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)

Twenty patients with myelodysplastic syndromes were treated with daily subcutaneous injections of interferon alpha 2a, at the initial dose of 3 x 10(6) U/m2. Hemogram, chemistry profile, natural killer (NK) cell activity and lymphokine-activated killer (LAK) cell cytotoxicity were monitored serially. Bone marrow with cytogenetic analysis was done before therapy and every three months afterwards. Normalization to the complete blood count, and wherever applicable, decrease in blast count of 5% or less were defined as a complete response. Improvement in hemoglobin level to 12 g/dl, neutrophil count to 1000/mm3 and platelets to 100,000/mm3 was considered a partial response. The median age was 71 (range 59-83) years and 16 of the patients were males. Two patients withdrew from the treatment in the first week and were considered ineligible. Among the other 18, two had refractory anemia, two refractory anemia with ringed sideroblasts, four chronic myelomonocytic leukemia, eight refractory anemia with excess blasts, and two refractory anemia with excess blasts in transformation to acute leukemia. Twelve patients were treated for six months, the other six were taken off the treatment after six to eight weeks because of disease progression. Only one patient with chronic myelomonocytic leukemia had a partial response for two months. NK cell activity remained unchanged before (18.3 +/- 4.6 lytic units) and during interferon therapy (19.6 +/- 5.3 lytic units). LAK cytotoxicity was not detected in any patient before therapy and was seen in only one patient (not the responder) during therapy (5.7 lytic units). The toxicity of the interferon therapy was substantial. Seventeen patients required a dose reduction and fifteen lost greater than 10% of body weight. Eleven patients (61%) developed infections requiring antibiotic therapy, and eight (44%) required hospitalization. Seven patients developed neurologic toxicity. Interferon alpha 2a is an ineffective but toxic therapy in these elderly patients with myelodysplastic syndromes.
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PMID:Phase II trial of recombinant human interferon alpha in myelodysplastic syndromes. 156 60

Recent clinical studies suggested that interleukin-2 (IL-2) has therapeutic potential for some hematologic malignancies, but the therapeutic role of IL-2 for myelodysplastic syndrome (MDS) is still unclear. MDS is a clonal malignant disorder which often involves a variety of immunologic abnormalities. Examination of the effects of IL-2 on MDS in vitro yielded the following results: (1) IL-2 did not induce the proliferation of blasts in most MDS cases. (2) The cytotoxicity of IL-2-induced lymphokine-activated killer (LAK) cells for cell lines and MDS blasts was reduced in the high-risk MDS group (refractory anemia with excess blasts (RAEB), RAEB in transformation and MDS transformed to acute leukemia), but it was still preserved in the low-risk MDS group (refractory anemia (RA) and RA with ringed sideroblasts). However, considerable variation in LAK cell cytotoxicity was noted in each group. (3) The reduced LAK cell cytotoxicity observed in MDS was explained, at least in part, by the presence of a reduced of number of natural killer (NK) cells amongst the LAK cells. (4) MDS patients who have a high blood soluble IL-2 receptor (sIL-2R) level often had defects in NK and CD8+ T cells. These in vitro findings suggest that the response to IL-2 is heterogeneous in MDS patients, and those who have a low-risk MDS subtype and/or a low blood sIL-2R level, may be prone to respond to IL-2 therapy. Clinical trials are mandatory in order to elucidate the efficacy of IL-2 therapy in the treatment of MDS.
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PMID:Interleukin-2 therapy for myelodysplastic syndrome: does it work? 754 31

The plasma soluble interleukin 2 receptor (sIL-2R) level and its relationships with haematologic and immunologic data were examined in 40 patients with myelodysplastic syndromes (MDS). The plasma sIL-2R level was significantly higher in the high-risk MDS group (refractory anaemia with excess blasts (RAEB), RAEB in transformation and chronic myelomonocytic leukaemia) than in the low-risk MDS group (refractory anaemia (RA) and RA with ringed sideroblasts) or in normal subjects, although there was considerable variation in the plasma sIL-2R level within each MDS group. The plasma sIL-2R level correlated positively with the bone marrow cellularity and bone marrow blast mass, but not with the absolute number of CD25+ lymphocytes. This may support the idea that plasma sIL-2R is derived from malignant MDS cells in the bone marrow. The plasma sIL-2R level correlated negatively with the absolute numbers of the CD8+, CD3-CD16+, and CD3-CD56+ cell populations in freshly isolated lymphocytes, the percentage of CD3-CD56+ cells in lymphokine (interleukin 2)-activated killer (LAK) cells, and the cytotoxicity of LAK cells. We conclude that MDS patients having a high plasma sIL-2R level often have a defect in natural killer and CD8+ T-cells.
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PMID:Elevated plasma soluble interleukin 2 receptor level correlates with defective natural killer and CD8+ T-cells in myelodysplastic syndromes. 793 36

