median 1,108 ng/mL; range 238-43,500; P = 0.72). Similarly, there was no difference in survival when patients were stratified by serum ferritin levels of < or > or =1,000 ng/mL at diagnosis or peak serum ferritin levels of <1,000, 1,000-5,000, or >5,000 ng/mL during follow-up. The current study does not support the contention that transfusional hemosiderosis is an adverse prognostic factor in "good risk" myelodysplastic syndrome.
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PMID:Neither serum ferritin nor the number of red blood cell transfusions affect overall survival in refractory anemia with ringed sideroblasts. 1844 62

We performed MRI and endocrine assessment in 27 adult Chinese patients with severe aplastic anemia (SAA) and myelodysplasia (MDS). Despite high ferritin levels, cardiac hemosiderosis and heart failure was not common, and were not concordant in most cases. However, significant correlation was found between cardiac T2/T2* MRI assessment, ejection fraction and ferritin levels. Furthermore, there was a high incidence subclinical pancreatic abnormality that was related to liver MRI T2* readings. Hence, chelating agents may still have a role to improve organ function. Prospective data with serial functional and imaging monitoring is needed.
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PMID:A pilot MRI study of organ specific hemosiderosis and functional correlation in Chinese patients with myelodysplasia and aplastic anemia with raised ferritin levels. 1848 75

The pharmacokinetics (PK) and pharmacodynamics (PD) of the once-daily, oral ironchelating agent, deferasirox (Exjade, ICL670), have been evaluated further in a Phase I, openlabel, multicenter, dose-escalation study in Japanese patients with myelodysplastic syndromes, aplastic anemia, and other anemias. Deferasirox was initially administered as a single dose of 5 (n = 6), 10 (n = 7), 20 (n = 6) or 30 (n = 7) mg/(kg day) and then after 7 days seven daily doses were administered. Linear PK (C (max) and AUC) were observed at all doses after a single dose and at steady state, and dose-dependent iron excretion was observed. Pharmacokinetic/pharmacodynamic parameters were similar to those reported in a Caucasian beta-thalassemia cohort. Following the single- and multiple-dose phases, 21 of 26 patients progressed to a 3-year extension phase of the study, where dose reductions and increases [5-30 mg/(kg day)] were allowed following safety and efficacy assessments. In the interim, 1-year data show that deferasirox was well tolerated, with generally infrequent and mild adverse events. Reductions in serum ferritin levels were observed and a negative iron balance achieved at doses of 20-30 mg/(kg day). These data suggest that deferasirox has a stable and predictable PK/PD profile, irrespective of underlying disease or race, and a predictable and manageable safety profile suitable for chronic administration.
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PMID:A safety, pharmacokinetic and pharmacodynamic investigation of deferasirox (Exjade, ICL670) in patients with transfusion-dependent anemias and iron-overload: a Phase I study in Japan. 1859 54

Only limited data are available regarding myocardial iron overload in adult patients with transfusion dependent acquired anemias. To address this topic using MRI T2* we studied 27 consecutive chronic transfusion dependent patients with acquired anemias: (22 myelodysplastic syndrome, 5 primary myelofibrosis). Cardiac MRI T2* values obtained ranged from 5.6 to 58.7 (median value 39.8) milliseconds. Of the 24 analyzable patients, cardiac T2* correlated with transfusion burden (p=0.0002). No patient who had received less than 290 mL/kg of packed red blood cells (101 units=20 grams of iron) had a pathological cardiac T2* value (< 20 ms). All patients who had received at least 24 PRBC units showed MRI T2* detectable hepatic iron (liver T2* value </=6.3 ms). Only patients with severe hepatic iron overload (T2* <1.4 ms) showed cardiac T2* value indicative of dangerous myocardial iron deposition. Serum ferritin was not significantly correlated with cardiac T2* (p=0.24). Gradient echo T2* magnetic resonance imaging provides a rapid and reproducible method for detecting myocardial iron overload which developed after a heavy transfusion burden equal to or greater than 290 mL/kg of packed red blood cell units.
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PMID:Myocardial iron overload assessment by T2* magnetic resonance imaging in adult transfusion dependent patients with acquired anemias. 1860 57

Blood transfusions represent a main component of supportive care in myelodysplastic syndromes (MDS). To avoid organ damage caused by transfusion-dependent iron overload, an adequate iron chelation therapy is required. Recently, a new oral iron chelator deferasirox (ICL670, Exjade) has become available. A study was conducted to demonstrate the efficacy and tolerability of deferasirox in transfusion-dependent iron-overloaded patients with MDS. The efficacy of deferasirox was monitored by changes in serum ferritin, bone marrow iron, and liver iron concentration (LIC), as determined by T2*-weighted magnetic resonance imaging. Twelve patients with MDS of different subtypes (median age 76 years, range 53-91) were enrolled. Deferasirox administered in a once-daily dose of 20-30 mg/kg for 12 months was effective in reducing median ferritin concentration from 1,515 microg/L (range 665-6,900) to 413 microg/L (range 105-3,052). Within the first 4 weeks of treatment before the continuous decline of ferritin levels, the values markedly rose in eight of 12 patients. The median LIC declined from 315 to 230 micromol/g (p=0.02) at the end of study, accompanied by a reduction of bone marrow siderosis. The most common adverse events were mild and transient gastrointestinal disturbances, skin rash, nonprogressive transient increases in serum creatinine and urine beta2-microglobulin, and a temporary reduction of the creatinine clearance. The renal parameters normalized after end of treatment. No hematologic toxicities were observed. Deferasirox proved to be effective in transfusion-dependent iron overload in MDS by mobilizing iron deposits in liver and at least stabilizing iron stores in bone marrow.
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PMID:Deferasirox in MDS patients with transfusion-caused iron overload--a phase-II study. 1881 Apr 37


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