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

Our understanding of the biology of leukemia and myelodysplasia is still only partial. The diagnosis of myelodysplasia is often based on quantitative and qualitative findings in the peripheral blood and bone marrow. These findings are often shared by other disorders. There is a need for sensitive and inexpensive laboratory tests to determine clonality and karyotypic abnormalities in this disorder. Future classifications of these syndromes will need to be based on morphologic and biologic markers that are closely linked to disease progression, response to treatment, and survival. Our limited understanding of the pathogenesis of MDS decreases the specificity and effectiveness of our therapeutic interventions. Agents that are minimally toxic such as CRA, danazol, 1,25-dihydroxyvitamin D3, androgens, and pyridoxine are seldom useful. Antileukemic therapy and allogeneic bone marrow transplantation have a major role to play in patients younger than 45 years of age; in older patients these treatment modalities remain controversial because of their toxicity. Hematopoietic growth factors, used alone or in combination, may improve the quality of life and improve survival of patients with MDS. Growth factors may also decrease treatment-related mortality associated with chemotherapy and bone marrow transplantation and render these treatment modalities available for a higher percentage of patients. The development of more specific differentiating agents may permit hematopoietic differentiation while minimizing side effects.
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PMID:Myelodysplastic syndromes. Pathogenesis, diagnosis and treatment. 137 18

63 evaluable patients with myelodysplastic syndromes (MDS) and 15 with acute myelogenous leukemia (AML) were randomized between low-dose ara-C (arm A) and low dose ara-C in combination with 13-cis-retinoic acid (13-CRA) and 1 alpha-hydroxy-vitamin D3 (1 alpha D3) (arm B). 69 patients were evaluable and 18 (26.1%) responded to therapy. The addition of 13-CRA and 1 alpha D3 had no positive influence on survival of the patients, remission rates or duration of remissions. 12/27 patients in arm A and 6/29 patients in arm B progressed from MDS to AML during the course of the study (p = 0.0527). Arm B gave significantly more side-effects than arm A (p = 0.005). Therapeutic effects of 13-CRA and 1 alpha D3 on MDS is not supported by this study. However, an inhibiting effect on AML development in some MDS subgroups cannot be excluded.
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PMID:Treatment of myelodysplastic syndromes with retinoic acid and 1 alpha-hydroxy-vitamin D3 in combination with low-dose ara-C is not superior to ara-C alone. Results from a randomized study. The Scandinavian Myelodysplasia Group (SMG). 226 51

A double-blind, placebo-controlled randomized trial of 13-cis retinoic acid was performed to determine if the drug has a therapeutic effect in patients with myelodysplastic syndromes (MDS). Sixty-eight evaluable patients with MDS were randomized to receive a single, daily oral dose of either 13-cis retinoic acid (13-CRA, 100 mg/m2) or matching placebo. Treatment was continued, when possible, for a period of 6 months. Determination of response to treatment was based on clinical course, repeat bone marrow biopsies, and aspirates and blood counts (CBC) with WBC differential, platelet, and reticulocyte numbers at specified intervals. No significant difference was noted between the two treatment groups in response to test drug (P = .66). One patient (3%) in the 13-CRA group and two patients (6%) in the placebo group had a minor response. Approximately 30% of patients in both groups had progression of their disease, and progression-free survival was nearly identical. Greater than 90% of the patients receiving 13-CRA developed mild or moderate skin toxicity that was reversible with decreasing or discontinuing the drug. Our study did not find that 13-CRA exerts a beneficial therapeutic effect in patients with MDS.
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PMID:Randomized study of 13-cis retinoic acid v placebo in the myelodysplastic disorders. 327 54

Responses have been reported in patients with myelodysplastic syndromes (MDS) after low-dose cytarabine (Ara-C) or 13-cis-retinoic acid (13-CRA) therapy. Recently, combination of these two substances in vitro was shown to produce a synergistic effect on differentiation of leukemic cells. We conducted a phase II trial with low-dose Ara-C (5 mg/m2 per 12 h s.c.) and 13-CRA (60 mg/m2 per day orally) in 14 patients with MDS, six of whom had refractory anemia with excess of blasts (RAEB), seven had RAEB in transformation (RAEBt) and one chronic myelomonocytic leukemia (CMML). The drugs were administered from day 1 to 14 and the treatment courses repeated every 4 to 8 weeks. One partial response and one minor response could be achieved. Major toxicity included dry skin, mucositis and cheilitis in 11 of the 14 patients. The response rate is no better than the results reported in the literature with either drugs alone. As yet there is no satisfactory treatment for MDS.
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PMID:Combination of low-dose cytarabine and 13-cis retinoic acid in the treatment of myelodysplastic syndromes. 332 May 77

We prospectively treated 46 patients with favorable myelodysplastic syndrome classified as refractory anemia (RA), refractory cytopenia (RC), or refractory anemia with ringed sideroblasts (RARS). These patients received one of two schedules of 13-Cis-Retinoic Acid (low dose 80 mg daily for 6 months vs. high dose 200 mg po daily for 3 months), or Danazol (800 mg po daily for 3 months), and were crossed over to the alternative drug in the absence of response or at progression. Using strict criteria of response we found little objective evidence of activity for either compound. Only two minor responses were seen among 22 patients treated with low dose 13-CRA, 1 response among 20 cases that received high dose 13-CRA, and 1 partial response and 1 minor response to Danazol among 34 cases. Neither 13-Cis-Retinoic Acid nor Danazol appear active enough in patients with favorable myelodysplastic syndrome to justify their use.
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PMID:Myelodysplastic syndrome treatment with danazol and cis-retinoic acid. 771 70

Clinical trials of differentiation therapy on MDS with retinoic acid are reviewed, and it is discussed whether the differentiation therapy with this drug has scientific relevance for MDS. 13-Cis retinoic acid (13-CRA) may have moderate effect on 20-30% of patients with MDS. In general, the responses are short and toxicity is significant. Since the responses may take at least three weeks and sometimes several months to occur, only patients with a relatively indolent clinical course of MDS would be suitable candidates for this therapy. However, a placebo-controlled prospective randomized study could not confirm the effectiveness of this retinoic acid on MDS. There are only a few clinical trials of all-trans retinoic acid (ATRA) for treatment of MDS. ATRA may have a moderate effect on MDS, but no such a remarkable effect shown on acute promyelocytic leukemia. A placebo-controlled randomized study as having been conducted in 13-CRA is definitely needed to confirm the effectiveness of ATRA on MDS.
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PMID:Differentiation therapy of myelodysplastic syndromes with retinoic acid. 781 99

The treatment of myelodysplastic disorders with vitamins A and D or derivatives and nutrients has been less than satisfactory. Combinations of vitamin D3 and 13-CRA with or without cytosine arabinoside appear to offer no advantage over any of the single agents alone. Until other vitamin D derivatives are developed that are effective but do not cause hypercalcemia, vitamin D3 cannot be recommended for the treatment of MDS. 13-CRA has been shown to be effective in some patients with MDS; however, it cannot be recommended as standard therapy because of the conflicting data cited above. Further clinical trials with 13-CRA perhaps in combination with vitamin E or colony-stimulating factors are clearly indicated for this disease for which we have no effective therapy.
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PMID:New uses for old vitamins. The treatment of myelodysplastic disorders. 832 Oct 79