WorldWideScience

Sample records for leukemia myelodysplastic syndrome

  1. BMS-214662 in Treating Patients With Acute Leukemia, Myelodysplastic Syndrome, or Chronic Myeloid Leukemia

    Science.gov (United States)

    2013-01-22

    Adult Acute Promyelocytic Leukemia (M3); Blastic Phase Chronic Myelogenous Leukemia; Childhood Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Excess Blasts in Transformation; Relapsing Chronic Myelogenous Leukemia

  2. Combination Chemotherapy in Treating Young Patients With Down Syndrome and Acute Myeloid Leukemia or Myelodysplastic Syndromes

    Science.gov (United States)

    2017-02-07

    Childhood Acute Basophilic Leukemia; Childhood Acute Eosinophilic Leukemia; Childhood Acute Erythroleukemia (M6); Childhood Acute Megakaryocytic Leukemia (M7); Childhood Acute Minimally Differentiated Myeloid Leukemia (M0); Childhood Acute Monoblastic Leukemia (M5a); Childhood Acute Monocytic Leukemia (M5b); Childhood Acute Myeloblastic Leukemia With Maturation (M2); Childhood Acute Myeloblastic Leukemia Without Maturation (M1); Childhood Acute Myelomonocytic Leukemia (M4); Childhood Myelodysplastic Syndromes; de Novo Myelodysplastic Syndromes; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies

  3. Ipilimumab and Decitabine in Treating Patients With Relapsed or Refractory Myelodysplastic Syndrome or Acute Myeloid Leukemia

    Science.gov (United States)

    2016-09-12

    Chimerism; Hematopoietic Cell Transplantation Recipient; Previously Treated Myelodysplastic Syndrome; RAEB-1; RAEB-2; Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  4. Decitabine in Treating Patients With Myelodysplastic Syndromes or Acute Myeloid Leukemia

    Science.gov (United States)

    2013-09-27

    Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative; de Novo Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Untreated Adult Acute Myeloid Leukemia

  5. Treosulfan, Fludarabine Phosphate, and Total Body Irradiation Before Donor Stem Cell Transplant in Treating Patients With Myelodysplastic Syndrome or Acute Myeloid Leukemia

    Science.gov (United States)

    2016-08-30

    Acute Myeloid Leukemia in Remission; Chronic Myelomonocytic Leukemia; Minimal Residual Disease; Myelodysplastic Syndrome; Myelodysplastic/Myeloproliferative Neoplasm; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable

  6. SB-715992 in Treating Patients With Acute Leukemia, Chronic Myelogenous Leukemia, or Advanced Myelodysplastic Syndromes

    Science.gov (United States)

    2013-01-10

    Acute Undifferentiated Leukemia; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Acute Promyelocytic Leukemia (M3); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Blastic Phase Chronic Myelogenous Leukemia; de Novo Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Excess Blasts in Transformation; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Untreated Adult Acute Myeloid Leukemia

  7. Donor Umbilical Cord Blood Transplant With or Without Ex-vivo Expanded Cord Blood Progenitor Cells in Treating Patients With Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, Chronic Myelogenous Leukemia, or Myelodysplastic Syndromes

    Science.gov (United States)

    2017-09-14

    Acute Biphenotypic Leukemia; Acute Erythroid Leukemia; Acute Lymphoblastic Leukemia in Remission; Acute Megakaryoblastic Leukemia; Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Acute Myeloid Leukemia in Remission; Blasts Under 10 Percent of Bone Marrow Nucleated Cells; Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Mixed Phenotype Acute Leukemia; Myelodysplastic Syndrome; Myelodysplastic Syndrome With Excess Blasts; Pancytopenia; Refractory Anemia; Secondary Acute Myeloid Leukemia

  8. Azacitidine With or Without Entinostat in Treating Patients With Myelodysplastic Syndromes, Chronic Myelomonocytic Leukemia, or Acute Myeloid Leukemia

    Science.gov (United States)

    2016-03-16

    Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); RUNX1-RUNX1T1; Adult Acute Myeloid Leukemia With t(9;11)(p22;q23); MLLT3-MLL; Adult Acute Promyelocytic Leukemia With t(15;17)(q22;q12); PML-RARA; Alkylating Agent-Related Acute Myeloid Leukemia; Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndrome; Previously Treated Myelodysplastic Syndrome; Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndrome; Untreated Adult Acute Myeloid Leukemia

  9. New treatment strategies in myelodysplastic syndromes and acute myeloid leukemia : Hypomethylating agents and proteasome inhibitors

    NARCIS (Netherlands)

    van der Helm, Lidia Henrieke

    2016-01-01

    New treatment strategies in leukemia and myelodysplastic syndromes Treatment of acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) is challenging, especially in the large group of patients older than 60 years. In these patients, results of standard chemotherapy are often disappointing

  10. [Precursors of acute leukemia: myelodysplastic syndromes and myeloproliferative neoplasms].

    Science.gov (United States)

    Kreipe, H H

    2011-11-01

    Myelodysplastic syndromes (MDS) and myeloproliferative neoplasms (MPN) represent neoplastic proliferations of hematopoietic stem cells, which may progress to loss of differentiation and acute myeloid leukemia (AML). Transitions between MDSs and MPNs as well as combinations between both disorders occur and MPNs may acquire dysplastic features combined with cytopenia. Myelodysplastic/myeloproliferative neoplasms show dysplastic and myeloproliferative properties and have in common genetic aberrations at the stem cell level (TET2, ASXL 1, CBL, IDH 1, IDH 2, EZH2, p53, Runx1), which may be found in one cell or may affect different hematopoietic stem cells, expanding in parallel. Progress to AML follows a linear clonal evolution only in a subset of cases. Alternatively AML derives from secondary clones, devoid of any marker mutation or originates from a common aberrant progenitor cell which shares other but not the JAK2 ( V617F ) mutation.

  11. Yttrium Y 90 Anti-CD45 Monoclonal Antibody BC8 Followed by Donor Stem Cell Transplant in Treating Patients With High-Risk Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, or Myelodysplastic Syndrome

    Science.gov (United States)

    2016-09-29

    Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Chronic Myelomonocytic Leukemia; Previously Treated Myelodysplastic Syndrome; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts; Secondary Acute Myeloid Leukemia

  12. Treosulfan, Fludarabine Phosphate, and Total-Body Irradiation Before Donor Stem Cell Transplant in Treating Patients With High-Risk Acute Myeloid Leukemia, Myelodysplastic Syndrome, Acute Lymphoblastic Leukemia

    Science.gov (United States)

    2013-10-29

    Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Blastic Phase Chronic Myelogenous Leukemia; Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Acute Myeloid Leukemia in Remission; Childhood Chronic Myelogenous Leukemia; Childhood Myelodysplastic Syndromes; Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Childhood Acute Lymphoblastic Leukemia

  13. Combination Chemotherapy With or Without Bone Marrow Transplantation in Treating Children With Acute Myelogenous Leukemia or Myelodysplastic Syndrome

    Science.gov (United States)

    2013-01-15

    Childhood Acute Erythroleukemia (M6); Childhood Acute Megakaryocytic Leukemia (M7); Childhood Acute Monoblastic Leukemia (M5a); Childhood Acute Monocytic Leukemia (M5b); Childhood Acute Myeloblastic Leukemia With Maturation (M2); Childhood Acute Myeloblastic Leukemia Without Maturation (M1); Childhood Acute Myelomonocytic Leukemia (M4); Childhood Myelodysplastic Syndromes; Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndromes; Refractory Anemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Excess Blasts in Transformation; Refractory Anemia With Ringed Sideroblasts; Secondary Myelodysplastic Syndromes; Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies

  14. Sorafenib in Treating Patients With Refractory or Relapsed Acute Leukemia, Myelodysplastic Syndromes, or Blastic Phase Chronic Myelogenous Leukemia

    Science.gov (United States)

    2015-04-27

    Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; Adult Acute Megakaryoblastic Leukemia; Adult Acute Monoblastic Leukemia; Adult Acute Monocytic Leukemia; Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With Maturation; Adult Acute Myeloid Leukemia With Minimal Differentiation; Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); RUNX1-RUNX1T1; Adult Acute Myeloid Leukemia With t(9;11)(p22;q23); MLLT3-MLL; Adult Acute Myeloid Leukemia Without Maturation; Adult Acute Myelomonocytic Leukemia; Adult Acute Promyelocytic Leukemia With t(15;17)(q22;q12); PML-RARA; Adult Erythroleukemia; Adult Pure Erythroid Leukemia; Alkylating Agent-Related Acute Myeloid Leukemia; Blastic Phase; de Novo Myelodysplastic Syndrome; Previously Treated Myelodysplastic Syndrome; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndrome

  15. Transformation of Myelodysplastic Syndrome to Acute Lymphoblastic Leukemia in a Child

    OpenAIRE

    2010-01-01

    Childhood myelodysplastic syndrome (MDS) is an uncommon condition. Unlike adult MDS, pediatric patients have a more progressive course and rapidly transform to acute myeloid leukemia. Evolution to acute lymphoblastic leukemia is extremely rare. We report a 5 year old female child who presented with refractory anemia with excess blasts and transformed into acute lymphoblastic leukemia 4 months after initial diagnosis.

  16. PS-341 in Treating Patients With Refractory or Relapsed Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, Chronic Myeloid Leukemia in Blast Phase, or Myelodysplastic Syndrome

    Science.gov (United States)

    2013-01-22

    Adult Acute Promyelocytic Leukemia (M3); Blastic Phase Chronic Myelogenous Leukemia; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Excess Blasts in Transformation; Relapsing Chronic Myelogenous Leukemia

  17. Pleural effusions in patients with acute leukemia and myelodysplastic syndrome.

    Science.gov (United States)

    Faiz, Saadia A; Bashoura, Lara; Lei, Xiudong; Sampat, Keeran R; Brown, Tiffany C; Eapen, George A; Morice, Rodolfo C; Ferrajoli, Alessandra; Jimenez, Carlos A

    2013-02-01

    Pleural effusions are rarely observed in patients with acute myelogenous leukemia (AML), acute lymphocytic leukemia (ALL) and myelodysplastic syndrome (MDS)/myeloproliferative neoplasm (MPN). Therefore the underlying etiology of pleural effusions and the efficacy and safety of pleural procedures in this population has not been well studied. In a retrospective review of cases from 1997 to 2007, we identified 111 patients with acute leukemia or MDS/MPN who underwent pleural procedures. Clinical characteristics were reviewed, and survival outcomes were estimated by Kaplan-Meier methods. A total of 270 pleural procedures were performed in 111 patients (69 AML, 27 ALL, 15 MDS/MPN). The main indications for pleural procedures were possible infection (49%) and respiratory symptoms (48%), and concomitant clinical symptoms included fever (34%), dyspnea (74%), chest pain (24%) and cough (37%). Most patients had active disease (61%). The most frequent etiology of pleural effusions was infection (47%), followed by malignancy (36%). Severe thrombocytopenia (platelet count < 20 × 10(3)/µL) was present in 43% of the procedures, yet the procedural complication rate was only 1.9%. Multivariate analysis revealed that older age, AML, MDS/MPN and active disease status were associated with a shorter median overall survival. Infection and malignant involvement are the most common causes of pleural effusion in patients with acute leukemia or MDS. After optimizing platelet count and coagulopathy, thoracentesis may be performed safely and with high diagnostic yield in this population. Survival in these patients is determined by the response to treatment of the hematologic malignancy.

  18. Thalidomide in Treating Patients With Myelodysplastic Syndrome

    Science.gov (United States)

    2013-01-23

    Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Refractory Anemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Excess Blasts in Transformation; Refractory Anemia With Ringed Sideroblasts; Secondary Myelodysplastic Syndromes

  19. Risk factors for therapy-related myelodysplastic syndrome and acute myeloid leukemia treated with allogeneic stem cell transplantation.

    OpenAIRE

    2009-01-01

    International audience; BACKGROUND: After successful treatment of malignant diseases, therapy-related myelodysplastic syndrome and acute myeloid leukemia have emerged as significant problems. DESIGN AND METHODS: The aim of this study was to investigate outcome and risk factors in patients with therapy-related myelodysplastic syndrome or acute myeloid leukemia who underwent allogeneic stem cell transplantation. Between 1981 and 2006, 461 patients with therapy-related myelodysplastic syndrome o...

  20. Transformation of myelodysplastic syndromes into acute myeloid leukemias

    Institute of Scientific and Technical Information of China (English)

    施均; 邵宗鸿; 刘鸿; 白洁; 曹燕然; 何广胜; 凃梅峰; 王秀丽; 郝玉书; 杨天楹; 杨崇礼

    2004-01-01

    Background Myelodysplastic syndromes (MDSs), also called preleukemias, are a group of myeloid hematopoietic malignant disorders. We studied the transformation of MDS into acute myeloid leukemia (AML).Methods Leukemic transformation in 151 patients with MDS was dynamically followed up. The clinical manifestation, peripheral blood and bone marrow condition, karyotypes, immunophenotypes, response to treatment, and prognosis of AML evolution from MDS (MDS-AML) were also observed.Results During the course of this study, over the past eight years and seven months, 21 (13.91%) of 151 MDS patients progressed to overt leukemia, with a median interval of 5 (1-23) months. There were no significant differences between rates of leukemic transformation in comparison with the refractory anemia (RA), RA with excess of blasts (RAEB), and RAEB in transformation (RAEB-t) patient groups. Transformation occurred either gradually or rapidly. There were five parameters positively correlated to leukemic transformation: under 40 years of age, pancytopenia of 3 lineages, more than 15% blasts in the bone marrow, at least two abnormal karyotypes, and treatment with combined chemotherapy. All of the 21 patients with leukemia suffered from MDS-AML, and most of them were M2, M4, or M5. Two (9.52%) MDS-AML patients developed extramedullary infiltration. Leukopenia was found in 47.62% of these patients. Two thirds of these patients, whose bone marrows were generally hypercellular, suffered from neutropenia. After developing AML, 8 (47.06%) patients developed abnormal karyotypes. High expression of immature myeloid antigens, including CD33 [(49.83±24.50)%], CD13 [(36.38±33.84)%], monocytic antigen CD14 [(38.50±24.60)%], and stem cell marker CD34 [(34.67±30.59)%], were found on bone marrow mononuclear cells from MDS-AML patients after leukemic transformation. In some cases, lymphoid antigens, such as CD5, CD7, CD9, and CD19, coexisted with myeloid antigens. A low complete remission rate (31

  1. Myelodysplastic Syndromes

    Science.gov (United States)

    ... your body, the white blood cells that fight infections, and the platelets that help with blood clotting. If you have a myelodysplastic syndrome, the stem cells do not mature into healthy blood cells. ... anemia, or easy bleeding. Myelodysplastic syndromes often do ...

  2. [Transformation of secondary myelodysplastic syndrome to atypical chronic myeloid leukemia in a female patient with acute myeloid leukemia].

    Science.gov (United States)

    Gritsaev, S V; Kostroma, I I; Zapreeva, I M; Shmidt, A V; Tiranova, S A; Balashova, V A; Martynkevich, I S; Chubukina, Zh V; Semenova, N Yu; Chechetkin, A V

    Secondary myeloid neoplasia may be a complication of intensive cytostatic therapy. The most common types of secondary neoplasias are acute myeloid leukemia and myelodysplastic syndrome. The development of secondary atypical chronic myeloid leukemia (aCML) is an extremely rare phenomenon. The paper describes transformation of secondary myelodysplastic syndrome to aCML 6 months after its diagnosis. The development of aCML was accompanied by additional chromosomal aberration as monosomy of chromosome 17. No mutations in the JAK2, MPL, and CalR genes were detected. It is concluded that the clinical course of secondary myeloid neoplasias is variable.

  3. Biological Therapy in Treating Patients With Advanced Myelodysplastic Syndrome, Acute or Chronic Myeloid Leukemia, or Acute Lymphoblastic Leukemia Who Are Undergoing Stem Cell Transplantation

    Science.gov (United States)

    2017-03-27

    Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); B-cell Adult Acute Lymphoblastic Leukemia; B-cell Childhood Acute Lymphoblastic Leukemia; Childhood Chronic Myelogenous Leukemia; Childhood Myelodysplastic Syndromes; Chronic Myelomonocytic Leukemia; Essential Thrombocythemia; Polycythemia Vera; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Excess Blasts in Transformation; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; T-cell Adult Acute Lymphoblastic Leukemia; T-cell Childhood Acute Lymphoblastic Leukemia

  4. Autologous stem cell transplantation for therapy-related acute myeloid leukemia and myelodysplastic syndrome.

    NARCIS (Netherlands)

    Kroger, N.; Brand, R.; Biezen, A. van; Cahn, J.; Slavin, S.; Blaise, D.; Sierra, J.; Zander, A.; Niederwieser, D.; Witte, T.J.M. de

    2006-01-01

    We report the results of 65 patients with treatment-related myelodysplastic syndrome (MDS)/acute myelogenous leukemia (AML) who were transplanted from an autograft and reported to the EBMT. The median age was 39 years (range, 3-69), and stem cell source was bone marrow (n = 31), or peripheral blood

  5. Study of nucleophosmin (NPM) gene mutation in patients with acute myeloid leukemia and myelodysplastic syndromes

    Institute of Scientific and Technical Information of China (English)

    张悦

    2006-01-01

    Objective To investigate nucleophosmin (NPM) gene mutations in patients with de novo acute myeloid leukemia (AML) with normal cytogenetics and primary myelodysplastic syndromes (MDS). Methods Genomic DNA corresponding to exon 12 of NPM gene was amplified by polymerase chain reaction (PCR) in 40 AML patients (28 case untreated and 12 in first remission) and

  6. Treatment-related Myelodysplastic Syndrome in a Child With Acute Myeloid Leukemia and TPMT Heterozygosity

    DEFF Research Database (Denmark)

    Stensman, Lars M; Kjeldsen, Eigil; Nersting, Jacob

    2014-01-01

    INTRODUCTION: We describe a patient diagnosed with acute myeloid leukemia (AML) and low activity of thiopurine methyltransferase (TPMT) who developed secondary myelodysplastic syndrome after treatment. OBSERVATION: A 10-year-old boy presented with AML-M2 with t(8;21)(q22;q22) and genotyping......-related myelodysplastic syndrome with ring chromosome 6. DISCUSSION: The clinical course of this patient raises the possibility that low-activity TPMT genotypes may influence 6TG toxicity in patients with AML and lead to an increased risk of developing secondary malignant neoplasms....

  7. Risk factors for therapy-related myelodysplastic syndrome and acute myeloid leukemia treated with allogeneic stem cell transplantation.

    NARCIS (Netherlands)

    Kroger, N.; Brand, R.; Biezen, A. van; Zander, A.; Dierlamm, J.; Niederwieser, D.; Devergie, A.; Ruutu, T.; Cornish, J.; Ljungman, P.; Gratwohl, A.; Cordonnier, C.; Beelen, D.; Deconinck, E.; Symeonidis, A.; Witte, T.J.M. de

    2009-01-01

    BACKGROUND: After successful treatment of malignant diseases, therapy-related myelodysplastic syndrome and acute myeloid leukemia have emerged as significant problems. DESIGN AND METHODS: The aim of this study was to investigate outcome and risk factors in patients with therapy-related myelodysplast

  8. Standardization of flow cytometry in myelodysplastic syndromes: report from the first European LeukemiaNet working conference on flow cytometry in myelodysplastic syndromes

    NARCIS (Netherlands)

    Loosdrecht, van de A.A.; Alhan, C.; Bene, M.C.; Porta, M.; Drager, A.M.; Feuillard, J.; Font, P.; Germing, U.; Haase, D.; Homburg, C.H.; Ireland, R.; Jansen, J.L.; Kern, W.; Malcovati, L.; Marvelde, J.G.T.; Mufti, G.J.; Ogata, K.; Orfao, A.; Ossenkoppele, G.J.; Porwit, A.; Preijers, F.W.M.B.; Richards, S.J.; Schuurhuis, G.J.; Subira, D.; Valent, P.; Velden, van der V.; Vyas, P.; Westra, A.H.; Witte, de T.M.; Wells, D.E.; Loken, M.R.; Westers, T.M.

    2009-01-01

    The myelodysplastic syndromes are a group of clonal hematopoietic stem cell diseases characterized by cytopenia(s), dysplasia in one or more cell lineages and increased risk of evolution to acute myeloid leukemia (AML). Recent advances in immunophenotyping of hematopoietic progenitor and maturing ce

  9. Standardization of flow cytometry in myelodysplastic syndromes: report from the first European LeukemiaNet working conference on flow cytometry in myelodysplastic syndromes.

    NARCIS (Netherlands)

    Loosdrecht, A.A. van de; Alhan, C.; Bene, M.C.; Porta, M.G. Della; Drager, A.M.; Feuillard, J.; Font, P.; Germing, U.; Haase, D.; Homburg, C.H.; Ireland, R.; Jansen, J.H.; Kern, W.; Malcovati, L.; Marvelde, J.G. Te; Mufti, G.J.; Ogata, K.; Orfao, A.; Ossenkoppele, G.J.; Porwit, A.; Preijers, F.W.M.B.; Richards, S.J.; Schuurhuis, G.J.; Subira, D.; Valent, P.; Velden, V.H. van der; Vyas, P.; Westra, A.H.; Witte, T.J.M. de; Wells, D.A.; Loken, M.R.; Westers, T.M.

    2009-01-01

    The myelodysplastic syndromes are a group of clonal hematopoietic stem cell diseases characterized by cytopenia(s), dysplasia in one or more cell lineages and increased risk of evolution to acute myeloid leukemia (AML). Recent advances in immunophenotyping of hematopoietic progenitor and maturing ce

  10. Standardization of flow cytometry in myelodysplastic syndromes: report from the first European LeukemiaNet working conference on flow cytometry in myelodysplastic syndromes

    NARCIS (Netherlands)

    Loosdrecht, van de A.A.; Alhan, C.; Bene, M.C.; Porta, M.; Drager, A.M.; Feuillard, J.; Font, P.; Germing, U.; Haase, D.; Homburg, C.H.; Ireland, R.; Jansen, J.L.; Kern, W.; Malcovati, L.; Marvelde, J.G.T.; Mufti, G.J.; Ogata, K.; Orfao, A.; Ossenkoppele, G.J.; Porwit, A.; Preijers, F.W.M.B.; Richards, S.J.; Schuurhuis, G.J.; Subira, D.; Valent, P.; Velden, van der V.; Vyas, P.; Westra, A.H.; Witte, de T.M.; Wells, D.E.; Loken, M.R.; Westers, T.M.

    2009-01-01

    The myelodysplastic syndromes are a group of clonal hematopoietic stem cell diseases characterized by cytopenia(s), dysplasia in one or more cell lineages and increased risk of evolution to acute myeloid leukemia (AML). Recent advances in immunophenotyping of hematopoietic progenitor and maturing

  11. Standardization of flow cytometry in myelodysplastic syndromes: report from the first European LeukemiaNet working conference on flow cytometry in myelodysplastic syndromes.

    NARCIS (Netherlands)

    Loosdrecht, A.A. van de; Alhan, C.; Bene, M.C.; Porta, M.G. Della; Drager, A.M.; Feuillard, J.; Font, P.; Germing, U.; Haase, D.; Homburg, C.H.; Ireland, R.; Jansen, J.H.; Kern, W.; Malcovati, L.; Marvelde, J.G. Te; Mufti, G.J.; Ogata, K.; Orfao, A.; Ossenkoppele, G.J.; Porwit, A.; Preijers, F.W.M.B.; Richards, S.J.; Schuurhuis, G.J.; Subira, D.; Valent, P.; Velden, V.H. van der; Vyas, P.; Westra, A.H.; Witte, T.J.M. de; Wells, D.A.; Loken, M.R.; Westers, T.M.

    2009-01-01

    The myelodysplastic syndromes are a group of clonal hematopoietic stem cell diseases characterized by cytopenia(s), dysplasia in one or more cell lineages and increased risk of evolution to acute myeloid leukemia (AML). Recent advances in immunophenotyping of hematopoietic progenitor and maturing

  12. Late effect of atomic bomb radiation on myeloid disorders: leukemia and myelodysplastic syndromes.

    Science.gov (United States)

    Tsushima, Hideki; Iwanaga, Masako; Miyazaki, Yasushi

    2012-03-01

    Leukemia was the first malignancy linked to radiation exposure in atomic bomb survivors. Clear evidence of the dose-dependent excess risk of three major types of leukemia (acute lymphocytic leukemia, acute myeloid leukemia [AML], and chronic myeloid leukemia) was found, especially in people exposed at young ages. Such leukemia risks were at their highest in the late 1950s, and declined gradually thereafter over the past 50 years. Findings from recent risk analyses, however, suggest the persistence of AML risk even after 1990, and evidence of increased risk of myelodysplastic syndromes (MDS) due to atomic bomb radiation has recently been shown. High-risk MDS and forms involving complex chromosomal aberrations were found to be much more frequent in people exposed to higher radiation doses. These lines of epidemiological evidence suggest that the risk of radiation-induced hematological malignancies has persisted for six decades since the initial exposure.

  13. [Molecular biology in myelodysplastic syndromes and acute myeloid leukemias "smoldering"].

    Science.gov (United States)

    Martinelli, Giovanni; Sartor, Chiara; Papayannidis, Cristina; Iacobucci, Ilaria; Paolini, Stefania; Clissa, Cristina; Ottaviani, Emanuela; Finelli, Carlo

    2014-03-01

    Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal hematopoietic disorders of the myeloid lineage characterized by peripheral cytopenias and frequent leukemic evolution. MDS differ for clinical presentation, disease behavior and progression and this is the reflection of remarkable variability at molecular level. To this moment disease diagnosis is still dependent on bone marrow morphology that, although high concordance rates among experts are reported, remains subjective. Karyotype analysis is mandatory but diagnosis may be difficult in presence of normal karyotype or non-informative cytogenetics. Standardized molecular markers are needed to better define diagnosis, prediction of disease progression and prognosis. Furthermore, a molecular biology analysis could provide an important therapeutic tool towards tailored therapy and new insights in the disease's biology.

  14. Iodine I 131 Monoclonal Antibody BC8, Fludarabine Phosphate, Cyclophosphamide, Total-Body Irradiation and Donor Bone Marrow Transplant in Treating Patients With Advanced Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, or High-Risk Myelodysplastic Syndrome

    Science.gov (United States)

    2016-07-18

    Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Myeloid Leukemia in Remission; Chronic Myelomonocytic Leukemia; Previously Treated Myelodysplastic Syndrome; Refractory Anemia With Excess Blasts; Refractory Anemia With Ring Sideroblasts; Refractory Cytopenia With Multilineage Dysplasia; Refractory Cytopenia With Multilineage Dysplasia and Ring Sideroblasts

  15. Subcutaneous histiocytoid Sweet's syndrome in a patient with myelodysplastic syndrome and acute myeloblastic leukemia.

    Science.gov (United States)

    Srisuttiyakorn, Chutika; Reeve, Jennifer; Reddy, Swapna; Imaeda, Suguru; Lazova, Rossitza

    2014-05-01

    Subcutaneous histiocytoid Sweet’s syndrome is a rare variant of histiocytoid Sweet’s syndrome (SS). We present a 68-year-old woman with subcutaneous histiocytoid SS in association with refractory myelodysplastic syndrome transformed to acute myeloblastic leukemia (AML), status post induction chemotherapy and with persistent blasts (50%) in the bone marrow and blood, accompanied with neutropenia. The patient presented to the emergency room with fever and altered mental status. Clinical examination revealed approximately 20 scattered 0.5-2 cm, pink to pink-purple non-tender firm nodules on the legs and left arm. The differential diagnosis included Sweet’s syndrome (deep), leukemia cutis, infection, polyarteritis nodosa and erythema nodosum. Histopathologic examination of a biopsy from the left arm revealed a nodular infiltrate of neutrophils and histiocytoid mononuclear cells solely in the lobular compartment of the subcutaneous fat with focal areas of necrosis. Most cells in the infiltrate labeled with myeloperoxidase (MPO) including the histiocytoid cells. The cells were negative for CD34 and CD117. All special stains for microorganisms were negative. A diagnosis of subcutaneous histiocytoid SS was made. A subcutaneous histiocytoid SS should be suspected when a neutrophilic/histiocytoid panniculitis, occurring in the setting of myeloid disorders, is encountered and after exclusion of an infectious process and leukemia cutis.

  16. p53 mutations in leukemia and myelodysplastic syndrome after ovarian cancer.

    Science.gov (United States)

    Leonard, Debra G B; Travis, Lois B; Addya, Kathakali; Dores, Graca M; Holowaty, Eric J; Bergfeldt, Kjell; Malkin, David; Kohler, Betsy A; Lynch, Charles F; Wiklund, Tom; Stovall, Marilyn; Hall, Per; Pukkala, Eero; Slater, Diana J; Felix, Carolyn A

    2002-05-01

    Although p53 mutations occur in alkylating agent-related leukemias, their frequency and spectrum in leukemias after ovarian cancer have not been addressed. The purpose of this study was to examine p53 mutations in leukemias after ovarian cancer, for which treatment with platinum analogues was widely used. Adequate leukemic or dysplastic cells were available in 17 of 82 cases of leukemia or myelodysplastic syndrome that occurred in a multicenter, population-based cohort of 23,170 women with ovarian cancer. Eleven of the 17 received platinum compounds and other alkylating agents with or without DNA topoisomerase II inhibitors and/or radiation. Six received other alkylating agents, in one case, with radiation. Genomic DNA was extracted and p53 exons 5, 6, 7, and 8 were amplified by PCR. Mutations and loss of heterozygosity were analyzed on the WAVE instrument (Transgenomic) followed by selected analysis by sequencing. Eleven p53 mutations involving all four exons studied and one polymorphism were identified. Genomic DNA analyses were consistent with loss of heterozygosity for four of the mutations. The 11 mutations occurred in 9 cases, such that 6 of 11 leukemias after platinum-based regimens (55%) and 3 of 6 leukemias after other treatments (50%) contained p53 mutations. Two leukemias that occurred after treatment with platinum analogues contained two mutations. Among eight mutations in leukemias after treatment with platinum analogues, there were four G-to-A transitions and one G-to-C transversion. p53 mutations are common in leukemia and myelodysplastic syndrome after multiagent therapy for ovarian cancer. The propensity for G-to-A transitions may reflect specific DNA damage in leukemias after treatment with platinum analogues.

  17. Vorinostat, Cytarabine, and Etoposide in Treating Patients With Relapsed and/or Refractory Acute Leukemia or Myelodysplastic Syndromes or Myeloproliferative Disorders

    Science.gov (United States)

    2013-05-01

    Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Acute Promyelocytic Leukemia (M3); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative; Blastic Phase Chronic Myelogenous Leukemia; Chronic Eosinophilic Leukemia; Chronic Myelomonocytic Leukemia; Chronic Neutrophilic Leukemia; de Novo Myelodysplastic Syndromes; Essential Thrombocythemia; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Polycythemia Vera; Previously Treated Myelodysplastic Syndromes; Primary Myelofibrosis; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes

  18. Decitabine Followed by Idarubicin and Cytarabine in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia or Myelodysplastic Syndromes

    Science.gov (United States)

    2013-10-09

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts

  19. RAS gene mutations in acute and chronic myelocytic leukemias, chronic myeloproliferative disorders, and myelodysplastic syndromes

    Energy Technology Data Exchange (ETDEWEB)

    Janssen, J.W.G.; Steenvoorden, A.C.M.; Lyons, J.; Anger, B.; Boehlke, J.U.; Bos, J.L.; Seliger, H.; Bartram, C.R.

    1987-12-01

    The authors report on investigations aimed at detecting mutated RAS genes in a variety of preleukemic disorders and leukemias of myeloid origin. DNA transfection analyses (tumorigenicity assay) and hybridization to mutation-specific oligonucleotide probes established NRAS mutations in codon 12 or 61 of 4/9 acute myelocytic leukemias (AML) and three AML lines. Leukemic cells of another AML patient showed HRAS gene activation. By using a rapid and sensitive dot-blot screening procedure based on the combination of in vitro amplification of RAS-specific sequences and oligonucleotide hybridization they additionally screened 15 myelodysplastic syndromes, 26 Philadelphia chromosome-positive chronic myelocytic leukemias in chronic or acute phase, and 19 other chronic myeloproliferative disorders. A mutation within NRAS codon 12 could thus be demonstrated in a patient with idiopathic myelofibrosis and in another with chronic myelomonocytic leukemia. Moreover, mutated NRAS sequences were detected in lymphocytes, in granulocytes, as well as in monocytes/macrophages of the latter case.

  20. 7-Hydroxystaurosporine and Perifosine in Treating Patients With Relapsed or Refractory Acute Leukemia, Chronic Myelogenous Leukemia or High Risk Myelodysplastic Syndromes

    Science.gov (United States)

    2013-09-27

    Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Acute Promyelocytic Leukemia (M3); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Blastic Phase Chronic Myelogenous Leukemia; Myelodysplastic/Myeloproliferative Neoplasms; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; T-cell Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Myeloid Leukemia

  1. Outcomes for Patients with Chronic Lymphocytic Leukemia (CLL) and Acute Leukemia or Myelodysplastic Syndrome

    Science.gov (United States)

    Tambaro, Francesco Paolo; Garcia-Manero, Guillermo; O’Brien, Susan M.; Faderl, Stefan H.; Ferrajoli, Alessandra; Burger, Jan A.; Pierce, Sherry; Wang, Xuemei; Do, Kim-Anh; Kantarjian, Hagop M.; Keating, Michael J.; Wierda, William G.

    2016-01-01

    Acute leukemia (AL) and myelodysplastic syndrome (MDS) are uncommon in CLL. We retrospectively identified 95 patients with CLL also diagnosed with AL (n=38) or MDS (n=57), either concurrently (n=5) or subsequent (n=90) to CLL diagnosis and report their outcomes. Median number of CLL treatments prior to AL and MDS was 2(0–9) and 1(0–8), respectively; the most common regimen was purine analogue combined with alkylating agent±CD20 mAb. Twelve had no prior CLL treatment. Among 38 with AL, 33 had AML, 3 had ALL (1Ph+), 1 had biphenotypic, and 1 had extramedullary (bladder) AML. Unfavorable AML karyotype was noted in 26, intermediate-risk in 7. There was no association between survival from AL and number of prior CLL regimens or karyotype. Expression of CD7 on blasts was associated with shorter survival. Among MDS cases, all IPSS were represented; karyotype was unfavorable in 36, intermediate in 6, and favorable in 12 patients; 10 experienced transformation to AML. Shorter survival from MDS correlated with higher-risk IPSS, poor-risk karyotype, and increased number of prior CLL treatments. Overall, outcomes for patients with CLL subsequently diagnosed with AL or MDS were poor; AL/MDS occurred without prior CLL treatment. Effective therapies for these patients are desperately needed. PMID:26290497

  2. The DAC system and associations with acute leukemias and myelodysplastic syndromes.

    Science.gov (United States)

    Bug, Gesine; Ottmann, Oliver G

    2010-12-01

    Imbalances of histone acetyltransferase (HAT) and deacetylase activity (DAC) that result in deregulated gene expression are commonly observed in leukemias. These alterations provide the basis for novel therapeutic approaches that target the epigenetic mechanisms implicated in leukemogenesis. As the acetylation status of histones has been linked to transcriptional regulation of genes involved particularly in differentiation and apoptosis, DAC inhibitors (DACi) have attracted considerable attention for treatment of hematologic malignancies. DACi encompass a structurally diverse family of compounds that are being explored as single agents as well as in combination with chemotherapeutic drugs, small molecule inhibitors of signaling pathways and hypomethylating agents. While DACi have shown clear evidence of activity in acute myeloid leukemia, myelodysplastic syndromes and lymphoid malignancies, their precise role in treatment of these different entities remain to be elucidated. Successful development of these compounds as elements of novel targeted treatment strategies for leukemia will require that clinical studies be performed in conjunction with translational research including efforts to identify predictive biomarkers.

  3. Comprehensive scanning of somatic mitochondrial DNA alterations in acute leukemia developing from myelodysplastic syndromes.

    Science.gov (United States)

    Linnartz, Bjoern; Anglmayer, Roswitha; Zanssen, Stefanie

    2004-03-15

    Myelodysplastic syndromes (MDS) are clonal myeloid disorders characterized by ineffective hematopoiesis resulting in refractory cytopenias. Transformation resulting in acute myeloblastic leukemia is the final stage in the multistep process of MDS evolution. Functional relevant mutations of mitochondrial DNA (mtDNA) have been related to sideroblastic anemia and MDS. To investigate the role of mtDNA in malignant transformation to acute leukemia, we used high-resolution techniques such as single-strand conformational polymorphism and fluorescence sequencing for investigation of the whole mitochondrial genome from blood cells of 10 patients with MDS. Functionally relevant point mutations in mitochondrial RNA and polypeptide-encoding genes were detected in 50% of patients with MDS. Their increasing mutation load connects MDS and the developing acute myeloid leukemias. Several point mutations of mtDNA, including secondary point mutations for Leber's hereditary optic neuropathy, occur in one bone marrow and may synergically affect bone marrow stem cells by an apoptotic pathway.

  4. Pulmonary Complications of Azanucleoside Therapy in Patients with Myelodysplastic Syndrome and Acute Myelogenous Leukemia

    Directory of Open Access Journals (Sweden)

    Manuel Molina

    2015-01-01

    Full Text Available Our primary aim was to identify potential risk factors and clinical outcome of azanucleoside induced pulmonary complications in patients with myelodysplastic syndrome (MDS and Acute Myelogenous Leukemia (AML. We present an 89-year-old female with MDS derived AML who developed fatigability, hypoxemia, and bilateral lung infiltrates indicating interstitial lung disease after 11 cycles of azanucleoside. In addition, we describe a cohort of six MDS patients with fever, cough, dyspnea, and pulmonary infiltrates at early time point during azanucleoside treatment. Early and late onset of pulmonary manifestations suggest different pathogenic mechanisms. Brief azanucleoside discontinuation and steroids led to rapid improvement in symptoms.

  5. ST-elevation myocardial infarction and myelodysplastic syndrome with acute myeloid leukemia transformation.

    Science.gov (United States)

    Jao, Geoffrey T; Knovich, Mary Ann; Savage, Rodney W; Sane, David C

    2014-04-01

    Acute myocardial infarction and acute myeloid leukemia are rarely reported as concomitant conditions. The management of ST-elevation myocardial infarction (STEMI) in patients who have acute myeloid leukemia is challenging: the leukemia-related thrombocytopenia, platelet dysfunction, and systemic coagulopathy increase the risk of bleeding, and the administration of thrombolytic agents can be fatal. We report the case of a 76-year-old man who presented emergently with STEMI, myelodysplastic syndrome, and newly recognized acute myeloid leukemia transformation. Standard antiplatelet and anticoagulation therapy were contraindicated by the patient's thrombocytopenia and by his reported ecchymosis and gingival bleeding upon admission. He declined cardiac catheterization, was provided palliative care, and died 2 hours after hospital admission. We searched the English-language medical literature, found 8 relevant reports, and determined that the prognosis for patients with concomitant STEMI and acute myeloid leukemia is clearly worse than that for either individual condition. No guidelines exist to direct the management of STEMI and concomitant acute myeloid leukemia. In 2 reports, dual antiplatelet therapy, anticoagulation, and drug-eluting stent implantation were used without an increased risk of bleeding in the short term, even in the presence of thrombocytopenia. However, we think that a more conservative approach--balloon angioplasty with the provisional use of bare-metal stents--might be safer. Simultaneous chemotherapy for the acute myeloid leukemia is crucial. Older age seems to be a major risk factor: patients too frail for emergent treatment can die within hours or days.

  6. Therapy-related myelodysplastic syndrome/acute myeloid leukemia after treatment with temozolomide in a patient with glioblastoma multiforme.

    Science.gov (United States)

    Kim, Sue Jung; Park, Tae Sung; Lee, Seung Tae; Song, Jaewoo; Suh, Borum; Kim, Se Hoon; Jang, Seon Jung; Lee, Chang Hoon; Choi, Jong Rak

    2009-01-01

    Therapy-related myelodysplastic syndrome and acute leukemia after treatment with temozolomide have rarely been described in the literature. Only 10 cases in association with temozolomide have been documented. The cases included anaplastic astrocytoma (4 cases), anaplastic oligodendroglioma (2 cases), low grade astrocytoma (2 cases), low grade oligodendroglioma (1 case), and one case of secondary Philadelphia-positive acute lymphoblastic leukemia in a patient with glioblastoma multiforme. Here we report a novel case of therapy-related myelodysplastic syndrome/acute myeloid leukemia associated with der(1;7)(q10;p10) in a glioblastoma multiforme patient treated with temozolomide. Results of bone marrow morphology, chromosome, and fluorescent in situ hybridization (FISH) analyses, as well as the clinical history, strongly suggest a treatment-related etiology in our case. In past reports, karyotypes in cases of therapy-related myelodysplastic syndrome/acute myeloid leukemia mostly demonstrated abnormalities in chromosomes 5 and 7. However, we report a case of temozolomide-related myelodysplastic syndrome/acute myeloid leukemia with der(1;7)(q10;p10), possibly the first reported case, to the authors' knowledge.

