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      Lenalidomide Plus Decitabine Treatment in a Myelodysplastic Syndrome Patient With Deletion 5q and Excess Blasts

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          Abstract

          This is the first case of decitabine plus lenalidomide treatment for a myelodysplastic syndrome (MDS) patient with 5q deletion (del(5q)) and elevated number of blasts. Upon bone marrow aspiration and biopsy with conventional cytogenetical studies she was diagnosed with MDS with del(5q) and refractory anemia with excess blasts (RAEB-1). Decitabine was started at a daily dose of 20 mg/m 2 1 - 5 days and lenalidomide was started at daily doses of 10 mg 6 - 20 days a month. After two cycles, her hemoglobin level increased and transfusion dependency ceased. After four cycles, bone marrow aspiration showed blast ratio of < 5%. Decitabine and lenalidomide were applied for three more cycles. Decitabine was terminated after seven cycles and lenalidomide has been continued for 12 months. Latest blood values (February 2020) were as follows: white blood cells (WBCs) of 8,670/mm 3, neutrophil count of 3,470/mm 3, hemoglobin (Hb) level of 11.7 g/dL and platelet count of 203,000/mm 3, and the patient continues to follow-up without treatment. In conclusion, combination of lenalidomide and decitabine seems to be an effective treatment modality without notable side effects in MDS patients with del(5q) and excess blasts. The efficacy of this combination should be validated with studies including large patient groups and with longer follow-up periods.

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          Most cited references17

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          Revised international prognostic scoring system for myelodysplastic syndromes.

          The International Prognostic Scoring System (IPSS) is an important standard for assessing prognosis of primary untreated adult patients with myelodysplastic syndromes (MDS). To refine the IPSS, MDS patient databases from international institutions were coalesced to assemble a much larger combined database (Revised-IPSS [IPSS-R], n = 7012, IPSS, n = 816) for analysis. Multiple statistically weighted clinical features were used to generate a prognostic categorization model. Bone marrow cytogenetics, marrow blast percentage, and cytopenias remained the basis of the new system. Novel components of the current analysis included: 5 rather than 3 cytogenetic prognostic subgroups with specific and new classifications of a number of less common cytogenetic subsets, splitting the low marrow blast percentage value, and depth of cytopenias. This model defined 5 rather than the 4 major prognostic categories that are present in the IPSS. Patient age, performance status, serum ferritin, and lactate dehydrogenase were significant additive features for survival but not for acute myeloid leukemia transformation. This system comprehensively integrated the numerous known clinical features into a method analyzing MDS patient prognosis more precisely than the initial IPSS. As such, this IPSS-R should prove beneficial for predicting the clinical outcomes of untreated MDS patients and aiding design and analysis of clinical trials in this disease.
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            International scoring system for evaluating prognosis in myelodysplastic syndromes.

            Despite multiple disparate prognostic risk analysis systems for evaluating clinical outcome for patients with myelodysplastic syndrome (MDS), imprecision persists with such analyses. To attempt to improve on these systems, an International MDS Risk Analysis Workshop combined cytogenetic, morphological, and clinical data from seven large previously reported risk-based studies that had generated prognostic systems. A global analysis was performed on these patients, and critical prognostic variables were re-evaluated to generate a consensus prognostic system, particularly using a more refined bone marrow (BM) cytogenetic classification. Univariate analysis indicated that the major variables having an impact on disease outcome for evolution to acute myeloid leukemia were cytogenetic abnormalities, percentage of BM myeloblasts, and number of cytopenias; for survival, in addition to the above, variables also included age and gender. Cytogenetic subgroups of outcome were as follows: "good" outcomes were normal, -Y alone, del(5q) alone, del(20q) alone; "poor" outcomes were complex (ie, > or = 3 abnormalities) or chromosome 7 anomalies; and "intermediate" outcomes were other abnormalities. Multivariate analysis combined these cytogenetic subgroups with percentage of BM blasts and number of cytopenias to generate a prognostic model. Weighting these variables by their statistical power separated patients into distinctive subgroups of risk for 25% of patients to undergo evolution to acute myeloid leukemia, with: low (31% of patients), 9.4 years; intermediate-1 (INT-1; 39%), 3.3 years; INT-2 (22%), 1.1 years; and high (8%), 0.2 year. These features also separated patients into similar distinctive risk groups for median survival: low, 5.7 years; INT-1, 3.5 years; INT-2, 1.2 years; and high, 0.4 year. Stratification for age further improved analysis of survival. Compared with prior risk-based classifications, this International Prognostic Scoring System provides an improved method for evaluating prognosis in MDS. This classification system should prove useful for more precise design and analysis of therapeutic trials in this disease.
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              Decitabine improves patient outcomes in myelodysplastic syndromes: results of a phase III randomized study.

              Aberrant DNA methylation, which results in leukemogenesis, is frequent in patients with myelodysplastic syndromes (MDS) and is a potential target for pharmacologic therapy. Decitabine indirectly depletes methylcytosine and causes hypomethylation of target gene promoters. A total of 170 patients with MDS were randomized to receive either decitabine at a dose of 15 mg/m2 given intravenously over 3 hours every 8 hours for 3 days (at a dose of 135 mg/m2 per course) and repeated every 6 weeks, or best supportive care. Response was assessed using the International Working Group criteria and required that response criteria be met for at least 8 weeks. Patients who were treated with decitabine achieved a significantly higher overall response rate (17%), including 9% complete responses, compared with supportive care (0%) (P < .001). An additional 12 patients who were treated with decitabine (13%) achieved hematologic improvement. Responses were durable (median, 10.3 mos) and were associated with transfusion independence. Patients treated with decitabine had a trend toward a longer median time to acute myelogenous leukemia (AML) progression or death compared with patients who received supportive care alone (all patients, 12.1 mos vs. 7.8 mos [P = 0.16]; those with International Prognostic Scoring System intermediate-2/high-risk disease, 12.0 mos vs. 6.8 mos [P = 0.03]; those with de novo disease, 12.6 mos vs. 9.4 mos [P = 0.04]; and treatment-naive patients, 12.3 mos vs. 7.3 mos [P = 0.08]). Decitabine was found to be clinically effective in the treatment of patients with MDS, provided durable responses, and improved time to AML transformation or death. The duration of decitabine therapy may improve these results further. 2006 American Cancer Society
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                Author and article information

                Journal
                J Hematol
                J Hematol
                Elmer Press
                Journal of Hematology
                Elmer Press
                1927-1212
                1927-1220
                April 2020
                23 April 2020
                : 9
                : 1-2
                : 33-36
                Affiliations
                [a ]Department of Hematology, University of Health Science, Istanbul Training and Research Hospital, Istanbul, Turkey
                [b ]Department of Hematology, University of Health Science, Okmeydani Training and Research Hospital, Istanbul, Turkey
                Author notes
                [c ]Corresponding Author: Istemi Serin, Department of Hematology, University of Health Science, Istanbul Training and Research Hospital, Istanbul 34098, Turkey. Email: serinistemi@ 123456hotmail.com
                Article
                10.14740/jh618
                7188382
                0836c0bc-bb7b-4cc0-a597-65df9015e960
                Copyright 2020, Dogu et al.

                This article is distributed under the terms of the Creative Commons Attribution Non-Commercial 4.0 International License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 1 March 2020
                : 23 March 2020
                Categories
                Case Report

                myelodysplastic syndrome,del(5q),decitabine,lenalidomide

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