To evaluate the clinical usefulness of interleukin 2 (IL-2) on myelodysplastic syndromes (MDS), the serum IL-2 level, the effect of IL-2 on the proliferation of blasts, and the cell-mediated cytotoxic effect of IL-2 on blasts were examined in MDS patients. Of 18 patients, 2 patients had an increased serum IL-2 level. Although the proliferation of blasts in most cases, including the two patients having a high serum IL-2 level, was not stimulated by IL-2, the blasts of one case apparently proliferated in response to IL-2. It was also clearly shown that IL-2-stimulated normal peripheral blood mononuclear cells (PBMNC) showed cytotoxicity against MDS blasts, whereas the PBMNC of the advanced stages of MDS were usually defective in regard to this IL-2-dependent cytotoxicity. The therapeutic usefulness of IL-2 or lymphokine-activated killer cells for MDS was not established by the present study.
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PMID:Effects of interleukin 2 on myelodysplastic syndromes. 842 90

We report the case of a patient treated with interleukin-2 (IL-2) for refractory anemia with excess blasts (RAEB), which developed during third complete remission of acute lymphoblastic leukemia. IL-2 was given subcutaneously at 2.5 x 10(5) IU (= 10(5) BRMP units) twice daily for 30 days. During treatment spontaneous natural killer (NK) activity was enhanced, circulating lymphokine-activated killer effector cells became detectable and CD56+/CD3- NK cells in the blood doubled. The response in the bone marrow was a reduction in myeloid blast cells (from 7 to 0%), ringed sideroblasts (from > 15 to 0%) and dysplasia (from trilineage to minimal megakaryocytic), and a decrease in metaphases with the RAEB karyotype (from 43 to 2%). Toxicity of IL-2 was minimal. Thus a relatively low dose of IL-2 caused immune activation and resulted in significant hematologic and cytogenetic response in this case of therapy-related myelodysplasia.
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PMID:Response of therapy-related myelodysplasia to low-dose interleukin-2. 844 51

A Phase II clinical trial was undertaken using roquinimex (Linomide) in patients with myelodysplastic syndromes (MDS). Roquinimex is an orally active drug with immunostimulating activities demonstrated in vitro and clinically. Seventeen patients with MDS were enrolled in the study. Eligibility was limited to cytopenic patients with <20% marrow blasts. The drug was given orally twice weekly for 12 weeks with frequent monitoring of clinical, hematologic, and immunologic parameters. An increase in CD8+ and CD56+/CD3- cells was detected by 3 weeks. There was, however, no augmentation of natural killer or lymphokine-activated killer cell activity; progenitor cells were unchanged. Four patients had improvement in neutrophil counts, and two patients had improvement in platelet counts. Despite this improvement, the responses were transient or not maintained after discontinuation of therapy. One patient with RAEB, who was red cell transfusion dependent, experienced a complete remission that has persisted 14 months after completion of therapy. Adverse events developed in >25% of patients and included arthralgia, fever, headache, and myalgia. These side effects led to early withdrawal of therapy in five patients. These findings suggest that roquinimex may be of occasional benefit to patients with myelodysplastic syndromes.
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PMID:Phase II study of roquinimex in myelodysplastic syndrome. 912 98

Patients with myelodysplastic syndromes (MDS) show a decrease in the number and function of natural killer (NK) cells, including lymphokine activated killer (LAK) cell activity. Interleukin-2 (IL-2) stimulates the proliferation and activity of these lymphocytes. Anecdotal clinical experience has shown haematological and cytogenetic improvement in myelodysplasia by low-dose IL-2 treatment. A total of 10 patients with MDS were treated with 1 million units of IL-2 subcutaneously daily for 12 weeks. Even though improvement in CD16+/CD56+ cell numbers was seen in a majority of the patients, the haematological status and transfusion requirements remained unchanged. There was minimal toxicity from this therapy.
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PMID:A phase II trial of interleukin-2 in myelodysplastic syndromes. 957 3