  7. Molecular determinants of juvenile myelomonosytic leukemia and childhood myelodysplastic syndrome

    NARCIS (Netherlands)

    A.C.H. de Vries (Andrica)

    2012-01-01

    textabstractIn the general population the probability of developing cancer before the age of 18 years is around 1 in 400. In the Netherlands, approximately 600 new children each year are diagnosed with cancer (Figure 1). The most common types of childhood cancer are leukemias and the distribution of

  8. A new high-throughput screening method for the detection of chronic lymphatic leukemia and myelodysplastic syndrome.

    Science.gov (United States)

    Haschke-Becher, Elisabeth; Vockenhuber, Michael; Niedetzky, Paul; Totzke, Uwe; Gabriel, Christian

    2008-01-01

    The VCS technology of Beckman Coulter differentiates white blood cells based on measures of their volume, conductivity and light scatter. The current study investigated the predictive value of index measures, known as research population data, for the detection of chronic lymphatic leukemia and myelodysplastic syndrome. Blood cell counts were performed in samples from 44 patients with chronic lymphatic leukemia, 19 patients with myelodysplastic syndrome and 199 healthy blood donors using the Beckman Coulter LH750. Means and standard deviations of volume, conductivity and scatter of lymphocytes and neutrophils were evaluated as predictors for both diseases. Their specificity and selectivity were evaluated by logistic regression and receiver operating characteristic curve analysis. Research population data were significantly different among groups. For chronic lymphatic leukemia, standard deviations of lymphocytes scatter and volume showed most relevant differences in comparison to healthy blood donors (sensitivity 88.6%, specificity 84.4%). For myelodysplastic syndrome, standard deviations of neutrophils conductivity were most predictive (sensitivity 73.7%, specificity 93.0%). Areas under corresponding receiver operating characteristic curves were 0.941 and 0.951, respectively. Based on their high predictive value, research population data could be routinely used to screen for chronic lymphatic leukemia and myelodysplastic syndrome.

  9. Monoclonal Antibody Therapy in Treating Patients With Ovarian Epithelial Cancer, Melanoma, Acute Myeloid Leukemia, Myelodysplastic Syndrome, or Non-Small Cell Lung Cancer

    Science.gov (United States)

    2013-01-09

    Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Myeloid Leukemia; Recurrent Melanoma; Recurrent Non-small Cell Lung Cancer; Recurrent Ovarian Epithelial Cancer; Stage IV Melanoma; Stage IV Non-small Cell Lung Cancer

  10. 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

    DEFF Research Database (Denmark)

    Grövdal, Michael; Khan, Rasheed; Aggerholm, Anni

    2007-01-01

    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...

  11. Screening features to improve the class prediction of acute myeloid leukemia and myelodysplastic syndrome.

    Science.gov (United States)

    Li, Kaishi; Yang, Meixue; Sablok, Gaurav; Fan, Jianping; Zhou, Fengfeng

    2013-01-10

    After more than three decades of intensive investigations, the underpinning mechanism of myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) pathogenesis still remains largely uncharacterized, and their diagnosis relies heavily on the subjective factors. Recently gene expression profiling technique showed significant improvement in classifying some subtypes of AML, but the model's discriminating power of MDS from AML is still in its infancy. Feature selection plays an important role in the classification of the samples on the basis of the gene expression profiles. Our hypothesis explains that a better choice of features could improve the classification of the diseased and normal stage samples, and the potential application of feature screening to produce feature sets, with better accuracies and lowest number of embedded features. The observed results suggest that feature selection proves to be an essential and affirmative step in the biomedical data mining models based on gene expression profiles.

  12. Early lymphocyte recovery predicts superior overall survival after unmanipulated haploidentical blood and marrow transplant for myelodysplastic syndrome and acute myeloid leukemia evolving from myelodysplastic syndrome.

    Science.gov (United States)

    Chang, Ying-Jun; Zhao, Xiang-Yu; Xu, Lan-Ping; Liu, Dai-Hong; Liu, Kai-Yan; Chen, Yu-Hong; Wang, Yu; Zhang, Xiao-Hui; Zhao, Xiao-Su; Han, Wei; Chen, Huan; Wang, Feng-Rong; Lv, Meng; Huang, Xiao-Jun

    2013-12-01

    We investigated whether early lymphocyte recovery, after unmanipulated, haploidentical, blood and marrow transplant (HBMT), affected clinical outcomes in 78 patients with myelodysplastic syndrome (MDS) or acute myeloid leukemia evolving from MDS. Lymphocyte recovery was based on the absolute lymphocyte count on day 30 (ALC-30). Patients with high ALC-30 (≥ 300 cells/μL) had lower relapse rates (13.8% vs. 35.5%, p = 0.049) and lower incidence of bacterial infections (3.4% vs. 25.8%, p = 0.015) than those with low ALC-30 values. Multivariate analysis showed that a high ALC-30 was associated with improved overall survival (OS, hazard ratio [HR]: 0.099, 95% confidence interval [CI]: 0.029-0.337; p leukemia-free survival (HR: 0.245, 95% CI: 0.112-0.539; p after unmanipulated HBMT.

  13. ST-Elevation Myocardial Infarction and Myelodysplastic Syndrome with Acute Myeloid Leukemia Transformation

    OpenAIRE

    2014-01-01

    Acute myocardial infarction and acute myeloid leukemia are rarely reported as concomitant conditions. The management of ST-elevation myocardial infarction (STEMI) in patients who have acute myeloid leukemia is challenging: the leukemia-related thrombocytopenia, platelet dysfunction, and systemic coagulopathy increase the risk of bleeding, and the administration of thrombolytic agents can be fatal. We report the case of a 76-year-old man who presented emergently with STEMI, myelodysplastic syn...

  14. Recurrent DNMT3A R882 Mutations in Chinese Patients with Acute Myeloid Leukemia and Myelodysplastic Syndrome

    OpenAIRE

    2011-01-01

    Somatic mutations of DNMT3A gene have recently been reported in acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). We examined the entire coding sequences of DNMT3A gene by high-resolution melting analysis and sequencing in Chinese patients with myeloid malignancies. R882 mutations were found in 12/182 AML and in 4/51 MDS, but not in either 79 chronic myeloid leukemia (CML), or 57 myeloproliferative neoplasms (MPNs), or 4 chronic monomyelocytic leukemia. No other DNMT3A mutation...

  15. Cellular immune profiling after sequential clofarabine and lenalidomide for high risk myelodysplastic syndromes and acute myeloid leukemia.

    Science.gov (United States)

    Jain, Prachi; Klotz, Jeffrey; Dunavin, Neil; Lu, Kit; Koklanaris, Eleftheria; Draper, Debbie; Superata, Jeanine; Chinian, Fariba; Yu, Quan; Keyvanfar, Keyvan; Wong, Susan; Muranski, Pawel; Barrett, A John; Ito, Sawa; Battiwalla, Minoo

    2017-01-01

    Patients with high risk myelodysplastic syndromes (MDS) and acute myelogenous leukemia (AML) are commonly older with multiple co-morbidities, rendering them unsuitable for intensive induction chemotherapy or transplantation. We report preliminary cellular immune profiling of four cases receiving sequential clofarabine and lenalidomide for high risk MDS and AML in a phase I study. Our results highlight the potential of immune profiling for monitoring immune-modifying agents in high risk MDS and AML.

  16. Cellular immune profiling after sequential clofarabine and lenalidomide for high risk myelodysplastic syndromes and acute myeloid leukemia

    Directory of Open Access Journals (Sweden)

    Prachi Jain

    2017-01-01

    Full Text Available Patients with high risk myelodysplastic syndromes (MDS and acute myelogenous leukemia (AML are commonly older with multiple co-morbidities, rendering them unsuitable for intensive induction chemotherapy or transplantation. We report preliminary cellular immune profiling of four cases receiving sequential clofarabine and lenalidomide for high risk MDS and AML in a phase I study. Our results highlight the potential of immune profiling for monitoring immune-modifying agents in high risk MDS and AML.

  17. Development of Myelodysplastic Syndrome and Acute Myeloid Leukemia 15 Years after Hydroxyurea Use in a Patient with Sickle Cell Anemia

    OpenAIRE

    2012-01-01

    We report a 41 year old male with sickle cell disease who developed a myelodysplastic syndrome and acute myeloid leukemia with complex karyotype involving chromosomes 5, 7 and 17 after 15 years of hydroxyurea treatment. He responded poorly to induction chemotherapy with cytarabine/idarubicin followed by high dose cytarabine and succumbed to neutropenic sepsis. Multiple systematic reviews, observational studies and clinical trials were conducted to identify the toxicity profile of hydroxurea. ...

  18. [Epigenetic dysregulation in myelodysplastic syndrome].

    Science.gov (United States)

    Sashida, Goro; Iwama, Atsushi

    2015-02-01

    Myelodysplastic syndrome (MDS) is a clonal hematopoietic stem cell disease characterized by impaired hematopoiesis and an increased risk of transformation to acute myeloid leukemia. Various epigenetic regulators are mutated in MDS patients, indicating that accumulation of epigenetic alterations together with genetic alterations plays a crucial role in the development of MDS.

  19. Allo-SCT conditioning for myelodysplastic syndrome and acute myeloid leukemia with clofarabine, cytarabine and ATG.

    Science.gov (United States)

    Martin, M G; Uy, G L; Procknow, E; Stockerl-Goldstein, K; Cashen, A; Westervelt, P; Abboud, C N; Augustin, K; Luo, J; DiPersio, J F; Vij, R

    2009-07-01

    The application of myeloablative Allo-SCT is limited by its associated morbidity and mortality. Reduced-intensity conditioning regimens attempt to diminish these, but are associated with a higher risk of disease relapse. Given the evidence of activity of clofarabine and cytarabine in myelodysplastic syndrome/acute myeloid leukemia (MDS/AML), we explored a novel reduced-intensity conditioning regimen based on this backbone. Patients received clofarabine 40 mg/m(2) i.v. on days -6 to -2, cytarabine 1 g/m(2) i.v. on days -6 to -2 and anti-thymocyte globulin (ATG) 1 mg/kg on day -4 and 2.5 mg/kg x 2 days on days -3 and -2. Seven patients were enrolled. Their median age was 54 years; three were with MDS and four with AML. The median duration of neutropenia was 14 days and that of thrombocytopenia was 22 days. Toxicities included hand-foot syndrome (57% grade 2), elevated alanine aminotransferase (ALT) (57% grade 3), elevated aspartate aminotransferase (AST) (86% grade 3) and hyperbilirubinemia (29% grade 3-5). No acute GVHD was observed. Enrollment to the trial was halted after three of the first seven patients expired on days +15, +26 and +32. Three of the four surviving patients have relapsed with a median TTP of 152 days. This regimen was not sufficiently immunosuppressive to ensure engraftment, and was associated with substantial morbidity and mortality.

  20. Myeloablative Versus Reduced-Intensity Hematopoietic Cell Transplantation for Acute Myeloid Leukemia and Myelodysplastic Syndromes.

    Science.gov (United States)

    Scott, Bart L; Pasquini, Marcelo C; Logan, Brent R; Wu, Juan; Devine, Steven M; Porter, David L; Maziarz, Richard T; Warlick, Erica D; Fernandez, Hugo F; Alyea, Edwin P; Hamadani, Mehdi; Bashey, Asad; Giralt, Sergio; Geller, Nancy L; Leifer, Eric; Le-Rademacher, Jennifer; Mendizabal, Adam M; Horowitz, Mary M; Deeg, H Joachim; Horwitz, Mitchell E

    2017-04-10

    Purpose The optimal regimen intensity before allogeneic hematopoietic cell transplantation (HCT) is unknown. We hypothesized that lower treatment-related mortality (TRM) with reduced-intensity conditioning (RIC) would result in improved overall survival (OS) compared with myeloablative conditioning (MAC). To test this hypothesis, we performed a phase III randomized trial comparing MAC with RIC in patients with acute myeloid leukemia or myelodysplastic syndromes. Patients and Methods Patients age 18 to 65 years with HCT comorbidity index ≤ 4 and < 5% marrow myeloblasts pre-HCT were randomly assigned to receive MAC (n = 135) or RIC (n = 137) followed by HCT from HLA-matched related or unrelated donors. The primary end point was OS 18 months post-random assignment based on an intent-to-treat analysis. Secondary end points included relapse-free survival (RFS) and TRM. Results Planned enrollment was 356 patients; accrual ceased at 272 because of high relapse incidence with RIC versus MAC (48.3%; 95% CI, 39.6% to 56.4% and 13.5%; 95% CI, 8.3% to 19.8%, respectively; P < .001). At 18 months, OS for patients in the RIC arm was 67.7% (95% CI, 59.1% to 74.9%) versus 77.5% (95% CI, 69.4% to 83.7%) for those in the MAC arm (difference, 9.8%; 95% CI, -0.8% to 20.3%; P = .07). TRM with RIC was 4.4% (95% CI, 1.8% to 8.9%) versus 15.8% (95% CI, 10.2% to 22.5%) with MAC ( P = .002). RFS with RIC was 47.3% (95% CI, 38.7% to 55.4%) versus 67.8% (95% CI, 59.1% to 75%) with MAC ( P < .01). Conclusion OS was higher with MAC, but this was not statistically significant. RIC resulted in lower TRM but higher relapse rates compared with MAC, with a statistically significant advantage in RFS with MAC. These data support the use of MAC as the standard of care for fit patients with acute myeloid leukemia or myelodysplastic syndromes.

  1. Prognostic significance of SETBP1 mutations in myelodysplastic syndromes, chronic myelomonocytic leukemia, and chronic neutrophilic leukemia: A meta-analysis

    Science.gov (United States)

    Shou, Li-Hong; Cao, Dan; Dong, Xiao-Hui; Fang, Qiu; Wu, Ying; Zhang, Yan; Fei, Ju-Ping; Xu, Bao-Lian

    2017-01-01

    Objectives This meta-analysis investigates the prognostic effect of SET binding protein 1 (SETBP1) mutations in patients with myelodysplastic syndromes (MDS), chronic myelomonocytic leukemia (CMML), or chronic neutrophilic leukemia (CNL). Methods Eligible studies from Pubmed, Embase, and Web of Science were searched from database inception through April 2016. Hazard ratios (HRs) and 95% confidence interval (CI) of overall survival (OS) were pooled to calculate the prognostic significance of SETBP1 mutation in patients. Results A total of 12 studies with 2321 patients were included in this meta-analysis; 4 studies for MDS, 5 studies for CMML, and 3 studies for CNL. Pooled results suggested that MDS and CMML patients with SETBP1 mutations had a significantly poorer prognosis when compared with patients with wild-type SETBP1 (MDS: HR = 1.808, 95% CI (1.218–2.685), P = 0.001; CMML: HR = 2.223, 95% CI (1.493–3.308), P<0.001). SETBP1 mutations in CNL patients however, showed no significant effect on the overall survival (HR = 1.773, 95% CI (0.877–3.582), P = 0.111). The Begg’s and Egger’s tests did not show significant publication bias in any groups. Conclusions Current evidence shows that SETBP1 mutation is associated with a poor prognosis in patients with MDS and CMML, but not in patients with CNL. PMID:28158286

  2. Childhood myelodysplastic syndrome.

    Science.gov (United States)

    Chatterjee, Tathagata; Choudhry, V P

    2013-09-01

    Myelodysplastic syndrome (MDS) comprises of a heterogeneous group of bone marrow disorders resulting from a clonal stem cell defect characterised by cytopenias despite a relatively hypercellular marrow, ineffective hematopoiesis, morphological dysplasia in the marrow elements, no response to hematinics such as iron, B12 or folic acid and risk of progression to leukemia. Myelodysplastic syndrome in childhood is extremely rare and accounts for less than 5% of all hematopoietic neoplasms in children below the age of 14 y. The primary MDS in children, also known as de novo MDS differs from secondary MDS which generally follows congenital or acquired bone marrow (BM) failure syndromes as well as from therapy related MDS, commonly resulting from cytotoxic therapy. MDS associated with Down syndrome which accounts for approximately one-fourth of cases of childhood MDS is now considered a unique biologic entity synonymous with Down syndrome-related myeloid leukemia and is biologically distinct from other cases of childhood MDS. Refractory cytopenia of childhood (RCC) is the commonest type of MDS. Genetic changes predisposing to MDS in childhood remain largely obscure. Monosomy 7 is by-far the commonest cytogenetic abnormality associated with childhood MDS; however most cases of RCC show a normal karyotype. Complex cytogenetic abnormalities and trisomy 8 and trisomy 21 are also occasionally observed. The most effective and curative treatment is Hematopoietic stem cell transplantation and this is particularly effective in children with the monosomy 7 genetic defect as well as those displaying complex karyotype abnormalities provided it is instituted early in the course of the disease.

  3. Therapy-related acute myeloid leukemia and myelodysplastic syndrome after hematopoietic cell transplantation for lymphoma.

    Science.gov (United States)

    Yamasaki, S; Suzuki, R; Hatano, K; Fukushima, K; Iida, H; Morishima, S; Suehiro, Y; Fukuda, T; Uchida, N; Uchiyama, H; Ikeda, H; Yokota, A; Tsukasaki, K; Yamaguchi, H; Kuroda, J; Nakamae, H; Adachi, Y; Matsuoka, K-I; Nakamura, Y; Atsuta, Y; Suzumiya, J

    2017-04-03

    Therapy-related acute myeloid leukemia and myelodysplastic syndrome (t-AML/MDS) represent severe late effects in patients receiving hematopoietic cell transplantation (HCT) for lymphoma. The choice between high-dose therapy with autologous HCT and allogeneic HCT with reduced-intensity conditioning remains controversial in patients with relapsed lymphoma. We retrospectively analyzed incidence and risk factors for the development of t-AML/MDS in lymphoma patients treated with autologous or allogeneic HCT. A total of 13 810 lymphoma patients who received autologous (n=9963) or allogeneic (n=3847) HCT between 1985 and 2012 were considered. At a median overall survival (OS) of 52 and 46 months in autologous and allogeneic HCT groups, respectively, lymphoma patients receiving autologous HCT (1.38% at 3 years after autologous HCT) had a significant risk for developing t-AML/MDS compared to allogeneic HCT (0.37% at 3 years after allogeneic HCT, Pafter autologous and allogeneic HCT were high-stage risk at HCT (P=0.04) or secondary malignancies (P<0.001) and receiving cord blood stem cell (P=0.03) or involved field radiotherapy (P=0.002), respectively. Strategies that carefully select lymphoma patients for autologous HCT, by excluding lymphoma patients with high-stage risk at HCT, may allow the identification of individual lymphoma patients at particular high risk for t-AML/MDS.Bone Marrow Transplantation advance online publication, 3 April 2017; doi:10.1038/bmt.2017.52.

  4. Hypocellular myelodysplastic syndrome with myelofibrosis in acute myeloid leukemia transformation: A case report.

    Science.gov (United States)

    Song, Kui; Xu, Xiaojun; Li, Min

    2015-07-01

    Primary myelodysplastic syndrome (MDS) with myelofibrosis is a rare hematological disorder that should be classified as a distinct subgroup of MDS. Treatment of MDS with myelofibrosis remains problematic and the prognosis is poor in these patients, particularly following transformation into acute myeloid leukemia (AML). The current study presents the case of a 28-year-old male diagnosed with MDS associated with myelofibrosis, together with hypocellular bone marrow features. Following induction chemotherapy consisting of mitoxantrone and cytarabine, the patient achieved complete remission, but developed severe myelofibrosis. The patient relapsed and the disease transformed into AML 12 months later. However, the extent of the myelofibrosis was markedly alleviated upon administration of a FLAG regimen that consisted of fludarabine, cytarabine and granulocyte colony-stimulating factor during the AML transformation. After one course of the FLAG regimen, the patient achieved a second complete remission. As there was no suitable donor for hematopoietic stem cell transplantation (HSCT), the patient relapsed and succumbed shortly after. In conclusion, MDS with fibrosis is an aggressive disease, but the degree of myelofibrosis may not be associated with the progression of hypocellular MDS, and allogeneic HSCT remains a potentially curative option for affected patients.

  5. Up-front allogeneic hematopoietic cell transplantation in acute myeloid leukemia arising from the myelodysplastic syndrome.

    Science.gov (United States)

    Choi, Yunsuk; Kim, Sung-Doo; Park, Young-Hoon; Lee, Jae Seok; Kim, Dae-Young; Lee, Jung-Hee; Lee, Kyoo-Hyung; Seol, Miee; Lee, Young-Shin; Kang, Young-Ah; Jeon, Mijin; Jung, Ah Rang; Lee, Je-Hwan

    2015-01-01

    In patients with secondary acute myeloid leukemia (s-AML) arising from the myelodysplastic syndrome (MDS), treatment outcome is unsatisfactory. We compared up-front allogeneic hematopoietic cell transplantation (HCT) to induction chemotherapy (IC) as an initial treatment in patients with s-AML arising from MDS. This retrospective study included 85 patients who were diagnosed with s-AML arising from MDS; 11 patients proceeded to up-front HCT without IC (HCT group) and 74 received IC (IC group) as an initial treatment for s-AML, 28 of whom subsequently underwent HCT. In the IC group, 41.9% achieved complete remission (CR) compared to 81.8% in the HCT group (p = 0.013). The HCT group showed a significantly longer event-free survival (EFS) than the IC group (median 29.2 vs. 5.2 months, p = 0.042). Overall survival of the HCT group was higher than that of the IC group, but the difference was not statistically significant (median 34.6 vs. 7.6 months, p = 0.149). After adjustment for other clinical factors, outcome in the HCT group was significantly better than in the IC group in terms of CR rate (hazard ratio, HR, 11.195; p = 0.007) and EFS (HR, 0.384; p = 0.029). Up-front HCT is a viable option in s-AML arising from MDS if an appropriate donor is available.

  6. Analyzing transformation of myelodysplastic syndrome to secondary acute myeloid leukemia using a large patient database.

    Science.gov (United States)

    Shukron, Ofir; Vainstein, Vladimir; Kündgen, Andrea; Germing, Ulrich; Agur, Zvia

    2012-09-01

    One-third of patients with myelodysplastic syndrome (MDS) progress to secondary acute myeloid leukemia (sAML), with its concomitant poor prognosis. Recently, multiple mutations have been identified in association with MDS-to-sAMLtransition, but it is still unclear whether all these mutations are necessary for transformation. If multiple independent mutations are required for the transformation, sAML risk should increase with time from MDS diagnosis. In contrast, if a single critical biological event determines sAML transformation; its risk should be constant in time elapsing from MDS diagnosis. To elucidate this question, we studied a database of 1079 patients with MDS. We classified patients according to the International Prognostic Scoring System (IPSS), using either the French-American-British (FAB) or the World Health Organization (WHO) criteria, and statistically analyzed the resulting transformation risk curves of each group. The risk of transformation after MDS diagnosis remained constant in time within three out of four risk groups, and in all four risk groups, when patients were classified according to FAB or to the WHO-determined criteria, respectively. Further subdivision by blast percentage or cytogenetics had no influence on this result. Our analysis suggests that a single random biological event leads to transformation to sAML, thus calling for the exclusion of time since MDS diagnosis from the clinical decision-making process.

  7. Abrupt evolution of Philadelphia chromosome-positive acute myeloid leukemia in myelodysplastic syndrome.

    Science.gov (United States)

    Fukunaga, Akiko; Sakoda, Hiroto; Iwamoto, Yoshihiro; Inano, Shojiro; Sueki, Yuki; Yanagida, Soshi; Arima, Nobuyoshi

    2013-03-01

    Myelodysplastic syndrome (MDS) is a clonal disorder arising from an alteration in multipotent stem cells, which lose the ability of normal proliferation and differentiation. Disease progression occurs in approximately 30% MDS cases. Specific chromosomal alterations seem responsible for each step in the evolution of acute myeloid leukemia (AML). Multiple genetic aberrations occur during the clonal evolution of MDS; however, few studies report the presence of the Philadelphia (Ph) chromosome. We report a rare case of Ph-positive AML, which evolved during the course of low-risk MDS. The patient, a 76-year-old man with mild leukocytopenia, was diagnosed with MDS, refractory neutropenia (RN). After 1.5 yr, his peripheral blood and bone marrow were suddenly occupied by immature basophils and myeloblasts, indicating the onset of AML. A bone marrow smear showed multilineage dysplasia, consistent with MDS evolution. Chromosomal analysis showed an additional t(9;22)(q34;q11) translocation. Because progression occurred concurrently with emergence of the Ph chromosome, we diagnosed this case as Ph-positive AML with basophilia arising from the clonal evolution of MDS. The patient was initially treated with nilotinib. A hematological response was soon achieved with disappearance of the Ph chromosome in the bone marrow. Emergence of Ph-positive AML in the course of low-risk MDS has rarely been reported. We report this case as a rare clinical course of MDS.

  8. Predictors of Neuropsychological Change in Patients with Chronic Myelogenous Leukemia and Myelodysplastic Syndrome

    Science.gov (United States)

    Meadows, Mary-Ellen; Chang, Grace; Jones, Jennifer A.; Antin, Joseph R.; Orav, E. John

    2013-01-01

    This study examined the course of neuropsychological functioning in patients with chronic myelogeous leukemia (n = 91) or myelodysplastic syndrome (n = 15) who underwent standard treatment for their disease or allogeneic hematopoietic stem cell transplantation (HSCT) at baseline, 12 months, and 18 months post-treatment. At baseline, 23% of the participants (n = 75) in the longitudinal sample had Z-scores on at least one of the neuropsychological tests that were <1.4. Participants in the study showed improvement over baseline at the 12 and 18 months assessments. The average Z-scores for the six cognitive domains in the longitudinal data set over the course of the study ranged from −0.89 to 0.59. Significant predictors of change in neuropsychological test scores included age, with older participants showing less improvement over time. Other predictors included baseline cognitive domains (language, memory, and attention), previous cocaine use, disease status, intelligence quotient, and quality of life measures. Findings support previous studies in patients with hematological malignancies who showed cognitive impairments at baseline prior to HSCT. However, there was little evidence for further cognitive decline over the course of 18 months. PMID:23391504

  9. U2AF1 mutations in Chinese patients with acute myeloid leukemia and myelodysplastic syndrome.

    Directory of Open Access Journals (Sweden)

    Jun Qian

    Full Text Available Somatic mutations of U2AF1 gene have recently been identified in myelodysplastic syndrome (MDS and acute myeloid leukemia (AML. In this study, we analyzed the frequency and clinical impact of U2AF1 mutations in a cohort of 452 Chinese patients with myeloid neoplasms. Mutations in U2AF1 were found in 2.5% (7/275 of AML and 6.3% (6/96 of MDS patients, but in none of 81 CML. All mutations were heterozygous missense mutations affecting codon S34 or Q157. There was no significant association of U2AF1 mutation with blood parameters, FAB subtypes, karyotypes and other gene mutations in AML. The overall survival (OS of AML patients with U2AF1 mutation (median 3 months was shorter than those without mutation (median 7 months (P = 0.035. No difference in the OS was observed between MDS patients with and without U2AF1 mutations. Our data show that U2AF1 mutation is a recurrent event at a low frequency in AML and MDS.

  10. Allogeneic transplantation for therapy-related myelodysplastic syndrome and acute myeloid leukemia.

    Science.gov (United States)

    Litzow, Mark R; Tarima, Sergey; Pérez, Waleska S; Bolwell, Brian J; Cairo, Mitchell S; Camitta, Bruce M; Cutler, Corey S; de Lima, Marcos; Dipersio, John F; Gale, Robert Peter; Keating, Armand; Lazarus, Hillard M; Luger, Selina; Marks, David I; Maziarz, Richard T; McCarthy, Philip L; Pasquini, Marcelo C; Phillips, Gordon L; Rizzo, J Douglas; Sierra, Jorge; Tallman, Martin S; Weisdorf, Daniel J

    2010-03-04

    Therapy-related myelodysplastic syndromes (t-MDSs) and acute myeloid leukemia (t-AML) have a poor prognosis with conventional therapy. Encouraging results are reported after allogeneic transplantation. We analyzed outcomes in 868 persons with t-AML (n = 545) or t-MDS (n = 323) receiving allogeneic transplants from 1990 to 2004. A myeloablative regimen was used for conditioning in 77%. Treatment-related mortality (TRM) and relapse were 41% (95% confidence interval [CI], 38-44) and 27% (24-30) at 1 year and 48% (44-51) and 31% (28-34) at 5 years, respectively. Disease-free (DFS) and overall survival (OS) were 32% (95% CI, 29-36) and 37% (34-41) at 1 year and 21% (18-24) and 22% (19-26) at 5 years, respectively. In multivariate analysis, 4 risk factors had adverse impacts on DFS and OS: (1) age older than 35 years; (2) poor-risk cytogenetics; (3) t-AML not in remission or advanced t-MDS; and (4) donor other than an HLA-identical sibling or a partially or well-matched unrelated donor. Five-year survival for subjects with none, 1, 2, 3, or 4 of these risk factors was 50% (95% CI, 38-61), 26% (20-31), 21% (16-26), 10% (5-15), and 4% (0-16), respectively (P < .001). These data permit a more precise prediction of outcome and identify subjects most likely to benefit from allogeneic transplantation.

  11. Maintenance Therapy with Decitabine after Allogeneic Stem Cell Transplantation for Acute Myelogenous Leukemia and Myelodysplastic Syndrome.

    Science.gov (United States)

    Pusic, Iskra; Choi, Jaebok; Fiala, Mark A; Gao, Feng; Holt, Matthew; Cashen, Amanda F; Vij, Ravi; Abboud, Camille N; Stockerl-Goldstein, Keith E; Jacoby, Meghan A; Uy, Geoffrey L; Westervelt, Peter; DiPersio, John F

    2015-10-01

    Decitabine is a hypomethylating agent that irreversibly inhibits DNA methyltransferase I, inducing leukemic differentiation and re-expression of epigenetically silenced putative tumor antigens. We assessed safety and efficacy of decitabine maintenance after allogeneic transplantation for acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). Decitabine maintenance may help eradicate minimal residual disease, decrease the incidence of graft-versus-host disease (GVHD), and facilitate a graft-versus-leukemia effect by enhancing the effect of T regulatory lymphocytes. Patients with AML/MDS in complete remission (CR) after allotransplantation started decitabine between day +50 and +100. We investigated 4 decitabine doses in cohorts of 4 patients: 5, 7.5, 10, and 15 mg/m(2)/day × 5 days every 6 weeks, for a maximum 8 cycles. The maximum tolerated dose (MTD) was defined as the maximum dose at which ≤ 25% of people experience dose-limiting toxicities during the first cycle of treatment. Twenty-four patients were enrolled and 22 were evaluable. All 4 dose levels were completed and no MTD was reached. Overall, decitabine maintenance was well tolerated. Grade 3 and 4 hematological toxicities were experienced by 75% of patients, including all patients treated at the highest dose level. Nine patients completed all 8 cycles and 8 of them remain in CR. Nine patients died from relapse (n = 4), infectious complications (n = 3), and GVHD (n = 2). Most occurrences of acute GVHD were mild and resolved without interruption of treatment; 1 patient died of acute gut GVHD. Decitabine maintenance did not clearly impact the rate of chronic GVHD. Although there was a trend of increased FOXP3 expression, results were not statistically significant. In conclusion, decitabine maintenance is associated with acceptable toxicities when given in the post-allotransplantation setting. Although the MTD was not reached, the dose of 10 mg/m(2) for 5 days every 6 weeks appeared to be the

  12. Myelodysplastic Syndrome with Myelofibrosis Transformed to a Precursor B-Cell Acute Lymphoblastic Leukemia: A Case Report with Review of the Literature

    OpenAIRE

    2012-01-01

    Myelodysplastic syndromes (MDS) comprise a group of heterogeneous clonal hematopoietic cell disorders characterized by cytopenias, bone marrow hypercellularity, and increased risk of transformation to acute leukemias. MDS usually transformed to acute myeloid leukemia, and transformation to acute lymphoblastic leukemia (ALL) is rare. Herein, we report a unique patient who presented with MDS with myelofibrosis. Two months after the initial diagnosis, she progressed to a precursor B-cell acute l...

  13. Stathmin 1 is involved in the highly proliferative phenotype of high-risk myelodysplastic syndromes and acute leukemia cells.

    Science.gov (United States)

    Machado-Neto, João Agostinho; de Melo Campos, Paula; Favaro, Patricia; Lazarini, Mariana; Lorand-Metze, Irene; Costa, Fernando Ferreira; Olalla Saad, Sara Teresinha; Traina, Fabiola

    2014-02-01

    Stathmin 1 is an important cytoplasmic microtubule-destabilizing protein that plays critical roles in proliferation and accurate chromosome segregation through regulation of microtubule dynamics. High levels of Stathmin 1 expression have been reported in leukemia and solid tumors. However, Stathmin 1 has not been studied in myelodysplastic syndrome cells. We, herein, report that significantly higher Stathmin 1 levels were observed in proliferating hematopoietic cells, in high-risk MDS and acute leukemia cells. In addition, Stathmin 1 silencing in U937 and Namalwa leukemia cells reduced cell proliferation and clonogenicity. Our data suggest that Stathmin 1 expression may be related to the highly proliferative phenotype of hematopoietic cells and add new insights into the participation of Stathmin 1 in hematological malignancies.

  14. Radiolabeled Monoclonal Antibody Therapy, Fludarabine Phosphate, and Low-Dose Total-Body Irradiation Followed by Donor Stem Cell Transplant and Immunosuppression Therapy in Treating Older Patients With Advanced Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndromes

    Science.gov (United States)

    2015-11-16

    Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Excess Blasts in Transformation; Refractory Anemia With Ringed Sideroblasts; Refractory Cytopenia With Multilineage Dysplasia; Secondary Myelodysplastic Syndromes; Untreated Adult Acute Myeloid Leukemia

  15. Iodine I 131 Monoclonal Antibody BC8, Fludarabine Phosphate, Total Body Irradiation, and Donor Stem Cell Transplant Followed by Cyclosporine and Mycophenolate Mofetil in Treating Patients With Advanced Acute Myeloid Leukemia or Myelodysplastic Syndrome

    Science.gov (United States)

    2016-11-14

    Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Childhood Myelodysplastic Syndromes; Chronic Myelomonocytic Leukemia; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Excess Blasts in Transformation; Refractory Anemia With Ringed Sideroblasts; Refractory Cytopenia With Multilineage Dysplasia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes

  16. Myelodysplastic Syndromes and Acute Myeloid Leukemia After Radiotherapy for Prostate Cancer: A Population-Based Study.

    Science.gov (United States)

    Wang, Rong; Zeidan, Amer M; Yu, James B; Soulos, Pamela R; Davidoff, Amy J; Gore, Steven D; Huntington, Scott F; Gross, Cary P; Ma, Xiaomei

    2017-04-01

    To understand the impact of radiotherapy on the development of myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) among elderly prostate cancer patients. We performed a retrospective cohort study of elderly prostate cancer patients diagnosed during 1999-2011 by using the National Cancer Institute's Surveillance, Epidemiology and End Results-Medicare linked database. Competing risk analyses adjusting for patient characteristics were conducted to assess the impact of radiotherapy on the development of subsequent MDS/AML, compared with surgery. Of 32,112 prostate cancer patients, 14,672 underwent radiotherapy, and 17,440 received surgery only. The median follow-up was 4.68 years. A total of 157 (0.47%) prostate cancer patients developed subsequent MDS or AML, and the median time to develop MDS/AML was 3.30 (range: 0.16-9.48) years. Compared with prostate cancer patients who received surgery only, patients who underwent radiotherapy had a significantly increased risk of developing MDS/AML (hazard ratio [HR] =1.51, 95% confidence interval [CI]: 1.07-2.13). When radiotherapy was further categorized by modalities (brachytherapy, conventional conformal radiotherapy, and intensity-modulated radiotherapy [IMRT]), increased risk of second MDS/AML was only observed in the IMRT group (HR = 1.66, 95% CI: 1.09-2.54). Our findings suggest that radiotherapy for prostate cancer increases the risk of MDS/AML, and the impact may differ by modality. Additional studies with longer follow-up are needed to further clarify the role of radiotherapy in the development of subsequent myeloid malignancies. A better understanding may help patients, physicians, and other stakeholders make more informed treatment decisions. Prostate 77:437-445, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  17. [Clinical observation of decitabine-treating patients with myelodysplastic syndrome and acute myeloid leukemia].

    Science.gov (United States)

    Yang, Hua; Zhu, Hai-Yan; Jiang, Meng-Meng; Wang, Quan-Shun; Han, Xiao-Ping; Huang, Wen-Rong; Jing, Yu; Wang, Shu-Hong; Zhang, Song-Song; Mei, Jun-Hui; Yu, Li

    2013-02-01

    This study was purposed to investigate the clinical efficiencies and adverse reactions of treating the myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) by using decitabine. The clinical data of 12 MDS and AML patients treated with decitabine were analyzed retrospectively. Among 12 patients there were 1 case of MDS-RA, 2 cases of MDS-RAEB-I, 3 cases of MDS-RAEB-II, 2 cases of AML-M4, 2 cases of AML-M5, 1 case of AML-M6 and 1 case of AML-M0. In decitabine chemotherapy program for 5 days (n = 8), decitabine 20 mg/(m(2)·d) × 5 days was applied, 4 weeks for 1 cycle; in program for 3 days (n = 2), decitabine 15 mg/m(2), once 8 h for 3 days, 6 weeks for 1 cycle; another program (n = 2), decitabine 20 mg/(m(2)·d) every other day for 5 times. For 1 patient achieved complete remission (CR) after treatment with decitabine, ID4 gene methylated level was detected by MS-PCR and ML-PCR before and after treatment. The results showed that 2 cases achieved CR, 1 case partial remission, 5 cases stable disease, 1 case progress of disease and 3 cases died. Disease control rate was 66.67% (8/12), the effective rate 25% (3/12). The average survival time was (11.5 ± 2.1) months. 1-year OS rate was 40%, 2-year OS rate was 16.7%. MS-PCR detection showed that the decitabine could significantly reduce the ID4 gene methylation level. It is concluded that decitabine can stabilize disease status of MDS patients, reduce blood transfusion dependence and improve the life quality of patients, and even some patients who transformed from MDS to leukemia achieved CR after treatment with decitabine. Decitabine can reduce the ID4 gene methylation level. The main adverse reaction of decitabine was myelosuppression, infection and so on. So the blood transfusions, antibiotics and other supportive treatments for these patients are needed. Most of patients well tolerate the adverse effects of decitabine after active symptomatic and supportive treatment. The efficacy and survival rate of

  18. [Etiological factors of myelodysplastic syndromes].

    Science.gov (United States)

    Nisse, C

    1997-09-01

    Specific epidemiologic data on myelodysplastic syndromes are rare. Analysis of data is in fact affected by problems of terminology and classification. The link between the exposure to ionizing radiation or alkylating agents and MDS is well established. Etiologic factors of acute leukemia, or new factors such as non ionizing radiation, solvent, ethylene oxide, glycol eters, tobacco smoke, exhaust gases, agricultural work have been hypothesized but should be confirmed by other studies on MDS.

  19. Development of myelodysplastic syndrome and acute myeloid leukemia 15 years after hydroxyurea use in a patient with sickle cell anemia.

    Science.gov (United States)

    Baz, Walid; Najfeld, Vesna; Yotsuya, Matthew; Talwar, Jotica; Terjanian, Terenig; Forte, Frank

    2012-01-01

    We report a 41 year old male with sickle cell disease who developed a myelodysplastic syndrome and acute myeloid leukemia with complex karyotype involving chromosomes 5, 7 and 17 after 15 years of hydroxyurea treatment. He responded poorly to induction chemotherapy with cytarabine/idarubicin followed by high dose cytarabine and succumbed to neutropenic sepsis. Multiple systematic reviews, observational studies and clinical trials were conducted to identify the toxicity profile of hydroxurea. Only six cases of leukemia/myelodysplastic syndrome were identified in patients with sickle cell anemia treated with hydroxyurea. Subsequently, it was concluded that hydroxyurea is not leukemogenic. However, it was noted that most of the published studies had only up to 9 years of follow-up. Our patient was started on hydroxyurea in 1990, before the widespread use of the drug and took hydroxyurea for 15 years. His presentation may reflect an outcome otherwise not yet observed because of the short follow-up of prior studies. We believe that the leukemogenic risk of hydroxyurea should be discussed with the patients and their families. Studies evaluating the adverse effects of hydroxyurea should have longer follow-up before definitive conclusions are drawn.

  20. Lactobacillus in Preventing Infection in Patients Undergoing a Donor Stem Cell Transplant for Hematologic Cancer or Myelodysplastic Syndrome

    Science.gov (United States)

    2017-02-02

    Breast Cancer; Chronic Myeloproliferative Disorders; Leukemia; Lymphoma; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasms; Neuroblastoma; Ovarian Cancer; Testicular Germ Cell Tumor

  1. Allogeneic stem cell transplantation for patients with acute myeloid leukemia or myelodysplastic syndrome who have chromosome 5 and/or 7 abnormalities.

    NARCIS (Netherlands)

    Straaten, H.M. van der; Biezen, A. van; Brand, R.; Schattenberg, A.V.M.B.; Egeler, R.M.; Barge, R.M.; Cornelissen, J.J.L.M.; Schouten, H.C.; Ossenkoppele, G.J.; Verdonck, L.F.

    2005-01-01

    BACKGROUND AND OBJECTIVES: Chromosome 5 and/or 7 abnormalities are cytogenetic findings indicative of a poor prognosis in patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). The only potential cure for such patients is allogeneic stem cell transplantation (SCT). As data on

  2. Clinical effect of increasing doses of lenalidomide in high-risk myelodysplastic syndrome and acute myeloid leukemia with chromosome 5 abnormalities

    DEFF Research Database (Denmark)

    Möllgård, Lars; Saft, Leonie; Treppendahl, Marianne Bach

    2011-01-01

    Background Patients with chromosome 5 abnormalities and high-risk myelodysplastic syndromes or acute myeloid leukemia have a poor outcome. We hypothesized that increasing doses of lenalidomide may benefit this group of patients by inhibiting the tumor clone, as assessed by fluorescence in situ hy...

