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)

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

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

As part of a broad phase I study of recombinant human granulocyte-macrophage colony-stimulating factor (rh GM-CSF), four patients were treated who had myelodysplastic syndrome (MDS) with excess blasts. The GM-CSF was given daily as an intravenous injection over a period of 30 min for 5 days. A total of 11 cycles were conducted. Each patient received at least two different dose levels. In three patients, three different dosages were delivered. The treatment course was interrupted by a 10-day rest period. Rh GM-CSF was well tolerated, with only minor side effects seen, which included bone discomfort at the lower back, sternum and ribs, and constitutional symptoms such as low grade fever, nausea/vomiting, and mild myalgias. Whereas no increases in platelet and reticulocyte counts were recorded, elevations of absolute neutrophil counts above 100 cells/microliters occurred in all patients. The most striking finding was, however, the development of increases in the number of circulating and bone marrow blast counts that were observed particularly when doses of greater than or equal to 500 micrograms/m2 of body surface area were administered. In line with data demonstrating in vitro induction of proliferation of leukemic blast cells by rh GM-CSF, one may take advantage of blastogenesis induced in vivo that may favor the use of a therapeutic strategy by recruiting quiescent cells into the mitotic cycle which would then represent optimum targets for a subsequent cycle-specific cytotoxic chemotherapy. Such an approach could form the basis for new clinical trials in MDS.
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PMID:Effect of recombinant human granulocyte-macrophage colony-stimulating factor in patients with myelodysplastic syndrome with excess blasts. 265 95

A phase II clinical trial on MDS was conducted in a cooperative study with orally administrable ara-C analogue, PLAC, which is resistant to cytidine deaminase and had shown an anti-tumor activity on various experimental tumors by oral route. Fifty MDS (3 RA, 18 RAEB, 11 RAEB-T, 18 RAEB-blast crisis (BC) were treated orally with 100 to 400mg/body of daily PLAC. One good response (GR) and 3 partial responses (PR) were obtained in 18 RAEB, and 2 complete remissions, 1 GR and 1 PR were noted in 11 RAEB-T, while 3 PR were seen in 18 RAEB-BC. Overall CR rates were 4%, GR rates 4% and PR rates 14%. Thus, 22% of MDS responded to oral PLAC. No clear daily dose-response was noted. Response, however, was dependent on the treatment period and was obtained in cases which had been treated for more than 20 days. Besides myelosuppression, side effects were mainly gastrointestinal, and anorexia (32%), nausea/vomiting (30%) and diarrhea (8%) were observed. Oral PLAC seems to be active on MDS which does not necessarily require admission to hospital.
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PMID:[Treatment of myelodysplastic syndromes (MDS) with oral administration of N4-palmitoyl-1-beta-D-arabinofuranosyl cytosine (PLAC)]. 338 95

Tumor necrosis factor (TNF) inhibits hematopoietic cell proliferation. The combination of pentoxifylline (PTX) and ciprofloxacin (Cipro) has been previously shown to reduce circulating serum levels of TNF. In this Phase II trial 14 patients with advanced myelodysplastic syndrome were treated with PTX (2,000 mg/day) and Cipro (1,000 mg/day) in order to determine tolerability and effect on peripheral blood cell counts, progenitor cell responsiveness to cytokines and circulating serum levels of interleukin-6 (IL6) and TNF. Toxicity attributed to PTX and Cipro were limited to nausea in 4 patients. Peripheral blood cell counts, platelet transfusion requirements and red blood cell transfusion requirements did not change during administration of PTX and Cipro (daily for 28 days). Marrow progenitor cells of patients entered into trial were less responsive to stimulation with cytokines in vitro at baseline and during the trial compared to normal volunteers. Eight patients had elevated IL6 levels before treatment with PTX and Cipro these levels did not change during therapy. Five patients had elevated TNF levels at baseline. There was a suggestion of decreased TNF levels during treatment with PTX and Cipro (P = .09). In conclusion, PTX and Cipro was well tolerated but no evidence of efficacy was observed.
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PMID:Pentoxifylline and ciprofloxacin in patients with myelodysplastic syndrome. A phase II trial. 774 4

