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)

To study the therapeutic effect of low-dose aclarubicin (ACR), we carried out comparative treatment of 15 patients with myelodysplastic syndrome (MDS) and atypical leukemia using this drug. Complete remission (CR) was achieved in three patients with RAEB-t and one patient with AML, partial remission was obtained in one patient with RAEB and hematological improvement in one patient with refractory anemia (RA). Interestingly, prolonged CR for more than 26 months with persistent chromosomal abnormalities was observed in a case of AML, which progressed from RA. Myelosuppression caused by low-dose ACR was milder than that caused by low-dose Ara-C. Furthermore, in vitro studies indicated that ACR induced differentiation of bone marrow cells from one patient with MDS. From these observations, it is suggested that low-dose ACR may be an alternative to low-dose Ara-C for treatment of MDS, and that the in vivo effect of ACR may be mediated by the differentiation of abnormal hemopoietic clones.
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PMID:Treatment of myelodysplastic syndrome and atypical leukemia with low-dose aclarubicin. 217 36

As part of a multicenter trial 12 patients with myelodysplastic syndromes (MDS) were treated with 14-day-cycles of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF; 250 micrograms/m2 day s.c.). In addition, all patients received 20 mg/m2/day s.c. cytosine-arabinoside (Ara-C) 12 h after GM-CSF except for patients suffering from refractory anemia (RA) according to FAB classification. Courses were repeated after 4 weeks. In 11 evaluable patients, results according to FAB-classified MDS were as follows: RA, 1/2 response (R), 1/2 stable disease (SD); RAEB, 2/3 R, 1/3 SD; RAEB-T, 1/6 CR, 1/6 PR, 2/6 R, 2/6 progression; CMML, 1/2 SD. In 2 patients with RAEB-T, overt acute myeloid leukemia was observed 2 and 10 weeks after initiation of treatment. With few exceptions, treatment resulted in a prompt increase in granulocytes and eosinophiles. This was associated with improvement of infectious complications. Increases in red cells and platelets occurred variably and was apparently associated with responses of the underlying disease. Dose limiting side effects consisted of fever, severe fatigue and dolent local reactions at the site of GM-CSF injection. In addition, nausea and diarrhoea occurred frequently. Less often, respiratory and cardiovascular side effects were encountered. In summary, GM-CSF +/- Ara-C in MDS results in objective remission with manageable toxicity. Conceivably, this regimen will serve as a base for future treatment strategies against MDS.
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PMID:Recombinant human granulocyte-macrophage colony-stimulating factor and low-dose cytosine-arabinoside in the treatment of patients with myelodysplastic syndromes. A phase II study. 218 22

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

Peculiar cytoplasmic connection between erythroblasts was observed in the smear preparation of human bone marrow; a pair of erythroblasts in the resting stage was connected by "cytoplasmic bridge" which is very thin and sometimes long compared with the telophase bridge appeared in the usual cytokinesis. Electron microscopy revealed that small amount of microtubules were running along in the cytoplasmic bridge but mid-body was not seen. Plasma membrane about the middle of the bridge bulged to form "bulging ring". Erythroblasts in various differentiating stages were connected by the cytoplasmic bridge and the stage of each pair was almost the same. The occurrence of the cytoplasmic bridge between erythroblasts was evaluated in the smear preparations of human bone marrow with hematological diseases or normal conditions. In the normal bone marrow, the mean value was 8.1 +/- 3.6% (n = 33). In patients suffered from autoimmune hemolytic anemia, it was 4.3 +/- 2.3% (n = 12), aplastic anemia, 3.2 +/- 2.1% (n = 6) and paroxysmal nocturnal hemoglobinuria, 5.0 +/- 1.4% (n = 3). While in the erythroleukemia the occurrence was very low showing 0.2 +/- 0.1% (n = 3) of total erythroblasts. In MDS, RAEB (2.5 +/- 2.4%) and RA (2.9 +/- 2.2+%) showed statistically significant lower occurrence. In the normal bone marrow the occurrence was higher, so the formation of cytoplasmic bridge could be essential for a normal proliferation of erythroblasts.
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PMID:[Occurrence of cytoplasmic bridge between erythroblasts--morphology and frequency in hematological disease]. 221 91