  3. Clinical effect of increasing doses of lenalidomide in high-risk myelodysplastic syndrome and acute myeloid leukemia with chromosome 5 abnormalities

    DEFF Research Database (Denmark)

    Möllgård, Lars; Saft, Leonie; Treppendahl, Marianne Bach;

    2011-01-01

    Patients with chromosome 5 abnormalities and high-risk myelodysplastic syndromes or acute myeloid leukemia have a poor outcome. We hypothesized that increasing doses of lenalidomide may benefit this group of patients by inhibiting the tumor clone, as assessed by fluorescence in situ hybridization...

  4. Outcome and medical costs of patients with invasive aspergillosis and acute myelogenous leukemia-myelodysplastic syndrome treated with intensive chemotherapy: An observational study

    OpenAIRE

    Slobbe, Lennert; Polinder, Suzanne; Doorduijn, Jeanette; Lugtenburg, Pieternella; Barzouhi, Abdelilah; Steyerberg, Ewout; Rijnders, Bart

    2008-01-01

    textabstractBackground. Invasive aspergillosis (IA) is a leading cause of mortality in patients with acute leukemia. Management of IA is expensive, which makes prevention desirable. Because hospital resources are limited, prevention costs have to be compared with treatment costs and outcome. Methods. In 269 patients treated for acute myelogenous leukemia-myelodysplastic syndrome (AML-MDS) during 2002-2007, evidence of IA was collected using high-resolution computed tomography and galactomanna...

  5. Suppression of the DNA damage response in acute myeloid leukemia versus myelodysplastic syndrome.

    Science.gov (United States)

    Boehrer, S; Adès, L; Tajeddine, N; Hofmann, W K; Kriener, S; Bug, G; Ottmann, O G; Ruthardt, M; Galluzzi, L; Fouassier, C; Tailler, M; Olaussen, K A; Gardin, C; Eclache, V; de Botton, S; Thepot, S; Fenaux, P; Kroemer, G

    2009-06-04

    The molecular mechanisms responsible for the evolution from the preleukemic entities of low-risk myelodysplastic syndrome (MDS) to the less favorable forms of high-risk MDS, as well as those enabling transformation to acute myeloid leukemia (AML), are still incompletely understood. Abundant evidence from solid tumors demonstrates that preneoplastic lesions activate signaling pathways of a DNA damage response (DDR), which functions as an 'anticancer barrier' hindering tumorigenesis. Testing the hypothesis that subgroups of MDS and AML differ with respect to DDR, we first assessed markers of DDR (phosphorylation of ATM, Chk-1, Chk-2 and H2AX) in cell lines representing different entities of MDS (P39, MOLM-13) and AML (MV4-11, KG-1) before and after gamma-irradiation. Although gamma-irradiation induced apoptosis and G(2)/M arrest and a concomitant increase in the phosphorylation of ATM, Chk-1 and H2AX in MDS-derived cell lines, this radiation response was attenuated in the AML-derived cell lines. It is noteworthy that KG-1, but not P39 cells exhibit signs of an endogenous activation of the DDR. Similarly, we found that the frequency of P-ATM(+) cells detectable in bone marrow (BM) biopsies increased in samples from patients with AML as compared with high-risk MDS samples and significantly correlated with the percentage of BM blasts. In contrast, the frequency of gamma-H2AX(+) cells was heterogeneous in all subgroups of AML and MDS. Whereas intermediate-1 MDS samples contained as little P-Chk-1 and P-Chk-2 as healthy controls, staining for both checkpoint kinases increased in intermediate-2 and high-risk MDS, yet declined to near-to-background levels in AML samples. Thus the activation of Chk-1 and Chk-2 behaves in accord with the paradigm established for solid tumors, whereas ATM is activated during and beyond transformation. In conclusion, we demonstrate the heterogeneity of the DDR response in MDS and AML and provide evidence for its selective suppression in AML

  6. Recurrent DNMT3A R882 mutations in Chinese patients with acute myeloid leukemia and myelodysplastic syndrome.

    Directory of Open Access Journals (Sweden)

    Jiang Lin

    Full Text Available Somatic mutations of DNMT3A gene have recently been reported in acute myeloid leukemia (AML and myelodysplastic syndrome (MDS. We examined the entire coding sequences of DNMT3A gene by high-resolution melting analysis and sequencing in Chinese patients with myeloid malignancies. R882 mutations were found in 12/182 AML and in 4/51 MDS, but not in either 79 chronic myeloid leukemia (CML, or 57 myeloproliferative neoplasms (MPNs, or 4 chronic monomyelocytic leukemia. No other DNMT3A mutations were detected in all patients. R882 mutations were associated with old age and more frequently present in monoblastic leukemia (M4 and M5, 7/52 compared to other subtypes (5/130. Furthermore, 14/16 (86.6% R882 mutations were observed in patients with normal karyotypes. The overall survival of mutated MDS patients was shorter than those without mutation (median 9 and 25 months, respectively. We conclude that DNMT3A R882 mutations are recurrent molecular aberrations in AML and MDS, and may be an adverse prognostic event in MDS.

  7. Gingival enlargement in myelodysplastic syndrome

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    Navia George

    2015-01-01

    Full Text Available The myelodysplastic syndrome (MDS is characterized by peripheral blood cytopenias and increased risk of transformation to acute myeloid leukemia. This syndrome affects blood cell production and behavior. MDS is difficult to diagnose because of the absence of symptoms in the early stage of the disease. Often it is accidentally discovered during a routine physical exam/blood test. Till date, only a few cases of gingival enlargement associated with MDS are reported in the literature. Here is a remarkable case of gingival enlargement heralding the presence of MDS.

  8. High-Dose Busulfan and High-Dose Cyclophosphamide Followed By Donor Bone Marrow Transplant in Treating Patients With Leukemia, Myelodysplastic Syndrome, Multiple Myeloma, or Recurrent Hodgkin or Non-Hodgkin Lymphoma

    Science.gov (United States)

    2010-08-05

    Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With T(15;17)(q22;q12); Adult Acute Myeloid Leukemia With T(16;16)(p13;q22); Adult Acute Myeloid Leukemia With T(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Acute Promyelocytic Leukemia (M3); Adult Erythroleukemia (M6a); Adult Nasal Type Extranodal NK/T-cell Lymphoma; Adult Pure Erythroid Leukemia (M6b); Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Burkitt Lymphoma; Childhood Acute Erythroleukemia (M6); Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Acute Megakaryocytic Leukemia (M7); Childhood Acute Monoblastic Leukemia (M5a); Childhood Acute Monocytic Leukemia (M5b); Childhood Acute Myeloblastic Leukemia With Maturation (M2); Childhood Acute Myeloblastic Leukemia Without Maturation (M1); Childhood Acute Myeloid Leukemia in Remission; Childhood Acute Myelomonocytic Leukemia (M4); Childhood Acute Promyelocytic Leukemia (M3); Childhood Chronic Myelogenous Leukemia; Childhood Myelodysplastic Syndromes; Chronic Phase Chronic Myelogenous Leukemia; Cutaneous B-cell Non-Hodgkin Lymphoma; De Novo Myelodysplastic Syndromes; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Peripheral T-Cell Lymphoma; Post-transplant Lymphoproliferative Disorder; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent

  9. Allogeneic hematopoietic cell transplantation for fanconi anemia in patients with pretransplantation cytogenetic abnormalities, myelodysplastic syndrome, or acute leukemia.

    Science.gov (United States)

    Ayas, Mouhab; Saber, Wael; Davies, Stella M; Harris, Richard E; Hale, Gregory A; Socie, Gerard; LeRademacher, Jennifer; Thakar, Monica; Deeg, H Joachim J; Al-Seraihy, Amal; Battiwalla, Minoo; Camitta, Bruce M; Olsson, Richard; Bajwa, Rajinder S; Bonfim, Carmem M; Pasquini, Ricardo; Macmillan, Margaret L; George, Biju; Copelan, Edward A; Wirk, Baldeep; Al Jefri, Abdullah; Fasth, Anders L; Guinan, Eva C; Horn, Biljana N; Lewis, Victor A; Slavin, Shimon; Stepensky, Polina; Bierings, Marc; Gale, Robert Peter

    2013-05-01

    Allogeneic hematopoietic cell transplantation (HCT) can cure bone marrow failure in patients with Fanconi anemia (FA). Data on outcomes in patients with pretransplantation cytogenetic abnormalities, myelodysplastic syndrome (MDS), or acute leukemia have not been separately analyzed. We analyzed data on 113 patients with FA with cytogenetic abnormalities (n = 54), MDS (n = 45), or acute leukemia (n = 14) who were reported to the Center for International Blood and Marrow Transplant Research from 1985 to 2007. Neutrophil recovery occurred in 78% and 85% of patients at days 28 and 100, respectively. Day 100 cumulative incidences of acute graft-versus-host disease grades B to D and C to D were 26% (95% CI, 19% to 35%) and 12% (95% CI, 7% to 19%), respectively. Survival probabilities at 1, 3, and 5 years were 64% (95% CI, 55% to 73%), 58% (95% CI, 48% to 67%), and 55% (95% CI, 45% to 64%), respectively. In univariate analysis, younger age was associated with superior 5-year survival (≤ v > 14 years: 69% [95% CI, 57% to 80%] v 39% [95% CI, 26% to 53%], respectively; P = .001). In transplantations from HLA-matched related donors (n = 82), younger patients (≤ v > 14 years: 78% [95% CI, 64% to 90%] v 34% [95% CI, 20% to 50%], respectively; P < .001) and patients with cytogenetic abnormalities only versus MDS/acute leukemia (67% [95% CI, 52% to 81%] v 43% [95% CI, 27% to 59%], respectively; P = .03) had superior 5-year survival. Our analysis indicates that long-term survival for patients with FA with cytogenetic abnormalities, MDS, or acute leukemia is achievable. Younger patients and recipients of HLA-matched related donor transplantations who have cytogenetic abnormalities only have the best survival.

  10. Immunophenotypic, cytogenetic, and mutational characterization of cell lines derived from myelodysplastic syndrome patients after progression to acute myeloid leukemia.

    Science.gov (United States)

    Palau, Anna; Mallo, Mar; Palomo, Laura; Rodríguez-Hernández, Ines; Diesch, Jeannine; Campos, Diana; Granada, Isabel; Juncà, Jordi; Drexler, Hans G; Solé, Francesc; Buschbeck, Marcus

    2017-03-01

    Leukemia cell lines have been widely used in the hematology field to unravel mechanistic insights and to test new therapeutic strategies. Myelodysplastic syndromes (MDS) comprise a heterogeneous group of diseases that are characterized by ineffective hematopoiesis and frequent progress to acute myeloid leukemia (AML). A few cell lines have been established from MDS patients after progression to AML but their characterization is incomplete. Here we provide a detailed description of the immunophenotypic profile of the MDS-derived cell lines SKK-1, SKM-1, F-36P; and MOLM-13. Specifically, we analyzed a comprehensive panel of markers that are currently applied in the diagnostic routine for myeloid disorders. To provide high-resolution genetic data comprising copy number alterations and losses of heterozygosity we performed whole genome single nucleotide polymorphism-based arrays and included the cell line OHN-GM that harbors the frequent chromosome arm 5q deletion. Furthermore, we assessed the mutational status of 83 disease-relevant genes. Our results provide a resource to the MDS and AML field that allows researchers to choose the best-matching cell line for their functional studies. © 2016 Wiley Periodicals, Inc.

  11. Acute leukemia / myelodysplastic syndrome as a sequelae of carcinoma breast: A report of five cases from north India

    Directory of Open Access Journals (Sweden)

    Bhatia Prateek

    2009-04-01

    Full Text Available A second malignant neoplasm has been found to be more frequent than might be expected from the general population rates. Therapy-related myelodysplastic syndrome and acute leukemia are dreaded long-term complications of five cases of hematological malignancies following treatment for successful breast cancer therapy (therapeutic drugs or radiotherapy. We encountered carcinoma from north India over a 7-year period from 1999 to 2005. The patients presented 2-5 years after treatment of breast carcinoma. Three patients underwent surgery and received chemoradiotherapy. One patient received chemotherapy after surgery. One patient underwent only surgery and after 3 years presented with acute myeloid leukemia and bone marrow metastasis of carcinoma of the breast. At the time of presentation, all the patients had either bicytopenia or pancytopenia. A close follow-up with complete blood cell counts of the patients who previously had carcinoma of the breast is suggested for early detection of hematological abnormalities. However, the poor prognosis, limited financial resources and poor health insurance coverage results in few patients and their family members opting for treatment.

  12. Therapy-related acute myeloid leukemia and myelodysplastic syndrome: a clinical and morphologic study of 65 cases

    Energy Technology Data Exchange (ETDEWEB)

    Michels, S.D.; McKenna, R.W.; Arthur, D.C.; Brunning, R.D.

    1985-06-01

    This study consists of 65 patients (pts) who developed a myelodysplastic syndrome (MDS) (39 pts) or acute myeloid leukemia (AML) (26 pts) following chemotherapy and/or radiotherapy; the interval from the onset of therapy to bone marrow abnormality ranged from 11 to 192 months (median, 58). Thirty-three patients had been previously treated for lymphoproliferative diseases, 29 for carcinoma, and three for a nonneoplastic disorder. Approximately 30% of the cases presenting in the MDS phase evolved to AML in one to 12 months (median, 3.5). The AML in 49% of the cases was not readily classified according to French-American-British (FAB) criteria; the primary difficulty in classification related to the involvement of multiple cell lines. Among the cases that could be classified, all FAB types were represented except for M1; M2 was the most frequent type. Clonal chromosome abnormalities were found in marrow specimens from 22 of 24 (92%) patients studied with G banding; 11 had abnormalities of chromosomes 5 and/or 7. The median survival for all patients was four months with no significant difference between those treated and not treated with antileukemic therapy. The median survival was three months for the patients presenting with AML, six months for the patients with AML following an MDS, and four months for the patients with an MDS that did not evolve to AML. The findings in the present study suggest that there are three stages of therapy-related panmyelosis: (1) pancytopenia with associated myelodysplastic changes, (2) a frank MDS, and (3) overt AML. Many patients will present in the stage of overt AML that differs from de novo AML primarily by the high incidence of trilineage involvement, difficulty in classification, frequent cytogenetic abnormalities, and poor response to antileukemic therapy.

  13. Myelodysplastic Syndrome with Myelofibrosis Transformed to a Precursor B-Cell Acute Lymphoblastic Leukemia: A Case Report with Review of the Literature

    Directory of Open Access Journals (Sweden)

    Ayed A. Algarni

    2012-01-01

    Full Text Available Myelodysplastic syndromes (MDS comprise a group of heterogeneous clonal hematopoietic cell disorders characterized by cytopenias, bone marrow hypercellularity, and increased risk of transformation to acute leukemias. MDS usually transformed to acute myeloid leukemia, and transformation to acute lymphoblastic leukemia (ALL is rare. Herein, we report a unique patient who presented with MDS with myelofibrosis. Two months after the initial diagnosis, she progressed to a precursor B-cell acute lymphoblastic leukemia. She was treated with induction therapy followed by allogenic stem cell transplantation. She was alive and doing well upon last followup. We have also reviewed the literature and discussed the clinicopathologic features of 36 MDS patients who progressed to ALL reported in the literature.

  14. Acute myeloid leukemia after myelodysplastic syndrome and failure of therapy with hypomethylating agents: an emerging entity with a poor prognosis.

    Science.gov (United States)

    Jabbour, Elias; Ghanem, Hady; Huang, Xuelin; Ravandi, Farhad; Garcia-Manero, Guillermo; O'Brien, Susan; Faderl, Stephan; Pierce, Sherry; Choi, Sangbum; Verstovsek, Srdan; Brandt, Mark; Cortes, Jorge; Kantarjian, Hagop

    2014-04-01

    We assessed the outcomes of 63 patients with acute myeloid leukemia (AML) arising from myelodysplastic syndrome (MDS) after hypomethylating agent failure. Their median age was 63 years. All 63 patients had received ≥ 1 salvage regimens for AML, and 35 patients (55%) had received ≥ 2. Of the 31 patients (49%) who had received high-dose cytarabine (HDAC) at first relapse, 2 (6%) achieved complete remission (CR) and 4 (13%) CR with incomplete platelet recovery (overall response rate, 19%). Of the 32 patients (51%) who had received other treatments, including investigational agents, 4 (12%) achieved CR and 4 (12%) CR with incomplete platelet recovery (overall response rate, 24%). The median response duration was 20 weeks. With a median follow-up of 42 months from the AML diagnosis, the median survival (21 weeks) was similar between the 2 groups. The 1- and 2-year survival rate was 19% and 8%, respectively. Multivariate analysis identified low albumin, HDAC treatment, and platelet count 65 years as independent adverse factors for survival. Thus, the outcome of AML evolving from MDS after hypomethylating agent failure is poor and not improved with HDAC. Novel therapies directed toward this emerging entity are urgently needed.

  15. Assessment of Drug Sensitivity in Hematopoietic Stem and Progenitor Cells From Acute Myelogenous Leukemia and Myelodysplastic Syndrome Ex Vivo.

    Science.gov (United States)

    Knorr, Katherine L B; Finn, Laura E; Smith, B Douglas; Hess, Allan D; Foran, James M; Karp, Judith E; Kaufmann, Scott H

    2016-11-07

    : Current understanding suggests that malignant stem and progenitor cells must be reduced or eliminated for prolonged remissions in myeloid neoplasms such as acute myelogenous leukemia (AML) or myelodysplastic syndrome (MDS). Multicolor flow cytometry has been widely used to distinguish stem and myeloid progenitor cells from other populations in normal and malignant bone marrow. In this study, we present a method for assessing drug sensitivity in MDS and AML patient hematopoietic stem and myeloid progenitor cell populations ex vivo using the investigational Nedd8-activating enzyme inhibitor MLN4924 and standard-of-care agent cytarabine as examples. Utilizing a multicolor flow cytometry antibody panel for identification of hematopoietic stem cells, multipotent progenitors, common myeloid progenitors, granulocyte-monocyte progenitors, and megakaryocyte-erythroid progenitors present in mononuclear cell fractions isolated from bone marrow aspirates, we compare stem and progenitor cell counts after treatment for 24 hours with drug versus diluent. We demonstrate that MLN4924 exerts a cytotoxic effect on MDS and AML stem and progenitor cell populations, whereas cytarabine has more limited effects. Further application of this method for evaluating drug effects on these populations ex vivo and in vivo may inform rational design and selection of therapies in the clinical setting.

  16. A phase I/II trial of Erlotinib in higher risk myelodysplastic syndromes and acute myeloid leukemia after azacitidine failure.

    Science.gov (United States)

    Thepot, Sylvain; Boehrer, Simone; Seegers, Valérie; Prebet, Thomas; Beyne-Rauzy, Odile; Wattel, Eric; Delaunay, Jacques; Raffoux, Emmanuel; Hunault, Mathilde; Jourdan, Eric; Chermat, Fatiha; Sebert, Marie; Kroemer, Guido; Fenaux, Pierre; Adès, Lionel

    2014-12-01

    Survival after azacitidine (AZA) failure in higher-risk myelodysplastic syndromes (MDS) is poor and new treatment options are needed. Erlotinib, an oral inhibitor of the epidermal-growth-factor-receptor (EGFR), has shown in preclinical models some efficacy in higher risk MDS and acute myeloid leukemia (AML). In this phase I/II trial, 30 patients received 100mg/day (n=5) or 150mg/day (n=25) of Erlotinib orally after primary or secondary resistance to AZA treatment. Eighteen MDS and 12 AML patients were treated. This outpatient treatment was well tolerated with limited grade III-IV extra hematological toxicities (skin (n=1), and diarrhea (n=3). Response was observed in 6 patients (20%) including 1 complete remission (CR), 1 marrow CR and 4 hematological improvement (2 erythroid and 2 on platelets). Median duration of response was 5 months. Erlotinib appears to induce a significant number of responses in higher risk MDS/AML having failed AZA treatment. Given the good safety profile of Erlotinib, its combination with other drugs could be tested in the future in MDS and AML.

  17. The role of p53 in myelodysplastic syndromes and acute myeloid leukemia: molecular aspects and clinical implications.

    Science.gov (United States)

    Zhang, Ling; McGraw, Kathy L; Sallman, David A; List, Alan F

    2017-08-01

    TP53 gene mutations occurring in patients with myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) are associated with high-risk karyotypes including 17p abnormalities, monosomal and complex cytogenetics. TP53 mutations in these disorders portend rapid disease progression and resistance to conventional therapeutics. Notably, the size of the TP53 mutant clone as measured by mutation allele burden is directly linked to overall survival (OS) confirming the importance of p53 as a negative prognostic variable. In nucleolar stress-induced ribosomopathies, such as del(5q) MDS, disassociation of MDM2 and p53 results in p53 accumulation in erythroid precursors manifested as erythroid hypoplasia. P53 antagonism by lenalidomide or other therapeutics such as antisense oligonucleotides, repopulates erythroid precursors and enhances effective erythropoiesis. These findings demonstrate that p53 is an intriguing therapeutic target that is currently under investigation in MDS and AML. This study reviews molecular advances in understanding the role of p53 in MDS and AML, and explores potential therapeutic strategies in this era of personalized medicine.

  18. Immune Mechanisms in Myelodysplastic Syndrome

    Directory of Open Access Journals (Sweden)

    Andreas Glenthøj

    2016-06-01

    Full Text Available Myelodysplastic syndrome (MDS is a spectrum of diseases, characterized by debilitating cytopenias and a propensity of developing acute myeloid leukemia. Comprehensive sequencing efforts have revealed a range of mutations characteristic, but not specific, of MDS. Epidemiologically, autoimmune diseases are common in patients with MDS, fueling hypotheses of common etiological mechanisms. Both innate and adaptive immune pathways are overly active in the hematopoietic niche of MDS. Although supportive care, growth factors, and hypomethylating agents are the mainstay of MDS treatment, some patients—especially younger low-risk patients with HLA-DR15 tissue type—demonstrate impressive response rates after immunosuppressive therapy. This is in contrast to higher-risk MDS patients, where several immune activating treatments, such as immune checkpoint inhibitors, are in the pipeline. Thus, the dual role of immune mechanisms in MDS is challenging, and rigorous translational studies are needed to establish the value of immune manipulation as a treatment of MDS.

  19. Role of minimal residual disease and chimerism after reduced-intensity and myeloablative allo-transplantation in acute myeloid leukemia and high-risk myelodysplastic syndrome.

    Science.gov (United States)

    Bernal, Teresa; Diez-Campelo, María; Godoy, Vicky; Rojas, Silvia; Colado, Enrique; Alcoceba, Miguel; González, Marcos; Vidriales, Belén; Sánchez-Guijo, Fermín M; López-Corral, Lucía; Luño, Elisa; del Cañizo, Consuelo

    2014-05-01

    We evaluated the impact of detection of minimal residual disease by flow cytometry (FCMRD) and CD3 chimerism in relapse in a cohort of 87 patients with acute myeloid leukemia or myelodysplastic syndrome undergoing stem cell transplantation. Patients with a positive FCMRD at day +100 after transplantation showed higher relapse rates and worse overall survival. In multivariate analysis, a positive FCMRD after transplantation was a significant predictor of relapse. Mixed chimerism showed a trend to statistical signification. We conclude that FCMRD at day 100 after SCT is the best predictor of relapse after SCT in patients with aggressive myeloid malignancies.

  20. Parameters detected by geriatric and quality of life assessment in 195 older patients with myelodysplastic syndromes and acute myeloid leukemia are highly predictive for outcome

    Science.gov (United States)

    Deschler, Barbara; Ihorst, Gabriele; Platzbecker, Uwe; Germing, Ulrich; März, Eva; de Figuerido, Marcelo; Fritzsche, Kurt; Haas, Peter; Salih, Helmut R.; Giagounidis, Aristoteles; Selleslag, Dominik; Labar, Boris; de Witte, Theo; Wijermans, Pierre; Lübbert, Michael

    2013-01-01

    Myelodysplastic syndromes and acute myeloid leukemia exemplify the complexity of treatment allocation in older patients as options range from best supportive care, non-intensive treatment (e.g. hypomethylating agents) to intensive chemotherapy/hematopoietic cell transplantation. Novel metrics for non-disease variables are urgently needed to help define the best treatment for each older patient. We investigated the feasibility and prognostic value of geriatric/quality of life assessments aside from established disease-specific variables in 195 patients aged 60 years or over with myelodysplastic syndromes/acute myeloid leukemia. These patients were grouped according to treatment intensity and assessed. Assessment consisted of eight instruments evaluating activities of daily living, depression, mental functioning, mobility, comorbidities, Karnofsky Index and quality of life. Patients with a median age of 71 years (range 60-87 years) with myelodysplastic syndromes (n=63) or acute myeloid leukemia (n=132) were treated either with best supportive care (n=47), hypomethylating agents (n=73) or intensive chemotherapy/hematopoietic cell transplantation (n=75). After selection of variables, pathological activities of daily living and quality of life/fatigue remained highly predictive for overall survival in the entire patient group beyond disease-related risk factors adverse cytogenetics and blast count of 20% or over. In 107 patients treated non-intensively activities of daily living of less than 100 (hazard ratio, HR 2.94), Karnofsky Index below 80 (HR 2.34) and quality of life/’fatigue’ of 50 or over (HR 1.77) were significant prognosticators. Summation of adverse features revealed a high risk of death (HR 9.36). In-depth evaluation of older patients prior to individual treatment allocation is feasible and provides additional information to standard assessment. Patients aged 60 years or over with newly diagnosed myelodysplastic syndromes/acute myeloid leukemia and

  1. Abnormal dicentric chromosome with co-amplification of sequences from chromosomes 11 and 19: a novel rearrangement in a patient with myelodysplastic syndrome transforming to acute myeloid leukemia.

    Science.gov (United States)

    Smith, A; Heaps, L S; Sharma, P; Jarvis, A; Forsyth, C

    2001-10-01

    A 66-year-old man with a myelodysplastic syndrome transforming to acute myeloid leukemia showed a complex abnormal karyotype on bone marrow aspirate. An unbalanced dicentric translocation with a very long der(11) long arm-dic(11;19)(q25;p13.4)-was present. Fluorescence in situ hybridization studies utilised paints for chromosomes 11 and 19 as well as the locus specific probe MLL, localised to 11q23. The abnormal chromosome 11q contained 6 copies of intact MLL and 6 copies of chromosome 19 (unidentified) sequences. To our knowledge, gene co-amplification of chromosomes 11 and 19 sequences has not been reported before.

  2. An exploratory phase 2 study of investigational Aurora A kinase inhibitor alisertib (MLN8237 in acute myelogenous leukemia and myelodysplastic syndromes

    Directory of Open Access Journals (Sweden)

    Stuart L. Goldberg

    2014-01-01

    Full Text Available Alisertib (MLN8237 is an investigational, oral, selective, Aurora A kinase (AAK inhibitor. In this phase 2 trial, 57 patients with acute myeloid leukemia (AML or high-grade myelodysplastic syndrome received alisertib 50 mg BID for 7 days in 21-day cycles. Responses in 6/35 AML patients (17% response rate with an additional 49% stable disease, 34% transfusion independence included 1 complete response lasting >1 year. No responses were observed in MDS patients. Adverse events >30% included diarrhea, fatigue, nausea, febrile neutropenia, and stomatitis. Results suggest modest activity in AML, supporting further research to better understand how AAK inhibition may induce leukemic cell senescence.

  3. Prognostic Limitations of Donor T Cell Chimerism after Myeloablative Allogeneic Stem Cell Transplantation for Acute Myeloid Leukemia and Myelodysplastic Syndromes.

    Science.gov (United States)

    Wong, Eric; Mason, Kate; Collins, Jenny; Hockridge, Barbara; Boyd, Janis; Gorelik, Alexandra; Szer, Jeffrey; Ritchie, David S

    2017-02-06

    Donor T cell chimerism is associated with relapse outcomes after allogeneic stem cell transplantation (alloSCT) for acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). However, measures of statistical association do not adequately assess the performance of a prognostic biomarker, which is best characterized by its sensitivity and specificity for the chosen outcome. We analyzed donor T cell chimerism results at day 100 (D100chim) after myeloablative alloSCT for AML or MDS in 103 patients and determined its sensitivity and specificity for relapse-free survival at 6 months (RFS6) and 12 months (RFS12) post-alloSCT. The area under the receiver operating characteristic curve for RFS6 was .68, demonstrating only modest utility as a predictive biomarker, although this was greater than RFS12 at .62. Using a D100chim threshold of 65%, the specificity for RFS6 was 96.6%; however, sensitivity was poor at 26.7%. This equated to a negative predictive value of 88.5% and positive predictive value of 57.1%. Changing the threshold for D100chim to 75% or 85% modestly improved the sensitivity of D100chim for RFS6; however, this was at the expense of specificity. D100chim is specific but lacks sensitivity as a prognostic biomarker of early RFS after myeloablative alloSCT for AML or MDS. Caution is required when using D100chim to guide treatment decisions including immunologic manipulation, which may expose patients to unwarranted graft-versus-host disease.

  4. Hematopoietic stem cell transplantation in children and young adults with secondary myelodysplastic syndrome and acute myelogenous leukemia after aplastic anemia.

    Science.gov (United States)

    Yoshimi, Ayami; Strahm, Brigitte; Baumann, Irith; Furlan, Ingrid; Schwarz, Stephan; Teigler-Schlegel, Andrea; Walther, Joachim-Ulrich; Schlegelberger, Brigitte; Göhring, Gudrun; Nöllke, Peter; Führer, Monika; Niemeyer, Charlotte M

    2014-03-01

    Secondary myelodysplastic syndrome and acute myelogenous leukemia (sMDS/sAML) are the most serious secondary events occurring after immunosuppressive therapy in patients with aplastic anemia. Here we evaluate the outcome of hematopoietic stem cell transplantation (HSCT) in 17 children and young adults with sMDS/sAML after childhood aplastic anemia. The median interval between the diagnosis of aplastic anemia and the development of sMDS/sAML was 2.9 years (range, 1.2 to 13.0 years). At a median age of 13.1 years (range, 4.4 to 26.7 years), patients underwent HSCT with bone marrow (n = 6) or peripheral blood stem cell (n = 11) grafts from HLA-matched sibling donors (n = 2), mismatched family donors (n = 2), or unrelated donors (n = 13). Monosomy 7 was detected in 13 patients. The preparative regimen consisted of busulfan, cyclophosphamide, and melphalan in 11 patients and other agents in 6 patients. All patients achieved neutrophil engraftment. The cumulative incidence of grade II-IV acute graft-versus-host disease (GVHD) was 47%, and that of chronic GVHD was 70%. Relapse occurred in 1 patient. The major cause of death was transplant-related complication (n = 9). Overall survival and event-free survival at 5 years after HSCT were both 41%. In summary, this study indicates that HSCT is a curative therapy for some patients with sMDS/sAML after aplastic anemia. Future efforts should focus on reducing transplantation-related mortality.

  5. Subsequent primary malignancies and acute myelogenous leukemia transformation among myelodysplastic syndrome patients treated with or without lenalidomide.

    Science.gov (United States)

    Rollison, Dana E; Shain, Kenneth H; Lee, Ji-Hyun; Hampras, Shalaka S; Fulp, William; Fisher, Kate; Al Ali, Najla H; Padron, Eric; Lancet, Jeffrey; Xu, Qiang; Olesnyckyj, Martha; Kenvin, Laurie; Knight, Robert; Dalton, William; List, Alan; Komrokji, Rami S

    2016-07-01

    The few studies that have examined rates of acute myeloid leukemia (AML) transformation in lenalidomide-treated myelodysplastic syndrome (MDS) patients have been limited to deletion 5q MDS. The association between lenalidomide and subsequent primary malignancies (SPMs) in MDS patients has not been evaluated previously. We conducted a retrospective cohort study to evaluate the risk of both SPM and AML in association with lenalidomide. A cohort of MDS patients (n = 1248) treated between 2004 and 2012 at Moffitt Cancer Center were identified, and incident cases of SPM and AML transformation were ascertained. Using a nested case-control design, MDS controls were 1:1 matched to SPM (n = 41) and AML (n = 150) cases, on age and date of MDS diagnosis, gender, follow-up time, IPSS, and del (5q). Associations between lenalidomide and (1) SPM incidence and (2) AML transformation were estimated with hazards ratios (HR) and 95% confidence intervals (CIs) in the cohort and odds ratios (OR) in the case-control analysis. SPM incidence did not differ significantly between cohort MDS patients treated with (0.7 per 100 person-years) or without lenalidomide (1.4 per 100 person-years) (HR = 1.04, 95% CI = 0.40-2.74), whereas a significantly reduced SPM risk was observed in the case-control sample (OR = 0.03, 95% CI = Lenalidomide was not associated with AML transformation in the cohort analysis (HR = 0.75, 95% CI = 0.44-1.27) or in the case-control analyses (OR = 1.16, 95% CI = 0.52-2.56), after adjustment for potential confounders. Lenalidomide was not associated with increased risk of SPM or AML transformation in a large cohort of MDS patients mostly including nondeletion 5q MDS.

  6. Obesity over the life course and risk of acute myeloid leukemia and myelodysplastic syndromes.

    Science.gov (United States)

    Poynter, Jenny N; Richardson, Michaela; Blair, Cindy K; Roesler, Michelle A; Hirsch, Betsy A; Nguyen, Phuong; Cioc, Adina; Warlick, Erica; Cerhan, James R; Ross, Julie A

    2016-02-01

    Overweight and obesity are known risk factors for a number of cancers, with recent evidence suggesting that risk of hematologic cancer is also increased in obese individuals. We evaluated associations between body mass index (BMI) at differing time points during the life course in population-based case control studies of acute myeloid leukemia (AML) and myelodysplatic syndromes (MDS). Cases were identified by the Minnesota Cancer Surveillance System. Controls were identified through the Minnesota State driver's license/identification card list. BMI was calculated using self-reported height and weight at ages 18, 35, and 50 years and two years prior to interview, and categorized as normal (18.5-25 kg/m(2)), overweight (25-29.9 kg/m(2)), obese class I (30-34.9 kg/m(2)), and obese class II/III (35+ kg/m(2)). All analyses were stratified by sex. Unconditional logistic regression was used to calculate odds ratios and 95% confidence intervals. We included 420 AML cases, 265 MDS cases and 1388 controls. Obesity two years prior to diagnosis was associated with AML in both males and females (OR=2.22, 95% CI 1.28, 3.85 and OR=1.85, 95% CI 1.08, 3.15 for BMI≥35 vs. BMI 18.5-24.9, respectively). In contrast, associations between obesity and MDS were observed only in females. Weight change in adulthood was not consistently associated with either outcome. Our results extend the emerging literature suggesting that obesity is a risk factor for hematologic malignancy and provide evidence that that the association remains regardless of timing of obesity. Obesity in adulthood is a modifiable risk factor for both MDS and AML. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. The quality and quantity of leukemia-derived dendritic cells from patients with acute myeloid leukemia and myelodysplastic syndrome are a predictive factor for the lytic potential of dendritic cells-primed leukemia-specific T cells.

    Science.gov (United States)

    Grabrucker, Christine; Liepert, Anja; Dreyig, Julia; Kremser, Andreas; Kroell, Tanja; Freudenreich, Markus; Schmid, Christoph; Schweiger, Cornelia; Tischer, Johanna; Kolb, Hans-Jochen; Schmetzer, Helga

    2010-06-01

    Adoptive immunotherapy is an important therapy option to reduce relapse rates after stem-cell transplantation in patients suffering from acute myeloid leukemia and myelodysplastic syndromes. Myeloid leukemic cells can regularly be induced to differentiate into leukemia-derived dendritic cells (DC(leu)), regaining the stimulatory capacity of professional dendritic cells (DCs) while presenting the known/unknown leukemic antigen repertoire. So far, induced antileukemic T-cell responses are variable or even mediate opposite effects. To further elicit DC/DC(leu)-induced T-cell-response patterns, we generated DC from 17 Acute myeloid leukemia (AML) and 2 myelodysplastic syndrome cases and carried out flowcytometry and (functional) nonradioactive fluorolysis assays before/after mixed lymphocyte cultures of matched (allogeneic) donor T cells (n=6), T cells prepared at relapse after stem-cell transplantation (n=4) or (autologous) patients' T cells (n=7) with blast containing mononuclear cells ("MNC") or DC(leu) ("DC"). Compared with "MNC", "DC" were better mediators of antileukemic-activity, although not in every case effective. We could define DC subtypes and cut-off proportions of DC subtypes/qualities (mature DC/DC(leu)) after "DC" priming, which were predictive for an antileukemic activity of primed T cells and the clinical course of the disease after immunotherapy (allogeneic stem-cell transplantation/donor lymphocytes infusion/therapy). In summary, our data show that the composition and quality of DC after a mixed lymphocyte culture-priming phase is predictive for a successful ex vivo antileukemic response, especially with respect to proportions of mature and leukemia-derived DC. These data contribute not only to predict DC-mediated functions or the clinical course of the diseases but also to develop and refine DC-vaccination strategies that may pave the way to develop and modify adoptive immunotherapy, especially for patients at relapse after allogeneic stem

  8. Double minute chromosomes in acute myeloid leukemia, myelodysplastic syndromes, and chronic myelomonocytic leukemia are associated with micronuclei, MYC or MLL amplification, and complex karyotype.

    Science.gov (United States)

    Huh, Yang O; Tang, Guilin; Talwalkar, Sameer S; Khoury, Joseph D; Ohanian, Maro; Bueso-Ramos, Carlos E; Abruzzo, Lynne V

    2016-01-01

    Double minute chromosomes (dmin) are small, paired chromatin bodies that lack a centromere and represent a form of extrachromosomal gene amplification. Dmin are rare in myeloid neoplasms and are generally associated with a poor prognosis. Most studies of dmin in myeloid neoplasms are case reports or small series. In the current study, we present the clinicopathologic and cytogenetic features of 22 patients with myeloid neoplasms harboring dmin. These neoplasms included acute myeloid leukemia (AML) (n = 18), myelodysplastic syndrome (MDS) (n = 3), and chronic myelomonocytic leukemia (CMML) (n = 1). The AML cases consisted of AML with myelodysplasia-related changes (n = 13) and therapy-related AML (n = 5). Dmin were detected in initial pre-therapy samples in 14 patients with AML or CMML; they were acquired during the disease course in 8 patients who had AML or MDS. The presence of dmin was associated with micronuclei (18/18; 100%), complex karyotype (17/22; 77.3%), and amplification of MYC (12/16; 75%) or MLL (4/16; 25%). Immunohistochemical staining for MYC performed on bone marrow core biopsy or clot sections revealed increased MYC protein in all 19 cases tested. Except for one patient, most patients failed to respond to risk-adapted chemotherapies. At last follow up, all patients had died of disease after a median of 5 months following dmin detection. In conclusion, dmin in myeloid neoplasms commonly harbor MYC or MLL gene amplification and manifest as micronuclei within leukemic blasts. Dmin are often associated with myelodysplasia or therapy-related disease, and complex karyotypes.

  9. Treatment-related myelodysplastic syndrome (t-MDS)/acute myeloid leukemia (AML) in children with cancer: A single-center experience.

    Science.gov (United States)

    Tragiannidis, Athanasios; Gombakis, Nikolaos; Papageorgiou, Maria; Hatzipantelis, Emmanuel; Papageorgiou, Theodotis; Hatzistilianou, Maria

    2016-12-01

    Treatment-related myelodysplastic syndrome (t-MDS)/acute myeloid leukemia (AML) is a devastating early or late complication of treatment for childhood cancer related with a significant morbidity and mortality. We retrospectively studied survivors of childhood cancer. Overall, 287 patients were recorded in the databases and we identified three (1.04%) with t-MDS. The primary cancer diagnoses were Langerhans cell histiocytosis (one patient) and acute lymphoblastic leukemia (ALL; two patients). The mean age of patients was 12.1 years. All patients had received systemic antifungal treatment for invasive pulmonary aspergillosis successfully treated with voriconazole and liposomal amphotericin B before diagnosis of t-MDS. Two patients (66%) remain alive after a median follow-up period of 3.5 years.

  10. Specific scoring systems to predict survival of patients with high-risk myelodysplastic syndrome (MDS) and de novo acute myeloid leukemia (AML) after intensive antileukemic treatment based on results of the EORTC-GIMEMA AML-10 and intergroup CRIANT studies

    NARCIS (Netherlands)

    Oosterveld, M.; Suciu, S.; Muus, P.; Germing, U.; Delforge, M.; Belhabri, A.; Aul, C.; Selleslag, D.; Ferrant, A.; Marie, J.P.; Amadori, S.; Jehn, U.; Mandelli, F.; Hess, U.; Hellstrom-Lindberg, E.; Cakmak-Wollgast, S.; Vignetti, M.; Labar, B.; Willemze, R.; Witte, T.J. de

    2015-01-01

    High-risk myelodysplastic syndrome (MDS) patients have usually a less favorable outcome after intensive treatment compared with de novo acute myeloid leukemia (AML) patients. This may reflect different disease-related and patient-related factors. The purpose of this analysis is to identify disease-s

  11. Molecular similarity between myelodysplastic form of chronic myelomonocytic leukemia and refractory anemia with ring sideroblasts.

