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- Broliden, Per Anders, et al.
(författare)
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Antithymocyte globulin and cyclosporine A as combination therapy for low-risk non-sideroblastic myelodysplastic syndromes
- 2006
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Ingår i: Haematologica. - 0390-6078 .- 1592-8721. ; 91:5, s. 667-670
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Tidskriftsartikel (refereegranskat)abstract
- The present study evaluated the combination of antithymocyte globulin (ATG) and cyclosporine A (CsA) in patients with low-risk myelodysplastic syndromes. Twenty patients (17 with refractory anemia and 3 with refractory anemia with excess blasts) received treatment with rabbit-ATG plus CsA. The overall response rate was 30% (6/20); three of the six responders had a complete response. The responses lasted 2-58 months, with two patients still being in complete remission at 42 and 58 months. Short-lasting cytogenetic remissions were achieved in two patients. ATG was poorly tolerated in patients over 70 years of age. Four out of 20 patients progressed to acute myeloid leukemia within a year. We conclude that immunosuppressive treatment may be a therapeutic option for selected patients with myelodysplastic syndrome.
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| 3. |
- Grövdal, Michael, et al.
(författare)
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Negative effect of DNA hypermethylation on the outcome of intensive chemotherapy in older patients with high-risk myelodysplastic syndromes and acute myeloid leukemia following myelodysplastic syndrome
- 2007
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Ingår i: Clinical Cancer Research. - 1078-0432 .- 1557-3265. ; 13:23, s. 7107-7112
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Promoter hypermethylation of, for example, tumor-suppressor genes, is considered to be an important step in cancerogenesis and a negative risk factor for survival in patients with myelodysplastic syndromes (MDS); however, its role for response to therapy has not been determined. This study was designed to assess the effect of methylation status on the outcome of conventional induction chemotherapy. EXPERIMENTAL DESIGN: Sixty patients with high-risk MDS or acute myeloid leukemia following MDS were treated with standard doses of daunorubicin and 1-beta-d-arabinofuranosylcytosine. Standard prognostic variables and methylation status of the P15(ink4b) (P15), E-cadherin (CDH), and hypermethylated in cancer 1 (HIC) genes were analyzed before treatment. RESULTS: Forty percent of the patients achieved complete remission (CR). CR rate was lower in patients with high WBC counts (P = 0.03) and high CD34 expression on bone marrow cells (P = 0.02). Whereas P15 status alone was not significantly associated with CR rate (P = 0.25), no patient with hypermethylation of all three genes achieved CR (P = 0.03). Moreover, patients with CDH methylation showed a significantly lower CR rate (P = 0.008), and CDH methylation retained its prognostic value also in the multivariate analysis. Hypermethylation was associated with increased CD34 expression, but not with other known predictive factors for response, such as cytogenetic profile. CONCLUSIONS: We show for the first time a significant effect of methylation status on the outcome of conventional chemotherapy in high-risk MDS and acute myelogenous leukemia following MDS. Provided confirmed in an independent study, our results should be used as a basis for therapeutic decision-making in this patient group.
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| 5. |
- Mellqvist, Ulf-Henrik, et al.
(författare)
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Cyclophosphamide plus dexamethasone is an efficient initial treatment before high-dose melphalan and autologous stem cell transplantation in patients with newly diagnosed multiple myeloma - Results of a randomized comparison with vincristine, doxorubicin
- 2008
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Ingår i: Cancer. - : Wiley. - 0008-543X .- 1097-0142. ; 112:1, s. 129-135
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND. Today, intensive therapy that includes high-close melphalan with autologous stein cell transplantation (ASCT) is considered standard therapy in younger patients with newly diagnosed myeloma. When the current trial was initiated, combined vincristine, doxorubicin, and dexamethasone (VAD) was the most commonly used induction therapy before ASCT and yielded rapid major responses without interfering with stein cell harvest. However, the administration of VAD demands a central venous access, and well-described toxicities are associated with the therapy. This randomized trial, which was initiated in 2001 by the Nordic Myeloma Study Group, was an attempt to bring a larger portion of patients to ASCT more quickly. METHODS. Patients were randomized to receive either 3 cycles of VAD or 2 courses of cyclophosphamide plus dexamethasone (Cy-Dex) (cyclophosphamide at a dose of 1000 mg/m(2) on Day 1 and dexamethasone at a dose of 40 mg per day on Days 1-4 and 9-12, repeated on Day 22) as initial therapy followed by stein cell mobilization, harvest, and finally ASCT. RESULTS. No significant difference was observed in the proportion of patients undergoing ASCT (VAD [86%] vs Cy-Dex [87%]). During the first 4 months after the initiation of therapy, the mortality rates were 5.8% for VAD and 1.9% for Cy-Dex (P =.08). The response rates after ASCT were comparable (partial response or better: VAD: 80% vs Cy-Dex: 81%). In both groups, the median event-free survival was 29 months, and the overall survival rate at 3 years was 75%. CONCLUSIONS. The current results indicated that Cy-Dex before ASCT has efficacy comparable to that of VAD. It also demonstrated that a short course of alkylater therapy using cyclophosphamide does not affect stem cell harvest or transplantation.
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