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

Hemoglobin (Hb) synthesis in colony-forming-unit erythroid (CFU-E) colonies from the bone marrow of 10 normal subjects and 6 patients with myelodysplastic syndromes (MDS) was studied using microcytofluorometry. Hb content was determined utilizing a photochemical reaction in which the intracellular Hb is converted into fluorescent porphyrin. Briefly, the CFU-E in plasma clots was assayed according to Tepperman's method. Bone-marrow mononuclear cells were then dispensed onto petri dishes containing the plasma clots. The cells in plasma clots were cultured for seven days and then air-dried. The samples were then fixed with pure methanol. Thereafter, the dishes were exposed to ultraviolet light (lambda = 405 nm) in the presence of an SH-donor (0.2 M mercaptoethylamine hydrochloride). The intensity of porphyrin fluorescence was measured using a microcytofluorometer. When the photochemical reaction was carried out for 50 min, the intensity of fluorescence was found to be proportional to the mean corpuscular Hb (MCH) level, suggesting that the intracellular Hb level can be determined as a function of the intensity of this fluorescence. The number of CFU-E colonies in MDS patients was smaller than that in normal subjects. In addition, intracolony Hb level was markedly lower in the MDS cases than in normal subjects. Our findings suggest that the maturation process of CFU-E is impaired in MDS patients.
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PMID:[Qualitative and quantitative evaluation of CFU-E colonies in myelodysplastic syndromes]. 177 72

The effect of a small dose of aclacinomycin-A (ACR) was examined in two patients with refractory anemia (RA) and two with refractory anemia with excess of blasts in transformation (RAEB-t). ACR (7 or 14 mg/m2) was given for 10 days in a 2-h per day drip infusion. Clinical symptoms and laboratory data improved in 3 of these 4 patients. In a patient with RA, marked increase in reticulocytes and elevation of the hemoglobin level from 6 to 9 g/dl was observed after two courses of ACR therapy. In two with RAEB-t, Auer's rod bearing cells disappeared in the bone marrow and megaloblastic change of the erythroblasts was diminished in one patient. Hemoglobin levels rose from 4.7 to 10 g/dl in one, and platelets and WBC increased in another. No effect was seen in a patient with RA. The cytoreductive effect of ACR was minor compared to the therapy with small dose of cytosine arabinoside (Ara-C). Therefore, ACR warrants further consideration for the treatment of patients with MDS.
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PMID:Treatment of four patients with myelodysplastic syndrome with a small dose of aclacinomycin-A. 347 62

In this phase I/II study, 9 patients with myelodysplastic syndromes (MDS) were treated with interleukin-3 (IL-3) followed by granulocyte-macrophage colony-stimulating factor (GM-CSF). Each treatment cycle was 28 days long and administered as follows: 1 microgram/kg/d IL-3 on days 1 through 7 and 3 micrograms/kg/d GM-CSF for days 8 through 21, followed by a 7-day rest period. IL-3 dose escalations were planned, but the dose of GM-CSF was fixed. Three patients had refractory anemia, 4 had refractory anemia with ringed sideroblasts, and 2 had refractory anemia with excess blasts. Six patients were dependent on red blood cell transfusions, 1 on platelet transfusions, and 2 on both. The absolute neutrophil count improved in 7 (77%) patients and the platelet count improved in 3 (33%) patients during therapy. Hemoglobin levels were unchanged. A clinically relevant response was seen in only 1 patient with thrombocytopenia, and he received five cycles of therapy. The neutrophil count decreased in 2 patients and the platelet count decreased in 4 patients during treatment. The toxicity of the treatment was significant. In the first cohort of 3 patients, 1 patient developed supraventricular tachycardia and congestive heart failure. In the second group, 1 patient developed progressive granulocytopenia and died of gram-negative septicemia. Because of the disparate toxicity, 3 more patients were treated at the same dose level. One of these experienced a high fever and bone pain requiring hospitalization. Because of these adverse effects, the IL-3 dose was not escalated and all patients received 1 microgram/kg/d for 7 days. We believe that sequential therapy with IL-3 and GM-CSF at these dose levels causes unacceptable toxicity in patients with MDS. The major toxic events occurred during weeks 4 and 5 after starting treatment and may have been primarily caused by GM-CSF therapy. Although neutrophil counts improve in most patients, the effect on red blood cells and platelets is minimal. At present, this form of therapy remains problematic and appears to have a limited potential in the management of MDS.
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PMID:A phase I/II study of sequential interleukin-3 and granulocyte-macrophage colony-stimulating factor in myelodysplastic syndromes. 828 36