    Science.gov (United States)

    Gelsi-Boyer, Véronique; Cervera, Nathalie; Bertucci, François; Brecqueville, Mandy; Finetti, Pascal; Murati, Anne; Arnoulet, Christine; Mozziconacci, Marie-Joelle; Mills, Ken I; Cross, Nicholas C P; Vey, Norbert; Birnbaum, Daniel

    2013-04-01

    Chronic myelomonocytic leukemia is similar to but a separate entity from both myeloproliferative neoplasms and myelodysplastic syndromes, and shows either myeloproliferative or myelodysplastic features. We ask whether this distinction may have a molecular basis. We established the gene expression profiles of 39 samples of chronic myelomonocytic leukemia (including 12 CD34-positive) and 32 CD34-positive samples of myelodysplastic syndromes by using Affymetrix microarrays, and studied the status of 18 genes by Sanger sequencing and array-comparative genomic hybridization in 53 samples. Analysis of 12 mRNAS from chronic myelomonocytic leukemia established a gene expression signature of 122 probe sets differentially expressed between proliferative and dysplastic cases of chronic myelomonocytic leukemia. As compared to proliferative cases, dysplastic cases over-expressed genes involved in red blood cell biology. When applied to 32 myelodysplastic syndromes, this gene expression signature was able to discriminate refractory anemias with ring sideroblasts from refractory anemias with excess of blasts. By comparing mRNAS from these two forms of myelodysplastic syndromes we derived a second gene expression signature. This signature separated the myelodysplastic and myeloproliferative forms of chronic myelomonocytic leukemias. These results were validated using two independent gene expression data sets. We found that myelodysplastic chronic myelomonocytic leukemias are characterized by mutations in transcription/epigenetic regulators (ASXL1, RUNX1, TET2) and splicing genes (SRSF2) and the absence of mutations in signaling genes. Myelodysplastic chronic myelomonocytic leukemias and refractory anemias with ring sideroblasts share a common expression program suggesting they are part of a continuum, which is not totally explained by their similar but not, however, identical mutation spectrum.

  12. Therapy-related myelodysplastic syndrome and acute myeloid leukemia following fludarabine combination chemotherapy.

    Science.gov (United States)

    Carney, D A; Westerman, D A; Tam, C S; Milner, A; Prince, H M; Kenealy, M; Wolf, M; Januszewicz, E H; Ritchie, D; Came, N; Seymour, J F

    2010-12-01

    Fludarabine combination chemotherapy achieves high response rates in chronic lymphocytic leukemia (CLL) and indolent lymphoma. The aim of this study was to investigate the incidence and characteristics of treatment-related myelodysplasia and acute myeloid leukemia (t-MDS/AML) after treatment with fludarabine in combination for lymphoproliferative disorders and identify risk factors for its development. In all, 176 patients treated with fludarabine combination were followed for a median of 41 months (range 6-125 months). In all, 19 cases of t-MDS/AML have been identified for an overall rate of 10.8%. Median overall survival post-t-MDS/AML diagnosis was 11 months. Patients developing t-MDS/AML included 11/54 with follicular lymphoma (FL) (crude rate 20.4%), 5/82 with CLL (6.1%) and 3/24 with Waldenstrom macroglobulinemia or marginal zone lymphoma (12.5%). Most patients had other cytotoxic treatments (median 4, range 0-7) but three with FL had fludarabine combination as their only line of treatment. Of the eleven patients (6.3%) who received mitoxantrone with their first fludarabine combination, four (36.4%) developed t-MDS/AML (P=0.007). There was a trend toward prior cytotoxic therapy increasing the risk for t-MDS/AML (P=0.067). Fludarabine combination chemotherapy is associated with a moderate risk of t-MDS/AML particularly when combined with mitoxantrone. This complication should be considered when evaluating the potential benefit of this treatment in lymphoproliferative disorders.

  13. [Association between multiple myeloma and acute myeloid leukemia secondary to myelodysplastic syndrome].

    Science.gov (United States)

    Jennane, Selim; Eddou, Hicham; Mahtat, El Mehdi; Konopacki, Johanna; Souleau, Bertrand; Malfuson, Jean Valère; Foissaud, Vincent; de Revel, Thierry

    2013-01-01

    We report a rare case of association of two distinct hematologic malignancies: refractory cytopenia with multilineage dysplasia associated with del(5q) and symptomatic multiple myeloma associated with del(17p) and del(13q). After 16 months, the patient presented an acute leukemic transformation of the myelodysplasic syndrome.

  14. T-cell receptor excision circle levels after allogeneic stem cell transplantation are predictive of relapse in patients with acute myeloid leukemia and myelodysplastic syndrome.

    Science.gov (United States)

    Uzunel, Mehmet; Sairafi, Darius; Remberger, Mats; Mattsson, Jonas; Uhlin, Michael

    2014-07-15

    In this retrospective study, 209 patients with malignant disease were analyzed for levels of T-cell receptor excision circles (TRECs) for the first 24 months after allogeneic stem cell transplantation. CD3(+) cells were separated by direct antibody-coupled magnetic beads, followed by DNA extraction according to a standard protocol. The δRec-ψJα signal joint TREC was measured with real-time quantitative PCR. Patients were grouped based on malignant disease: chronic myeloid leukemia, chronic lymphatic leukemia, acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), and myelodysplastic syndrome (MDS). Patients were further subdivided based on TREC levels below (low-TREC) or above (high-TREC) median at each time point. TREC levels were then correlated to relapse incidence and relapse-free survival (RFS). For patients with AML, low TREC levels 2 months post-transplantation were correlated to high relapse incidence at 5 years (Pleukemia, high TREC levels were correlated with improved RFS (Pafter allogeneic hematopoietic stem cell transplantation.

  15. Patterns of infection in patients with myelodysplastic syndromes and acute myeloid leukemia receiving azacitidine as salvage therapy. Implications for primary antifungal prophylaxis.

    Science.gov (United States)

    Falantes, Jose F; Calderón, Cristina; Márquez-Malaver, Francisco J; Aguilar-Guisado, Manuela; Martín-Peña, Almudena; Martino, María L; Montero, Isabel; González, Jose; Parody, Rocío; Pérez-Simón, Jose A; Espigado, Ildefonso

    2014-02-01

    Incidence, etiology, and outcome of infectious episodes in patients with myeloid neoplasms receiving azacitidine are uncertain, with no prospective data available in this group of patients. The aim of the current study was to analyze the incidence and factors related to the probability of infection in a cohort of patients with myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) treated with azacitidine who did not receive any type of antimicrobial prophylaxis. Significantly, the group of patients who received prior intensive chemotherapy had more infectious episodes (P = 10(-4)), and particularly, invasive aspergillosis (P = .015), than patients who received frontline azacitidine. Primary antifungal prophylaxis might be recommended in MDS and AML patients receiving azacitidine as salvage therapy after intensive regimens.

  16. A phase II study of AZD2171 (cediranib) in the treatment of patients with acute myeloid leukemia or high-risk myelodysplastic syndrome.

    Science.gov (United States)

    Mattison, Ryan; Jumonville, Alcee; Flynn, Patrick James; Moreno-Aspitia, Alvaro; Erlichman, Charles; LaPlant, Betsy; Juckett, Mark B

    2015-07-01

    Patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) not fit for intensive treatment need novel therapy options. Vascular endothelial growth factor (VEGF) receptor inhibition is one potential mechanism by which AML and MDS could be treated. The receptor tyrosine kinase inhibitor AZD2171 (cediranib) has activity against VEGF receptors KDR and FLT-1. This multicenter phase II study was designed to test cediranib's activity in patients with AML or high-risk MDS. The primary endpoint was confirmed disease response defined as a composite of complete remission, partial remission or hematologic improvement. The study enrolled 23 subjects in the AML cohort and 16 subjects in the MDS cohort. There were no confirmed responses in either group. Since the study met the stopping rule after the first stage of enrollment, the trial was closed to further accrual. Common adverse events in both cohorts included thrombocytopenia, neutropenia, anemia, fatigue, dyspnea, diarrhea, nausea and dehydration.

  17. Cladribine, cytarabine, filgrastim, and mitoxantrone (CLAG-M) compared to standard induction in acute myeloid leukemia from myelodysplastic syndrome after azanucleoside failure.

    Science.gov (United States)

    Jaglal, Michael V; Duong, Vu H; Bello, Celeste M; Al Ali, Najla H; Padron, Eric; Fernandez, Hugo F; List, Alan F; Lancet, Jeffrey E; Komrokji, Rami S

    2014-04-01

    For patients with acute myeloid leukemia from antecedent myelodysplastic syndrome particularly after azanucleoside treatment failure, outcome is poor. Here, we conducted a case-control study in these patients to compare the efficacy of CLAG-M induction (28 patients) versus standard 3+7 induction chemotherapy (24 patients). Response rates (P=0.014) and median overall survival (P=0.025) were 64% and 202 days (95% CI 37-367 days) versus 29% and 86 days (95% CI 36-136) in the CLAG-M and 3+7 cohorts, respectively. Median overall survival was 202 (95% CI 37-367 days) versus 86 days (95% CI 36-136) (P=0.025), respectively. CLAG-M has encouraging activity in this patient group.

  18. Long-term Survival and Late Effects among 1-year Survivors of Second Allogeneic Hematopoietic Cell Transplantation for Relapsed Acute Leukemia and Myelodysplastic Syndromes

    Science.gov (United States)

    Duncan, Christine N.; Majhail, Navneet S.; Brazauskas, Ruta; Wang, Zhiwei; Cahn, Jean-Yves; Frangoul, Haydar A.; Hayashi, Robert J.; Hsu, Jack W.; Kamble, Rammurti T.; Kasow, Kimberly A.; Khera, Nandita; Lazarus, Hillard M.; Loren, Alison W.; Marks, David I.; Maziarz, Richard T.; Mehta, Paulette; Myers, Kasiani C.; Norkin, Maxim; Pidala, Joseph A.; Porter, David L.; Reddy, Vijay; Saber, Wael; Savani, Bipin N.; Schouten, Harry C.; Steinberg, Amir; Wall, Donna A.; Warwick, Anne B.; Wood, William A.; Yu, Lolie C.; Jacobsohn, David A.; Sorror, Mohamed L.

    2014-01-01

    We analyzed the outcomes of patients who survived disease-free for 1-year or more following second allogeneic hematopoietic cell transplantation (HCT) for relapsed acute leukemia or myelodysplastic syndromes between 1980 and 2009. A total of 1285 patients received a second allogeneic transplant following disease relapse; among these 325 survived relapse-free at 1-year after the second HCT. The median time from first to second HCT was 17 and 24 months for children and adults, respectively. A myeloablative preparative regimen was used in the second transplant in 62% of children and 45% of adult patients. The overall 10-year conditional survival rates after second transplantation in this cohort of patients who had survived disease-free for at least one year were 55% in children and 39% in adults. Relapse was the leading cause of mortality (77% and 54% of deaths in children and adults, respectively). In multivariate analyses, only disease status prior to second HCT was significantly associated with higher risk for overall mortality (HR 1.71 for patients with disease not in complete remission prior to second HCT, Ptransplant. Chronic GVHD was the leading cause of non-relapse mortality followed by organ failure and infection. The cumulative incidence of developing at least one of the studied late effects at 10-years after second HCT was 63% in children and 55% in adults. The most frequent late effects in children were growth disturbance (10-year cumulative incidence 22%) and cataracts (20%), and in adults were cataracts (20%) and avascular necrosis (13%). Among patients with acute leukemia and myelodysplastic syndromes who receive a second allogeneic HCT for relapse and survive disease-free for at least 1-year, many can be expected to survive long term. However, they continue to be at risk for relapse and non-relapse morbidity and mortality. Novel approaches are needed to minimize relapse risk and long-term transplant morbidity in this population. PMID:25316109

  19. Phase I Dose-Escalation Trial of Clofarabine Followed by Escalating Doses of Fractionated Cyclophosphamide in Children With Relapsed or Refractory Acute Leukemias

    Science.gov (United States)

    2010-09-21

    Myelodysplastic Syndrome; Acute Myeloid Leukemia; Myeloproliferative Disorders; Acute Lymphocytic Leukemia; Acute Promyelocytic Leukemia; Acute Leukemia; Chronic Myelogenous Leukemia; Myelofibrosis; Chronic Myelomonocytic Leukemia; Juvenile Myelomonocytic Leukemia

  20. Molecular studies in myelodysplastic syndromes

    NARCIS (Netherlands)

    Dijk, Jeroen Peter van

    2003-01-01

    This thesis describes molecular studies of myelodysplastic syndromes (MDS). The first question was if high-dose chemotherapy could induce polyclonal remission. Disease clonality was investigated with karyotyping in patients with large chromosomal aberrations and determination of X-chromosome inactiv

  1. IDH1 mutations in patients with myelodysplastic syndromes are associated with an unfavorable prognosis

    Science.gov (United States)

    Thol, Felicitas; Weissinger, Eva M.; Krauter, Jürgen; Wagner, Katharina; Damm, Frederik; Wichmann, Martin; Göhring, Gudrun; Schumann, Christiane; Bug, Gesine; Ottmann, Oliver; Hofmann, Wolf-Karsten; Schlegelberger, Brigitte; Ganser, Arnold; Heuser, Michael

    2010-01-01

    Background Myelodysplastic syndromes are a heterogeneous group of hematopoietic stem cell disorders with a high propensity to transform into acute myeloid leukemia. Heterozygous missense mutations in IDH1 at position R132 and in IDH2 at positions R140 and R172 have recently been reported in acute myeloid leukemia. However, little is known about the incidence and prognostic impact of IDH1 and IDH2 mutations in myelodysplastic syndromes. Design and Methods We examined 193 patients with myelodysplastic syndromes and 53 patients with acute myeloid leukemia arising from myelodysplastic syndromes for mutations in IDH1 (R132), IDH2 (R172 and R140), and NPM1 by direct sequencing. Results We found that mutations in IDH1 occurred with a frequency of 3.6% in myelodysplastic syndromes (7 mutations in 193 patients) and 7.5% in acute myeloid leukemia following myelodysplastic syndromes (4 mutations in 53 patients). Three mutations in codon R140 of IDH2 and one mutation in codon R172 were found in patients with acute myeloid leukemia following myelodysplastic syndromes (7.5%). No IDH2 R140 or R172 mutations were identified in patients with myelodysplastic syndromes. The presence of IDH1 mutations was associated with a shorter overall survival (HR 3.20; 95% CI 1.47–6.99) and a higher rate of transformation into acute myeloid leukemia (67% versus 28%, P=0.04). In multivariate analysis when considering karyotype, transfusion dependence and International Prognostic Scoring System score, IDH1 mutations remained an independent prognostic marker in myelodysplastic syndromes (HR 3.57; 95% CI 1.59–8.02; P=0.002). Conclusions These results suggest that IDH1 mutations are recurrent molecular aberrations in patients with myelodysplastic syndromes, and may become useful as a poor risk marker in these patients. These findings await validation in prospective trials. PMID:20494930

  2. Autoimmune diseases and myelodysplastic syndromes.

    Science.gov (United States)

    Komrokji, Rami S; Kulasekararaj, Austin; Al Ali, Najla H; Kordasti, Shahram; Bart-Smith, Emily; Craig, Benjamin M; Padron, Eric; Zhang, Ling; Lancet, Jeffrey E; Pinilla-Ibarz, Javier; List, Alan F; Mufti, Ghulam J; Epling-Burnette, Pearlie K

    2016-05-01

    Immune dysregulation and altered T-cell hemostasis play important roles in the pathogenesis of myelodysplastic syndromes (MDS). Recent studies suggest an increased risk of MDS among patients with autoimmune diseases. Here, we investigated the prevalence of autoimmune diseases among MDS patients, comparing characteristics and outcomes in those with and without autoimmune diseases. From our study group of 1408 MDS patients, 391 (28%) had autoimmune disease, with hypothyroidism being the most common type, accounting for 44% (n = 171) of patients (12% among all MDS patients analyzed). Other autoimmune diseases with ≥5% prevalence included idiopathic thrombocytopenic purpura in 12% (n = 46), rheumatoid arthritis in 10% (n = 41), and psoriasis in 7% (n = 28) of patients. Autoimmune diseases were more common in female MDS patients, those with RA or RCMD WHO subtype, and those who were less dependent on red blood cell transfusion. Median overall survival (OS) was 60 months (95% CI, 50-70) for patients with autoimmune diseases versus 45 months (95% CI, 40-49) for those without (log-rank test, P = 0.006). By multivariate analysis adjusting for revised IPSS and age >60 years, autoimmune diseases were a statistically significant independent factor for OS (HR 0.78; 95% CI, 0.66-0.92; P = 0.004). The rate of acute myeloid leukemia (AML) transformation was 23% (n = 89) in MDS patients with autoimmune disease versus 30% (n = 301) in those without (P = 0.011). Patient groups did not differ in response to azacitidine or lenalidomide treatment. Autoimmune diseases are prevalent among MDS patients. MDS patients with autoimmune diseases have better OS and less AML transformation.

  3. Standardization of flow cytometry in myelodysplastic syndromes: a report from an international consortium and the European LeukemiaNet Working Group.

    NARCIS (Netherlands)

    Westers, T.M.; Ireland, R.; Kern, W.; Alhan, C.; Balleisen, J.S.; Bettelheim, P.; Burbury, K.; Cullen, M.; Cutler, J.A.; Porta, M.G. Della; Drager, A.M.; Feuillard, J.; Font, P.; Germing, U.; Haase, D.; Johansson, U.; Kordasti, S.; Loken, M.R.; Malcovati, L.; Marvelde, J.G. Te; Matarraz, S.; Milne, T.; Moshaver, B.; Mufti, G.J.; Ogata, K.; Orfao, A.; Porwit, A.; Psarra, K.; Richards, S.J.; Subira, D.; Tindell, V.; Vallespi, T.; Valent, P.; Velden, V.H. van der; Witte, T.J.M. de; Wells, D.A.; Zettl, F.; Bene, M.C.; Loosdrecht, A.A. van de

    2012-01-01

    Flow cytometry (FC) is increasingly recognized as an important tool in the diagnosis and prognosis of myelodysplastic syndromes (MDS). However, validation of current assays and agreement upon the techniques are prerequisites for its widespread acceptance and application in clinical practice.

  4. Therapy-related myelodysplastic syndrome/acute myeloid leukemia with del(7)(q22) in a patient with de novo AML.

    Science.gov (United States)

    Kim, Yang Gyun; Cho, Sun Young; Park, Tae Sung; Oh, Seung Hwan; Yoon, Hwi-Joong

    2011-01-01

    A 55-year-old Korean woman was initially diagnosed with acute myelomonocytic leukemia (AML). After induction chemotherapy was performed using cytarabine, idarubicin, and G-CSF, complete remission (CR) was subsequently achieved following reinduction chemotherapy using the same chemotherapeutic agents. Thirty-six months after the initial CR, an increase in immature cells (up to 12.0%) was observed in the patient's bone marrow. Because chromosome analysis revealed a karyotype of 46,XX,del(7)(q22) in all of the analyzed cells, the patient was diagnosed with therapy-related myelodysplastic syndrome (t-MDS). Although the patient subsequently received chemotherapy and G-CSF for neutropenia, t-MDS rapidly progressed after 3 months to therapy-related acute myeloid leukemia (t-AML). Although very rare, de novo AML can progress to a secondary MDS/AML with del(7q) after chemotherapy with cytarabine, idarubicin, and G-CSF. Further investigation into the role of genes located in 7q22 may provide more information about the mechanisms of leukemogenesis.

  5. Identification of a common microdeletion cluster in 7q21.3 subband among patients with myeloid leukemia and myelodysplastic syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Asou, Hiroya; Matsui, Hirotaka; Ozaki, Yuko; Nagamachi, Akiko; Nakamura, Megumi; Aki, Daisuke [Department of Molecular Oncology and Leukemia Program Project, Research Institute for Radiation Biology and Medicine, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553 (Japan); Inaba, Toshiya, E-mail: tinaba@hiroshima-u.ac.jp [Department of Molecular Oncology and Leukemia Program Project, Research Institute for Radiation Biology and Medicine, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553 (Japan)

    2009-05-29

    Monosomy 7 and interstitial deletions in the long arm of chromosome 7 (-7/7q-) is a common nonrandom chromosomal abnormality found frequently in myeloid disorders including acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), and juvenile myelomonocytic leukemia (JMML). Using a short probe-based microarray comparative genomic hybridization (mCGH) technology, we identified a common microdeletion cluster in 7q21.3 subband, which is adjacent to 'hot deletion region' thus far identified by conventional methods. This common microdeletion cluster contains three poorly characterized genes; Samd9, Samd9L, and a putative gene LOC253012, which we named Miki. Gene copy number assessment of three genes by real-time PCR revealed heterozygous deletion of these three genes in adult patients with AML and MDS at high frequency, in addition to JMML patients. Miki locates to mitotic spindles and centrosomes and downregulation of Miki by RNA interference induced abnormalities in mitosis and nuclear morphology, similar to myelodysplasia. In addition, a recent report indicated Samd9 as a tumor suppressor. These findings indicate the usefulness of the short probe-based CGH to detect microdeletions. The three genes located to 7q21.3 would be candidates for myeloid tumor-suppressor genes on 7q.

  6. Gene mutations differently impact the prognosis of the myelodysplastic and myeloproliferative classes of chronic myelomonocytic leukemia.

    Science.gov (United States)

    Cervera, Nathalie; Itzykson, Raphael; Coppin, Emilie; Prebet, Thomas; Murati, Anne; Legall, Stevan; Vey, Norbert; Solary, Eric; Birnbaum, Daniel; Gelsi-Boyer, Véronique

    2014-06-01

    Initially classified in the myelodysplastic syndromes (MDSs), chronic myelomonocytic leukemia (CMML) is currently considered as a MDS/myeloproliferative neoplasm. Two classes-myelodysplastic and myeloproliferative-have been distinguished upon the level of the white blood cell count (threshold 13 G/L). We analyzed mutations in 19 genes reported in CMML to determine if and how these mutations impacted the respective prognosis of the two classes. We defined four major mutated pathways (DNA methylation, ASXL1, splicing, and signaling) and determined their prognostic impact. The number of mutated pathways impacted overall survival in the myelodysplastic class but not in the myeloproliferative class. The myeloproliferative class had a worse prognosis than the myelodysplastic class and was impacted by RUNX1 mutations only. Our results argue for a reclassification of CMML based on the myelodysplastic/myeloproliferative status. © 2014 Wiley Periodicals, Inc.

  7. G-CSF priming, clofarabine, and high dose cytarabine (GCLAC) for upfront treatment of acute myeloid leukemia, advanced myelodysplastic syndrome or advanced myeloproliferative neoplasm.

    Science.gov (United States)

    Becker, Pamela S; Medeiros, Bruno C; Stein, Anthony S; Othus, Megan; Appelbaum, Frederick R; Forman, Stephen J; Scott, Bart L; Hendrie, Paul C; Gardner, Kelda M; Pagel, John M; Walter, Roland B; Parks, Cynthia; Wood, Brent L; Abkowitz, Janis L; Estey, Elihu H

    2015-04-01

    Prior study of the combination of clofarabine and high dose cytarabine with granulocyte colony-stimulating factor (G-CSF) priming (GCLAC) in relapsed or refractory acute myeloid leukemia resulted in a 46% rate of complete remission despite unfavorable risk cytogenetics. A multivariate analysis demonstrated that the remission rate and survival with GCLAC were superior to FLAG (fludarabine, cytarabine, G-CSF) in the relapsed setting. We therefore initiated a study of the GCLAC regimen in the upfront setting in a multicenter trial. The objectives were to evaluate the rates of complete remission (CR), overall and relapse-free survival (OS and RFS), and toxicity of GCLAC. Clofarabine was administered at 30 mg m(-2) day(-1) × 5 and cytarabine at 2 g m(-2) day(-1) × 5 after G-CSF priming in 50 newly-diagnosed patients ages 18-64 with AML or advanced myelodysplastic syndrome (MDS) or advanced myeloproliferative neoplasm (MPN). Responses were assessed in the different cytogenetic risk groups and in patients with antecedent hematologic disorder. The overall CR rate was 76% (95% confidence interval [CI] 64-88%) and the CR + CRp (CR with incomplete platelet count recovery) was 82% (95% CI 71-93%). The CR rate was 100% for patients with favorable, 84% for those with intermediate, and 62% for those with unfavorable risk cytogenetics. For patients with an antecedent hematologic disorder (AHD), the CR rate was 65%, compared to 85% for those without an AHD. The 60 day mortality was 2%. Thus, front line GCLAC is a well-tolerated, effective induction regimen for AML and advanced myelodysplastic or myeloproliferative disorders.

  8. Long-term survival and late effects among one-year survivors of second allogeneic hematopoietic cell transplantation for relapsed acute leukemia and myelodysplastic syndromes.

    Science.gov (United States)

    Duncan, Christine N; Majhail, Navneet S; Brazauskas, Ruta; Wang, Zhiwei; Cahn, Jean-Yves; Frangoul, Haydar A; Hayashi, Robert J; Hsu, Jack W; Kamble, Rammurti T; Kasow, Kimberly A; Khera, Nandita; Lazarus, Hillard M; Loren, Alison W; Marks, David I; Maziarz, Richard T; Mehta, Paulette; Myers, Kasiani C; Norkin, Maxim; Pidala, Joseph A; Porter, David L; Reddy, Vijay; Saber, Wael; Savani, Bipin N; Schouten, Harry C; Steinberg, Amir; Wall, Donna A; Warwick, Anne B; Wood, William A; Yu, Lolie C; Jacobsohn, David A; Sorror, Mohamed L

    2015-01-01

    We analyzed the outcomes of patients who survived disease-free for 1 year or more after a second allogeneic hematopoietic cell transplantation (HCT) for relapsed acute leukemia or myelodysplastic syndromes between 1980 and 2009. A total of 1285 patients received a second allogeneic transplant after disease relapse; among these, 325 were relapse free at 1 year after the second HCT. The median time from first to second HCT was 17 and 24 months for children and adults, respectively. A myeloablative preparative regimen was used in the second transplantation in 62% of children and 45% of adult patients. The overall 10-year conditional survival rates after second transplantation in this cohort of patients who had survived disease-free for at least 1 year was 55% in children and 39% in adults. Relapse was the leading cause of mortality (77% and 54% of deaths in children and adults, respectively). In multivariate analyses, only disease status before second HCT was significantly associated with higher risk for overall mortality (hazard ratio, 1.71 for patients with disease not in complete remission before second HCT, P < .01). Chronic graft-versus-host disease (GVHD) developed in 43% and 75% of children and adults after second transplantation. Chronic GVHD was the leading cause of nonrelapse mortality, followed by organ failure and infection. The cumulative incidence of developing at least 1 of the studied late effects within 10 years after second HCT was 63% in children and 55% in adults. The most frequent late effects in children were growth disturbance (10-year cumulative incidence, 22%) and cataracts (20%); in adults they were cataracts (20%) and avascular necrosis (13%). Among patients with acute leukemia and myelodysplastic syndromes who receive a second allogeneic HCT for relapse and survive disease free for at least 1 year, many can be expected to survive long term. However, they continue to be at risk for relapse and nonrelapse morbidity and mortality. Novel

  9. Effect of low-dose cytarabine, homoharringtonine and granulocyte colony-stimulating factor priming regimen on patients with advanced myelodysplastic syndrome or acute myeloid leukemia transformed from myelodysplastic syndrome.

    Science.gov (United States)

    Wu, Lingyun; Li, Xiao; Su, Jiying; Chang, Chunkang; He, Qi; Zhang, Xi; Xu, Li; Song, Luxi; Pu, Quan

    2009-09-01

    A total of 32 patients (25 with advanced MDS and 7 with t-AML) were enrolled in this study to evaluate the efficacy and toxicity of the low-dose cytarabine and homoharringtonine in combination with granulocyte colony-stimulating factor (G-CSF) (CHG protocol) in patients with advanced myelodysplastic syndromes (MDS) or MDS-transformed acute myeloid leukemia (t-AML). All the patients were administered the CHG regimen comprising low-dose cytarabine (25 mg/day, intravenous continuous infusion, days 1-14), homoharringtonine (1 mg/day, intravenous continuous infusion, days 1-14), and G-CSF (300 microg/day, subcutaneous injection, days 0-14, interrupted when the peripheral white blood cell count reached >20 x 10(9)/L). The overall response rate was 71.9% after the administration of one course of the CHG regimen. Of the 32 patients, 15 (46.9%) achieved complete remission (CR) and 8 (25%) achieved partial remission (PR). This regimen was followed by a post-remission therapy that included conventional chemotherapy, when CR was achieved. Of the patients with CR who just received post-remission regimens as homoharringtonine and cytarabine (HA) and daunorubicin and cytarabine (DA) 6 relapsed rapidly and just had a mean 6.1 months of CR. Otherwise, the other 8 out of 14 patients with CR alternatively received subsequent chemotherapy, which combined mitoxantrone, idarubicin, pirarubicin, or aclarubicin with cytarabine. The mean CR duration of the 8 patients had reached 10.6 months, and 5 of the 8 still kept a continuous CR. The median overall survival (OS) was 18.2 months. There were no statistically significant differences for CR, PR, and OS when the patients were grouped by age, blasts in bone marrow, and karyotypes, respectively. No treatment-related deaths were observed. Myelosuppression was mild to moderate, and no severe non-hematological toxicity was observed. Thus, a CHG priming regimen as an induction therapy was well tolerated and effective in patients with advanced MDS

  10. Low CD34 dose is associated with poor survival after reduced-intensity conditioning allogeneic transplantation for acute myeloid leukemia and myelodysplastic syndrome.

    Science.gov (United States)

    Törlén, Johan; Ringdén, Olle; Le Rademacher, Jennifer; Batiwalla, Minoo; Chen, Junfang; Erkers, Tom; Ho, Vincent; Kebriaei, Partow; Keever-Taylor, Carolyn; Kindwall-Keller, Tamila; Lazarus, Hillard M; Laughlin, Mary J; Lill, Michael; O'Brien, Tracey; Perales, Miguel-Angel; Rocha, Vanderson; Savani, Bipin N; Szwajcer, David; Valcarcel, David; Eapen, Mary

    2014-09-01

    Reduced-intensity conditioning/nonmyeloablative conditioning regimens are increasingly used in allogeneic hematopoietic cell transplantation (HCT). Reports have shown CD34(+) dose to be important for transplantation outcome using myeloablative conditioning. The role of CD34(+) dose of peripheral blood progenitor cells (PBPC) has not been previously analyzed in a large population undergoing reduced-intensity conditioning/nonmyeloablative HCT. We studied 1054 patients, ages 45 to 75 years, with acute myeloid leukemia or myelodysplastic syndrome who underwent transplantation between 2002 and 2011. Results of multivariate analysis showed that PBPC from HLA-matched siblings containing after myeloablative HCT, CD34(+) dose did not affect relapse or graft-versus-host disease with either donor type. An upper cell dose limit was not associated with adverse outcomes. These data suggest that PBPC CD34(+) doses >4 × 10(6) CD34(+)/kg and >6 × 10(6) CD34(+)/kg are optimal for HLA-matched sibling and unrelated donor HCT, respectively.

  11. Therapy-related myelodysplastic syndrome and acute myeloid leukemia following chemotherapy (paclitaxel and carboplatin) and radiation therapy in ovarian cancer: a case report.

    Science.gov (United States)

    Ishikawa, M; Nakayama, K; Rahman, M T; Rahman, M; Katagiri, H; Katagiri, A; Ishibashi, T; Iida, K; Nakayama, N; Miyazaki, K

    2014-01-01

    In recent years, the incidence of therapy-related myelodysplastic syndrome (t-MDS) and therapy-related acute myeloid leukemia (t-AML) that occur during chemotherapy for ovarian cancer has increased. While alkylating agents and topoisomerase II inhibitors are particularly mutagenic and have strong leukemogenic potential, paclitaxel and combination chemotherapy/radiation therapy also appear to induce t-MDS. The present authors report a case of t-MDS that developed during chemotherapy and radiation therapy for ovarian cancer. The patient was a 75-year-old woman who received six courses of cyclophosphamide/doxorubicin/cisplatin (CAP) therapy after initial surgery for Stage IIIc grade ovarian cancer in 1995. Beginning in February 2005, the patient experienced multiple recurrences due to sternal metastasis. Chemotherapy, including paclitaxel and carboplatin (TC), was administered intermittently and was combined with radiation therapy to a sternal metastatic lesion. Pancytopenia was observed in December 2008, and she was diagnosed with t-MDS (WHO subtype, refractory cytopenias with multilineage dysplasia [RCMD]): the time from first chemotherapy to t-MDS onset was 106 months. Without evidence of blast crisis, the recurrent lesions continued to grow and caused multiple cerebral infarctions, from which she eventually died. The cumulative doses of paclitaxel and carboplatin administered to this patient were 1,968 mg and 6,480 mg, respectively.

  12. Therapy-Related Myelodysplastic Syndrome Following Treatment for Childhood Acute Lymphoblastic Leukemia: Outcome of Patients Registered in the EWOG-MDS 98/06 Studies

    DEFF Research Database (Denmark)

    Strahm, Birgitte; Amann, Roland; De Moerloose, Barbara

    Objective: Therapy-related myelodysplastic syndrome (tMDS) following treatment of childhood acute lymphoblastic leukemia (ALL) is one of the most frequently observed secondary malignancies in survivors of childhood cancer. Allogeneic stem cell transplantation (SCT) is the only curative treatment....... This analysis was performed to asses the outcome of patients with tMDS following treatment for childhood ALL reported to the EWOG-MDS study group. Patients and Transplant Procedure: Forty-three patients (19 male/24 female) were diagnosed with tMDS between August 1989 and August 2009. The median age at diagnosis...... was 8.9 yrs (3.4–20.5). The median interval from diagnosis of ALL to the diagnosis of tMDS was 3.3 yrs (1.7–7.0). Five patients did not receive SCT and died due to progressive disease at a median of 5.6 mo after diagnosis. Thirty-eight patients were transplanted. One patient was excluded from...

  13. MLL gene amplification in acute myeloid leukemia and myelodysplastic syndromes is associated with characteristic clinicopathological findings and TP53 gene mutation.

    Science.gov (United States)

    Tang, Guilin; DiNardo, Courtney; Zhang, Liping; Ravandi, Farhad; Khoury, Joseph D; Huh, Yang O; Muzzafar, Tariq; Medeiros, L Jeffrey; Wang, Sa A; Bueso-Ramos, Carlos E

    2015-01-01

    MLL gene rearrangements are well-recognized aberrations in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). In contrast, MLL gene amplification in AML/MDS remains poorly characterized. Here, we report a series of 21 patients with myeloid neoplasms associated with MLL gene amplification from 1 institution. This series included 13 men and 8 women, with a median age of 64 years. Eleven patients presented as AML with myelodysplasia-related changes, 6 as therapy-related AML, and 4 as therapy-related MDS. All patients had a highly complex karyotype, including frequent -5/del(5q), -18, and -17/del(17p) abnormalities; 16 patients were hypodiploid. TP53 mutations were detected in all 12 patients tested, and 3 patients showed TP53 mutation before MLL amplification. Morphologically, the leukemic cells frequently showed cytoplasmic vacuoles, bilobed nuclei, and were associated with background dyspoiesis. Immunophenotypically, 15 patients had a myeloid and 4 had myelomonocytic immunophenotype. Laboratory coagulopathies were common; 7 patients developed disseminated intravascular coagulopathy, and 3 died of intracranial bleeding. All patients were refractory to therapy; the median overall survival was 1 month, after MLL gene amplification was detected. We concluded that AML/MDS with MLL gene amplification is likely a subset of therapy-related AML/MDS or AML with myelodysplasia-related changes, associated with distinct clinicopathological features, frequent disseminated intravascular coagulopathy, a highly complex karyotype, TP53 deletion/mutation, and an aggressive clinical course.

  14. Review of the results of WT1 peptide vaccination strategies for myelodysplastic syndromes and acute myeloid leukemia from 9 different studies

    Directory of Open Access Journals (Sweden)

    Antonio eDi Stasi

    2015-02-01

    Full Text Available We performed a systematic review of data from seven clinical trials of WT1 peptide vaccination in patients with myelodysplastic syndromes and/or acute myeloid leukemia (MDS/AML, published between 2004 and 2012. A total of fifty-one patients were eligible for analysis. Vaccination with WT1 peptides proved safe and feasible in patients with MDS/AML, in studies from different institutions. Additionally, clinical responses and clinical benefit were observed, with some patients achieving and maintaining remission long term (more than 8 years. A significant correlation between induction of WT1 specific T cells and normalization/reduction of WT1 mRNA levels and progression free survival was noted in a number of studies. However larger studies are warranted to confirm these results. Interestingly, the majority of trials reported the presence of WT1 specific T cells with limited or absent functionality prior to vaccination, which increased in frequency and function after vaccination. In conclusion, WT1 peptide vaccination strategies were safe in this heterogeneous group of patient with MDS/AML. Larger and more homogeneous studies or randomized clinical trials are needed to quantify the contribution of WT1 peptide vaccines to clinical responses and long term survival.

  15. Therapy-related patterns of cytogenetic abnormalities in acute myeloid leukemia and myelodysplastic syndrome post polycythemia vera: single center experience and review of literature.

    Science.gov (United States)

    Swolin, Birgitta; Rödjer, Stig; Westin, Jan

    2008-06-01

    A minor fraction of patients with polycythemia vera (PV) develop a terminal acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). Analysis of the cytogenetic abnormalities during AML or MDS may help in understanding if this development is part of the natural course of the disease or induced by myelosuppressive therapy. Thirty-six cases with AML or MDS post PV, collected in a single Swedish institution during a 33-year period, are described with special regard to time to development of AML or MDS, therapy given during active PV, and cytogenetic findings during AML or MDS. A further 118 cases of AML or MDS post PV, in whom type of therapy during active PV and cytogenetic findings during AML or MDS were reported, were collected from the literature. AML or MDS developed in our own series after 1-30 years with a fairly constant rate (two cases per year). The most frequent cytogenetic abnormalities were +1q, -5, 5q-, -7, 7q-, +8, +9, 11q-, 13q-, and 20q-. When patients in the total material (n = 154) were divided with regard to treatment during active PV, marked differences were observed. The highest frequency of abnormalities was found in patients given multiple lines of therapy (n = 61), dominating features being -5/5q- in 28 patients (46%), -7/7q- in 19 patients (31%), numerous translocations in 24 patients (39%), and unidentified markers in 22 patients (36%). Half of the patients treated with hydroxyurea alone showed a -5 or 5q- abnormality. In patients treated with phlebotomy alone, +8 and +9 were the most frequent findings. The type of therapy given during active PV influences the type of chromosome abnormalities present during terminal AML or MDS and can also be instrumental in the development of leukemia.

  16. Monosomal karyotype predicts poor survival after allogeneic stem cell transplantation in chromosome 7 abnormal myelodysplastic syndrome and secondary acute myeloid leukemia

    NARCIS (Netherlands)

    Gelder, M. van; Wreede, L.C. de; Schetelig, J.; Biezen, A. van; Volin, L.; Maertens, J.; Robin, M.; Petersen, E.; Witte, T.J.M. de; Kroger, N.

    2013-01-01

    Treatment algorithms for poor cytogenetic-risk myelodysplastic syndrome (MDS), defined by chromosome 7 abnormalities or complex karyotype (CK), include allogeneic stem cell transplantation (alloSCT). We studied outcome of alloSCT in chromosome 7 abnormal MDS patients as this data are scarce in liter

  17. Standardization of flow cytometry in myelodysplastic syndromes: a report from an international consortium and the European LeukemiaNet Working Group.

    NARCIS (Netherlands)

    Westers, T.M.; Ireland, R.; Kern, W.; Alhan, C.; Balleisen, J.S.; Bettelheim, P.; Burbury, K.; Cullen, M.; Cutler, J.A.; Porta, M.G. Della; Drager, A.M.; Feuillard, J.; Font, P.; Germing, U.; Haase, D.; Johansson, U.; Kordasti, S.; Loken, M.R.; Malcovati, L.; Marvelde, J.G. Te; Matarraz, S.; Milne, T.; Moshaver, B.; Mufti, G.J.; Ogata, K.; Orfao, A.; Porwit, A.; Psarra, K.; Richards, S.J.; Subira, D.; Tindell, V.; Vallespi, T.; Valent, P.; Velden, V.H. van der; Witte, T.J.M. de; Wells, D.A.; Zettl, F.; Bene, M.C.; Loosdrecht, A.A. van de

    2012-01-01

    Flow cytometry (FC) is increasingly recognized as an important tool in the diagnosis and prognosis of myelodysplastic syndromes (MDS). However, validation of current assays and agreement upon the techniques are prerequisites for its widespread acceptance and application in clinical practice. Therefo

  18. Revisiting guidelines for integration of flow cytometry results in the WHO classification of myelodysplastic syndromes-proposal from the International/European LeukemiaNet Working Group for Flow Cytometry in MDS.

    Science.gov (United States)

    Porwit, A; van de Loosdrecht, A A; Bettelheim, P; Brodersen, L Eidenschink; Burbury, K; Cremers, E; Della Porta, M G; Ireland, R; Johansson, U; Matarraz, S; Ogata, K; Orfao, A; Preijers, F; Psarra, K; Subirá, D; Valent, P; van der Velden, V H J; Wells, D; Westers, T M; Kern, W; Béné, M C

    2014-09-01

    Definite progress has been made in the exploration of myelodysplastic syndromes (MDS) by flow cytometry (FCM) since the publication of the World Health Organization 2008 classification of myeloid neoplasms. An international working party initiated within the European LeukemiaNet and extended to include members from Australia, Canada, Japan, Taiwan and the United States has, through several workshops, developed and subsequently published consensus recommendations. The latter deal with preanalytical precautions, and propose small and large panels, which allow evaluating immunophenotypic anomalies and calculating myelodysplasia scores. The current paper provides guidelines that strongly recommend the integration of FCM data with other diagnostic tools in the diagnostic work-up of MDS.

  19. Clonal evolution in myelodysplastic syndromes

    Science.gov (United States)

    da Silva-Coelho, Pedro; Kroeze, Leonie I.; Yoshida, Kenichi; Koorenhof-Scheele, Theresia N.; Knops, Ruth; van de Locht, Louis T.; de Graaf, Aniek O.; Massop, Marion; Sandmann, Sarah; Dugas, Martin; Stevens-Kroef, Marian J.; Cermak, Jaroslav; Shiraishi, Yuichi; Chiba, Kenichi; Tanaka, Hiroko; Miyano, Satoru; de Witte, Theo; Blijlevens, Nicole M. A.; Muus, Petra; Huls, Gerwin; van der Reijden, Bert A.; Ogawa, Seishi; Jansen, Joop H.