A 55-year-old female presented with sore throat and slight fever. The patient was admitted to our hospital on December 13, 1993. Full blood count showed hemoglobin 10.7 g/dl, white cell count 960/microliters (neutrophils 14%, lymphocytes 82%, blasts 2%) and platelets 13,000/microliters. Bone marrow examination showed hypocellularity with 4.5% of myeloblast positive for peroxidase. The bone marrow specimens on Dec. 20 showed 15.5% of myeloblasts, some of which had Auer rods. These findings led to the diagnosis of refractory anemia with excess myeloblast in transformation (RAEB-T) of French-American-British Cooperative Group. The patient was transfused and treated with cytarabine ocfosfate (SP-AC) (100 mg tid) and 6-mercaptopurine (50 mg tid) for 14 days. During chemotherapy she complained of nausea and anorexia, but they were managed easily with medication. On Feb. 7, 1994, forty-two days after the start of administration, peripheral blood and bone marrow aspirate were compatible with a complete remission. Although complete remission was sustained with courses of chemotherapy for 4 months, relapse occurred and the patient died of septicemia on August 29, 1994 after induction failure. Observation suggested that oral SPAC in combination with 6-mercaptopurine had a good antileukemic effect on the myelodysplastic syndrome. However, the duration response was short, and further improvement of the therapy is needed.
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PMID:[Refractory anemia with excess myeloblast in transformation induced remission by combined oral administration of cytarabine ocfosfate and 6-mercaptopurine]. 779 1

50 cases were treated with Myelodysplastic Syndrome (MDS) by combined TCM-WM therapy. They were classified into RA 17 cases, RAS 6, RAEB 19, CMML 1 and RAEBT 7. The patients were divided into two groups, one with RA and RAS receiving treatment of hemopoietic and immune drugs plus Chinese medicinal herbs, the other with RAEB, CMML and RAEBT receiving treatment of LD Ara-c and LD Hom chemotherapy plus medicinal herbs. The effective rates were 47.83% and 62.96% respectively, the total effective rate being 56%. 6 cases (RAEB 4, RA 1, RAS 1) were treated with all-trans retinoic acid used as an inducer of differentiation, 2 of them were effective. 11 patients with MDS who had transformed into acute leukemia were treated by LD Ara-c and combined TCM-WM chemotherapy, the remission rate was 54.55% and the survival period was 9-27 months after remission. In some cases low dose chemotherapy resulted in hemocytopenia, bone marrow inhibition, infection, mild nausea and anorexia.
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PMID:[Treatment of myelodysplastic syndrome by combined traditional Chinese medicine and Western medicine therapy]. 825 23

FK506 (Tacrolimus) is an immunosuppressive drug that blocks the activation of antigen-specific T lymphocytes, a major component in the pathogenesis of graft-versus-host disease (GVHD). This study was designed to obtain first estimates of the safety and efficacy of FK506 monotherapy in the prevention of GVHD following HLA-identical sibling marrow transplantation. Additionally, a subset of patients was studied to define the pharmacokinetic profile of FK506. Twenty-seven adult patients with leukemia or myelodysplasia received FK506 starting the day before transplant at a dose of 0.04 mg/kg/d by continuous intravenous infusion. When clinically possible, FK506 was given orally in two divided doses starting at five times the daily intravenous dose. FK506 doses were adjusted to target a steady state or trough blood level between 10 to 30 ng/mL. These patients were followed for 6 months posttransplant. All patients had sustained marrow engraftment. Frequently noted adverse events included reversible renal dysfunction, diarrhea, fever, nausea, vomiting, and headache. Most patients required FK506 dose reductions associated with elevated serum creatinine. Two (7%) patients relapsed, one of whom died of the disease within the 6-month study period. A second patient died due to pulmonary mucor. Whole blood pharmacokinetic parameters indicated a half-life of 18.2 +/- 12.1 hours; volume of distribution of 1.67 +/- 1.02 L/kg; clearance of 71 +/- 34 mL/h/kg; and bioavailability of 32 +/- 24%. Eleven of 27 (41%) patients developed grade II to IV acute GVHD, including 10 grade II and one grade III. Six of 24 (25%) evaluable patients developed chronic GVHD. These data indicate that FK506 monotherapy has activity in preventing GVHD. Further studies of FK506 with lower doses to improve tolerability and in combination with other immunosuppressants to augment efficacy are warranted.
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PMID:FK506 (Tacrolimus) monotherapy for prevention of graft-versus-host disease after histocompatible sibling allogenic bone marrow transplantation. 860 72