A prospective study was undertaken to elucidate the clinical and laboratory differences between de novo acute myeloid leukemia (AML) and AML with trilineage myelodysplasia (AML-TMDS). One hundred and seven patients with AML were diagnosed at the University Hospital between January 1987 and July 1992, and were followed until July 1995. TMDS was identified in 17 of them (16%). With regard to age and sex distribution no difference was found between AML patients with and without TMDS (p = 0.43, p = 0.54, respectively). The duration of symptoms at presentation in AML-TMDS was similar to those observed in de novo AML (p = 0.29). Hemoglobin values and platelet counts were similar in both groups of patients (p = 0.45, p = 0.44, respectively). However, peripheral white blood cell and neutrophil counts, as well as blast counts in AML-TMDS patients were lower than those observed in AML without TMDS patients (p < 0.001 for all of them). Bone marrow blast counts in de novo AML were higher than the values observed in AML-TMDS patients (p < 0.001). TMDS occurred predominantly in M2 and M6 FAB types, and was absent in the M3 type. Bone marrow histology showed no particular feature that could be of diagnostic relevance. The remission rates were similar in both groups of patients (p = 0.55). The same was true for the probability of disease-free survival and overall survival during the period of study (p = 0.50, p = 0.33, respectively). These results suggest that: 1) in AML-TMDS patients, leukemia transformation occurs in a more undifferentiated pluripotent stem cell, leading to a dysplastic residual hemopoiesis besides the blast proliferation; 2) the incidence of TMDS in our group of patients did not influence the clinical outcome after treatment of the disease.
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PMID:The significance of trilineage myelodysplasia in de novo acute myeloblastic leukemia: clinical and laboratory features. 928 8

Reactivation of fetal hemoglobin synthesis in adulthood can be seen in hematological disorders affecting the erythropoietic system. The objective of the present study was to evaluate the incidence and prognostic significance of increased hemoglobin F in patients with myelodysplastic syndrome. Hemoglobin F concentrations and Ggamma/Ggamma + A gamma-globin chain ratios were determined in 26 patients with primary myelodysplastic syndrome. Median age of the patients was 65 years; all FAB subtypes were included. Increased hemoglobin F concentration of up to 20% of total hemoglobin (normal: below 2%) was seen in 16 patients; ten patients had normal values. There was a significant relation between hemoglobin F concentration and the course of disease, e.g., 12 of the 16 patients with elevated hemoglobin F survived at least 1 year after the examination, in contrast to only three of the ten patients with normal hemoglobin F (p < 0.025). All of six patients with hemoglobin F above 5% survived at least 1 year. There was no significant difference in the hemoglobin F concentration between patients with and without cytogenetic anomalies. The Ggamma/Ggamma + A gamma-globin chain ratio was slightly elevated in all patients, with a weak correlation to the degree of hemoglobin F elevation. The values were not of additional prognostic significance. The data of the present study suggest that the hemoglobin F concentration may be a prognostic parameter in myelodysplastic syndrome; increased hemoglobin F concentration may indicate a better prognosis.
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PMID:Hemoglobin F in myelodysplastic syndrome. 961 30

This randomized, placebo-controlled trial was designed to assess the efficacy and safety of therapy with granulocyte-macrophage colony-stimulating factor (GM-CSF) and erythropoietin (epoetin alfa) in anemic, neutropenic patients with myelodysplastic syndrome. Sixty-six patients were enrolled according to the following French-American-British classification: refractory anemia (20), refractory anemia with excess blasts (35), refractory anemia with ringed sideroblasts (9), and refractory anemia with excess blasts in transformation (2). Patients were stratified by their serum erythropoietin levels (less than or equal to 500 mU/mL, n = 37; greater than 500 mU/mL, n = 29) and randomized, in a 2:1 ratio, to either GM-CSF (0.3-5.0 microg/kg.d) + epoetin alfa (150 IU/kg 3 times/wk) or GM-CSF (0.3-5.0 microg/kg.d) + placebo (3 times/wk). The mean neutrophil count rose from 948 to 3831 during treatment with GM-CSF +/- epoetin alfa. Hemoglobin response (increase greater than or equal to 2 g/dL, unrelated to transfusion) occurred in 4 of 45 (9%) patients in the GM-CSF + epoetin alfa group compared with 1 of 21 (5%) patients with GM-CSF + placebo group (P = NS). Percentages of patients in the epoetin alfa and the placebo groups requiring transfusions of red blood cells were 60% and 92%, respectively, for the low-endogenous erythropoietin patients and 95% and 89% for the high-endogenous erythropoietin patients (P = NS). Similarly, the average numbers of units of red blood cells transfused during the 12-week study in the epoetin alfa and the placebo groups were 5.9 and 9.5, respectively, in the low-endogenous erythropoietin patients and 9.7 and 8.6 in the high-endogenous erythropoietin patients (P = NS). GM-CSF +/- epoetin alfa had no effect on mean platelet count. Treatment was well tolerated in most patients, though 10 withdrew from the study for reasons related predominantly to GM-CSF toxicity. (Blood. 2000;95:1175-1179)
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PMID:Effect of recombinant human erythropoietin combined with granulocyte/ macrophage colony-stimulating factor in the treatment of patients with myelodysplastic syndrome. GM/EPO MDS Study Group. 1066 87