    2017-01-01

    Cancer development is a dynamic process during which the successive accumulation of mutations results in cells with increasingly malignant characteristics. Here, we show the clonal evolution pattern in myelodysplastic syndrome (MDS) patients receiving supportive care, with or without lenalidomide (follow-up 2.5–11 years). Whole-exome and targeted deep sequencing at multiple time points during the disease course reveals that both linear and branched evolutionary patterns occur with and without disease-modifying treatment. The application of disease-modifying therapy may create an evolutionary bottleneck after which more complex MDS, but also unrelated clones of haematopoietic cells, may emerge. In addition, subclones that acquired an additional mutation associated with treatment resistance (TP53) or disease progression (NRAS, KRAS) may be detected months before clinical changes become apparent. Monitoring the genetic landscape during the disease may help to guide treatment decisions. PMID:28429724

  20. Expression of CDKN1C in the bone marrow of patients with myelodysplastic syndrome and secondary acute myeloid leukemia is associated with poor survival after conventional chemotherapy.

    Science.gov (United States)

    Radujkovic, Aleksandar; Dietrich, Sascha; Andrulis, Mindaugas; Benner, Axel; Longerich, Thomas; Pellagatti, Andrea; Nanda, Kriti; Giese, Thomas; Germing, Ulrich; Baldus, Stefan; Boultwood, Jacqueline; Ho, Anthony D; Dreger, Peter; Luft, Thomas

    2016-09-15

    We tested the hypothesis that proliferative activity of hematopoietic stem cells has impact on survival in newly diagnosed patients with myelodysplastic syndrome (MDS) and secondary acute myeloid leukemia (AML). RNA expression profiles of CD34(+) cells were analyzed in 125 MDS patients and compared to healthy controls. Prognostic impact on overall survival (OS) of mRNA proliferation signatures established for solid tumor cells was analyzed retrospectively. For validation on the protein level, immunofluorescence and immunohistochemistry analyses in bone marrow (BM) biopsies were performed, and an independent cohort of 223 MDS and secondary AML patients was investigated. Lower proliferative activity correlated with the expression of cyclin-dependent kinase inhibitor 1C (CDKN1C) and with shorter OS (p < 0.001). In multivariable analysis, higher CDKN1C expression was associated with worse OS (p = 0.02). On the BM level, a total of 84 (38%) patients showed CDKN1C protein expression before start of treatment. Patient, disease and treatment characteristics did not differ between CDKN1C-positive and -negative patients. Positive CDKN1C BM status was associated with shorter OS in multivariable analysis (HR 1.54, p = 0.04). There was an interaction between CDKN1C BM status and subsequent treatment with negative impact on OS being most pronounced in patients receiving conventional cytotoxic chemotherapy (n = 83, 2-year OS 30% versus 58%, p = 0.002). In conclusion, low-proliferative phenotype and CDKN1C expression were associated with shorter OS. CDKN1C protein expression in the BM of newly diagnosed, treatment-naïve MDS and secondary AML patients was identified as a prognostic factor for poor survival in patients treated with antiproliferative chemotherapy.

  1. Mixed T Lymphocyte Chimerism after Allogeneic Hematopoietic Transplantation Is Predictive for Relapse of Acute Myeloid Leukemia and Myelodysplastic Syndromes.

    Science.gov (United States)

    Lee, Hans C; Saliba, Rima M; Rondon, Gabriela; Chen, Julianne; Charafeddine, Yasmeen; Medeiros, L Jeffrey; Alatrash, Gheath; Andersson, Borje S; Popat, Uday; Kebriaei, Partow; Ciurea, Stefan; Oran, Betul; Shpall, Elizabeth; Champlin, Richard

    2015-11-01

    Chimerism testing after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) represents a promising tool for predicting disease relapse, although its precise role in this setting remains unclear. We investigated the predictive value of T lymphocyte chimerism analysis at 90 to 120 days after allo-HSCT in 378 patients with AML/MDS who underwent busulfan/fludarabine-based myeloablative preparative regimens. Of 265 (70%) patients with available T lymphocyte chimerism data, 43% of patients in first or second complete remission (CR1/CR2) at the time of transplantation had complete (100%) donor T lymphocytes at day +90 to +120 compared with 60% of patients in the non-CR1/CR2 cohort (P = .005). In CR1/CR2 patients, donor T lymphocyte chimerism ≤ 85% at day +90 to +120 was associated with a higher frequency of 3-year disease progression (29%; 95% confidence interval [CI], 18% to 46% versus 15%; 95% CI, 9% to 23%; hazard ratio [HR], 2.1; P = .04). However, in the more advanced, non-CR1/CR2 cohort, mixed T lymphocyte chimerism was not associated with relapse (37%; 95% CI, 20% to 66% versus 34%; 95% CI, 25% to 47%; HR, 1.3; P = .60). These findings demonstrate that early T lymphocyte chimerism testing at day +90 to +120 is a useful approach for predicting AML/MDS disease recurrence in patients in CR1/CR2 at the time of transplantation.

  2. Single nucleotide polymorphism array-based karyotyping in acute myeloid leukemia or myelodysplastic syndrome with trisomy 8 as the sole chromosomal abnormality.

    Science.gov (United States)

    Hahm, Chorong; Mun, Yeung Chul; Seong, Chu Myong; Han, Sung-Hee; Chung, Wha Soon; Huh, Jungwon

    2013-01-01

    The clinical heterogeneity of patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) with trisomy 8 as the sole abnormality may result from cytogenetically undetectable genetic changes. The purpose of this study was to identify hidden genomic aberrations not detected by metaphase cytogenetics (MC) using high-resolution single nucleotide polymorphism array (SNP-A)-based karyotyping in AML/MDS patients with a sole trisomy 8. The study group included 8 patients (3 AML and 5 MDS) and array-based karyotyping was done using whole-genome SNP-A (SNP 6.0 and SNP 2.7M). By SNP-A, additional genomic aberrations not detected by MC were identified in 2 patients: 1 AML patient exhibited a copy-neutral loss of heterozygosity (CN-LOH) of 3q21.1-q29 and 11q13.1-q25 and the other patient with MDS (refractory cytopenia with unilineage dysplasia) had CN-LOH of 2p25.3-p15. In particular, the latter patient progressed to AML 18 months after the diagnosis. In 3 patients, aberrations in addition to trisomy 8 were not identified by SNP-A. In the remaining 3 patients, SNP-A could not detect trisomy 8, while trisomy 8 was found in 25-67% of metaphase cells by MC. This study suggests that additional genomic aberrations may in fact be present even in cases of trisomy 8 as sole abnormality by MC, and SNP-A could be a useful karyotyping tool to identify hidden aberrations such as CN-LOH.

  3. New Comprehensive Cytogenetic Scoring System for Primary Myelodysplastic Syndromes (MDS) and Oligoblastic Acute Myeloid Leukemia After MDS Derived From an International Database Merge

    Science.gov (United States)

    Schanz, Julie; Tüchler, Heinz; Solé, Francesc; Mallo, Mar; Luño, Elisa; Cervera, José; Granada, Isabel; Hildebrandt, Barbara; Slovak, Marilyn L.; Ohyashiki, Kazuma; Steidl, Christian; Fonatsch, Christa; Pfeilstöcker, Michael; Nösslinger, Thomas; Valent, Peter; Giagounidis, Aristoteles; Aul, Carlo; Lübbert, Michael; Stauder, Reinhard; Krieger, Otto; Garcia-Manero, Guillermo; Faderl, Stefan; Pierce, Sherry; Le Beau, Michelle M.; Bennett, John M.; Greenberg, Peter; Germing, Ulrich; Haase, Detlef

    2012-01-01

    Purpose The karyotype is a strong independent prognostic factor in myelodysplastic syndromes (MDS). Since the implementation of the International Prognostic Scoring System (IPSS) in 1997, knowledge concerning the prognostic impact of abnormalities has increased substantially. The present study proposes a new and comprehensive cytogenetic scoring system based on an international data collection of 2,902 patients. Patients and Methods Patients were included from the German-Austrian MDS Study Group (n = 1,193), the International MDS Risk Analysis Workshop (n = 816), the Spanish Hematological Cytogenetics Working Group (n = 849), and the International Working Group on MDS Cytogenetics (n = 44) databases. Patients with primary MDS and oligoblastic acute myeloid leukemia (AML) after MDS treated with supportive care only were evaluated for overall survival (OS) and AML evolution. Internal validation by bootstrap analysis and external validation in an independent patient cohort were performed to confirm the results. Results In total, 19 cytogenetic categories were defined, providing clear prognostic classification in 91% of all patients. The abnormalities were classified into five prognostic subgroups (P < .001): very good (median OS, 61 months; hazard ratio [HR], 0.5; n = 81); good (49 months; HR, 1.0 [reference category]; n = 1,809); intermediate (26 months; HR, 1.6; n = 529); poor (16 months; HR, 2.6; n = 148); and very poor (6 months; HR, 4.2; n = 187). The internal and external validations confirmed the results of the score. Conclusion In conclusion, these data should contribute to the ongoing efforts to update the IPSS by refining the cytogenetic risk categories. PMID:22331955

  4. A High Occurrence of Acquisition and/or Expansion of C-CBL Mutant Clones in the Progression of High-Risk Myelodysplastic Syndrome to Acute Myeloid Leukemia

    Directory of Open Access Journals (Sweden)

    Hsiao-Wen Kao

    2011-11-01

    Full Text Available The molecular pathogenesis of myelodysplastic syndrome (MDS and its progression to secondary acute myeloid leukemia (sAML remain to be explored. Somatic C-CBL mutations were recently described in MDS. Our study aimed to determine the role of C-CBL mutations in the progression of MDS to sAML and sought to correlate with clinicohematological features and outcome. Bone marrow samples from 51 patients with high-risk MDS (13 with refractory cytopenia with multilineage dysplasia, 19 with refractory anemia with excess blast 1, and 19 with refractory anemia with excess blast 2 were analyzed for C-CBL mutations at both diagnosis and sAML in the same individuals. Mutational analysis was performed for exons 7 to 9 of C-CBL gene. Of the 51 paired samples, C-CBL mutations were identified in 6 patients at the sAML phase. One patient retained the identical C-CBL mutation (G415S at sAML evolution and exhibited clonal expansion. The other five patients acquired C-CBL mutations (Y371S, F418S, L370_Y371 ins L, L399V, and C416W during sAML evolution. Three of the six patients harboring C-CBL mutations at sAML had additional gene mutations including JAK2V617F, PTPN11, or N-RAS. There was no significant difference in clinicohematological features and overall survival with respect to C-CBL mutation status. Our results show that C-CBL mutation is very rare (0.6% in MDS, but acquisition and/or expansion of C-CBL mutant clones occur in 11.8% of patients during sAML transformation. The findings suggest that C-CBL mutations play a role at least in part in a subset of MDS patients during sAML transformation.

  5. Advanced Myelodysplastic Syndromes (MDS) and Juvenile Myelomonocytic Leukemia (JMML) | EU Clinical Trials Register [EU Clinical Trials Register

    Lifescience Database Archive (English)

    Full Text Available trattamento con Azacitidina (Vidaza®) in pazienti pediatrici con sindrome mielodisplastica avanzata, o con leucemia...venile Myelomonocytic Leukemia (JMML) sindrome mielodisplastica avanzata (MDS) e con leucemia mielomonocitic...anomalie genetiche caratterisitche di leucemia mieloide acuta- pazienti con JMML nei quail sia sospettata un

  6. Outcome of Allogeneic Stem Cell Transplantation for Patients Transformed to Myelodysplastic Syndrome or Leukemia from Severe Aplastic Anemia: A Report from the MDS Subcommittee of the Chronic Malignancies Working Party and the Severe Aplastic Anemia Working Party of the European Group for Blood and Marrow Transplantation

    NARCIS (Netherlands)

    Hussein, A.A.; Halkes, C.M.; Socie, G.; Tichelli, A.; Borne, P.A. von dem; Schaap, M.N.; Foa, R.; Ganser, A.; Dufour, C.; Bacigalupo, A.; Locasciulli, A.; Aljurf, M.; Peters, C.; Robin, M.; Biezen, A.A. van; Volin, L.; Witte, T.J. de; Marsh, J.; Passweg, J.R.; Kroger, N.

    2014-01-01

    One hundred and forty patients who had undergone hematopoietic stem cell transplantation (HSCT) for myelodysplastic syndrome (MDS) or acute myelogenous leukemia (AML) transformation after treatment of severe aplastic anemia (SAA) were identified in the European Group for Blood and Marrow Transplanta

  7. Tuberculosis in patients with myelodysplastic syndromes

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Hyo-Cheol; Goo, Jin Mo; Kim, Hyun Beom; Lee, Joon Woo; Seo, Joon Beom; Im, Jung-Gi

    2002-05-01

    AIM: The purpose of our study was to describe radiological manifestations of tuberculosis in patients with myelodysplastic syndromes. MATERIALS AND METHODS: Chest radiographs and CTs of 12 patients with tuberculosis among 195 consecutive patients with myelodysplastic syndrome, proved by bone marrow biopsy, were reviewed. Six of the 12 patients presented with tuberculosis and were subsequently found to have myelodysplastic syndrome. RESULTS: Chest radiographs and CTs revealed pulmonary tuberculosis in all 12 patients and extrapulmonary tuberculous involvement in six (50%). Initial chest radiographic findings of pulmonary tuberculosis included a primary pattern (n = 6), a post-primary pattern (n = 3), a miliary pattern (n = 1), atypical infiltrates (n = 1) and normal radiograph (n = 1). Tuberculosis involved extrathoracic lymph nodes (n = 5), liver (n = 2), spleen (n = 2), kidney (n 2), bowel (n = 2), pericardium (n = 2) peritoneum (n = 1) and rib (n = 1). CONCLUSION: Tuberculosis is a relatively common cause of infection in patients with myelodysplastic syndromes. The radiological appearance of pulmonary tuberculosis in myelodysplastic syndromes is often a primary pattern, and there is frequently extrapulmonary involvement. Kim, H-C. et al. (2002)

  8. Implementation of erythroid lineage analysis by flow cytometry in diagnostic models for myelodysplastic syndromes

    Science.gov (United States)

    Cremers, Eline M.P.; Westers, Theresia M.; Alhan, Canan; Cali, Claudia; Visser-Wisselaar, Heleen A.; Chitu, Dana A.; van der Velden, Vincent H.J.; te Marvelde, Jeroen G.; Klein, Saskia K.; Muus, Petra; Vellenga, Edo; de Greef, Georgina E.; Legdeur, Marie-Cecile C.J.C.; Wijermans, Pierre W.; Stevens-Kroef, Marian J.P.L.; da Silva-Coelho, Pedro; Jansen, Joop H.; Ossenkoppele, Gert J.; van de Loosdrecht, Arjan A.

    2017-01-01

    Flow cytometric analysis is a recommended tool in the diagnosis of myelodysplastic syndromes. Current flow cytometric approaches evaluate the (im)mature myelo-/monocytic lineage with a median sensitivity and specificity of ~71% and ~93%, respectively. We hypothesized that the addition of erythroid lineage analysis could increase the sensitivity of flow cytometry. Hereto, we validated the analysis of erythroid lineage parameters recommended by the International/European LeukemiaNet Working Group for Flow Cytometry in Myelodysplastic Syndromes, and incorporated this evaluation in currently applied flow cytometric models. One hundred and sixty-seven bone marrow aspirates were analyzed; 106 patients with myelodysplastic syndromes, and 61 cytopenic controls. There was a strong correlation between presence of erythroid aberrancies assessed by flow cytometry and the diagnosis of myelodysplastic syndromes when validating the previously described erythroid evaluation. Furthermore, addition of erythroid aberrancies to two different flow cytometric models led to an increased sensitivity in detecting myelodysplastic syndromes: from 74% to 86% for the addition to the diagnostic score designed by Ogata and colleagues, and from 69% to 80% for the addition to the integrated flow cytometric score for myelodysplastic syndromes, designed by our group. In both models the specificity was unaffected. The high sensitivity and specificity of flow cytometry in the detection of myelodysplastic syndromes illustrates the important value of flow cytometry in a standardized diagnostic approach. The trial is registered at www.trialregister.nl as NTR1825; EudraCT n.: 2008-002195-10 PMID:27658438

  9. Defining incidence, risk factors, and impact on survival of central line-associated blood stream infections following hematopoietic cell transplantation in acute myeloid leukemia and myelodysplastic syndrome.

    Science.gov (United States)

    Lukenbill, Joshua; Rybicki, Lisa; Sekeres, Mikkael A; Zaman, Muhammad Omer; Copelan, Alexander; Haddad, Housam; Fraser, Thomas; DiGiorgio, Megan J; Hanna, Rabi; Duong, Hien; Hill, Brian; Kalaycio, Matt; Sobecks, Ronald; Bolwell, Brian; Copelan, Edward

    2013-05-01

    Central line-associated blood stream infections (CLABSI) commonly complicate the care of patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) after allogeneic stem cell transplantation (HCT). We developed a modified CLABSI (MCLABSI) definition that attempts to exclude pathogens usually acquired because of disruption of mucosal barriers during the vulnerable neutropenic period following HCT that are generally included under the original definition (OCLABSI). We conducted a retrospective study of all AML and MDS patients undergoing HCT between August 2009 and December 2011 at the Cleveland Clinic (N = 73), identifying both OCLABSI and MCLABSI incidence. The median age at transplantation was 52 years (range, 16 to 70); 34 had a high (≥3) HCT comorbidity index (HCT-CI); 34 received bone marrow (BM), 24 received peripheral stem cells (PSC), and 15 received umbilical cord blood cells (UCB). Among these 73 patients, 23 (31.5%) developed OCLABSI, of whom 16 (69.6%) died, and 8 (11%) developed MCLABSI, of whom 7 (87.5%) died. OCLABSI was diagnosed a median of 9 days from HCT: 5 days (range, 2 to 12) for UCB and 78 days (range, 7 to 211) for BM/PSC (P < .001). MCLABSI occurred a median of 12 days from HCT, with similar earlier UCB and later BM/PSC diagnosis (P = .030). Risk factors for OCLABSI in univariate analysis included CBC (P < .001), human leukocyte antigen (HLA)-mismatch (P = .005), low CD34(+) count (P = .007), low total nucleated cell dose (P = .016), and non-Caucasian race (P = .017). Risk factors for OCLABSI in multivariable analysis were UCB (P < .001) and high HCT-CI (P = .002). There was a significant increase in mortality for both OCLABSI (hazard ratio, 7.14; CI, 3.31 to 15.37; P < .001) and MCLABSI (hazard ratio, 6.44; CI, 2.28 to 18.18; P < .001). CLABSI is common and associated with high mortality in AML and MDS patients undergoing HCT, especially in UCB recipients and those with high HCT-CI. We propose

  10. Chemotherapy versus Hypomethylating Agents for the Treatment of Relapsed Acute Myeloid Leukemia and Myelodysplastic Syndrome after Allogeneic Stem Cell Transplant.

    Science.gov (United States)

    Motabi, Ibraheem H; Ghobadi, Armin; Liu, Jingxia; Schroeder, Mark; Abboud, Camille N; Cashen, Amanda F; Stockler-Goldstein, Keith E; Uy, Geoffrey L; Vij, Ravi; Westervelt, Peter; DiPersio, John F

    2016-07-01

    Allogeneic stem cell transplantation (allo-SCT) is a potentially curative treatment for high-risk acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). For patients with relapsed disease after transplantation, intensive chemotherapy followed by donor lymphocyte infusion (DLI) or a second allo-SCT may result in a durable response in some patients. High-intensity chemotherapy and less aggressive therapy with hypomethylating agents (HAs) with and without DLI are often used for relapse after allo-SCT. Here we compared the treatment outcomes of intensive chemotherapy with that of HAs in relapsed AML and MDS after allo-SCT. Patients who had received a second SCT within 90 days of the relapse date were excluded. The primary endpoints were overall response rate (ORR) and overall survival (OS). Secondary endpoints were complete remission (CR) rate and progression-free survival (PFS). One hundred patients were included: 73 patients received chemotherapy and 27 patients received an HA. Fifty-six percent of patients in the chemotherapy group and 33% of patients in the HA group received at least 1 DLI after treatment. Treatment with chemotherapy resulted in a higher ORR (51% versus 19%, P = .004) and a higher CR rate (40% versus 7%, P = .002). The median OS (6 versus 3.9 months, P = .01) and PFS (4.9 versus 3.8 months, P = .02) were longer in the chemotherapy group. Similar benefit of chemotherapy over HAs was maintained in all treatment outcomes after controlling for the use of DLI. The use of chemotherapy followed by DLI offered the greatest benefit (ORR, 68%; CR, 59%, 1-year OS, 44%; and median OS, 9.8 months). In conclusion, in our hands, with limited numbers, the use of more conventional salvage chemotherapy, with DLI when possible, for the treatment of relapsed AML and MDS after allo-SCT is associated with better outcomes than nonchemotherapy (HA) options.

  11. Radiolabeled anti-CD45 antibody with reduced-intensity conditioning and allogeneic transplantation for younger patients with advanced acute myeloid leukemia or myelodysplastic syndrome.

    Science.gov (United States)

    Mawad, Raya; Gooley, Ted A; Rajendran, Joseph G; Fisher, Darrell R; Gopal, Ajay K; Shields, Andrew T; Sandmaier, Brenda M; Sorror, Mohamed L; Deeg, Hans Joachim; Storb, Rainer; Green, Damian J; Maloney, David G; Appelbaum, Frederick R; Press, Oliver W; Pagel, John M

    2014-09-01

    We treated patients under age 50 years with iodine-131 ((131)I)-anti-CD45 antibody combined with fludarabine and 2 Gy total body irradiation to create an improved hematopoietic cell transplantation (HCT) strategy for advanced acute myeloid leukemia or high-risk myelodysplastic syndrome patients. Fifteen patients received 332 to 1561 mCi of (131)I, delivering an average of 27 Gy to bone marrow, 84 Gy to spleen, and 21 Gy to liver. Although a maximum dose of 28 Gy was delivered to the liver, no dose-limiting toxicity was observed. Marrow doses were arbitrarily capped at 43 Gy to avoid radiation-induced stromal damage; however, no graft failure or evidence of stromal damage was observed. Twelve patients (80%) developed grade II graft-versus-host disease (GVHD), 1 patient developed grade III GVHD, and no patients developed grade IV GVHD during the first 100 days after HCT. Of the 12 patients with chronic GVHD data, 10 developed chronic GVHD, generally involving the skin and mouth. Six patients (40%) are surviving after a median of 5.0 years (range, 4.2 to 8.3 years). The estimated survival at 1 year was 73% among the 15 treated patients. Eight patients relapsed, 7 of whom subsequently died. The median time to relapse among these 8 patients was 54 days (range, 26 to 1364 days). No cases of nonrelapse mortality were observed in the first year after transplantation. However, 2 patients died in remission from complications of chronic GVHD and cardiomyopathy, at 18 months and 14 months after transplantation, respectively. This study suggests that patients may tolerate myeloablative doses >28 Gy delivered to the liver using (131)I-anti-CD45 antibody in addition to standard reduced-intensity conditioning. Moreover, the arbitrary limit of 43 Gy to the marrow may be unnecessarily conservative, and continued escalation of targeted radioimmunotherapy doses may be feasible to further reduce relapse.

  12. Myelodysplastic syndrome in children and adolescents.

    Science.gov (United States)

    Niemeyer, Charlotte M; Baumann, Irith

    2008-01-01

    Myelodysplastic syndromes (MDS) are clonal disorders characterized by ineffective hematopoiesis and subsequent frequent development of acute myeloid leukemia (AML). In children and adolescents, MDS are uncommon disorders, accounting for less than 5% of hematopoietic malignancy, with great heterogeneity in presentation and clinical course. The genetic changes predisposing children to MDS are largely obscure. Monosomy 7 is the most common chromosomal abnormality, often occurring as a sole abnormality. The recent pediatric modification of the World Health Organization (WHO) classification has greatly facilitated the diagnostic process. Refractory cytopenia (RC) is the most common MDS subtype in children, occurring in about half of all MDS cases. There is consensus that the relationship between MDS with increased blast count and de novo AML is better defined by biological and clinical features than by blast count. Because monosomy 7 is the only chromosomal abnormality strongly suggestive of MDS, children presenting with a low blast count and other chromosomal aberrations or normal karyotype must be closely observed before a diagnosis of MDS can be established. With an increasing number of children surviving primary cancer with chemotherapy or radiation therapy, the incidence of secondary therapy-related MDS is rising. The MDS risk is also increased in patients with inherited bone marrow failure disorders; this relationship provides valuable insights into MDS biology. Allogeneic hematopoietic stem cell transplantation (HSCT) from a matched related or suitable unrelated donor is the choice for most children with MDS and can rescue a large proportion of patients.

  13. Myelodysplastic syndromes: therapeutic problems and decisions (review

    Directory of Open Access Journals (Sweden)

    S. V. Semochkin

    2012-01-01

    Full Text Available Myelodysplastic syndromes (MDS are a group of heterogeneous clonal disorders of myeloid hematopoietic stem cells characterized by an ineffective hematopoiesis associated with cytopenias, morphologic dysplasia and a progression to acute myeloid leukemia. The only potentially curative MDS treatment is hematopoietic stem cell transplantation, which is usually not even discussed because most patients with advanced age at diagnosis. Currently only three drugs are approved by US Food and Drug Administration (FDA and European Medicines Agency for therapy of MDS. For low and intermediate-1 risk MDS del(5q the novel immunomodulatory drug lenalidomide is asserted, and for intermediate-2 and high risk the two hypomethylating agents (azacitidine, decitabine are approved. The results of completed clinical trials demonstrating the efficacy and safety of these agents are presented. The new data indicating that the successful future of MDS treatment rests in the combination of multiple treatments modalities to achieve improved clinical outcomes are discussed in this review.

  14. Myelodysplastic syndromes: therapeutic problems and decisions (review

    Directory of Open Access Journals (Sweden)

    S. V. Semochkin

    2014-07-01

    Full Text Available Myelodysplastic syndromes (MDS are a group of heterogeneous clonal disorders of myeloid hematopoietic stem cells characterized by an ineffective hematopoiesis associated with cytopenias, morphologic dysplasia and a progression to acute myeloid leukemia. The only potentially curative MDS treatment is hematopoietic stem cell transplantation, which is usually not even discussed because most patients with advanced age at diagnosis. Currently only three drugs are approved by US Food and Drug Administration (FDA and European Medicines Agency for therapy of MDS. For low and intermediate-1 risk MDS del(5q the novel immunomodulatory drug lenalidomide is asserted, and for intermediate-2 and high risk the two hypomethylating agents (azacitidine, decitabine are approved. The results of completed clinical trials demonstrating the efficacy and safety of these agents are presented. The new data indicating that the successful future of MDS treatment rests in the combination of multiple treatments modalities to achieve improved clinical outcomes are discussed in this review.

  15. Historical perspectives on myelodysplastic syndromes.

    Science.gov (United States)

    Steensma, David P

    2012-12-01

    Although Georg Hegel quipped, "We learn from history that we do not learn from history", Aldous Huxley expressed a more nuanced view: "The charm of history and its enigmatic lesson consist in the fact that, from age to age, nothing changes and yet everything is completely different." In order to understand present-day positions and peculiarities in any field of human endeavor, familiarity with the past is essential. Those of us who study myelodysplastic syndromes (MDS) or care for patients diagnosed with these troublesome conditions may wonder also how the current state of affairs evolved with respect to our narrow area of focus, and how we know what we think we know now about these still-enigmatic bone marrow diseases. Here, I review a number of developments that collectively represent a brief "history of MDS." I first highlight a few landmark observations that preceded any concept of MDS by hundreds of years. Twentieth-century case descriptions and series with hypotheses about the etiology and nature of disorders described as "refractory anemia", "preleukemia", and with other terminology culminated in the efforts of the French-American-British (FAB) Co-operative Group of morphologists, whose landmark 1976 and 1982 papers provided the first widely-used classification of MDS. More recent developments in the MDS field include new mechanistic biological insights, regulatory approval of several somewhat-effective treatments, and improved organizational support and advocacy. The history of a disease concept like MDS, as for history in general, provides both inspiration and cautionary tales that can inform present and future work.

  16. Single- vs double-unit cord blood transplantation for children and young adults with acute leukemia or myelodysplastic syndrome.

    Science.gov (United States)

    Michel, Gérard; Galambrun, Claire; Sirvent, Anne; Pochon, Cecile; Bruno, Benedicte; Jubert, Charlotte; Loundou, Anderson; Yakoub-Agha, Ibrahim; Milpied, Noel; Lutz, Patrick; Marie-Cardine, Aude; Gandemer, Virginie; Blaise, Didier; Michallet, Mauricette; Rialland, Fanny; Renard, Cecile; Oudin, Claire; Esmiol, Sophie; Seux, Mylene; Baumstarck, Karine; Mohty, Mohamad; Rocha, Vanderson; Dalle, Jean-Hugues

    2016-06-30

    Transplantation of 2 unrelated cord blood (UCB) units instead of 1 has been proposed to increase the cell dose. We report a prospective randomized study, designed to compare single- vs double-UCB transplantation in children and young adults with acute leukemia in remission or myelodysplasia. Eligible patients had at least two 4-6 HLA-identical UCBs with >3 × 10(7) nucleated cells/kg for the first and >1.5 × 10(7) for the second. The primary end point was the 2-year cumulative incidence of transplantation strategy failure, a composite end point including transplant-related mortality (TRM), engraftment failure, and autologous recovery. Randomized patients who did not proceed to transplantation due to refractory disease were considered transplantation failures. A total of 151 patients were randomized and included in the intent-to-treat analysis; 137 were transplanted. Double-UCB transplantation did not decrease transplantation strategy failure (23.4% ± 4.9% vs 14.9% ± 4.2%). Two-year posttransplant survival, disease-free survival, and TRM were 68.8% ± 6.0%, 67.6% ± 6.0%, and 5.9% ± 2.9% after single-unit transplantation compared with 74.8% ± 5.5%, 68.1% ± 6.0%, and 11.6% ± 3.9% after double-unit transplantation. The final relapse risk did not significantly differ, but relapses were delayed after double-unit transplantation. Overall incidences of graft-versus-host disease (GVHD) were similar, but chronic GVHD was more frequently extensive after double-UCB transplantation (31.9% ± 5.7% vs 14.7% ± 4.3%, P = .02). In an exploratory subgroup analysis, we found a significantly lower relapse risk after double-unit transplantation in patients receiving total body irradiation without antithymocyte globulin (ATG), whereas the relapse risk was similar in the group treated with busulfan, cyclophosphamide, and ATG. Single-UCB transplantation with adequate cell dose remains the standard of care and leads to low TRM. Double-unit transplantation should be reserved for

  17. Selumetinib in Treating Patients With Recurrent or Refractory Acute Myeloid Leukemia

    Science.gov (United States)

    2015-07-06

    Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Promyelocytic Leukemia (M3); Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasms; Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia

  18. Innate Immunity Dysregulation in Myelodysplastic Syndromes

    Science.gov (United States)

    2013-10-01

    IL, interleukin; ITAM, immunoreceptor tyrosine-based activating motif; MDS, myelodysplastic syndromes; NADPH, nicotinamide adenine dinucleotide...differentiation, including macrophage, skin cells and neurons.19,2on In this study, we have shown that knock down of JMJ03 in BM C034 + cells of lower

  19. Myelodysplastic syndromes: histopathology as prognostic factor

    Directory of Open Access Journals (Sweden)

    Romeo Maura

    2001-01-01

    Full Text Available Bone marrow biopsy allows evaluation of cellularity, abnormal localization of immature precursors and fibrosis in myelodysplastic syndrome. It has been considered important to make diagnosis and prognosis of this disorder. The object of this study evaluated the influence of histopathological parameters, such as cellularity, erythroid/myeloid ratio, abnormal localization of immature precursors and marrow fibrosis, on survival of myelodysplastic syndrome patients. Forty-six patients, admitted from April 1985 to June 1998, and diagnosed as being myelodysplastic syndrome according to French-American-British criteria, were selected. There were 20 males and 26 females, with median age of 61 years. Forty-six bone marrow smears and 36 trephine biopsies were reviewed. Mean survival of hypocellular cases was 64.8 months and of hyper and normocellular cases was 31.8 months. Patients with predominance of erythroid hyperplasia had mean survival of 50.8 months, greater than those with predominance of myeloid hyperplasia (20.3 months. There was no statistical difference in survival of patients with or without abnormal localization of immature precursors and with or without marrow fibrosis. Bone marrow biopsy is a useful tool for the identification of parameters that influence prognosis in myelodysplastic syndrome. Hypocellularity and erythroid hyperplasia were correlated with longer survival while myeloid hyperplasia with poorer survival.

  20. IER3 Expression in Childhood Myelodysplastic Syndrome

    DEFF Research Database (Denmark)

    de Vries, Andrica; Zwaan, Christian M.; Danen van Ooschot, Astrid

    Background: Childhood myelodysplastic syndrome (MDS) is a rare disease accounting for less than 5% of all hematological malignancies. In about 50% of the MDS cases an abnormal karyotype is found by conventional karyotyping, of which chromosome 6 is involved in 10%. The immediate-early-response 3 ...

  1. Valproic acid for the treatment of low-risk myelodysplastic syndromes: A case report and a review of the literature

    OpenAIRE

    2013-01-01

    Myelodysplastic syndromes are heterogeneous myeloid neoplasms ranging from indolent conditions with a near-normal life expectancy to forms approaching acute myeloid leukemia. Here we report a 51-year-old woman with depression and severe obesity who was diagnosed with an International Prognostic Scoring System low-risk myelodysplastic syndrome, presenting mainly with thrombocytopenia, treated with escalating dose of valproic acid as a single agent. After two years of treatment her platelet cou...

  2. Increased relative risk of myelodysplastic syndrome in atomic bomb survivors

    Energy Technology Data Exchange (ETDEWEB)

    Oda, Kenji [Hiroshima City Hospital (Japan); Kimura, Akiro; Matsuo, Tatsuki; Tomonaga, Masao; Kodama, Kazunori; Mabuchi, Kiyohiko

    1998-12-01

    It was investigated what blood disorders except leukemia increased the relative risk with dose dependency in atomic bomb survivors. Subjects were 217 patients of atomic bomb survivors in Hiroshima and Nagasaki, who had blood disorders except leukemia and died between 1950 and 1990. Their medical records were analyzed and their diagnoses were reevaluated. Sixteen cases were diagnosed as the aplastic anemia and 12 as the myelodysplastic syndrome (MDS). In the aplastic anemia, there was no correlation between the exposure dose and the mortality. In MDS, the excess relative risk (ERR)/bone marrow exposure dose of 1 Sv was very high (13.0). These results supports the hypothesis that MDS would be broken out by the clonal abnormality of the hematopoietic stem cell and radiation exposure could cause the appearance of the abnormal stem cell clone. (K.H.)

  3. Molecular bases of myelodysplastic syndromes: lessons from animal models.

    Science.gov (United States)

    Komeno, Yukiko; Kitaura, Jiro; Kitamura, Toshio

    2009-06-01

    Myelodysplastic syndrome (MDS) is a clonal disorder of hematopietic stem cells characterized by ineffective hematopoiesis, peripheral blood cytopenia, morphologic dysplasia, and susceptibility to acute myeloid leukemia. Several mechanisms have been suggested as causes of MDS: unbalanced chromosomal abnormalities reflecting a gain or loss of chromosomal material, point mutations of transcription factors, and inactivation of p53. However, appropriate animal models that mimic MDS have long been lacking. We recently reported a novel murine model of MDS that recapitulates trilineage dysplasia and transformation to AML. In this review, we summarize the animal models of MDS and discuss the molecular bases of MDS as well as those of leukemia and myeloproliferative disorders (MPD). J. Cell. Physiol. 219: 529-534, 2009. (c) 2009 Wiley-Liss, Inc.

  4. Myelodysplastic syndrome with inv(3)(q21q26.2) or t(3;3)(q21;q26.2) has a high risk for progression to acute myeloid leukemia.

    Science.gov (United States)

    Cui, Wei; Sun, Jianlan; Cotta, Claudiu V; Medeiros, L Jeffrey; Lin, Pei

    2011-08-01

    Acute myeloid leukemia (AML) with inv(3) (q21q26.2) or t(3;3)(q21;q26.2) is a distinct subtype in the World Health Organization classification. The natural history of myelodysplastic syndrome (MDS) associated with these cytogenetic aberrations is poorly understood. We studied 17 MDS (11 de novo and 6 therapy related) and 3 chronic myelomonocytic leukemia (CMML) cases associated with inv(3) (q21q26.2) or t(3;3)(q21;q26.2). The de novo cases were further classified as refractory cytopenia with multilineage dysplasia (n = 8) and refractory anemia with excess blasts (n = 3). Isolated inv(3)/t(3;3) was identified in 4 cases, whereas -7/7q (n = 13) and -5/5q (n = 6) were common additional aberrations. Nineteen patients died, including 13 in whom the disease progressed to AML after a median of 7 months. Median survival for patients with de novo disease was similar to that for patients with therapy-related MDS (13 vs 17.5 months). MDS or CMML with inv(3)/t(3;3) are aggressive diseases with a high risk of progression to AML.

  5. Monosomal karyotype predicts poor survival after allogeneic stem cell transplantation in chromosome 7 abnormal myelodysplastic syndrome and secondary acute myeloid leukemia.

    Science.gov (United States)

    van Gelder, M; de Wreede, L C; Schetelig, J; van Biezen, A; Volin, L; Maertens, J; Robin, M; Petersen, E; de Witte, T; Kröger, N

    2013-04-01

    Treatment algorithms for poor cytogenetic-risk myelodysplastic syndrome (MDS), defined by chromosome 7 abnormalities or complex karyotype (CK), include allogeneic stem cell transplantation (alloSCT). We studied outcome of alloSCT in chromosome 7 abnormal MDS patients as this data are scarce in literature. We specifically focused on the impact of the extra presence of CK and monosomal karyotype (MK). The European Group for Blood and Marrow Transplantation database contained data on 277 adult MDS patients with a chromosome 7 abnormality treated with alloSCT. Median age at alloSCT was 45 years. Median follow-up of patients alive was 5 years. Five-year progression-free survival (PFS) and overall survival (OS) were 22% and 28%, respectively. In multivariate analysis, statistically significant predictors for worse PFS were higher MDS stages treated, but not in complete remission (CR) (hazards ratio (HR) 1.7), and the presence of CK (HR 1.5) or MK (HR 1.8). Negative predictive factors for OS were higher MDS stages treated, but not in CR (HR 1.8), and the presence of CK (HR 1.6) or MK (HR 1.7). By means of the cross-validated log partial likelihood, MK showed to have a better predictive value than CK. The results are relevant when considering alloSCT for higher-stage MDS patients having MK including a chromosome 7 abnormality.

  6. Long-Term Outcomes after Treatment with Clofarabine ± Fludarabine with Once-Daily Intravenous Busulfan as Pretransplant Conditioning Therapy for Advanced Myeloid Leukemia and Myelodysplastic Syndrome.

    Science.gov (United States)

    Alatrash, Gheath; Thall, Peter F; Valdez, Benigno C; Fox, Patricia S; Ning, Jing; Garber, Haven R; Janbey, Selma; Worth, Laura L; Popat, Uday; Hosing, Chitra; Alousi, Amin M; Kebriaei, Partow; Shpall, Elizabeth J; Jones, Roy B; de Lima, Marcos; Rondon, Gabriela; Chen, Julianne; Champlin, Richard E; Andersson, Borje S

    2016-10-01

    Pretransplant conditioning regimens critically determine outcomes in the setting of allogeneic stem cell transplantation (allo-SCT). The use of nucleoside analogs such as fludarabine (Flu) in combination with i.v. busulfan (Bu) has been shown to be highly effective as a pretransplant conditioning regimen in acute myeloid leukemia (AML), chronic myeloid leukemia (CML), and myelodysplastic syndrome (MDS). Because leukemia relapse remains the leading cause of death after allo-SCT, we studied whether clofarabine (Clo), a nucleoside analog with potent antileukemia activity, can be used to complement Flu. In a preliminary report, we previously showed the safety and efficacy of Clo ± Flu with i.v. Bu in 51 patients with high-risk AML, CML, and MDS. The study has now been completed, and we present long-term follow-up data on the entire 70-patient population, which included 49 (70%), 8 (11%), and 13 (19%) patients with AML, MDS, and CML, respectively. Thirteen patients (19%) were in complete remission, and 41 patients (59%) received matched unrelated donor grafts. Engraftment was achieved in all patients. Sixty-three patients (90%) achieved complete remission. There were no deaths reported at day +30, and the 100-day nonrelapse mortality rate was 4% (n = 3). Thirty-one percent of patients (n = 22) developed grades II to IV acute graft-versus-host disease, and the median overall survival and progression-free survival times were 2.4 years and .9 years, respectively. Our results confirm the safety and overall and progression-free survival advantage of the arms with higher Clo doses and lower Flu doses, which was most prominent in the AML/MDS group.

  7. Myelodysplastic Syndrome Occurring in a Patient with Gorlin Syndrome.

    Science.gov (United States)

    Mull, Jamie L; Madden, Lisa M; Bayliss, Susan J

    2016-07-01

    We report a case of myelodysplastic syndrome (MDS) occurring in an African American boy with Gorlin syndrome with a novel PTCH1 mutation. Before developing MDS, the patient had been treated with chemotherapy and radiation for a medulloblastoma. He received a bone marrow transplant for the MDS and eventually died of treatment complications. Secondary hematologic malignancies are a known complication of certain chemotherapeutics, although whether a patient with Gorlin syndrome has a greater propensity for the development of such malignancies is unclear.