A high remission rate (75%) was achieved in a preliminary study using bestatin in patients with refractory anemia with excess blasts (RAEB) and RAEB in transformation (RAEB-t). One of 2 patients with RAEB-t and 3 of 6 patients with RAEB obtained complete response. Two patients with RAEB achieved good response, but one with refractory anemia failed. Clonogenic marrow cell culture studies in patients with myelodysplastic syndromes have demonstrated intrinsic hematopoietic stem cell abnormalities, in particular defective erythroid colony formation. After bestatin treatment, these abnormalities as well as hematologic findings were markedly improved. The results suggest that bestatin has an enhancing effect on burst promoting activity production of helper (CD4 positive) T lymphocytes and the effect on hematopoiesis of bestatin may be mediated by T lymphocytes.
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PMID:Bestatin treatment of myelodysplastic syndromes (MDS) and the effects of bestatin on hematopoiesis in MDS. 222 53

We performed chromosomal analysis in 18 patients with myelodysplastic syndrome (MDS). According to the French-American-British (FAB) cooperative study group and Research Group of Japanese Ministry of Welfare Classification, our cases with MDS were classified into four subtypes as follows; refractory anemia [RA], 6 cases; refractory anemia with excess of blasts [RAEB], 4; chronic myelomonocytic leukemia [CMML], 3; refractory anemia with excess of blasts in transformation [RAEB-T], 4; and refractory cytopenia [RC], 1. Thirteen patients (72%) had chromosomal abnormalities and frequently observed chromosomal abnormalities were trisomy 8, -7/7q-, 20q-, trisomy 1q and 5q-. The mean survival were as follows; RA: 22.5 months, RAEB: 13.2 months, CMML: 15 months, RAEB-T: 5.5 months. Progression to overt leukemia occurred in 5 patients (27.7%): 1 of four patients with RAEB, 1 of three patients with CMML and 3 of four patients with RAEB-T. In conclusion, chromosomal abnormalities were most frequently observed in the patient with RAEB-T who had shortest survival time among the patients with MDS. On the other hand, chromosomal abnormalities were less frequently observed in the patients with RA and they showed relatively better prognosis than the other types of MDS.
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PMID:[Chromosome abnormalities in myelodysplastic syndrome]. 223 53

Five patients with myelodysplastic syndrome (RA: 4 cases, RAEB in T: 1 case) were treated with myeloablative immunosuppressive therapy followed by bone marrow transplantation (BMT). Median age was 20-y-o (11-31-y-o). All patients were prepared with cyclophosphamide and total body irradiation. Engraftment was documented in all patients. One patients (case 4, 31-y-o female) died of brain hemorrhage due to the thrombocytopenia refractory to platelet transfusion because of anti-platelet antibody in 34 days after BMT. A patient with RAEB in T was also died of respiratory failure from interstitial pneumonia on Day 173. One patient (case 1, 22-y-o, female) progressively became granulocytopenic and thrombocytopenic status after BMT. She suffered from life-threatening infection and then received a second bone marrow cell infusion from the same donor without any preparative conditioning. These results suggest that BMT could be the treatment of choice for MDS, especially for the patients with RA who have poor prognostic factors including life-threatening cytopenia and or cytogenetical abnormalities.
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PMID:[Bone marrow transplantation for MDS]. 224 23