Twenty-one patients of autoimmune hemolytic anemia (AIHA), aged 2 months to 57 years were analyzed. The common presenting feature was pallor (89%), fever (38%), Jaundice (43%) and hepatomegaly and splenomegaly was seen in 76% and 81% respectively. Fifteen cases were of idiopathic etiology and in 6 cases the etiology could be identified as systemic lupus erythematosus, systemic sclerosis, pregnancy, maternal AIHA, typhoid fever and myelodysplastic syndrome (one each). Hemoglobin level ranged between 1.9 to 11.7 gm/dl (mean 6.8 gm/dl) and reticulocyte counts between 6% to 42% (mean (20.2%). Four patients had thrombocytopenia. Direct antiglobulin test (DAT) was positive in 19 and indirect antiglobulin test (IAT) in 7 cases. There was no correlation between DAT positivity and severity of anemia. All patients had warm antibodies of IgG type. Ten of fourteen patients responded to steroid therapy. Patients with secondary AIHA had a significantly poorer prognosis compared to the idiopathic group.
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PMID:Clinico-hematological spectrum of auto-immune hemolytic anemia: an Indian experience. 1099 63

The efficacy and toxicity of amifostine (300 mg/m(2) three times a week for three consecutive weeks for a maximum of six courses) was evaluated in 12 patients with primary myelodysplastic syndromes. Dose escalation up to 400 mg/m(2) was allowed to patients who failed to respond. Hemoglobin concentration was increased > or = 1.5 g/dl in two (18%) of the 11 anemic patients. These two patients obtained transfusion independence for 20 weeks. Reticulocyte counts and ANC increased > or = 50% of baseline in four (44%) of the nine patients with reticulocytopenia and in three (25%) of the 12 neutropenic patients. Platelet count increased in three (50%) of the six patients with thrombocytopenia. Progenitor growth of CFU-GMs and BFU-Es improved in 8/12 patients. No major side effects were observed. In conclusion amifostine is well tolerated and can promote the growth of primitive hematopoietic progenitors and ameliorate the cytopenias in MDS patients.
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PMID:Treatment of patients with myelodysplastic syndrome with amifostine. 1139 71

Chronic myelomonocytic leukemia (CMML) is a hematologic malignancy characterized by wide heterogeneity of clinical presentation and course. CMML shares myelodysplastic characteristics with features of myeloproliferative disorders. No treatment has proven effective in modifying the natural course of the disease. To improve the prognostic assessment of clinical outcome, the associations of patient and disease characteristics with survival times of 213 patients with CMML was investigated retrospectively. Median survival was 12 months. Univariate analysis identified low hemoglobin level; low platelet count; high white blood cell, monocyte, and lymphocyte counts; presence of circulating immature myeloid cells, high percentage of marrow blasts, low percentage of marrow erythroid cells, abnormal cytogenetics, and high levels of serum lactate dehydrogenase and beta(2)-microglobulin as characteristics associated with shorter survival. Hemoglobin level below 120 g/L (12 g/dL), presence of circulating immature myeloid cells, absolute lymphocyte count above 2.5 x 10(9)/L, and marrow blasts 10% or more were independently associated with shorter survival by multivariate analysis and were used to generate a prognostic score. The model identified 4 subgroups of patients with median survival of 24, 15, 8, and 5 months for low, intermediate-1, intermediate-2, and high risk, respectively. Researchers could not confer objective evidence suggesting that arbitrary divisions of CMML by white blood cell counts into "dysplastic" and "proliferative" categories reflect clinical entities differing in the risk of acute leukemia development, although a trend of shorter survival in patients with leukocytosis was observed. The prognostic model was compared with 6 previously published scoring systems for myelodysplastic syndrome/CMML. The reported results should provide an improved assessment of prognosis in CMML.
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PMID:Prognostic factors and scoring systems in chronic myelomonocytic leukemia: a retrospective analysis of 213 patients. 1180 85

Hemoglobin and myoglobin heme pigments and iron have acute and chronic nephrotoxic effects, which are often associated with massive hemolysis and rhabdomyolysis. We report a patient with a myelodysplastic syndrome and paroxysmal nocturnal hemoglobinuria phenotype who developed an acute renal failure after a severe haemolytic crisis. There was not evidence of renal vascular pathology, urinary tract obstruction or prerenal factors. Renal biopsy showed features of acute tubular necrosis, with extended iron deposits in tubule cell cytoplasm and tubulo-interstitial fibrosis and atrophy. The patient was oliguric requiring hemodialisys during three weeks, recovering renal function on the fourth week after admission. This case underlines the nephrotoxic role of heme pigment and iron, and possible pathophysiologic mechanisms involved in acute and chronic toxicity of both agents are reviewed.
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PMID:[Acute renal failure in a patient with myelodysplastic syndrome and paroxysmal nocturnal hemoglobinuria phenotype]. 1521 70


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