  8. Prognostic value of circulating CD34+ cells in myelodysplastic syndromes.

    Science.gov (United States)

    Cesana, Clara; Klersy, Catherine; Brando, Bruno; Nosari, Annamaria; Scarpati, Barbara; Scampini, Linda; Molteni, Alfredo; Nador, Guido; Santoleri, Luca; Formenti, Marta; Valentini, Marina; Mazzone, Antonino; Morra, Enrica; Cairoli, Roberto

    2008-11-01

    We studied circulating (C)CD34(+) cells by flow cytometry in 96 patients with myelodysplastic syndromes (MDS) at diagnosis, and in a subset of 35 cases during follow-up. CCD34(+) counts were stratified within both International Prognostic Scoring System (IPSS) and World Health Organization (WHO) categories. Counts >10/microl were associated with poorer leukemia-free survival, a prognostic value for evolution independent from that of WHO, and a higher progression probability within intermediate-risk IPSS and WHO classes. When serial measurements were performed, counts >10/microl more frequently correlated to evolution. Separating newly diagnosed patients on the basis of 10/microl cut-off of circulating CD34(+) cells retains prognostic utility, especially in intermediate-risk MDS.

  9. [Clinical efficacy of decitabine plus improved CAG chemotherapy and haplo-identical donor peripheral lymphocyte infusion regimen on elderly patients with high risk myelodysplastic syndrome and acute myeloid leukemia].

    Science.gov (United States)

    Dou, Li-Ping; Jing, Yu; Wang, Quan-Shun; Mei, Jun-Hui; Yu, Li

    2013-06-01

    This study was aimed to observe the clinical efficacy and adverse effects of decitabine plus improved CAG chemotherapy and haploid-identical donor peripheral lymphocyte infusion regimen on elderly patients with myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Five elderly patients with MDS and AML were treated with decitabine plus improved CAG chemotherapy and donor peripheral lymphocyte infusion regimen. Examinations on liver and renal function, electrocardiogram and bone marrow analysis were performed before and after treatment, and adverse effects were observed. The results indicated that after a course of treatment by decitabine plus improved CAG chemotherapy and haplo-identical donor peripheral lymphocyte infusion regimen, the total effective rate was 100%, and 4 patients (80%) achieved complete remission, 1 patient achieved partial remission. The dominant clinical adverse effect was bone marrow depression, the median time of neutrophil>0.5×10(9)/L and platelet>20×10(9)/L was 15 d and 16 d respectively for patients without previous MDS. It is concluded that decitabine plus improved CAG chemotherapy and haploid-identical donor peripheral lymphocyte infusion regimen may be effective with less adverse effects for elderly primary AML and high risk MDS patients, it is a promising therapeutic methods and worthy to deeply study.

  10. Treatment of acute myeloid leukemia or myelodysplastic syndrome relapse after allogeneic stem cell transplantation with azacitidine and donor lymphocyte infusions--a retrospective multicenter analysis from the German Cooperative Transplant Study Group.

    Science.gov (United States)

    Schroeder, Thomas; Rachlis, Elena; Bug, Gesine; Stelljes, Matthias; Klein, Stefan; Steckel, Nina Kristin; Wolf, Dominik; Ringhoffer, Mark; Czibere, Akos; Nachtkamp, Kathrin; Dienst, Ariane; Kondakci, Mustafa; Stadler, Michael; Platzbecker, Uwe; Uharek, Lutz; Luft, Thomas; Fenk, Roland; Germing, Ulrich; Bornhäuser, Martin; Kröger, Nicolaus; Beelen, Dietrich W; Haas, Rainer; Kobbe, Guido

    2015-04-01

    To expand the current knowledge about azacitidine (Aza) and donor lymphocyte infusions (DLI) as salvage therapy for relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and to identify predictors for response and survival, we retrospectively analyzed data of 154 patients with acute myeloid leukemia (AML, n = 124), myelodysplastic (MDS, n = 28), or myeloproliferative syndrome (n = 2). All patients received a median number of 4 courses of Aza (range, 4 to 14) and DLI were administered to 105 patients (68%; median number of DLI, 2; range, 1 to 7). Complete and partial remission rates were 27% and 6%, respectively, resulting in an overall response rate of 33%. Multivariate analysis identified molecular-only relapse (hazard ratio [HR], 9.4; 95% confidence interval [CI], 2.0 to 43.5; P = .004) and diagnosis of MDS (HR, 4.1; 95% CI, 1.4 to 12.2; P = .011) as predictors for complete remission. Overall survival (OS) at 2 years was 29% ± 4%. Molecular-only relapse (HR, .14; 95% CI, .03 to .59; P = .007), diagnosis of MDS (HR, .33; 95% CI, .16 to .67; P = .002), and bone marrow blasts after allo-HSCT, in particular those with MDS or AML and low disease burden. The latter finding emphasizes the importance of stringent disease monitoring and early intervention.

  11. Allogeneic hematopoietic cell transplantation after conditioning with I-131-anti-CD45 antibody plus fludarabine and low-dose total body irradiation for elderly patients with advanced acute myeloid leukemia or high-risk myelodysplastic syndrome.

    Energy Technology Data Exchange (ETDEWEB)

    Pagel, John M.; Gooley, T. A.; Rajendran, Joseph G.; Fisher, Darrell R.; Wilson, Wendy A.; Sandmaier, B. M.; Matthews, D. C.; Deeg, H. Joachim; Gopal, Ajay K.; Martin, P. J.; Storb, R.; Press, Oliver W.; Appelbaum, Frederick R.

    2009-12-24

    We conducted a study to estimate the maximum tolerated dose (MTD) of I-131-anti-CD45 antibody (Ab; BC8) that can be combined with a standard reduced-intensity conditioning regimen before allogeneic hematopoietic cell transplantation. Fifty-eight patients older than 50 years with advanced acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (MDS) were treated with (131)I-BC8 Ab and fludarabine plus 2 Gy total body irradiation. Eighty-six percent of patients had AML or MDS with greater than 5% marrow blasts at the time of transplantation. Treatment produced a complete remission in all patients, and all had 100% donor-derived CD3(+) and CD33(+) cells in the blood by day 28 after the transplantation. The MTD of I-131-BC8 Ab delivered to liver was estimated to be 24 Gy. Seven patients (12%) died of nonrelapse causes by day 100. The estimated probability of recurrent malignancy at 1 year is 40%, and the 1-year survival estimate is 41%. These results show that CD45-targeted radiotherapy can be safely combined with a reduced-intensity conditioning regimen to yield encouraging overall survival for older, high-risk patients with AML or MDS. This study was registered at www.clinicaltrials.gov as #NCT00008177.

  12. Allogeneic hematopoietic cell transplantation after conditioning with 131I-anti-CD45 antibody plus fludarabine and low-dose total body irradiation for elderly patients with advanced acute myeloid leukemia or high-risk myelodysplastic syndrome.

    Science.gov (United States)

    Pagel, John M; Gooley, Theodore A; Rajendran, Joseph; Fisher, Darrell R; Wilson, Wendy A; Sandmaier, Brenda M; Matthews, Dana C; Deeg, H Joachim; Gopal, Ajay K; Martin, Paul J; Storb, Rainer F; Press, Oliver W; Appelbaum, Frederick R

    2009-12-24

    We conducted a study to estimate the maximum tolerated dose (MTD) of (131)I-anti-CD45 antibody (Ab; BC8) that can be combined with a standard reduced-intensity conditioning regimen before allogeneic hematopoietic cell transplantation. Fifty-eight patients older than 50 years with advanced acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (MDS) were treated with (131)I-BC8 Ab and fludarabine plus 2 Gy total body irradiation. Eighty-six percent of patients had AML or MDS with greater than 5% marrow blasts at the time of transplantation. Treatment produced a complete remission in all patients, and all had 100% donor-derived CD3(+) and CD33(+) cells in the blood by day 28 after the transplantation. The MTD of (131)I-BC8 Ab delivered to liver was estimated to be 24 Gy. Seven patients (12%) died of nonrelapse causes by day 100. The estimated probability of recurrent malignancy at 1 year is 40%, and the 1-year survival estimate is 41%. These results show that CD45-targeted radiotherapy can be safely combined with a reduced-intensity conditioning regimen to yield encouraging overall survival for older, high-risk patients with AML or MDS. This study was registered at www.clinicaltrials.gov as #NCT00008177.

  13. Cytoreductive treatment with clofarabine/ara-C combined with reduced-intensity conditioning and allogeneic stem cell transplantation in patients with high-risk, relapsed, or refractory acute myeloid leukemia and advanced myelodysplastic syndrome.

    Science.gov (United States)

    Buchholz, Stefanie; Dammann, Elke; Stadler, Michael; Krauter, Juergen; Beutel, Gernot; Trummer, Arne; Eder, Matthias; Ganser, Arnold

    2012-01-01

    The combination of cytoreductive chemotherapy with reduced-intensity conditioning (RIC) is a highly effective antileukemic therapy. Purpose of this retrospective analysis was to evaluate the antileukemic efficacy and toxicity of clofarabine-based chemotherapy followed by RIC and allogeneic stem cell transplantation (SCT) for high-risk, relapsed, or refractory acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS). From May 2007 until October 2009, a total of 27 patients underwent allogeneic SCT after treatment with clofarabine and ara-C for 5d and RIC (4Gy TBI/cyclophosphamide/ATG). Prophylaxis of graft-versus-host disease (GvHD) consisted of cyclosporine and mycophenolate mofetil. Unmanipulated G-CSF mobilized PBSC (n=26) or bone marrow cells (n=1) were transplanted from unrelated (n=21) or matched related (n=6) donors. Non-hematological toxicities of this regimen mainly affected liver and skin and were all reversible. Seven patients relapsed within a median time of 5.7 months. The overall survival (OS) and relapse-free survival rates were 56% and 52% at 2 yr, respectively. In this cohort of patients, cytoreduction with clofarabine/ara-C (ClAraC) followed by RIC allogeneic SCT was well tolerated and showed good antileukemic efficacy even in patients with high-risk AML or MDS, with engraftment and GvHD-incidence comparable to other RIC regimens.

  14. Effect of Granulocyte Colony-Stimulating Factor-Combined Conditioning in Cord Blood Transplantation for Myelodysplastic Syndrome and Secondary Acute Myeloid Leukemia: A Retrospective Study in Japan.

    Science.gov (United States)

    Konuma, Takaaki; Takahashi, Satoshi; Uchida, Naoyuki; Kuwatsuka, Yachiyo; Yamasaki, Satoshi; Aoki, Jun; Onishi, Yasushi; Aotsuka, Nobuyuki; Ohashi, Kazuteru; Mori, Takehiko; Masuko, Masayoshi; Nakamae, Hirohisa; Miyamura, Kouichi; Kato, Koji; Atsuta, Yoshiko; Kato, Seiko; Asano, Shigetaka; Takami, Akiyoshi; Miyazaki, Yasushi

    2015-09-01

    Granulocyte colony-stimulating factor (G-CSF) increases the susceptibility of dormant malignant or nonmalignant hematopoietic cells to cytarabine arabinoside (Ara-C) through the induction of cell cycle entry. Therefore, G-CSF-combined conditioning before allogeneic stem cell transplantation might positively contribute to decreased incidences of relapse and graft failure without having to increase the dose of cytotoxic drugs. We conducted a retrospective nationwide study of 336 adult patients with myelodysplastic syndrome (MDS) and secondary acute myeloid leukemia (sAML) after single-unit cord blood transplantation (CBT) who underwent 4 different kinds of conditioning regimens: total body irradiation (TBI) ≥ 8 Gy + Ara-C/G-CSF + cyclophosphamide (CY) (n = 65), TBI ≥ 8 Gy + Ara-C + CY (n = 119), TBI ≥ 8 Gy + other (n = 104), or TBI < 8 Gy or non-TBI (n = 48). The TBI ≥ 8 Gy + Ara-C/G-CSF + CY regimen showed significantly higher incidence of neutrophil engraftment (hazard ratio, 1.52; 95% confidence interval [CI], 1.10 to 2.08; P = .009) and lower overall mortality (hazard ratio, .46; 95% CI, .26 to .82; P = .008) rates compared with those without a G-CSF regimen. This retrospective study shows that the G-CSF-combined conditioning regimen provides better engraftment and survival results in CBT for adults with MDS and sAML.

  15. Specific scoring systems to predict survival of patients with high-risk myelodysplastic syndrome (MDS) and de novo acute myeloid leukemia (AML) after intensive antileukemic treatment based on results of the EORTC-GIMEMA AML-10 and intergroup CRIANT studies.

    Science.gov (United States)

    Oosterveld, Margriet; Suciu, Stefan; Muus, Petra; Germing, Ulrich; Delforge, Michel; Belhabri, Amin; Aul, Carlo; Selleslag, Dominik; Ferrant, Augustin; Marie, Jean-Pierre; Amadori, Sergio; Jehn, Ulrich; Mandelli, Franco; Hess, Uwe; Hellström-Lindberg, Eva; Cakmak-Wollgast, Songuel; Vignetti, Marco; Labar, Boris; Willemze, Roel; de Witte, Theo

    2015-01-01

    High-risk myelodysplastic syndrome (MDS) patients have usually a less favorable outcome after intensive treatment compared with de novo acute myeloid leukemia (AML) patients. This may reflect different disease-related and patient-related factors. The purpose of this analysis is to identify disease-specific prognostic factors and to develop prognostic scores for both patient groups. A total of 692 patients in the EORTC/GIMEMA AML-10 study and 289 patients in the CRIANT study received identical remission-induction and consolidation treatment. Estimated 5-year survival rate was 34 % in the AML-10 versus 27 % in the CRIANT study, and estimated disease-free survival was 40 % versus 28 %, respectively. In multivariate analysis, cytogenetic characteristics, white blood count, and age appeared prognostic for survival in both studies. French-American-British (FAB) subtype and performance status were prognostic in the AML-10 study only, whereas number of cytopenias and duration of antecedent hematologic disorder >6 months were prognostic in the CRIANT study only. The prognostic scores distinguish three groups with a 5-year survival rate of 54, 38, and 19 % in the AML-10 study versus 69, 37, and 5 % in the CRIANT study. The prognostic value of these scores has been validated on two external series. The new scoring systems form a practical tool to predict the outcome of individual MDS and AML patients treated with intensive antileukemic therapy.

  16. Combined mutations of ASXL1, CBL, FLT3, IDH1, IDH2, JAK2, KRAS, NPM1, NRAS, RUNX1, TET2 and WT1 genes in myelodysplastic syndromes and acute myeloid leukemias

    Directory of Open Access Journals (Sweden)

    Vey Norbert

    2010-08-01

    Full Text Available Abstract Background Gene mutation is an important mechanism of myeloid leukemogenesis. However, the number and combination of gene mutated in myeloid malignancies is still a matter of investigation. Methods We searched for mutations in the ASXL1, CBL, FLT3, IDH1, IDH2, JAK2, KRAS, NPM1, NRAS, RUNX1, TET2 and WT1 genes in 65 myelodysplastic syndromes (MDSs and 64 acute myeloid leukemias (AMLs without balanced translocation or complex karyotype. Results Mutations in ASXL1 and CBL were frequent in refractory anemia with excess of blasts. Mutations in TET2 occurred with similar frequency in MDSs and AMLs and associated equally with either ASXL1 or NPM1 mutations. Mutations of RUNX1 were mutually exclusive with TET2 and combined with ASXL1 but not with NPM1. Mutations in FLT3 (mutation and internal tandem duplication, IDH1, IDH2, NPM1 and WT1 occurred primarily in AMLs. Conclusion Only 14% MDSs but half AMLs had at least two mutations in the genes studied. Based on the observed combinations and exclusions we classified the 12 genes into four classes and propose a highly speculative model that at least a mutation in one of each class is necessary for developing AML with simple or normal karyotype.

  17. A FISH comparison of variant derivatives of the recurrent dic(17;20) of myelodysplastic syndromes and acute myeloid leukemia: Obligatory retention of genes on 17p and 20q may explain the formation of dicentric chromosomes.

    Science.gov (United States)

    MacKinnon, Ruth N; Patsouris, Cris; Chudoba, Ilse; Campbell, Lynda J

    2007-01-01

    The dic(17;20) is a recurrent unbalanced translocation occurring rarely in myelodysplastic syndromes and acute myeloid leukemia. We have studied eleven cases with the dic(17;20) or a more complex derivative, all of which showed deletion of 17p and 20q material. The tumor suppressor gene TP53 was not always lost, supporting a more distal gene as the target of these 17p deletions. All derivatives could be interpreted as having initially been formed as a dicentric chromosome, those with a larger amount of material between the centromeres having undergone further rearrangement to stabilize the chromosome while retaining proximal 17p and proximal 20q material. We propose that critical sequences on both 17p and 20q proximal to the sites of deletion must be retained during the critical 17p and 20q deletions. This would explain the excess of dicentric chromosomes resulting from 17;20 translocation, and the apparent stabilization of the unstable derivatives by further rearrangements which preserve 17p and 20q material.

  18. Clinical, cytogenetic and dual-color FISH studies on five cases of myelodysplastic syndrome or acute myeloid leukemia patients with 1;7 translocation

    Institute of Scientific and Technical Information of China (English)

    申咏梅; 薛永权; 李建勇; 潘金兰; 吴亚芳

    2003-01-01

    Objective To study the clinical and cytogenetic characteristics of four patients with myel odysplastic syndrome (MDS) and one with acute myeloid leukemia experiencing t(1; 7).Methods Five patients seen in our hospital from 1992 to 2001 were diagnosed as MDS and acute myelocytic leukemia (AML) according to the French-American-British (FAB) criteria. Chromosomes were prepared using the direct method as well as 24-hou r unstimulated cultures of fresh heparinized bone marrow for each subject, while R-banding was used to analyze karyotypes. Dual-color fluorescence in situ hy bridization (FISH) using SpectrumRed and SpectrumGreen directly labeled chromoso me 1-specific α-satellite DNA probe (red) and chromosome 7- specific α-sat ellite DNA probe (green) was performed for three cases. Results Of the five patients, three had 1;7 translocation due to along history of expos ure to benzene. In three cases, dual-color FISH resulted in three red signals and two green ones, in which one red signal adjoining one green signal in 27.6% , 84% and 18.5% metaphases, respectively. Conclusions Exposure to benzene may be the cause for Chinese MDS and AML patients with t(1;7 ) translocation. The result of dual-color FISH convincingly confirmed that the centromere of the derivative chromosome 7p/1q resulting from 1;7 translocation was made up of centromeres from both chromosomes 1 and 7.

  19. The use of low-dose protracted oral clofarabine in a patient with myelodysplastic syndrome after failing 5-azacitidine

    OpenAIRE

    2013-01-01

    Patients with myelodysplastic syndrome who fail hypomethylating agents have a very short median survival and about 25% risk of disease transformation to acute myeloid leukemia. We report our experience with low-dose protracted oral clofarabine in one patient who achieved stable disease for more than two years after failing 5-azacitidine.

  20. Myelodysplastic syndrome: classification and prognostic systems

    Directory of Open Access Journals (Sweden)

    Rosangela Invernizzi

    2011-12-01

    Full Text Available Myelodysplastic syndromes (MDS are acquired clonal disorders of hematopoiesis, that are characterized most frequently by normocellular or hypercellular bone marrow specimens, and maturation that is morphologically and functionally dysplastic. MDS constitute a complex hematological problem: differences in disease presentation, progression and outcome have made it necessary to use classification systems to improve diagnosis, prognostication and treatment selection. On the basis of new scientific and clinical information, classification and prognostic systems have recently been updated and minimal diagnostic criteria forMDS have been proposed by expert panels. In addition, in the last few years our ability to define the prognosis of the individual patient with MDS has improved. In this paper World Health Organization (WHO classification refinements and recent prognostic scoring systems for the definition of individual risk are highlighted and current criteria are discussed. The recommendations should facilitate diagnostic and prognostic evaluations in MDS and selection of patients for new effective targeted therapies.

  1. Sweet syndrome associated with myelodysplastic syndrome: report of a case. Review of the literature.

    Science.gov (United States)

    Reina, Delia; Cerdà, Dacia; Roig, Daniel; Fíguls, Ramon; Villegas, M Luz; Corominas, Hèctor

    2013-01-01

    Sweet's syndrome or acute neutrophilic febrile dermatosis is a systemic disease of unknown etiology characterized by the appearance of skin lesions produced by a neutrophilic dermal infiltrate, fever and peripheral leukocytosis. It may be associated with hematologic diseases, including leukemia, with immune diseases as rheumatoid arthritis, or can occur in isolation. The myelodysplasias are hematological disorders characterized by one or more cytopenias secondary to bone marrow dysfunction. We present the case of a patient with Sweet's syndrome associated with myelodysplastic syndrome and treated with glucocorticoids who did not present a good clinical outcome. We discuss the different treatment of these diseases because in most cases glucocorticoids, which are the treatment of choice in Sweet's syndrome, may be insufficient.

  2. Fludarabine Phosphate and Total Body Irradiation Followed by a Donor Peripheral Stem Cell Transplant in Treating Patients With Myelodysplastic Syndromes or Myeloproliferative Disorders

    Science.gov (United States)

    2016-05-19

    Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative; Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndrome; Essential Thrombocythemia; Myeloproliferative Neoplasm; Paroxysmal Nocturnal Hemoglobinuria; Polycythemia Vera; Polycythemia Vera, Post-Polycythemic Myelofibrosis Phase; Primary Myelofibrosis; Refractory Anemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Ring Sideroblasts; Refractory Cytopenia With Multilineage Dysplasia; Refractory Cytopenia With Multilineage Dysplasia and Ring Sideroblasts

  3. Whole-arm translocation of der(5;17)(p10;q10) with concurrent TP53 mutations in acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS): A unique molecular-cytogenetic subgroup.

    Science.gov (United States)

    Hong, Ming; Hao, Suyang; Patel, Keyur P; Kantarjian, Hagop M; Garcia-Manero, Guillermo; Yin, C Cameron; Medeiros, L Jeffrey; Lin, Pei; Lu, Xinyan

    2016-05-01

    Der(5;17)(p10;q10) is a recurrent but rare aberration reported in myeloid neoplasms (MNs). We report 48 such patients including 19 acute myeloid leukemia (AML) and 29 myelodysplastic syndrome (MDS), to characterize their clinicopathological features. There were 29 men and 19 women, with a median age of 61 years (range, 18-80). 62.5% patients had therapy-related diseases (t-MNs), 70.8% had multilineage dysplasia and 83.3% showed complex karyotypes. In 39 patients tested, FLT3, NPM1, CEBPA, KIT were all wild type and NRAS, KRAS, IDH1, APC, TET2 mutations were detected in single case(s) respectively. TP53 mutations were identified in 8 of 10 cases (80%) tested. Median disease-free survival (DFS) and overall survival (OS) were 3 and 10 months, respectively and did not differ between AML or MDS cases, or between de novo versus therapy-related cases, or between the groups with or without complex karyotypes. In 19 patients who achieved complete remission after chemotherapy, and in 9 patients who underwent stem cell transplantation, the OS was better (14 and 17.5 months, P = 0.0128 and P = 0.0086, respectively). The der(5;17)(p10;q10) represents a unique molecular-cytogenetic subgroup in t-MNs and, associated with complex karyotypes. TP53 inactivation, resulting from 17p deletion coupled with TP53 mutation, likely contributes to the poor clinical outcome of these patients.

  4. Impact of aerobic exercise training during chemotherapy on cancer related cognitive impairments in patients suffering from acute myeloid leukemia or myelodysplastic syndrome - Study protocol of a randomized placebo-controlled trial.

    Science.gov (United States)

    Zimmer, P; Oberste, M; Bloch, W; Schenk, A; Joisten, N; Hartig, P; Wolf, F; Baumann, F T; Garthe, A; Hallek, M; Elter, T

    2016-07-01

    Cancer related cognitive impairments (CRCI) are frequently reported by patients prior to, during and after medical treatment. Although this cognitive decline severely affects patients' quality of life, little is known about effective treatments. Exercise programs represent a promising supportive strategy in this field. However, evidence is sparse and existing studies display methodological limitations. In the planned study, 83 men and women newly diagnosed with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) will be randomized into one of three treatment groups. During 4weeks of induction chemotherapy with Anthracycline and Cytarabin patients allocated to exercise group will cycle 3×/week for 30min at moderate to vigorous intensity on an ergometer. Patients allocated to placebo group will receive a supervised myofascial release training (3×/week, approx. 30min) and patients at control group will get usual care. As primary endpoints a cognitive test battery will be conducted measuring performances depending on verbal/spatial memory and executive functioning. Secondary endpoints will be self-perceived cognitive functioning, as well as neurotrophic and inflammatory serum markers. All assessments will be conducted immediately after hospitalization and before chemotherapy is commenced, immediately before discharge of hospital after 4-5weeks as well as before continuing medical treatment 3-4weeks after discharge. This will be the first study investigating the impact of an aerobic exercise training on CRCI in AML/MDS patients. We hope that the study design and the state-of-the-art assessments will help to increase knowledge about CRCI in general and exercise as potential treatment option in this under investigated population.

  5. Regulation and Function of TIFAB in Myelodysplastic Syndrome

    Science.gov (United States)

    2014-08-01

    Title: Role of TRAF6 in Myelodysplastic Syndromes Period: 7/14-6/18 $1,250,000 7. Edwards P. Evans Foundation Type: Research Grant... Syndrome PRINCIPAL INVESTIGATOR: Daniel Starczynowski CONTRACTING ORGANIZATION: REPORT DATE: TYPE OF REPORT: Final... Syndrome 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER 5e

  6. Complex karyotype newly defined: The strongest prognostic factor in advanced childhood myelodysplastic syndrome

    NARCIS (Netherlands)

    G. Göhring (Gudrun); K. Michalova (Kyra); H.B. Beverloo (Berna); D. Betts (David); J. Harbott (Jochen); O.A. Haas (Oskar); G. Kerndrup (Gitte); L. Sainati (Laura); E. Bergstraesser (Eva); H. Hasle (Henrik); J. Stary (Jan); M. Trebo (Monica); M.M. van den Heuvel-Eibrink (Marry); M. Zecca (Marco); E.R. van Wering (Elisabeth); A. Fischer (Alexandra); P. Noellke (Peter); B. Strahm (Brigitte); F. Locatelli (Franco); C.M. Niemeyer (Charlotte); B. Schlegelberger (Brigitte)

    2010-01-01

    textabstractTo identify cytogenetic risk factors predicting outcome in children with advanced myelodysplastic syndrome, overall survival of 192 children prospectively enrolled in European Working Group of Myelodysplastic Syndrome in Childhood studies was evaluated with regard to karyotypic complexit

  7. Suspected myelodysplastic/myeloproliferative neoplasm in a feline leukemia virus-negative cat.

    Science.gov (United States)

    Weeden, Amy L; Taylor, Kyle R; Terrell, Scott P; Gallagher, Alexander E; Wamsley, Heather L

    2016-12-01

    A 10-year-old castrated Domestic Short-Haired cat was presented to a primary care veterinarian for a wellness examination and laboratory examination for monitoring of diabetes mellitus. The CBC revealed marked thrombocytosis, leukopenia and macrocytic, normochromic anemia. The cat tested negative for FeLV and feline immunodeficiency virus, but was positive for Mycoplasma haemominutum by PCR. Hematologic abnormalities were not responsive to therapy, so a repeat CBC and a bone marrow aspiration for cytology were performed. Additional blood smear findings included anisocytosis with megaloblastic erythroid precursors, large platelets, eosinophilic myelocytes and metamyelocytes, and rare unidentified blasts. The bone marrow smear was highly cellular, and the cytologic pattern was consistent with myelodysplastic syndrome with an erythroid predominance. At that time, 15% blasts were present. The cat was treated with a vitamin K2 analog, doxycycline, and prednisolone, but without a clinical response. Within 3 months, euthanasia was elected due to declining quality of life, and a necropsy was performed. Postmortem bone marrow smears were highly cellular and dominated by monomorphic blasts of unknown line of origin (52%), persistent marked erythroid and megakaryocytic dysplasia, and ineffective erythropoiesis and granulopoiesis. Immunohistochemical, immunocytochemical, and cytochemical stains resulted in a diagnosis of acute myeloid leukemia of unclassified type. Additional histologic findings included mixed hepatitis with trematode infestation and lymphoplasmacytic interstitial nephritis with fibrosis. The marked thrombocytosis with myelodysplastic syndrome and the FeLV-negative status of this cat were unusual. The difficulty in classifying the myelodysplasia and subsequent leukemia highlights a need for further reporting and characterization of these types of disease.

  8. Myelodysplastic Syndromes and Iron Chelation Therapy

    Science.gov (United States)

    Angelucci, Emanuele; Urru, Silvana Anna Maria; Pilo, Federica; Piperno, Alberto

    2017-01-01

    Over recent decades we have been fortunate to witness the advent of new technologies and of an expanded knowledge and application of chelation therapies to the benefit of patients with iron overload. However, extrapolation of learnings from thalassemia to the myelodysplastic syndromes (MDS) has resulted in a fragmented and uncoordinated clinical evidence base. We’re therefore forced to change our understanding of MDS, looking with other eyes to observational studies that inform us about the relationship between iron and tissue damage in these subjects. The available evidence suggests that iron accumulation is prognostically significant in MDS, but levels of accumulation historically associated with organ damage (based on data generated in the thalassemias) are infrequent. Emerging experimental data have provided some insight into this paradox, as our understanding of iron-induced tissue damage has evolved from a process of progressive bulking of organs through high-volumes iron deposition, to one of ‘toxic’ damage inflicted through multiple cellular pathways. Damage from iron may, therefore, occur prior to reaching reference thresholds, and similarly, chelation may be of benefit before overt iron overload is seen. In this review, we revisit the scientific and clinical evidence for iron overload in MDS to better characterize the iron overload phenotype in these patients, which differs from the classical transfusional and non-transfusional iron overload syndrome. We hope this will provide a conceptual framework to better understand the complex associations between anemia, iron and clinical outcomes, to accelerate progress in this area. PMID:28293409

  9. MHC Class I Chain-Related Gene A (MICA) Donor-Recipient Mismatches and MICA-129 Polymorphism in Unrelated Donor Hematopoietic Cell Transplantations Has No Impact on Outcomes in Acute Lymphoblastic Leukemia, Acute Myeloid Leukemia, or Myelodysplastic Syndrome: A Center for International Blood and Marrow Transplant Research Study.

    Science.gov (United States)

    Askar, Medhat; Sobecks, Ronald; Wang, Tao; Haagenson, Mike; Majhail, Navneet; Madbouly, Abeer; Thomas, Dawn; Zhang, Aiwen; Fleischhauer, Katharina; Hsu, Katharine; Verneris, Michael; Lee, Stephanie J; Spellman, Stephen R; Fernández-Viña, Marcelo

    2017-03-01

    Single-center studies have previously reported associations of MHC Class I Chain-Related Gene A (MICA) polymorphisms and donor-recipient MICA mismatching with graft-versus-host disease (GVHD) after unrelated donor hematopoietic cell transplantation (HCT). In this study, we investigated the association of MICA polymorphism (MICA-129, MM versus MV versus VV) and MICA mismatches after HCT with 10/10 HLA-matched (n = 552) or 9/10 (n = 161) unrelated donors. Included were adult patients with a first unrelated bone marrow or peripheral blood HCT for acute lymphoblastic leukemia, acute myeloid leukemia, or myelodysplastic syndrome that were reported to the Center for International Blood and Marrow Transplant Research between 1999 and 2011. Our results showed that neither MICA mismatch nor MICA-129 polymorphism were associated with any transplantation outcome (P acute GVHD grades II to IV (HR, 1.4; P = .013) There were no significant interactions between MICA mismatches and HLA matching (9/10 versus 10/10). In conclusion, the findings in this cohort did not confirm prior studies reporting that MICA polymorphism and MICA mismatches were associated with HCT outcomes.

  10. Outcome and medical costs of patients with invasive aspergillosis and acute myelogenous leukemia-myelodysplastic syndrome treated with intensive chemotherapy: An observational study

    NARCIS (Netherlands)

    L. Slobbe (Lennert); S. Polinder (Suzanne); J.K. Doorduijn (Jeanette); P.J. Lugtenburg (Pieternella); A. el Barzouhi (Abdelilah); E.W. Steyerberg (Ewout); B.J.A. Rijnders (Bart)

    2008-01-01

    textabstractBackground. Invasive aspergillosis (IA) is a leading cause of mortality in patients with acute leukemia. Management of IA is expensive, which makes prevention desirable. Because hospital resources are limited, prevention costs have to be compared with treatment costs and outcome. Methods

  11. MR imaging findings of the femoral marrow in myelodysplastic syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Tanaka, Osamu; Takagi, Shojiro; Matsuura, Katsuhiko; Ichikawa, Tamaki; Kobayashi, Yasuyuki; Nagai, Jun [Jichi Medical School, Minamikawachi, Tochigi (Japan)

    1995-10-01

    MR imaging of the femoral marrow was performed in 30 patients with myelodysplastic syndrome (MDS), 11 cases of which evolved to acute myeloid leukemia (AML). The MRI appearance was classified into five patterns: fatty marrow; faint signal; nodular pattern; heterogeneous infiltration; and diffuse infiltration. For each type of MDS, MRI patterns of the femoral marrow were evaluated and compared with those in normal subjects as well as in patients with aplastic anemia. Signal intensity alteration, a low signal on T1-weighted SE image and a high signal on STIR image, began in the proximal femoral marrow almost symmetrically in patients with MDS. The area of abnormal signal intensity tended to gradually extend towards the distal portion of the femur as the disease progressed. MRI patterns of the femoral marrow correlated with marrow cellularity, and diffuse marrow infiltration was noted in patients with a more advanced type of MDS or with severe anemia. There were limitations to making an accurate diagnosis of the MDS type on the basis of the MRI pattern. Progression of the MRI appearance in the course of MDS was thought to be a sign suggesting evolution to AML. It was difficult to differentiate hypoplastic MDS from aplastic anemia, although the nodular pattern was commonly seen in the latter disease. (author).

  12. Hematological Changes Mimicking Myelodysplastic Syndrome Following Treatment for Osteosarcoma.

    Science.gov (United States)

    Løhmann, Ditte J A; Hasle, Henrik

    2015-04-01

    Therapy-related myelodysplastic syndrome/acute myeloid leukemia (t-MDS/AML) is a feared long-term complication of pediatric cancer. Few osteosarcoma patients develop t-MDS/AML, but the frequency of hematological abnormalities after therapy is unknown. We reviewed biochemistry from osteosarcoma patients up to 3 years posttreatment. All children diagnosed with osteosarcoma at our department from 2006 to 2012 without relapse 1 month posttherapy were included (n=14). Serial blood counts posttherapy were analyzed. The median increase of mean corpuscular volume (MCV) from baseline was 8 fL 6 months posttherapy and remained >5 throughout follow-up. All posttreatment levels of MCV were above 90 fL in 5 patients. Six months posttherapy, the median difference for platelets, white blood count, and absolute neutrophil count had decreased from baseline. They remained under baseline throughout follow-up. Hemoglobin remained stable. Ferritin level was associated with increased MCV. MDS with monosomy 7 was diagnosed in 1 patient. Hypoplastic refractory cytopenia was found in another patient showing spontaneous normalization of hematologic values. More than a third of patients treated for osteosarcoma developed hematological abnormalities mimicking early MDS, but only 1 developed t-MDS/AML. Close hematological monitoring of patients recovering from osteosarcoma is essential and it is worth noting that hematological abnormalities are frequent and may be transitory.

  13. Nuclear Nox4-Derived Reactive Oxygen Species in Myelodysplastic Syndromes

    Directory of Open Access Journals (Sweden)

    Marianna Guida

    2014-01-01

    Full Text Available A role for intracellular ROS production has been recently implicated in the pathogenesis and progression of a wide variety of neoplasias. ROS sources, such as NAD(PH oxidase (Nox complexes, are frequently activated in AML (acute myeloid leukemia blasts and strongly contribute to their proliferation, survival, and drug resistance. Myelodysplastic syndromes (MDS comprise a heterogeneous group of disorders characterized by ineffective hematopoiesis, with an increased propensity to develop AML. The molecular basis for MDS progression is unknown, but a key element in MDS disease progression is the genomic instability. NADPH oxidases are now recognized to have specific subcellular localizations, this targeting to specific compartments for localized ROS production. Local Nox-dependent ROS production in the nucleus may contribute to the regulation of redox-dependent cell growth, differentiation, senescence, DNA damage, and apoptosis. We observed that Nox1, 2, and 4 isoforms and p22phox and Rac1 subunits are expressed in MDS/AML cell lines and MDS samples, also in the nuclear fractions. Interestingly, Nox4 interacts with ERK and Akt1 within nuclear speckle domain, suggesting that Nox4 could be involved in regulating gene expression and splicing factor activity. These data contribute to the elucidation of the molecular mechanisms used by nuclear ROS to drive MDS evolution to AML.

  14. Superoxide anion production by neutrophils in myelodysplastic syndromes (preleukemia.

    Directory of Open Access Journals (Sweden)

    Takahashi,Isao

    1988-02-01

    Full Text Available Superoxide anion (O2- production by neutrophils from 14 untreated patients with acute nonlymphocytic leukemia (ANLL was significantly less than that of healthy controls (4.93 +/- 1.99 vx 6.20 +/- 1.53 nmol/min/10(6 neutrophils, p less than 0.05. In 10 patients with myelodysplastic syndrome (MDS, however, it was not significantly different from the control level although 6 of the 10 patients had low levels, when individual patients were compared with the lower limit of the control range. An inverse correlation between the O2- production of neutrophils and the percentage of leukemic cells in the marrow existed in ANLL (r = -0.55, p less than 0.01, but not in MDS. Three of 4 MDS patients who died of pneumonia prior to leukemic conversion showed a low level of O2- production. The impaired O2- production by neutrophils from some MDS patients, probably due to the faulty differentiation from leukemic clones, may be one of the causes of enhanced susceptibility to infection.

  15. Cytogenetic studies of Brazilian pediatric myelodysplastic syndrome cases: challenges and difficulties in a large and emerging country

    Directory of Open Access Journals (Sweden)

    E.D.R.P. Velloso

    2013-01-01

    Full Text Available Myelodysplastic syndromes (MDS and juvenile myelomonocytic leukemia (JMML are rare hematopoietic stem cell diseases affecting children. Cytogenetics plays an important role in the diagnosis of these diseases. We report here the experience of the Cytogenetic Subcommittee of the Brazilian Cooperative Group on Pediatric Myelodysplastic Syndromes (BCG-MDS-PED. We analyzed 168 cytogenetic studies performed in 23 different cytogenetic centers; 84 of these studies were performed in patients with confirmed MDS (primary MDS, secondary MDS, JMML, and acute myeloid leukemia/MDS+Down syndrome. Clonal abnormalities were found in 36.9% of the MDS cases and cytogenetic studies were important for the detection of constitutional diseases and for differential diagnosis with other myeloid neoplasms. These data show the importance of the Cooperative Group for continuing education in order to avoid a late or wrong diagnosis.

  16. Myelodysplastic syndrome complicated by central diabetes insipidus and cerebral salt wasting syndrome with peculiar change in magnetic resonance images.

    Science.gov (United States)

    Sano, Soichi; Yamagami, Keiko; Morikawa, Takashi; Yoshioka, Katsunobu

    2010-01-01

    Central diabetes insipidus (CDI) could occurs in patients with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML), because of infiltration of leukemic cells into the neurohypophysis or some other reason and it is closely associated with abnormalities of chromosome 7. We report a case of MDS with abnormalities of chromosome 7, presenting as CDI followed by deterioration of polyuria and hyponatremia with a decreased extracellular fluid volume. Magnetic resonance imaging (MRI) revealed symmetrically enhanced lesions in the hypothalamus. Fludrocortisone treatment normalized his serum sodium level and cerebral salt wasting syndrome (CSWS) was suspected.

  17. Survival Advantage and Comparable Toxicity in Reduced-Toxicity Treosulfan-Based versus Reduced-Intensity Busulfan-Based Conditioning Regimen in Myelodysplastic Syndrome and Acute Myeloid Leukemia Patients after Allogeneic Hematopoietic Cell Transplantation.

    Science.gov (United States)

    Sakellari, Ioanna; Mallouri, Despina; Gavriilaki, Eleni; Batsis, Ioannis; Kaliou, Maria; Constantinou, Varnavas; Papalexandri, Apostolia; Lalayanni, Chrysavgi; Vadikolia, Chrysanthi; Athanasiadou, Anastasia; Yannaki, Evangelia; Sotiropoulos, Damianos; Smias, Christos; Anagnostopoulos, Achilles

    2017-03-01

    Treosulfan has been incorporated in conditioning regimens for sustained remission without substantial toxicity and treatment-related mortality (TRM). We aimed to analyze the safety and efficacy of a fludarabine 150 mg/m(2) and treosulfan 42 g/m(2) (FluTreo) conditioning regimen in medically infirm patients. Outcomes were compared with those of a similar historical group treated with fludarabine 150 mg/m(2) to 180 mg/m(2), busulfan 6.4 mg/kg, and antithymocyte globulin (ATG) 5 mg/kg to 7.5 mg/kg (FluBuATG). Thirty-one consecutive patients with acute myeloid leukemia (AML; n = 21), myelodysplastic syndrome (MDS; n = 6), or treatment-related AML (n = 4) received FluTreo conditioning. The historical group consisted of 26 consecutive patients treated with FluBuATG. In the FluTreo group, engraftment was prompt in all patients and 74% achieved >99% donor chimerism by day +30. No grades III or IV organ toxicities were noted. One-year cumulative incidences (CI) of acute and chronic graft-versus-host disease (GVHD) were 19.4% and 58.4%. The groups were similar for age, disease risk, lines of treatment, hematopoietic cell transplantation-specific comorbidity index, and acute or chronic GVHD incidence, except that there were more matched unrelated donor recipients in the FluTreo group (P < .001). With 20 (range, 2 to 36) months follow-up for FluTreo and 14 (range, 2 to 136) for FluBuATG, the 1-year cumulative overall survival (OS) probability was 76% versus 57%, respectively (P = .026); 1-year disease-free survival (DFS) was 79% versus 38% (P < .001). In multivariate analysis, the only significantly favorable factor for OS and DFS was FluTreo (P = .010 and P = .012). The CI of relapse mortality was markedly decreased in FluTreo versus FluBuATG (7.4% versus 42.3%, P < .001). In conclusion, the treosulfan-based regimen resulted in favorable OS and DFS with acceptable toxicity and low relapse rates compared with busulfan-based conditioning.