A phase III prospective randomized multicenter study was performed to determine whether quinine could improve the response rate of poor-risk acute leukemias (ALs) to standard chemotherapy including a multidrug resistance (MDR)-related cytotoxic agent. The rationale of the study was based on the negative prognostic value of MDR phenotype in ALs and the ability of quinine to reverse this phenotype both in vitro and ex vivo. Three hundred fifteen patients (median age, 49 years; range, 16 to 65) with relapsed (n = 108) or refractory (n = 32) acute myeloblastic leukemia (AML), relapsed (n = 27) or refractory (n = 9) acute lymphoblastic leukemia (ALL), secondary AL (n = 22) or blastic transformation of myelodysplastic syndrome ([MDS] n = 74) or myeloproliferative syndrome ([MPS] n = 43) were randomly assigned to receive mitoxantrone ([MXN] 12 mg/m2/d, days 2 to 5) and cytarabine ([Ara-C] 1 g/m2/12 h, days 1 to 5) alone or in combination with quinine (30 mg/kg/d, days 1 to 5; continuous intravenous infusion beginning 24 hours before MXN infusion). Side effects of quinine were observed in 56 of 161 quinine-treated patients and disappeared in all but four cases after one or two 20% dose decreases. Sera from quinine-treated patients showed increased MXN uptake in an MDR-positive cell line compared with matched sera obtained before quinine infusion. Quinine induced a significant increase in the incidence of nausea, vomiting, mucositis, and cardiac toxicity. A complete response (CR) was observed in 85 of 161 patients (52.8%) from the quinine-treated group versus 70 of 154 patients (45.5%) in the control group (P = .19). The most important differences between quinine and control group CR rates were observed in patients with refractory AMLs and blastic transformation of MDS and MPS. The CR rate was higher in P-glycoprotein-positive cases, although the difference was not significant. Failure of the regimen due to blastic persistence or blast number increase was higher in the control group (61 of 154 patients) than in the quinine group (45 of 161, P = .04). Early death was observed in eight cases (four in each arm) and death in aplasia in 27 cases (20 in quinine group v seven in control group, P = .01). The significant increase of toxicity in the quinine arm could have masked the clinical benefit of MDR reversion in poor-risk ALs.
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PMID:Combination of quinine as a potential reversing agent with mitoxantrone and cytarabine for the treatment of acute leukemias: a randomized multicenter study. 869 37

Ilmofosine, an ether lipid derivative of lysophosphatidylcholine has antineoplastic activity in vitro and in vivo. Maximum efficacy in preclinical models is associated with prolonged exposure to the drug. In a Phase I trial of a weekly 2 hour infusion schedule of ilmofosine, a syndrome of lethargy, diminished performance status, and mild hepatotoxicity was dose-limiting at 550 mg/m2. To avoid the higher drug concentrations associated with a brief infusion, a Phase I study of a weekly 24 hour infusional schedule was undertaken in an attempt to maximize dose-intensity. Doses were escalated from 550 to 800 mg/m2. Toxicities included nausea, anorexia, fatigue, and minor elevations of liver function tests. The dose limiting toxicity at 800 mg/m2 was a syndrome of severe abdominal pain. No neutropenia or thrombocytopenia was observed except in one patient who was found to have a myelodysplastic syndrome, thought not to be related to drug therapy. The more prolonged infusion schedule of ilmofosine did not result in a substantial increase in the tolerable dose.
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PMID:Phase I trial of ilmofosine as a 24 hour infusion weekly. 872 47


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