The authors analyze data of 259 patients assembled in seven haematological departments by the Czechoslovak cooperative MDS group and compare them with world-wide groups. The mean age of 60 years of our patients is by 5-10 years lower than of groups reported abroad. In our group and in the majority of groups abroad refractory anaemia predominates over "preleukaemic" types of MDS. CMML is obviously a heterogeneous group from the diagnostic aspect. With the exception of CMML there is marked agreement as regards survival of different types of MDS starting with the longest survival of RAS, via RA, RAEB and finally the lowest survival of patients with RAEB-T. The diagnostic classification is thus to a certain extent also the prognosis of the patient with MDS. Transformation into AL (in 22% in our group) belongs to groups with a lower incidence of AL. Nevertheless more than 50% of the patients do not die from AL but from the sequelae of cytopenia. The incidence of secondary MDS (in the authors' group 13% patients, most frequently after mutagens) is mentioned in groups reported abroad only in one quarter of the papers. The incidence of chromosomal aberrations in our group is one of the highest in the world and along with the low average age of our patients is an alarming finding.
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PMID:[Analysis of 259 patients with myelodysplastic syndromes. The Czechoslovak MDS Cooperative Group]. 225 65

Phase II study of YNK01 (1-beta-D-arabinofuranosylcytosine-5'-stearylphosphate), a derivative of cytosine arabinoside, on hematological malignancies was conducted by multi-institutional cooperative group. YNK01 was administered orally at dose of 100-300 mg/body/day for more than 2 weeks. The number of registered and evaluated patients were 211 and 156, respectively. Of 23 patients with acute myelogeneous leukemia (AML), 2 complete response (CR), one partial response (PR) were observed (CR + PR: 13.0%). Hypoplastic leukemia (1/4: 25%), acute unclassified leukemia (1/1: 100%). Of 45 patients with MDS, 2CRs, 6 good response (GR) and 5PRs were observed (CR + PR: 28.9%). AML developing after a prior history of MDS (5/17: 29.4%), CML-BC (2/9: 22.2%). Of 19 patients with CML, 9 achieved CR, 3 achieved PR (63.2%). Of 11 patients with polycythemia vera, 4 achieved CR, 5 achieved PR (81.8%). Of 6 patients with essential thrombocytosis, 2 achieved CR, one achieved PR (50%). The major adverse effects included gastrointestinal toxicities such as nausea, vomiting, anorexia, diarrhea, and elevation of GOT and GPT which were tolerable and reversible. This study indicates that YNK01 is a useful agent against acute leukemia and MDS, especially RAEB, RAEB in T, CMMoL.
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PMID:[Phase II study of YNK01 (1-beta-D-arabinofuranosylcytosine-5'-stearylphosphate) on hematological malignancies]. 226 Aug 76

One hundred and thirty-three cases of myelodysplastic syndromes studied during the last ten years were revised. Of them, 79 were males and 54 females, and their ages ranged between 15 and 91 years (median, 69 years). Five patients (3.7%) had secondary myelodysplasias. The haematological phenotype (FAB) of the cases was: RA, 41.3%; SRA, 24%; RAEB, 18%; RAEBT, 3.7%; CMML, 8.3%. Leucopenia/thrombocytopenia without initial anaemia was present in 4.5% of the cases. Abnormal karyotype was found in 54 patients (40.6%), MIKA in 41 cases and MAKA in 13 cases. The cytogenetic anomalies most commonly found were +8, 5q-, -7, 11q- and 13q-. Cytogenetic abnormalities were commonest amongst the RAEB (50%), and least frequent in CMML (18.2%). Thirty-one patients evolved into acute leukaemia (29 ANLL and 2 ALL). Such blastic changes were more frequent in RAEB (62.5%) and rarest in SRA (9.4%), and they appeared mostly in patients with complex karyotype (MAKA) (53.8%) as compared with those who had normal karyotype (17.7%). Short-lasting complete remission was achieved by 40% of the patients treated with conventional chemotherapy. The survival of the group as a whole (median 30 months) varied in accordance with the haematological phenotype: SRA, 81 months; RA, 65 months; CMML, 13 months; RAEB +/- T, 8 months. The finding of a MAKA karyotype significantly shortened the survival (4 months) with regard to MIKA (44 months) or normal karyotype (39 months). The following median survivals were attained after patients' staging (Bournemouth's criteria): stage A, 84 months; stage B, 22 months, and stage C, 5 months.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Myelodysplastic syndromes. Hematologic phenotypes, cytogenetic expression and clinical course in 133 cases (1979-1989)]. 227 38


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