  18. Upfront allogeneic blood stem cell transplantation for patients with high-risk myelodysplastic syndrome or secondary acute myeloid leukemia using a FLAMSA-based high-dose sequential conditioning regimen.

    Science.gov (United States)

    Saure, Christian; Schroeder, Thomas; Zohren, Fabian; Groten, Anke; Bruns, Ingmar; Czibere, Akos; Galonska, Lars; Kondakci, Mustafa; Weigelt, Christian; Fenk, Roland; Germing, Ulrich; Haas, Rainer; Kobbe, Guido

    2012-03-01

    Patients suffering from high-risk myelodysplastic syndrome (MDS) or acute myelogenous leukemia (AML) secondary to MDS (sAML) are characterized by poor response to conventional cytotoxic chemotherapy. The purpose of our prospective single-center study was to examine the safety and efficacy of an allogeneic hematopoietic stem cell transplantation (HSCT) following a sequential conditioning regimen as first-line therapy for previously untreated patients with high-risk MDS or sAML. Between November 2003 and June 2010, 30 patients (20 high-risk MDS, 10 sAML) received fludarabine (4 × 30 mg/m(2)), amsacrine (4 × 100 mg/m(2)), and Ara-C (4 × 2 g/m(2), FLAMSA). After 2 to 3 days of rest, patients received high-dose melphalan alone (200 mg/m(2) for patients with an age 60 years; n = 24) or melphalan and thiotepa (10 mg/kg, Mel/Thio, n = 6). Following these high-dose conditioning regimens, a median number of 7.7 × 10(6) CD34(+) cells/kg body weight (range: 2.9 × 10(6)-17.2 × 10(6)) were transplanted from 13 related or 17 unrelated donors. Antithymocyte globulin (Fresenius 30-60 mg/kg) as well as tacrolimus and mycophenolate mofetil were used for graft-versus-host disease (GVHD) prophylaxis. All patients except 1 with primary graft failure achieved complete remission after HSCT. After a median follow-up time of 28 months (range: 7-81), 21 patients (70%) were alive and free of disease. Overall, 4 patients relapsed. At 2 years, overall survival, event-free survival, and treatment-related mortality were 70%, 63%, and 30%, respectively. Because of undue toxicity, thiotepa is no longer part of the conditioning regimen. Our results add to the body of evidence that a FLAMSA-based sequential conditioning therapy is effective for previously untreated patients with high-risk MDS or sAML.

  19. A phase II study of decitabine and gemtuzumab ozogamicin in newly diagnosed and relapsed acute myeloid leukemia and high-risk myelodysplastic syndrome.

    Science.gov (United States)

    Daver, N; Kantarjian, H; Ravandi, F; Estey, E; Wang, X; Garcia-Manero, G; Jabbour, E; Konopleva, M; O'Brien, S; Verstovsek, S; Kadia, T; Dinardo, C; Pierce, S; Huang, X; Pemmaraju, N; Diaz-Pines-Mateo, M; Cortes, J; Borthakur, G

    2016-02-01

    Decitabine may open the chromatin structure of leukemia cells making them accessible to the calicheamicin epitope of gemtuzumab ozogamicin (GO). A total of 110 patients (median age 70 years; range 27-89 years) were treated with decitabine and GO in a trial designed on model-based futility to accommodate subject heterogeneity: group 1: relapsed/refractory acute myeloid leukemia (AML) with complete remission duration (CRD) decitabine 20 mg/m(2) daily for 5 days and GO 3 mg/m(2) on day 5. Post-induction therapy included five cycles of decitabine+GO followed by decitabine alone. Complete remission (CR)/CR with incomplete count recovery was achieved in 39 (35%) patients; group 1= 5/28 (17%), group 2=3/5 (60%), group 3=24/57 (42%) and group 4=7/20 (35%). The 8-week mortality in groups 3 and 4 was 16% and 10%, respectively. Common drug-related adverse events included nausea, mucositis and hemorrhage. Decitabine and GO improved the response rate but not overall survival compared with historical outcomes in untreated AML ⩾60 years.

  20. Cronkhite-Canada syndrome associated with myelodysplastic syndrome

    Institute of Scientific and Technical Information of China (English)

    Rei Suzuki; Atsushi Irisawa; Takuto Hikichi; Yuta Takahashi; Hiroko Kobayashi; Hiromi Kumakawa; Hiromasa Ohira

    2009-01-01

    We report a case of Cronkhite-Canada syndrome (CCS) associated with myelodysplastic syndrome (MDS). A 54-year-old woman, diagnosed as MDS the prior year after evaluation of anemia, visited our hospital with the chief complaint of epigastric discomfort. She also had dysgeusia, alopecia, atrophic nail change, and pigmentation of the palm, all of which began several months ago. Blood tests revealed severe hypoalbuminemia. Colonoscopy (CS) showed numerous, dense, red polyps throughout the colon and rectum. Biopsy specimens showed stromal edema, infiltration of lymphocytes, and cystic dilatation of the crypt. Her clinical manifestations and histology were consistent with CCS. We prescribed corticosteroids, which dramatically improved her physical findings, laboratory data, and endoscopic findings. This is the first report of CCS in a patient with MDS.

  1. Clinical research of decitabine combined with chemotherapy in the treatment of myelodysplastic syndrome transformed leukemia%地西他滨联合化疗治疗骨髓增生异常综合征转化白血病的临床研究

    Institute of Scientific and Technical Information of China (English)

    马茉莉

    2016-01-01

    Objective To investigate the efficacy of decitabine combined with chemotherapy in the treatment of myelodysplastic syndrome transformed leukemia.Methods 68 cases of myelodysplastic syndrome transformed leukemia in our hospital from January 2013 to January 2014 were randomly divided into study group and control group,34 cases in each group.Control group was given conventional chemotherapy treatment,study group was given decitabine combined with chemotherapy.Clinical efficacy and impact on patients' survival time of two groups were compared and analyzed.Results The overall control rate of treatment,the rate of adverse reactions,the survival rate 6 months,1 year,2 years after treatment,and patients' satisfaction of study group were significantly better than those of control group,with statistically significant differences (P<0.05).Conclusion The clinical efficacy of decitabine combined with chemotherapy in the treatment of myelodysplastic syndrome transformed leukemia is better,with less toxicity,patients are with well tolerated,survival rate is improved,worthy of clinical application.%目的 探讨地西他滨联合化疗治疗骨髓增生异常综合征转化白血病的疗效.方法 将本院2013年1月至2014年1月间骨髓增生异常综合征转化白血病患者68例,随机将其分成研究组与对照组,每组34例.对照组采取常规化疗治疗,研究组采取地西他滨联合化疗,分析比较两组患者的疗效及对患者生存时间的影响.结果 研究组治疗总控制率、不良反应率、治疗后的6个月、1年、2年生存及满意度等指标均明显优于对照组患者,两组各项指标之间比较差异有统计学意义(P<0.05).结论 在骨髓增生异常综合征转化白血病治疗中地西他滨联合化疗方案临床疗效较好,且毒副反应小,患者耐受性好,可提高生存率,建议临床推广应用.

  2. Myelodysplastic syndrome evolving from aplastic anemia treated with immunosuppressive therapy: efficacy of hematopoietic stem cell transplantation.

    Science.gov (United States)

    Kim, Sung-Yong; Le Rademacher, Jennifer; Antin, Joseph H; Anderlini, Paolo; Ayas, Mouhab; Battiwalla, Minoo; Carreras, Jeanette; Kurtzberg, Joanne; Nakamura, Ryotaro; Eapen, Mary; Deeg, H Joachim

    2014-12-01

    A proportion of patients with aplastic anemia who are treated with immunosuppressive therapy develop clonal hematologic disorders, including post-aplastic anemia myelodysplastic syndrome. Many will proceed to allogeneic hematopoietic stem cell transplantation. We identified 123 patients with post-aplastic anemia myelodysplastic syndrome who from 1991 through 2011 underwent allogeneic hematopoietic stem cell transplantation, and in a matched-pair analysis compared outcome to that in 393 patients with de novo myelodysplastic syndrome. There was no difference in overall survival. There were no significant differences with regard to 5-year probabilities of relapse, non-relapse mortality, relapse-free survival and overall survival; these were 14%, 40%, 46% and 49% for post-aplastic anemia myelodysplastic syndrome, and 20%, 33%, 47% and 49% for de novo myelodysplastic syndrome, respectively. In multivariate analysis, relapse (hazard ratio 0.71; P=0.18), non-relapse mortality (hazard ratio 1.28; P=0.18), relapse-free survival (hazard ratio 0.97; P=0.80) and overall survival (hazard ratio 1.02; P=0.88) of post-aplastic anemia myelodysplastic syndrome were similar to those of patients with de novo myelodysplastic syndrome. Cytogenetic risk was independently associated with overall survival in both groups. Thus, transplant success in patients with post-aplastic anemia myelodysplastic syndrome was similar to that in patients with de novo myelodysplastic syndrome, and cytogenetics was the only significant prognostic factor for post-aplastic anemia myelodysplastic syndrome patients.

  3. In vivo measurements of the T1 relaxation processes in the bone marrow in patients with myelodysplastic syndrome. A magnetic resonance imaging study

    DEFF Research Database (Denmark)

    Jensen, K E; Nielsen, H; Thomsen, C

    1989-01-01

    Nine patients with myelodysplastic syndrome (MDS) were examined with magnetic resonance imaging and in vivo T1 relaxation time measurements of the vertebral bone marrow in a 1.5 tesla whole body scanner. Two patients underwent transformation to acute myeloid leukemia and were evaluated at follow...

  4. Hematopoietic stem cell and progenitor cell mechanisms in myelodysplastic syndromes

    Science.gov (United States)

    Pang, Wendy W.; Pluvinage, John V.; Price, Elizabeth A.; Sridhar, Kunju; Arber, Daniel A.; Greenberg, Peter L.; Schrier, Stanley L.; Park, Christopher Y.; Weissman, Irving L.

    2013-01-01

    Myelodysplastic syndromes (MDS) are a group of disorders characterized by variable cytopenias and ineffective hematopoiesis. Hematopoietic stem cells (HSCs) and myeloid progenitors in MDS have not been extensively characterized. We transplanted purified human HSCs from MDS samples into immunodeficient mice and show that HSCs are the disease-initiating cells in MDS. We identify a recurrent loss of granulocyte-macrophage progenitors (GMPs) in the bone marrow of low risk MDS patients that can distinguish low risk MDS from clinical mimics, thus providing a simple diagnostic tool. The loss of GMPs is likely due to increased apoptosis and increased phagocytosis, the latter due to the up-regulation of cell surface calreticulin, a prophagocytic marker. Blocking calreticulin on low risk MDS myeloid progenitors rescues them from phagocytosis in vitro. However, in the high-risk refractory anemia with excess blasts (RAEB) stages of MDS, the GMP population is increased in frequency compared with normal, and myeloid progenitors evade phagocytosis due to up-regulation of CD47, an antiphagocytic marker. Blocking CD47 leads to the selective phagocytosis of this population. We propose that MDS HSCs compete with normal HSCs in the patients by increasing their frequency at the expense of normal hematopoiesis, that the loss of MDS myeloid progenitors by programmed cell death and programmed cell removal are, in part, responsible for the cytopenias, and that up-regulation of the “don’t eat me” signal CD47 on MDS myeloid progenitors is an important transition step leading from low risk MDS to high risk MDS and, possibly, to acute myeloid leukemia. PMID:23388639

  5. Decitabine and Total-Body Irradiation Followed By Donor Bone Marrow Transplant and Cyclophosphamide in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

    Science.gov (United States)

    2017-01-09

    Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); de Novo Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia

  6. Significant association between polymorphism of the erythropoietin gene promoter and myelodysplastic syndrome

    Directory of Open Access Journals (Sweden)

    O'Brien Susan

    2010-11-01

    Full Text Available Abstract Background Myelodysplastic syndrome (MDS may be induced by certain mutagenic environmental or chemotherapeutic toxins; however, the role of susceptibility genes remains unclear. The G/G genotype of the single-nucleotide polymorphism (SNP rs1617640 in the erythropoietin (EPO promoter has been shown to be associated with decreased EPO expression. We examined the association of rs1617640 genotype with MDS. Methods We genotyped the EPO rS1617640 SNP in 189 patients with MDS, 257 with acute myeloid leukemia (AML, 106 with acute lymphoblastic leukemia, 97 with chronic lymphocytic leukemia, 353 with chronic myeloid leukemia, and 95 healthy controls. Results The G/G genotype was significantly more common in MDS patients (47/187; 25.1% than in controls (6/95; 6.3% or in patients with other leukemias (101/813; 12.4% (all P P = 0.03. Time to neutrophils recovery after therapy was significantly longer in MDS patients with the G/G genotype (P = 0.02. Conclusions These findings suggest a strong association between the rs1617640 G/G genotype and MDS. Further studies are warranted to investigate the utility of screening for this marker in individuals exposed to environmental toxins or chemotherapy.

  7. A retrospective comparison of autologous and unrelated donor hematopoietic cell transplantation in myelodysplastic syndrome and secondary acute myeloid leukemia: a report on behalf of the Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation (EBMT).

    NARCIS (Netherlands)

    Al-Ali, H.K.; Brand, R.; Biezen, A. van; Finke, J.; Boogaerts, M.; Fauser, A.A.; Egeler, M.; Cahn, J.Y.; Arnold, R.; Biersack, H.; Niederwieser, D.; Witte, T.J.M. de

    2007-01-01

    Hematopoietic cell transplantation (HCT) is an effective treatment for myelodysplasia (MDS) and secondary acute myeloid leukemia (sAML). In this study, outcome of 593 patients with MDS/sAML after autologous and allogeneic HCT from a matched unrelated donor (MUD) were compared. A total of 167 (28%) p

  8. Down syndrome preleukemia and leukemia.

    Science.gov (United States)

    Maloney, Kelly W; Taub, Jeffrey W; Ravindranath, Yaddanapudi; Roberts, Irene; Vyas, Paresh

    2015-02-01

    Children with Down syndrome (DS) and acute leukemias acute have unique biological, cytogenetic, and intrinsic factors that affect their treatment and outcome. Myeloid leukemia of Down syndrome (ML-DS) is associated with high event-free survival (EFS) rates and frequently preceded by a preleukemia condition, the transient abnormal hematopoiesis (TAM) present at birth. For acute lymphoblastic leukemia (ALL), their EFS and overall survival are poorer than non-DS ALL, it is important to enroll them on therapeutic trials, including relapse trials; investigate new agents that could potentially improve their leukemia-free survival; and strive to maximize the supportive care these patients need.

  9. Value of allogeneic versus autologous stem cell transplantation and chemotherapy in patients with myelodysplastic syndromes and secondary acute myeloid leukemia. Final results of a prospective randomized European Intergroup Trial

    Science.gov (United States)

    de Witte, Theo; Hagemeijer, Anne; Suciu, Stefan; Belhabri, Amin; Delforge, Michel; Kobbe, Guido; Selleslag, Dominik; Schouten, Harry C.; Ferrant, Augustin; Biersack, Harald; Amadori, Sergio; Muus, Petra; Jansen, Joop H.; Hellström-Lindberg, Eva; Kovacsovics, Tibor; Wijermans, Pierre; Ossenkoppele, Gert; Gratwohl, Alois; Marie, Jean-Pierre; Willemze, Roel

    2010-01-01

    Background Allogeneic stem cell transplantation is usually considered the only curative treatment option for patients with advanced or transformed myelodysplastic syndromes in complete remission, but post-remission chemotherapy and autologous stem cell transplantation are potential alternatives, especially in patients over 45 years old. Design and Methods We evaluated, after intensive anti-leukemic remission-induction chemotherapy, the impact of the availability of an HLA-identical sibling donor on an intention-to treat basis. Additionally, all patients without a sibling donor in complete remission after the first consolidation course were randomized to either autologous peripheral blood stem cell transplantation or a second consolidation course consisting of high-dose cytarabine. Results The 4-year survival of the 341 evaluable patients was 28%. After achieving complete remission, the 4-year survival rates of patients under 55 years old with or without a donor were 54% and 41%, respectively, with an adjusted hazard ratio of 0.81 (95% confidence interval [95% CI], 0.49–1.35) for survival and of 0.67 (95% CI, 0.42–1.06) for disease-free survival. In patients with intermediate/high risk cytogenetic abnormalities the hazard ratio in multivariate analysis was 0.58 (99% CI, 0.22–1.50) (P=0.14) for survival and 0.46 (99% CI, 0.22–1.50) for disease-free survival (P=0.03). In contrast, in patients with low risk cytogenetic characteristics the hazard ratio for survival was 1.17 (99% CI, 0.40–3.42) and that for disease-free survival was 1.02 (99% CI, 0.40–2.56). The 4-year survival of the 65 patients randomized to autologous peripheral blood stem cell transplantation or a second consolidation course of high-dose cytarabine was 37% and 27%, respectively. The hazard ratio in multivariate analysis was 1.22 (95% CI, 0.65–2.27) for survival and 1.02 (95% CI, 0.56–1.85) for disease-free survival. Conclusions Patients with a donor and candidates for allogeneic stem

  10. ROLE AND TIMING OF HEMATOPOIETIC CELL TRANSPLANTATION FOR MYELODYSPLASTIC SYNDROME

    Directory of Open Access Journals (Sweden)

    Teresa L Field

    2010-07-01

    Full Text Available Allogeneic hematopoietic cell transplantation (HCT is the only curative treatment for patients with myelodysplastic syndromes (MDS.  Most patients with MDS are older than 60 years and age-associated morbidities limit the patients’ options for curative transplant therapy.  Since the development of conditioning regimens with reduced toxicity, the age limitations for HCT have waned for those patients with good performance status. This review will discuss the role of HCT for MDS based on prognostic features, the optimal timing of HCT, and outcomes based on patient age.

  11. [Acquired hemoglobin H disease associated with a myelodysplastic syndrome].

    Science.gov (United States)

    Pérez Calvo, J; González Fernández, F A; Santillana, T; Alarcón, C; Fariñas, M; Sánchez, J; Martínez Martínez, R; Villegas, A

    1994-06-01

    Some patients found to have clonal panmyelopathies develop an acquired defect of haemoglobin synthesis clinically similar to haemoglobin H disease. A 58 year-old male diagnosed of simple refractory anaemia developed microcytosis and hypochromia. At the same time, his myelodysplastic syndrome became a refractory anaemia with excess of blasts. 33% of the red blood cells had "golf ball" inclusions after incubation with brilliant cresyl blue. Cellulose acetate electrophoresis revealed an haemoglobin H band. The globin chain synthesis alpha/beta ratio was 0.69. The molecular analysis demonstrated the integrity of both alpha genes in each chromosome. There were no familiar antecedent of haemoglobinopathy.

  12. Treatment of myelodysplastic syndromes: practical tools for effective management.

    Science.gov (United States)

    Kurtin, Sandra E; Demakos, Erin P; Hayden, Janet; Boglione, Claudia

    2012-06-01

    Myelodysplastic syndromes (MDS) are a heterogeneous group of myeloid malignancies with variability in clinical presentation, disease trajectory, treatment goals, and expected outcomes. The treatment of patients with MDS, therefore, often differs from patient to patient. Tools are needed to aid effective communication with patients, their caregivers, and their dedicated team of healthcare professionals. The use of methods often employed in clinical trials can help healthcare providers diagnose and classify risk status, track trends within patient responses, manage adverse events, set treatment expectations, and provide ongoing supportive care. This article discusses several tools and strategies available for the management of patients with MDS throughout the continuum of their disease.

  13. Optic Neuritis Associated with Myelodysplastic Syndrome Accompanied by Eosinophilic Crisis.

    Science.gov (United States)

    Nagasaki, Joji; Nishimoto, Mitsutaka; Nakamae, Hirohisa; Nakane, Takahiko; Koh, Hideo; Yoshimoto, Kumiko; Shiraki, Kunihiko; Hino, Masayuki

    2015-01-01

    Myelodysplastic syndrome (MDS) was diagnosed in a 64-year-old man. Three months later, he presented with right-sided visual loss. A diagnosis of optic neuritis caused by both ischemic and non-ischemic changes was established. Concurrently, prominent eosinophilia was seen in both the peripheral blood and bone marrow. A partial improvement of visual loss was obtained concomitant with a rapid decrease of the eosinophils after treatment with corticosteroids. Optic neuritis related to MDS is a rare condition and its etiology has not yet been identified. We herein report a case of optic neuritis associated with MDS and accompanied by an eosinophilic crisis.

  14. Myelodysplastic syndromes: recent progress in diagnosis and understanding of their pathophysiology.

    Science.gov (United States)

    Ogata, Kiyoyuki

    2006-12-01

    Myelodysplastic syndromes (MDS) are common malignant disorders with a poor prognosis. MDS are a group of highly heterogeneous disorders but show certain universal findings including a high incidence in the elderly population, cytopenia, dysplastic myeloid cells, and frequent transformation to acute myeloid leukemia. Until recently, the vast majority of MDS patients were treated with supportive therapy alone, such as transfusions. Allogeneic stem cell transplantation (SCT) has the potential for cure, although due to the age and comorbidity of MDS patients, the role of allogeneic SCT in MDS has been limited. Recently, research in MDS has shown substantial advances that have deepened our understanding of MDS pathophysiology and changed our approach to MDS patients. This review touches on some recent developments in the diagnosis and pathophysiology of MDS.

  15. Donor Killer Immunoglobulin-Like Receptor Profile Bx1 Imparts a Negative Effect and Centromeric B-Specific Gene Motifs Render a Positive Effect on Standard-Risk Acute Myeloid Leukemia/Myelodysplastic Syndrome Patient Survival after Unrelated Donor Hematopoietic Stem Cell Transplantation.

    Science.gov (United States)

    Bao, Xiaojing; Wang, Miao; Zhou, Huifen; Zhang, Huanhuan; Wu, Xiaojin; Yuan, Xiaoni; Li, Yang; Wu, Depei; He, Jun

    2016-02-01

    Donor killer immunoglobulin-like receptor (KIR) group B profiles (Bx) and homozygous of centromeric motif B (Cen-B/B) are the most preferable KIR gene content motifs for hematopoietic stem cell transplantation (HSCT). The risk of transplant from Bx1 donors and the benefit of the presence of Cen-B (regardless of number) were observed for standard-risk acute myeloid leukemia/myelodysplastic syndrome (AML/MDS) patients in this 4-year retrospective study. A total of 210 Chinese patients who underwent unrelated donor HSCT were investigated. Donor KIR profile Bx was associated with significantly improved overall survival (OS; P = .026) and relapse-free survival (RFS; P = .021) and reduced nonrelapse mortality (NRM; P = .017) in AML/MDS patients. A significantly lower survival rate was observed for transplants from Bx1 donors compared with Bx2, Bx3, and Bx4 donors for patients in first complete remission (n = 82; OS: P = .024; RFS: P = .021). Transplant from donors with Cen-B resulted in improved OS (HR = .256; 95% CI, .084 to .774; P = .016) and RFS (HR = .252; 95% CI, .084 to .758; P = .014) in AML/MDS patients at standard risk. However, this particular effect did not increase with a higher number of Cen-B motifs (cB/B versus cA/B; OS: P = .755; RFS: P = .768). No effect was observed on high-risk AML/MDS, acute lymphoblastic leukemia/non-Hodgkin lymphoma, and chronic myelogenous leukemia patients. Avoiding the selection of HSCT donors of KIR profile Bx1 is strongly advisable for standard-risk AML/MDS patients. The presence of the Cen-B motif rather than its number was more important in donor selection for the Chinese population.

  16. Splicing factor SF3B1 mutations and ring sideroblasts in myelodysplastic syndromes: a Brazilian cohort screening study

    Directory of Open Access Journals (Sweden)

    Flávia Sacilotto Donaires

    Full Text Available ABSTRACT Background: Myelodysplastic syndromes (MDS comprise a group of malignant clonal hematologic disorders characterized by ineffective hematopoiesis and propensity for progression to acute myeloid leukemia. Acquired mutations in the gene encoding RNA splicing factor 3B subunit 1 (SF3B1 are highly associated with the MDS subtypes presenting ring sideroblasts, and represent a specific nosological entity. The effects of these mutations on clinical outcomes are diverse and contrasting. Methods: A cohort of 91 Brazilian MDS patients, including patients with ring sideroblasts in the bone marrow, were screened for mutations in the SF3B1 hotspots (exons 12-15 by direct Sanger sequencing. Results: SF3B1 heterozygous mutations were identified in six patients (7%, all of them with ring sideroblasts, thus confirming the association between SF3B1 mutations and myelodysplastic syndrome subtypes bearing this morphologic feature (frequency of 6/13, p-value < 0.0001. Conclusion: This is the first screening of SF3B1 mutations in a cohort of Brazilian myelodysplastic syndrome patients. Our findings confirm that mutations in this splicing gene correlate with bone marrow ringed sideroblasts.

  17. Decitabine With or Without Bortezomib in Treating Older Patients With Acute Myeloid Leukemia

    Science.gov (United States)

    2016-03-14

    Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Adult Acute Megakaryoblastic Leukemia; Adult Acute Monoblastic Leukemia; Adult Acute Monocytic Leukemia; Adult Acute Myeloid Leukemia With Minimal Differentiation; Adult Acute Myeloid Leukemia With t(9;11)(p22;q23); MLLT3-MLL; Adult Acute Myeloid Leukemia Without Maturation; Adult Erythroleukemia; Adult Pure Erythroid Leukemia; Alkylating Agent-Related Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  18. Spotlight on decitabine for myelodysplastic syndromes in Chinese patients

    Directory of Open Access Journals (Sweden)

    Jing Y

    2015-10-01

    Full Text Available Yu Jing,1,* Xue Shen,2,* Qian Mei,3 Weidong Han3 1Department of Hematology, PLA General Hospital, 2Department of Cell Biology, School of Basic Medical Sciences, Peking University Health Science Center, 3Department of Molecular Biology, Institute of Basic Medicine, Chinese PLA General Hospital, Beijing, People’s Republic of China *These authors contributed equally to this work Abstract: Myelodysplastic syndromes (MDSs are a group of heterogeneous clonal hematopoietic stem cell malignancies with advanced median age. The silencing of tumor suppressor genes caused by DNA hypermethylation plays a crucial role in the pathogenesis of MDS. Decitabine, the available hypomethylating agent, is successfully used for the treatment and improves the outcome of MDS, and has become one of the most frequently administered disease-modifying therapies. With an aging population and a growing number of people exposed to benzene, the incidence of MDS has been increasing rapidly. The blinded regimen choice and the lack of a unified strategy create challenges for the treatment of MDS. Here, we present a review of clinical progress and prospects of decitabine treatment of MDS in the People’s Republic of China. We also discuss the optimization of therapy issues to improve the cure rate and prolong survival in patients with MDS. Keywords: myelodysplastic syndromes (MDSs, decitabine, hypomethylating agents, People’s Republic of China, traditional Chinese medicine

  19. Lenalidomide, Cytarabine, and Idarubicin in Treating Patients With Acute Myeloid Leukemia

    Science.gov (United States)

    2014-12-22

    Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); RUNX1-RUNX1T1; Adult Acute Myeloid Leukemia With t(9;11)(p22;q23); MLLT3-MLL; Adult Acute Promyelocytic Leukemia With t(15;17)(q22;q12); PML-RARA; Alkylating Agent-Related Acute Myeloid Leukemia; de Novo Myelodysplastic Syndrome; Previously Treated Myelodysplastic Syndrome; Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndrome; Untreated Adult Acute Myeloid Leukemia

  20. Research progress on the mechanism of transformation of myelodysplastic syndrome to acute myeloid leukemia%骨髓增生异常综合征转化为急性髓系白血病机制的研究进展

    Institute of Scientific and Technical Information of China (English)

    马东升

    2015-01-01

    骨髓增生异常综合征(MDS)是一组源于造血干/祖细胞的克隆性疾病,有向急性髓系白血病(AML)转化的高风险.由于转化为AML后缺乏有效治疗手段,且预后差,目前唯一治愈的方法是通过骨髓移植,但是仅有少部分患者适合移植.因此对MDS转化为AML机制的研究对临床开发有效药物尤为重要.现就MDS转化为AML发生机制的研究进展进行综述.%Myelodysplastic syndrome (MDS) is a group of clonal diseases originating from hematopoietic stem/progenitor cells with high risk of transformation to acute myeloid leukemia (AML).Due to the lack of effective treatment after transformation into AML and the poor prognosis, now the bone marrow transplantation is the only way to cure this disease, but only a few of patients are suitable for transplantation.So the study on the mechanism of transformation of MDS to AML is important for development of effective drugs are.This paper presents a review of the latest update on mechanism of transformation of MDS to AML.

  1. Biclonal chromosomal aberrations in a child with myelodysplastic syndrome.

    Science.gov (United States)

    Jakab, Z; Balogh, E; Kiss, C; Pajor, L; Oláh, E

    1999-01-01

    Hematological malignancies and premalignant diseases are generally of monoclonal origin. The prognostic and therapeutic significance of finding two genetically independent clones remains to be determined. We followed a case of childhood myelodysplastic syndrome showing biclonal chromosomal abnormalities (+8, -7) by conventional cytogenetic examination and double target fluorescence in situ hybridization (FISH). A 7-year-old girl presented with Plaut-Vincent angina and leukopenia. The cytogenetic aberration of +8 was the first sign to suggest MDS. Serial bone marrow controls, prompted by a progressive clinical course detected myelodysplastic changes and a new clonal aberration (-7). The presence of -7 and +8 in two independent clones was verified by double-target FISH. While at diagnosis and during cytokine treatment more cells showed +8, after successful all-trans retinoic acid (ATRA) therapy, the clone with -7 predominated. Following allogeneic bone marrow transplantation the patient displayed donor-derived hematopoesis. Our data stress the significance of cytogenetic and FISH examinations in detecting specific genetic abnormalities and progressive clonal changes as an indicator and guideline for therapy. Different cell clones characterized by different genetic changes might be associated with different biologic features reflected in their response to treatment.

  2. Clinical utility of lenalidomide in the treatment of myelodysplastic syndromes

    Directory of Open Access Journals (Sweden)

    Abou Zahr A

    2014-12-01

    Full Text Available Abdallah Abou Zahr,1 Ehab Saad Aldin,2 Rami S Komrokji,3 Amer M Zeidan4 1Section of Hematology/Oncology, Department of Internal Medicine, Mount Sinai Beth Israel, New York City, New York, NY, 2Department of Internal Medicine, Medstar Good Samaritan Hospital, Baltimore, MD, 3Department of Malignant Hematology, H Lee Moffitt Cancer Center and Research Institute, Tampa, FL, 4Division of Hematology, Department of Medicine, Yale University, New Haven, CT, USA Abstract: Myelodysplastic syndromes (MDS represent a heterogeneous group of acquired clonal hematopoietic disorders characterized by peripheral blood cytopenias, paradoxical BM hypercellularity, ineffective hematopoiesis, and increased risk of leukemic transformation. Risk stratification, using different prognostic scores and markers, is at the core of MDS management. Deletion 5q [del(5q] MDS is a distinct class of MDS characterized by the haploinsufficiency of specific genes, microRNAs, and proteins, which has been linked to increased sensitivity to the drug lenalidomide. Phase II and III clinical trials have demonstrated the efficacy of lenalidomide in improving clinical outcomes of patients with del(5q MDS, including reduction in red blood cell transfusion requirements and improvements in quality of life. Lenalidomide has also demonstrated some activity in non-del(5q lower-risk MDS as well as higher-risk MDS, especially in combination with other agents. In this paper, we review the pathogenesis of del(5q MDS, the proposed mechanisms of action of lenalidomide, the major clinical trials that documented the activity of lenalidomide in different MDS populations, potential predictors of benefit from the drug and suggested mechanisms of resistance, and the use of combination strategies to expand the clinical utility of lenalidomide in MDS. Keywords: deletion 5q, lenalidomide, myelodysplastic syndromes, 5q-syndrome

  3. Study on phenotypic and cytogenetic characteristics of bone marrow mesenchymal stem cells in myelodysplastic syndromes

    Institute of Scientific and Technical Information of China (English)

    宋陆茜

    2013-01-01

    Objective To investigate phenotype,cell differentiation and cytogenetic properties of bone marrow(BM) mesenchymal stem cells(MSC)separated from the myelodysplastic syndrome(MDS) patients,and to analyze cytogenetic

  4. Differential expression of ribosomal proteins in myelodysplastic syndromes.

    Science.gov (United States)

    Rinker, Elizabeth B; Dueber, Julie C; Qualtieri, Julianne; Tedesco, Jason; Erdogan, Begum; Bosompem, Amma; Kim, Annette S

    2016-02-01

    Aberrations of ribosomal biogenesis have been implicated in several congenital bone marrow failure syndromes, such as Diamond-Blackfan anaemia, Shwachman-Diamond syndrome and Dyskeratosis Congenita. Recent studies have identified haploinsufficiency of RPS14 in the acquired bone marrow disease isolated 5q minus syndrome, a subtype of myelodysplastic syndromes (MDS). However, the expression of various proteins comprising the ribosomal subunits and other proteins enzymatically involved in the synthesis of the ribosome has not been explored in non-5q minus MDS. Furthermore, differences in the effects of these expression alterations among myeloid, erythroid and megakaryocyte lineages have not been well elucidated. We examined the expression of several proteins related to ribosomal biogenesis in bone marrow biopsy specimens from patients with MDS (5q minus patients excluded) and controls with no known myeloid disease. Specifically, we found that there is overexpression of RPS24, DKC1 and SBDS in MDS. This overexpression is in contrast to the haploinsufficiency identified in the congenital bone marrow failure syndromes and in acquired 5q minus MDS. Potential mechanisms for these differences and aetiology for these findings in MDS are discussed.

  5. Case report with literatures review on Decitabine treatment of myelodysplastic syndromes into acute myeloid leukemia in complete remission%地西他滨治疗骨髓增生异常综合征转为急性髓系白血病完全缓解1例并文献复习

    Institute of Scientific and Technical Information of China (English)

    杨华; 朱海燕; 韩晓萍; 王全顺; 于力

    2012-01-01

    Introduction Decitabine to treatment of patients with MDS into AML patients achieved complete remission during the treatment, in order to learn about the efficacy and side effects of anti -tumor drugs DNA methylation inhibitor Decitabine. Decitabine for MDS patients can significantly improve the quality of life, reduce transfusion dependence, even able to make the transformation to leukemia patients achieved complete remission with the side effect of bone marrow suppression. And a comprehensive review of the literatures is made to Decitabine clinical application in recent years, to provide help for the clinical application of the medicine.%通过介绍地西他滨治疗1例骨髓增生异常综合征(myelodysplastic syndrome,MDS)转为急性髓系白血病(acute myeloid leukemia,AML)的患者达到完全缓解的治疗过程,了解抗肿瘤新药DNA甲基化转移酶抑制剂地西他滨的疗效及副作用.地西他滨对MDS患者能明显改善生活质量,减轻输血的依赖,甚至能够使向白血病转化的MDS患者达到完全缓解,但有骨髓抑制的副作用.并通过文献复习来全面介绍近几年地西他滨的临床研究情况,为临床应用该药提供帮助.

  6. Leukemia in donor cells after allogeneic hematopoietic stem cell transplant

    OpenAIRE

    2002-01-01

    The development of leukemia in donor cells after allogeneic hematopoietic stem cell transplant is an extremely rare event. We report here the case of a patient who developed myelodysplastic syndrome/acute myeloid leukemia, in cells of donor origin 3.5 years after related donor HSCT for refractory chronic lymphocytic leukemia and therapy-induced myelodysplastic syndrome. The origin of the leukemia was determined by analysis of minisatillite polymorphism tested on CD34(+) cells.

  7. p53 protein expression independently predicts outcome in patients with lower-risk myelodysplastic syndromes with del(5q)

    Science.gov (United States)

    Saft, Leonie; Karimi, Mohsen; Ghaderi, Mehran; Matolcsy, András; Mufti, Ghulam J.; Kulasekararaj, Austin; Göhring, Gudrun; Giagounidis, Aristoteles; Selleslag, Dominik; Muus, Petra; Sanz, Guillermo; Mittelman, Moshe; Bowen, David; Porwit, Anna; Fu, Tommy; Backstrom, Jay; Fenaux, Pierre; MacBeth, Kyle J.; Hellström-Lindberg, Eva

    2014-01-01

    Del(5q) myelodysplastic syndromes defined by the International Prognostic Scoring System as low- or intermediate-1-risk (lower-risk) are considered to have an indolent course; however, recent data have identified a subgroup of these patients with more aggressive disease and poorer outcomes. Using deep sequencing technology, we previously demonstrated that 18% of patients with lower-risk del(5q) myelodysplastic syndromes carry TP53 mutated subclones rendering them at higher risk of progression. In this study, bone marrow biopsies from 85 patients treated with lenalidomide in the MDS-004 clinical trial were retrospectively assessed for p53 expression by immunohistochemistry in association with outcome. Strong p53 expression in ≥1% of bone marrow progenitor cells, observed in 35% (30 of 85) of patients, was significantly associated with higher acute myeloid leukemia risk (P=0.0006), shorter overall survival (P=0.0175), and a lower cytogenetic response rate (P=0.009), but not with achievement or duration of 26-week transfusion independence response. In a multivariate analysis, p53-positive immunohistochemistry was the strongest independent predictor of transformation to acute myeloid leukemia (P=0.0035). Pyrosequencing analysis of laser-microdissected cells with strong p53 expression confirmed the TP53 mutation, whereas cells with moderate expression predominantly had wild-type p53. This study validates p53 immunohistochemistry as a strong and clinically useful predictive tool in patients with lower-risk del(5q) myelodysplastic syndromes. This study was based on data from the MDS 004 trial (clinicaltrials.gov identifier: NCT00179621). PMID:24682512

  8. Low-dose decitabine versus best supportive care in elderly patients with intermediate- or high-risk myelodysplastic syndrome (MDS) ineligible for intensive chemotherapy: final results of the randomized phase III study of the European Organisation for Research and Treatment of Cancer Leukemia Group and the German MDS Study Group

    NARCIS (Netherlands)

    Lubbert, M.; Suciu, S.; Baila, L.; Ruter, B.H.; Platzbecker, U.; Giagounidis, A.; Selleslag, D.; Labar, B.; Germing, U.; Salih, H.R.; Beeldens, F.; Muus, P.; Pfluger, K.H.; Coens, C.; Hagemeijer, A.; Eckart Schaefer, H.; Ganser, A.; Aul, C.; Witte, T.J.M. de; Wijermans, P.W.

    2011-01-01

    PURPOSE: To compare low-dose decitabine to best supportive care (BSC) in higher-risk patients with myelodysplastic syndrome (MDS) age 60 years or older and ineligible for intensive chemotherapy. PATIENTS AND METHODS: Two-hundred thirty-three patients (median age, 70 years; range, 60 to 90 years)

  9. Low-dose decitabine versus best supportive care in elderly patients with intermediate- or high-risk myelodysplastic syndrome (MDS) ineligible for intensive chemotherapy: final results of the randomized phase III study of the European Organisation for Research and Treatment of Cancer Leukemia Group and the German MDS Study Group

    NARCIS (Netherlands)

    Lubbert, M.; Suciu, S.; Baila, L.; Ruter, B.H.; Platzbecker, U.; Giagounidis, A.; Selleslag, D.; Labar, B.; Germing, U.; Salih, H.R.; Beeldens, F.; Muus, P.; Pfluger, K.H.; Coens, C.; Hagemeijer, A.; Eckart Schaefer, H.; Ganser, A.; Aul, C.; Witte, T.J.M. de; Wijermans, P.W.

    2011-01-01

    PURPOSE: To compare low-dose decitabine to best supportive care (BSC) in higher-risk patients with myelodysplastic syndrome (MDS) age 60 years or older and ineligible for intensive chemotherapy. PATIENTS AND METHODS: Two-hundred thirty-three patients (median age, 70 years; range, 60 to 90 years) wer

  10. Therapeutic approaches in myelofibrosis and myelodysplastic/myeloproliferative overlap syndromes

    Directory of Open Access Journals (Sweden)

    Sochacki AL

    2016-04-01

    Full Text Available Andrew L Sochacki,1 Melissa A Fischer,1 Michael R Savona1,2 1Department of Internal Medicine, Vanderbilt University Medical Center, 2Vanderbilt-Ingram Cancer Center, Nashville, TN, USA Abstract: The discovery of JAK2V617F a decade ago led to optimism for a rapidly developing treatment revolution in Ph- myeloproliferative neoplasms. Unlike BCR–ABL, however, JAK2 was found to have a more heterogeneous role in carcinogenesis. Therefore, for years, development of new therapies was slow, despite standard treatment options that did not address the overwhelming symptom burden in patients with primary myelofibrosis (MF, post-essential thrombocythemia MF, post-polycythemia vera MF, and myelodysplastic syndrome (MDS/myeloproliferative neoplasm (MPN syndromes. JAK–STAT inhibitors have changed this, drastically ameliorating symptoms and ultimately beginning to show evidence of impact on survival. Now, the genetic foundations of myelofibrosis and MDS/MPN are rapidly being elucidated and contributing to targeted therapy development. This has been empowered through updated response criteria for MDS/MPN and refined prognostic scoring systems in these diseases. The aim of this article is to summarize concisely the current and rationally designed investigational therapeutics directed at JAK–STAT, hedgehog, PI3K–Akt, bone marrow fibrosis, telomerase, and rogue epigenetic signaling. The revolution in immunotherapy and novel treatments aimed at previously untargeted signaling pathways provides hope for considerable advancement in therapy options for those with chronic myeloid disease. Keywords: MDS/MPN neoplasms, emerging therapy

  11. 地西他滨联合预激方案治疗中高危骨髓增生异常综合征及急性髓系白血病20例分析%Analyse Decitabine Combined with CAG/HAG to Treat 20 Patients with Medium and High Risk Myelodysplastic Syndrome or Acute Myeloid Leukemia

    Institute of Scientific and Technical Information of China (English)

    曹静; 黄琨; 徐敏

    2016-01-01

    Objective To explore the clinical value of the combination of decitabine and CAG/HAG in the treatment of high risk patients with myelodysplastic syndrome and acute myeloid leukemia. Methods Convenient selection and analyse the clinical efficacy and safety of 20 patients with medium /high risk MDS and AML that were treated with the combina-tion of decitabine and CAG/HAG in our department from August 2012 to August 2015 . Results 8 cases of CR, 6 cases of PR, in which 2 cases after two courses of treatment complete remission, 6 cases of NR. The total effective rate was 70%, and the complete remission rate was 40% in 1 treatment course. IV degree of bone marrow suppression 100%, remission of patients with chemotherapy after the normal time of platelet recovery 17~23 d, the white blood cells to restore normal time compared with platelets, the average 25 days or so. Conclusion in patients with acute myeloid leukemia / myelodysplastic syndrome, the use of the treatment of the decitabine can achieve satisfactory results. Risk control, the elderly are also able to tolerate, but patients with poor chromosomal or mutant gene have poor prognosis .%目的:探究地西他滨联合预激方案治疗中高危骨髓增生异常综合征及急性髓系白血病的临床价值。方法方便选取并分析2012年8月―2015年8月该院收治的用地西他滨联合预激方案治疗的20例中高危MDS和AML患者,观察其临床疗效及安全性。结果8例患者为CR,6例PR,在此其中2例经两个疗程治疗后完全缓解,6例NR。总有效率70%,l疗程完全缓解率40%。Ⅳ度骨髓抑制100%,缓解患者化疗后血小板恢复正常时间17~23 d,白细胞恢复正常时间较血小板晚,平均25 d左右。结论对于急性髓系白血病/骨髓增生异常综合症患者,使用地西他宾治疗可以取得满意效果。风险可控,老年人也能耐受,但有不良预后的染色体或突变基因的患者效果不佳。

  12. Deferasirox for managing iron overload in people with myelodysplastic syndrome.

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    Meerpohl, Joerg J; Schell, Lisa K; Rücker, Gerta; Fleeman, Nigel; Motschall, Edith; Niemeyer, Charlotte M; Bassler, Dirk

    2014-10-28

    The myelodysplastic syndrome (MDS) comprises a diverse group of haematopoietic stem cell disorders. Due to symptomatic anaemia, most people with MDS require supportive therapy including repeated red blood cell (RBC) transfusions. In combination with increased iron absorption, this contributes to the accumulation of iron resulting in secondary iron overload and the risk of organ dysfunction and reduced life expectancy. Since the human body has no natural means of removing excess iron, iron chelation therapy, i.e. the pharmacological treatment of iron overload, is usually recommended. However, it is unclear whether or not the newer oral chelator deferasirox leads to relevant benefit. To evaluate the effectiveness and safety of oral deferasirox for managing iron overload in people with myelodysplastic syndrome (MDS). We searched the following databases up to 03 April 2014: MEDLINE, EMBASE, The Cochrane Library, Biosis Previews, Web of Science, Derwent Drug File and four trial registries: Current Controlled Trials (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov), ICTRP (www.who.int./ictrp/en/), and German Clinical Trial Register (www.drks.de). Randomised controlled trials (RCTs) comparing deferasirox with no therapy, placebo or with another iron-chelating treatment schedule. We did not identify any trials eligible for inclusion in this review. No trials met our inclusion criteria. However, we identified three ongoing and one completed trial (published as an abstract only and in insufficient detail to permit us to decide on inclusion) comparing deferasirox with deferoxamine, placebo or no treatment. We planned to report evidence from RCTs that evaluated the effectiveness of deferasirox compared to either placebo, no treatment or other chelating regimens, such as deferoxamine, in people with MDS. However, we did not identify any completed RCTs addressing this question.We found three ongoing and one completed RCT (published as an abstract only and

  13. Prognostic analysis of refractory anaemia in adult myelodysplastic syndromes

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    WANG Xiao-qin; CHEN Zi-xing; CHEN Shu-chang; LIN Guo-wei; JI Mei-rong; LIANG Jian-ying; LIU Dun-dan; LI De-gao; MA Yan

    2008-01-01

    Background Patients with myelodysplastic syndrome (MDS) display a very diverse pattem. In this study, we investigated prognostic factors and survival rate in adult patients with MDS refractory anaemia (MDS-RA) diagnosed according to French-American-British classification and evaluated the International Prognostic Scoring System (IPSS) for Chinese patients.Methods A multi-center study on diagnosis of MDS-RA was conducted to charactedze the clinical features of Chinese MDS patients. The morphological criteria for the diagnosis of MDS-RA were first standardized. Clinical data of 307 MDS-RA patients collected from Shanghai, Suzhou and Beijing from 1995 to 2006 were analyzed using Kaplan-Meier curve, log rank and Cox regression model.Results The median age of 307 MDS-RA cases was 52 years. The frequency of 2 or 3 lineage cytopenias was 85.6%. Abnormal karyotype occurred in 35.7% of 235 patients. There were 165 cases (70.2%) in the good IPSS cytogenetic subgroup, 44 cases (18.7%) intermediate and 26 cases (11.1%) poor. IPSS showed 20 (8.5%) categodzed as low dsk,195 cases (83.0%) as intermediate-I risk and 20 cases (8.5%) as intermediate-ll dsk. The 1-, 2-, 3-, 4- and 5-year survival rates were 90.8%, 85.7%, 82.9%, 74.9% and 71.2% respectively. Fifteen cases (4.9%) transformed to acute myeloid leukaemia (median time 15.9 months, range 3-102 months). Lower white blood ceil count (<1.5x109/L), platelet count (<30x109/L) and cytogenetic abnormalities were independent prognostic factors by multivariate analysis, but age (≥65 years), IPSS cytogenetic subgroup and IPSS risk subgroup were not independent prognostic factors associated with survival time.Conclusions Chinese patients were younger, and had lower incidence of cytogenetic abnormalities, more severe cytopenias but a more favourable prognosis than Western patients. The major prognostic factors were lower white blood cell count, lower platelet count and fewer abnormal karyotypes. The intemational prognostic scodng

  14. Tumor suppressor p53 protein expression: prognostic significance in patients with low-risk myelodysplastic syndrome

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    Fernando Barroso Duarte

    2014-06-01

    Full Text Available BACKGROUND: At the time of diagnosis, more than 50% of patients with myelodysplastic syndrome have a normal karyotype and are classified as having a favorable prognosis. However, these patients often show very variable clinical outcomes. Furthermore, current diagnostic tools lack the ability to look at genetic factors beyond karyotyping in order to determine the cause of this variability.OBJECTIVE: To evaluate the impact of p53 protein expression at diagnosis in patients with low-risk myelodysplastic syndrome.METHODS: This study enrolled 38 patients diagnosed with low-risk myelodysplastic syndrome. Clinical data were collected by reviewing medical records, and immunohistochemical p53 staining was performed on bone marrow biopsies.RESULTS: Of the 38 participants, 13 (34.21% showed p53 expression in their bone marrow. At diagnosis, this group of patients also presented clinical features characteristic of a poor prognosis more often than patients who did not express p53. Furthermore, patients expressing p53 had a shorter median survival time compared to those without p53 expression.CONCLUSION: This study shows that the expression of p53 at diagnosis is a useful indicator of distinct clinical characteristics and laboratory profiles found in low-risk myelodysplastic syndrome patients. These data indicate that the immunohistochemical analysis of p53 may be a prognostic tool for myelodysplastic syndrome and should be used as an auxiliary test to help determine the best therapeutic choice.

  15. The biology of myelodysplastic syndromes: unity despite heterogeneity

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    Azra Raza

    2010-06-01

    Full Text Available Myelodysplastic syndromes (MDS traditionally have been grouped together as a disease entity based on clinical phenomena seen in association. Despite the similarities, there is great heterogeneity among the syndromes. Recent insights have shown, however, that there exists a biologically cohesive theme that unifies and thereby validates the conceptual interconnectedness. The first suggestion that such a relationship existed where biology could directly explain the observed cytopenias was the finding of excessive premature apoptosis of hematopoietic cells in MDS marrows. This apoptosis was mediated by paracrine as well as autocrine factors implicating both the seed and the soil in the pathology of the disease. Pro-inflammatory cytokines in the marrow microenvironment were mainly the paracrine mediators of apoptosis, but how the clonal cells committed suicide because of autocrine stimulation had remained a mystery for more than a decade. It has been shown now that deregulation of ribosome biogenesis can initiate a stress response in the cell through the p53 signaling pathway. Congenital anemias had been associated with mutations in ribosomal protein genes. The surprise came with the investigation of 5q- syndrome patients where haplo-insufficiency of the ribosomal protein gene RPS14 was found to be the cause of this MDS subtype. Similar ribosomal deregulation was shown to be present in all varieties of MDS patients, serving as another unifying characteristic. In addition to these findings, there are other DNA-related abnormalities such as uniparental disomy, mutations in the TET2 gene, and epigenetic phenomena that are associated with and occur across all types of MDS. This paper summarizes the themes unifying this heterogeneous group of diseases.

  16. Frequent chromatin rearrangements in myelodysplastic syndromes--what stands behind?

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    Pagáčová, E; Falk, M; Falková, I; Lukášová, E; Michalová, K; Oltová, A; Raška, I; Kozubek, S

    2014-01-01

    Myelodysplastic syndromes (MDS) represent a clinically and genetically heterogeneous group of clonal haematopoietic diseases characterized by a short survival and high rate of transformation to acute myeloid leukaemia (AML). In spite of this variability, MDS is associated with typical recurrent non-random cytogenetic defects. Chromosomal abnormalities are detected in the malignant bone-marrow cells of approximately 40-80 % of patients with primary or secondary MDS. The most frequent chromosomal rearrangements involve chromosomes 5, 7 and 8. MDS often shows presence of unbalanced chromosomal changes, especially large deletions [del(5), del(7q), del(12p), del(18q), del(20q)] or losses of whole chromosomes (7 and Y). The most typical cytogenetic abnormality is a partial or complete deletion of 5q- that occurs in roughly 30 % of all MDS cases either as the sole abnormality or in combination with other aberrations as a part of frequently complex karyotypes. The mechanisms responsible for the formation of MDS-associated recurrent translocations and complex karyotypes are unknown. Since some of the mentioned aberrations are characteristic for several haematological malignancies, more general cellular conditions could be expected to play a role. In this article, we introduce the most common rearrangements linked to MDS and discuss the potential role of the non-random higher-order chromatin structure in their formation. A contribution of the chromothripsis - a catastrophic event discovered only recently - is considered to explain how complex karyotypes may occur (during a single event).

  17. Diagnostic Utility of Flow Cytometry in Myelodysplastic Syndromes

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    Della Porta, Matteo G.; Picone, Cristina

    2017-01-01

    The pathological hallmark of myelodysplastic syndromes (MDS) is marrow dysplasia, which represents the basis of the WHO classification of these disorders. This classification provides clinicians with a useful tool for defining the different subtypes of MDS and individual prognosis. The WHO proposal has raised some concern regarding minimal diagnostic criteria particularly in patients with normal karyotype without robust morphological markers of dysplasia (such as ring sideroblasts or excess of blasts). Therefore, there is clearly need to refine the accuracy to detect marrow dysplasia. Flow cytometry (FCM) immunophenotyping has been proposed as a tool to improve the evaluation of marrow dysplasia. The rationale for the application of FCM in the diagnostic work up of MDS is that immunophenotyping is an accurate method for quantitative and qualitative evaluation of hematopoietic cells and that MDS have been found to have abnormal expression of several cellular antigens. To become applicable in clinical practice, FCM analysis should be based on parameters with sufficient specificity and sensitivity, data should be reproducible between different operators, and the results should be easily understood by clinicians. In this review, we discuss the most relevant progresses in detection of marrow dysplasia by FCM in MDS

  18. Cyclosporine Combined with Levamisole for Lower-Risk Myelodysplastic Syndromes.

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    Li, Xingxin; Shi, Jun; Wang, Min; Nie, Neng; Shao, Yingqi; Ge, Meili; Huang, Jinbo; Huang, Zhendong; Zhang, Jing; Zheng, Yizhou

    2015-01-01

    Clinical and experimental evidence suggests an immune-mediated pathophysiology in subjects with lower-risk myelodysplastic syndromes (MDS) in whom immunosuppressive therapy may be effective. The novel immunosuppressive strategy of cyclosporine A (CsA) alternately combined with levamisole (LMS; CsA + LMS regimen) can dramatically improve the response rate and survival in aplastic anemia from those of our previous study. Herein, we retrospectively analyzed the data of 89 lower-risk MDS patients who received the CsA + LMS regimen. A total of 63 patients (70.8%) achieved either complete remission or hematological improvement at 4 months. Overall, 51, 41 and 19 patients had erythroid, platelet and neutrophil responses, respectively. Following the CsA + LMS regimen, 6 patients progressed to more advanced MDS at a median interval of 5 months (range, 3-42 months). The estimated 24-month progression-free survival was 82.2% (95% CI, 72.84-91.56) for all patients. Within the median follow-up of 18.5 months (range, 7.0-61.0), 6 patients died. In conclusion, the CsA + LMS regimen alleviated cytopenias and improved survival and freedom from evolution, suggesting that it could be reserved as an alternative choice for lower-risk MDS.

  19. Myelodysplastic Syndromes in the Elderly: Treatment Options and Personalized Management.

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    Burgstaller, Sonja; Wiesinger, Petra; Stauder, Reinhard

    2015-11-01

    Myelodysplastic syndromes (MDS) are typical diseases of the elderly, with a median age of 68-75 years at initial diagnosis. Demographic changes producing an increased proportion of elderly in our societies mean the incidence of MDS will rise dramatically. Considering the increasing number of treatment options, ranging from best supportive care to hematopoietic stem cell transplantation (HSCT), decision making is rather complex in this cohort of patients. Moreover, aspects of the aging process also have to be considered in therapy planning. Treatment of elderly MDS patients is dependent on the patient's individual risk and prognosis. Comorbidities play an essential role as predictors of survival and therapy tolerance. Age-adjusted models and the use of geriatric assessment scores are described as a basis for individualized treatment algorithms. Specific treatment recommendations for the different groups of patients are given. Currently available therapeutic agents, including supportive care, erythropoiesis-stimulating agents (ESAs), immune-modulating agents, hypomethylating agents, and HSCT are described in detail and discussed with a special focus on elderly MDS patients. The inclusion of elderly patients in clinical trials is of utmost importance to obtain data on efficacy and safety in this particular group of patients. Endpoints relevant for the elderly should be integrated, including maintenance of quality of life and functional activities as well as evaluation of use of healthcare resources.

  20. EARLY DIAGNOSIS OF MYELODYSPLASTIC SYNDROMES USING CLONAL ANALYSES

    Institute of Scientific and Technical Information of China (English)

    钱军; 薛永权; 虞斐; 吴亚芳; 潘金兰; 陆定伟

    2002-01-01

    Objective: To study the value of clonal analysis to the early diagnosis of myelodysplastic syndrome (MDS). Methods: Four types of clonal analyses were performed on the bone marrow samples from 50 patients suspected of MDS: (1) Conventional Cytogenetics (CC) for clonal chromosomal abnormalities; (2) BrdU-Sister Chromatid Differentiation (BrdU-SCD) for cell cycle kinetics; (3) Fluorescence in Situ Hybridization (FISH) for trisomy 8; (4) Polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) for N-ras mutation. Results: The diagnosis of forty-three patients was compatible with the FAB criteria for MDS. The other seven cases didn't meet the FAB criteria, with only one lineage of dyspoiesis or with no obvious dysplastic changes. Among these seven cases, two were morphologically diagnosed with suspicious refractory anemia, one with sideroblastic anemia, one with leukemoid reaction, one with hypercellular anemia and two with chronic aplastic anemia. Clonal analyses of the 7 patients showed that six cases had clonal karyotype abnormalities, four had prolonged cell cycle patterns, four had trisomy 8 of different proportions and one had mutation of the exon 1 of N-RAS. Thus, they were revaluated as MDS patients. Conclusion: The untypical MDS patients with one lineage dyspoiesis or without obvious dysplastic changes can be diagnosed early by combining multiple clonal analysis techniques such as CC, SCD, FISH and PCR-SSCR.

  1. Diagnostic Utility of Flow Cytometry in Myelodysplastic Syndromes

    Science.gov (United States)

    Aanei, Carmen Mariana; Picot, Tiphanie; Tavernier, Emmanuelle; Guyotat, Denis; Campos Catafal, Lydia

    2016-01-01

    Myelodysplastic syndromes (MDSs) are clonal disorders of hematopoiesis that exhibit heterogeneous clinical presentation and morphological findings, which complicates diagnosis, especially in early stages. Recently, refined definitions and standards in the diagnosis and treatment of MDS were proposed, but numerous questions remain. Multiparameter flow cytometry (MFC) is a helpful tool for the diagnostic workup of patients with suspected MDS, and various scores using MFC data have been developed. However, none of these methods have achieved the sensitivity that is required for a reassuring diagnosis in the absence of morphological abnormalities. One reason may be that each score evaluates one or two lineages without offering a broad view of the dysplastic process. The combination of two scores (e.g., Ogata and Red Score) improved the sensitivity from 50–60 to 88%, but the positive (PPV) and negative predictive values (NPV) must be improved. There are prominent differences between study groups when these scores are tested. Further research is needed to maximize the sensitivity of flow cytometric analysis in MDS. This review focuses on the application of flow cytometry for MDS diagnosis and discusses the advantages and limitations of different approaches. PMID:27446807

  2. Coalesced Multicentric Analysis of 2,351 Patients With Myelodysplastic Syndromes Indicates an Underestimation of Poor-Risk Cytogenetics of Myelodysplastic Syndromes in the International Prognostic Scoring System

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    Schanz, Julie; Steidl, Christian; Fonatsch, Christa; Pfeilstöcker, Michael; Nösslinger, Thomas; Tuechler, Heinz; Valent, Peter; Hildebrandt, Barbara; Giagounidis, Aristoteles; Aul, Carlo; Lübbert, Michael; Stauder, Reinhard; Krieger, Otto; Garcia-Manero, Guillermo; Kantarjian, Hagop; Germing, Ulrich; Haase, Detlef; Estey, Elihu

    2011-01-01

    Purpose The International Prognostic Scoring System (IPSS) remains the most commonly used system for risk classification in myelodysplastic syndromes (MDSs). The IPSS gives more weight to blast count than to cytogenetics. However, previous publications suggested that cytogenetics are underweighted in the IPSS. Here we investigate the prognostic impact of cytogenetic subgroups compared with that of bone marrow blast count in a large, multicentric, international patient cohort. Patients and Methods In total, 2,351 patients with MDS who have records in the German-Austrian and the MD Anderson Cancer Center databases were included and analyzed in univariate and multivariate models regarding overall survival and risk of transformation to acute myeloid leukemia (AML). The data were analyzed separately for patients treated with supportive care without specific therapy, with AML-like chemotherapy, or with other therapy regimens (low-dose chemotherapy, demethylating agents, immune modulating agents, valproic acid, and cyclosporine). Results The prognostic impact of poor-risk cytogenetic findings (as defined by the IPSS classification) on overall survival was as unfavorable as an increased (> 20%) blast count. The hazard ratio (compared with an abnormal karyotype or a bone marrow blast count < 5%) was 3.3 for poor-risk cytogenetics, 4.8 for complex abnormalities harboring chromosomes 5 and/or 7, and 3.1 for a blast count of 21% to 30% (P < .01 for all categories). The predictive power of the IPSS cytogenetic subgroups was unaffected by type of therapy given. Conclusion The independent prognostic impact of poor-risk cytogenetics on overall survival is equivalent to the impact of high blast counts. This finding should be considered in the upcoming revision of the IPSS. PMID:21519021

  3. Trisomy 8, a Cytogenetic Abnormality in Myelodysplastic Syndromes, Is Constitutional or Not?

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    Sílvia Saumell

    Full Text Available Isolated trisomy 8 is not considered presumptive evidence of myelodysplastic syndrome (MDS in cases without minimal morphological criteria. One reason given is that trisomy 8 (+8 can be found as a constitutional mosaicism (cT8M. We tried to clarify the incidence of cT8M in myeloid neoplasms, specifically in MDS, and the diagnostic value of isolated +8 in MDS. Twenty-two MDS and 10 other myeloid neoplasms carrying +8 were studied. Trisomy 8 was determined in peripheral blood by conventional cytogenetics (CC and on granulocytes, CD3+ lymphocytes and oral mucosa cells by fluorescence in situ hybridization (FISH. In peripheral blood CC, +8 was seen in 4/32 patients. By FISH, only one patient with chronic myelomonocytic leukemia showed +8 in all cell samples and was interpreted as a cT8M. In our series +8 was acquired in all MDS. Probably, once discarded cT8M by FISH from CD3+ lymphocytes and non-hematological cells, +8 should be considered with enough evidence to MDS.

  4. Molecular and Cellular Mechanisms of Myelodysplastic Syndrome: Implications on Targeted Therapy

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    Harinder Gill

    2016-03-01

    Full Text Available Myelodysplastic syndrome (MDS is a group of heterogeneous clonal hematopoietic stem cell disorders characterized by cytopenia, ineffective hematopoiesis, and progression to secondary acute myeloid leukemia in high-risk cases. Conventional prognostication relies on clinicopathological parameters supplemented by cytogenetic information. However, recent studies have shown that genetic aberrations also have critical impacts on treatment outcome. Moreover, these genetic alterations may themselves be a target for treatment. The mutation landscape in MDS is shaped by gene aberrations involved in DNA methylation (TET2, DNMT3A, IDH1/2, histone modification (ASXL1, EZH2, the RNA splicing machinery (SF3B1, SRSF2, ZRSR2, U2AF1/2, transcription (RUNX1, TP53, BCOR, PHF6, NCOR, CEBPA, GATA2, tyrosine kinase receptor signaling (JAK2, MPL, FLT3, GNAS, KIT, RAS pathways (KRAS, NRAS, CBL, NF1, PTPN11, DNA repair (ATM, BRCC3, DLRE1C, FANCL, and cohesion complexes (STAG2, CTCF, SMC1A, RAD21. A detailed understanding of the pathogenetic mechanisms leading to transformation is critical for designing single-agent or combinatorial approaches in target therapy of MDS.

  5. Use of azacitidine for myelodysplastic syndromes: controversial issues and practical recommendations

    Science.gov (United States)

    Kim, Yoo-Jin; Jang, Jun Ho; Kwak, Jae-Yong; Lee, Je-Hwan

    2013-01-01

    Azacitidine is recommended for patients with higher-risk myelodysplastic syndromes (MDS) who are not eligible for intensive therapy or for patients with lower-risk MDS who have thrombocytopenia or neutropenia or have anemia that is unresponsive to other therapies. However, standard treatment with azacitidine has not been optimized and many issues about the use of azacitidine remain unresolved. The use of azacitidine is expanding rapidly, but limited comparative clinical trial data are available to (i) define the optimal use of azacitidine in patients with higher-risk MDS or around the time of allogeneic hematopoietic stem cell transplantation, (ii) identify those patients with lower-risk MDS who may benefit from treatment, and (iii) guide physicians on alternative therapies after treatment failure. Increasing evidence suggests that the clinical features, prognostic factors, and cytogenetic profiles of patients with MDS in Asia differ significantly from those of patients in Western countries, so the aim of this review is to summarize the evidence and provide practical recommendations on the use of azacitidine in patients with MDS in the Republic of Korea. Evidence considered in this review is based on published clinical data and on the clinical experience of an expert panel from the acute myeloid leukemia/MDS Working Party of the Korean Society of Hematology. PMID:23826577

  6. Spectrum of complex chromosomal aberrations in a myelodysplastic syndrome and a brief review

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    Bani Bandana Ganguly

    2016-01-01

    Full Text Available Myelodysplastic syndrome (MDS is a heterogeneous premalignant condition characterized by cytopenia, ineffective hematopoiesis, dysplastic marrow, and risk of progression to acute myeloid leukemia. Cytogenetic abnormalities, including del(3q/5q/7q/11q/12p/20q, monosomy 5/7, trisomy 8/19, i(17q, and -Y, are the indicators of diagnosis and risk stratification. The present case with bicytopenia detected with highly complex chromosome rearrangements with variability in numerical and structural combinations. Chromosome analysis was carried out following unstimulated marrow culture and G-banding. In addition to known MDS-aberrations, der(9p, der(12 dic(12;?19, +15, −18, and ring and marker chromosomes were recorded having, at least, nine abnormal chromosomes/cell. To our knowledge, this is the first case with all MDS-aberrations in one single individual. The case has been discussed in relevance to current MDS research. In the present case, i(17q/-17, der(12p, del(5q26, del(7q36, and del(20q11 indicate possible alterations in TP53, ETV6, IDH2, EZH2, and SRSF2 genes, which are responsible for pathomechanism, genetic instability, clonal evolution, and advancement of disease condition.

  7. [Point mutations of genes encoding proteins involvedin RNA splicing in patients with myelodysplastic syndromes].

    Science.gov (United States)

    Barańska, Marta; Czerwińska-Rybak, Joanna; Gil, Lidia; Komarnicki, Mieczysław

    2015-01-01

    The myelodysplastic syndromes (MDS) constitute heterogeneous group of clonal disorders, characterized by ineffective hematopoiesis, peripheral cytopenia and increased risk of acute myeloid leukemia development. Molecular mechanisms behind MDS have not been fully explained, however recent studies based on new technologies confirmed that epigenetic abnormalities and somatic mutation in the spliceasome machinery are crucial in pathogenesis of these diseases. Abnormal mRNA splicing (excision of intronic sequences from mRNA) has been found in over half of all MDS patients and resulted in accumulation of cytogenetical and molecular changes. The biological impact of splicing factor genes mutations has been evaluated only in a limited extend and current studies concentrate on analysis of MDS transcriptome. Molecular characteristic of classical and alternative splicing is presented in the paper, according to current knowledge. We review the most prominent findings from recent years concerning mutation in the spliceasome machinery with respect to MDS phenotype and disease prognosis. Perspectives in applying of novel diagnostic and therapeutic possibilities for myelodysplasia, based on spliceosome mutations identification are also presented.

  8. A prospective, multicenter, observational study of long-term decitabine treatment in patients with myelodysplastic syndrome.

    Science.gov (United States)

    Jeong, Seong Hyun; Kim, Yoo-Jin; Lee, Je-Hwan; Kim, Yeo-Kyeoung; Kim, Soo Jeong; Park, Sung Kyu; Do, Young Rok; Kim, Inho; Mun, Yeung-Chul; Kim, Hoon Gu; Lee, Won Sik; Yi, Hyeon Gyu; Joo, Young-Don; Choi, Chul Won; Kim, Suk Ran; Na, Sang Min; Jang, Jun Ho

    2015-12-29

    This prospective observational study evaluated the efficacy and safety of long-term decitabine treatment in patients with myelodysplastic syndrome (MDS). Decitabine 20 mg/m(2)/day was administered intravenously for 5 consecutive days every 4 weeks to MDS patients in intermediate-1 or higher International Prognostic Scoring System (IPSS) risk categories. Active antimicrobial prophylaxis was given to prevent infectious complications. Overall response rate (ORR), overall survival (OS), progression-free survival (PFS), and time to response were evaluated, as were adverse events. The final analysis included 132 patients. IPSS risk was intermediate-2/high in 34.9% patients. The patients received a median of 5 cycles, with responders receiving a median of 8 cycles (range, 2-30). ORR was 62.9% (complete response [CR], 36; partial response [PR], 3; marrow complete response [mCR], 19; and hematologic improvement, 25). Among responders, 39% showed first response at cycle 3 or later. OS at 2 years was 60.9%, with 17% progressing to acute myeloid leukemia. PFS at 2 years was 51.0%. Patients achieving mCR showed comparable survival outcomes to those with CR/PR. With active antibiotic prophylaxis, febrile neutropenia events occurred in 61 of 1,033 (6%) cycles. Long-term decitabine treatment with antibiotic prophylaxis showed favorable outcomes in MDS patients, and mCR predicted favorable survival outcomes.

  9. Bilateral sudden sensorineural hearing loss as an initial presentation of myelodysplastic syndrome.

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    Lee, Eun Jung; Yoon, Yong Joo

    2012-01-01

    This study reports an unusual case in which myelodysplastic syndrome presented bilateral sudden sensorineural hearing loss as the first symptom of the disease. The aural symptoms and signs such as tinnitus, dizziness, and hearing impairment of a hematologic disease are common. However, sudden hearing loss as the first manifestation of a hematologic disease is extremely rare. A 76-year-old woman presented with bilateral sudden hearing loss. The patient was found to have myelodysplastic syndrome during a workup for her hearing loss. Unfortunately, the patient's hearing loss did not improve after the medical treatment.

  10. Azathioprine-associated myelodysplastic syndrome in two patients with ulcerative colitis.

    Science.gov (United States)

    Ahmad, Omer F; Keane, Margaret G; McCartney, Sara; Khwaja, Asim; Bloom, Stuart L

    2013-07-01

    Azathioprine is a commonly used immunosuppressive agent in post-transplantation regimens and autoimmune diseases. An increased risk of lymphoma with thiopurine therapy in patients with inflammatory bowel disease has been described previously; however, there are few reported cases of azathioprine therapy-related myelodysplastic syndrome and acute myeloid leukaemia. We report two patients with ulcerative colitis who subsequently developed azathioprine-related myelodysplastic syndrome. It is imperative that gastroenterologists remain vigilant for this rare complication as this subset of patients has a particularly poor prognosis. These cases are also important in considering the risk of open-ended thiopurine therapy.

  11. An Unexpected Innocent Complication Associated with Azacitidine Treatment of Myelodysplastic Syndrome: Erythema Annulare Centrifugum

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    Esra Turan Erkek

    2016-03-01

    Full Text Available Skin lesions accompanying hematological malignancies can be formed due to either direct tumor infiltration of the skin or indirect effects. Indirectly developing lesions may be a component of paraneoplastic syndrome. Erythema annulare centrifugum (EAC is considered to be a hypersensitivity reaction developed against various antigens associated with infections, drugs, and endocrine diseases. EAC, rarely seen in neoplastic diseases, has been reported in lymphoma, leukemia, histiocytosis, and prostate cancer. Here we report EAC in a patient using a hypomethylating agent, azacitidine. A 69-year-old female patient was admitted to our polyclinic with weakness and ecchymosis in her legs existing for 3 months. She was considered as having refractory anemia with excess blasts-2 according to myelodysplastic syndrome (MDS classification [1]. Because there was only hyperdiploidy in conventional cytogenetic examination, she was classified in group intermediate-2 of the International Prognostic Scoring System. She had a history of radical mastectomy and adjuvant chemoradiotherapy for breast cancer 3 years ago. She said that variously sized round and oval erythematous, itching, painless lesions had formed in the abdominal region on the 4th day of azacitidine usage (75 mg/m2/day, 7 days, s.c. (Figure 1 and 2. There were no concomitant complaints or physical examination findings except fatigue. After azacitidine was stopped, a skin biopsy was taken. In the biopsy, mild perivascular inflammatory infiltration accompanying vascular ectasia in the papillary dermis was detected. The possibility of paraneoplastic syndrome was excluded due to the disappearance of all lesions by 1 week after cessation of treatment. During the second course of azacitidine, the lesions reoccurred on the second day. Subsequently to the second course, the patient died of sepsis, which developed after pneumonia.

  12. Reduced-intensity bone marrow transplantation from an alternative unrelated donor for myelodysplastic syndrome of first-donor origin.

    Science.gov (United States)

    Komeno, Yukiko; Kanda, Yoshinobu; Kandabashi, Koji; Kawazu, Masahito; Goyama, Susumu; Takeshita, Masataka; Nannya, Yasuhito; Niino, Miyuki; Nakamoto, Tetsuya; Kurokawa, Mineo; Tsujino, Shiho; Ogawa, Seishi; Aoki, Katsunori; Chiba, Shigeru; Motokura, Toru; Hirai, Hisamaru

    2003-03-01

    A male patient had a relapse of myelodysplastic syndrome (MDS) 2 years after BMT from a female matched unrelated donor. Conventional cytogenetics, FISH, and short-tandem repeat chimerism analysis proved a relapse of donor origin. He underwent reduced-intensity BMT after a conditioning with fludarabine and busulfan, since he had impaired renal, liver, and pulmonary functions. Chimerism analysis on day 28 after the second BMT showed mixed chimerism of the first and the second donors, which later turned to full second-donor chimerism on day 60. He developed grade II acute GVHD of the skin and cytomegalovirus reactivation, but both were improved with methylprednisolone and ganciclovir, respectively. He remains in complete remission 6 months after the second BMT. Reduced-intensity second BMT from an alternative donor appeared to be a tolerable treatment option for donor-derived leukemia/MDS after the first conventional transplantation.

  13. Clinical features and prognosis of patients with myelodysplastic syndromes who were exposed to atomic bomb radiation in Nagasaki.

    Science.gov (United States)

    Matsuo, Masatoshi; Iwanaga, Masako; Kondo, Hisayoshi; Soda, Midori; Jo, Tatsuro; Horio, Kensuke; Takasaki, Yumi; Kawaguchi, Yasuhisa; Tsushima, Hideki; Imaizumi, Yoshitaka; Imanishi, Daisuke; Taguchi, Jun; Sawayama, Yasushi; Hata, Tomoko; Miyazaki, Yasushi

    2016-10-01

    There is evidence that radiation exposure is a causative factor of myelodysplastic syndromes (MDS). However, little is known about whether radiation exposure is also a prognostic factor of MDS. We investigated the impact of radiation exposure on the prognosis of MDS in Nagasaki atomic bomb survivors using the International Prognostic Scoring System (IPSS) and the revised version (IPSS-R). Subjects were 140 patients with primary MDS diagnosed between 1985 and 2011 and evaluable for IPSS, IPSS-R, and exposure distance. Of those, 31 were exposed at atomic bomb survivors, but exposure distance was not associated with any poor outcomes. These suggest that exposure to the greater dose of atomic bomb radiation is associated with developing poor cytogenetic abnormalities in MDS, which might consequently lead to overt leukemia among atomic bomb survivors. © 2016 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  14. Meeting report: Vienna 2008 Workshop of the German-Austrian Working Group for Studying Prognostic Factors in Myelodysplastic Syndromes.

    Science.gov (United States)

    Valent, Peter; Hofmann, Wolf-Karsten; Büsche, Guntram; Sotlar, Karl; Horny, Hans-Peter; Haase, Detlef; Haferlach, Torsten; Kern, Wolfgang; Bettelheim, Peter; Baumgartner, Christian; Sperr, Wolfgang R; Nösslinger, Thomas; Wimazal, Friedrich; Giagounidis, Aristoteles A; Lübbert, Michael; Krieger, Otto; Kolb, Hans-Jochem; Stauder, Reinhard; Pfeilstöcker, Michael; Gattermann, Norbert; Fonatsch, Christa; Aul, Carlo; Germing, Ulrich

    2009-07-01

    Criteria, scoring systems, and treatment algorithms for myelodysplastic syndromes (MDS) have been updated repeatedly in recent years. This apparently results from increased awareness and early recognition of the disease, an increasing number of new diagnostic and prognostic markers and tools, and new therapeutic options that may change the course and thus prognosis in MDS. To address these challenges and to create useful new diagnostic and prognostic parameters and scores, the German-Austrian Working Group for Studying Prognostic Factors in MDS was established in 2003 and later was extended to centers in Switzerland (D-A-CH group). In addition, the group cooperates with the European LeukemiaNet, the MDS Foundation, and other national and international working groups in order to improve diagnosis and prognostication. The current article represents a meeting report from the latest workshop organized by the group in Vienna in October 2008.

  15. Differential diagnosis of myelodysplastic syndrome and aplastic anemia using MRI

    Energy Technology Data Exchange (ETDEWEB)

    Jung, Seung Eun; Park, Jung Mi; Lee, Jae Mun; Kim, Ki Tae; Kim, Dong Wook; Kim, Chun Choo; Kim, Chun Yul; Shinn, Kyung Sub [Catholic University Medical College, Seoul (Korea, Republic of)

    1995-04-15

    To assess the patterns of myelodysplastic syndrome (MDS) and aplastic anemia (AA) on MRI of the spinal bone marrow and to find the differential points between the two groups. Fourteen patients with MDS (n=7) and AA (n=7) were studied using magnetic resonance imaging. Sagittal images from the lower thoracic and lumbar vertebral marrow were evaluated on T1-weighted and STIR images. Five distinct patterns of signal intensity of the T1-weighted and STIR images were classified. T1 and T2 relaxation times and T1 marrow/fat signal intensity ratio were measured and analyzed (t-test). The cellularity of bone marrow was evaluated on histologic slides. MDS showed homogeneously low signal intensity on T1WI and high signal intensity on STIR image, indicating hypercellular marrow, whereas AA showed relative high signal intensity on T1WI and low signal intensity on STIR image, representing fatty marrow. T1 and T2 relaxation time (T1 for MDS=750.26 msec {+-} 177.50, T1 for AA=413.21 msec {+-} 167.39 ({rho} < 0.000), T2 for MDS=91.86 msec {+-} 14.16, T2 for AA=81.44 msec {+-} 15.31 ({rho} < 0.001) and T1 marrow/fat signal intensity ratio (0.22 {+-} 0.048 in MDS, 0.30 {+-} 0.083 in AA ({rho} < 0.000) revealed statistically significant difference between the two groups. Although the marrow aspiration and needle biopsy are mandatory in hematologic disease for diagnosis, there are limited in assessing the change of total marrow mass. Therefore MRI of bone marrow might be useful in distinguishing MDS from AA because of its ability of representation of total marrow mass.

  16. Pathohistological characteristics of myelodysplastic syndromes: Diagnostic and prognostic significance

    Directory of Open Access Journals (Sweden)

    Marisavljević Dragomir

    2005-01-01

    Full Text Available INTRODUCTION Pathohistological (PH analysis is recommended as basic diagnostic procedure during the investigation of myelodysplastic syndromes (MDS. AIM The aim of this paper was to investigate diagnostic and prognostic significance of bone marrow PH features in patients with MDS, and its relation to cytoiogical characteristics of bone marrow aspirate. METHODS Cellularity, disorder of marrow histotopography, quantity of hematopoiesis lineages, cellular atypia, the amount of myeloblasts, and stromal changes were particularly analyzed in trephines of 236 patients with primary MDS. RESULTS In most cases (78.4% hypercellular bone marrow was observed, although in 10.2% patients hypocellular subtype of MDS was diagnosed. Erythropoiesis dislocation was present in 64.7% patients, dislocation of MK-poiesis in 50.9% patients, while 61.3% had dislocation of granulopoesis (so-called ALIP phenomenon. In most cases three lineage hyperplasia was present, while relative hypoplasia of E- and MK-lineage was found in1/4 cases, each, particularly in advanced MDS. Morphological features of dyseritropoiesis and dysmegakaryocytopoiesis were present in 42.5% and 75.7% cases, respectively. Different stages of reticulin and collagen fibrosis were observed in 55.5% patients, while 7.6% had hyperfibrotic subtype of MDS. Comparative analysis of cytoiogical and histological features of MDS bone marrow showed positive correlation between two methods only in respect of estimation of eritropoiesis quantity, presence of dismegakaryocytopoiesis and „reactive" cells. The univariate analysis showed that MK- and G-lineage dislocation, quantity of E- and G-lineage, and presence of dysmegakaryocytopoiesis, were prognostic indicators for short survival and evolution of the disease in MDS patients. However, multivariate analysis showed that only G-lineage dislocation was independent prognostic variable for survival in MDS cases. CONCLUSION PH analysis is irreplaceable diagnostic

  17. Mechanisms of resistance to decitabine in the myelodysplastic syndrome.

    Directory of Open Access Journals (Sweden)

    Taichun Qin

    Full Text Available PURPOSE: The DNA methylation inhibitor 5-aza-2'-deoxycytidine (DAC is approved for the treatment of myelodysplastic syndromes (MDS, but resistance to DAC develops during treatment and mechanisms of resistance remain unknown. Therefore, we investigated mechanisms of primary and secondary resistance to DAC in MDS. PATIENTS AND METHODS: We performed Quantitative Real-Time PCR to examine expression of genes related to DAC metabolism prior to therapy in 32 responders and non-responders with MDS as well as 14 patients who achieved a complete remission and subsequently relapsed while on therapy (secondary resistance. We then performed quantitative methylation analyses by bisulfite pyrosequencing of 10 genes as well as Methylated CpG Island Amplification Microarray (MCAM analysis of global methylation in secondary resistance. RESULTS: Most genes showed no differences by response, but the CDA/DCK ratio was 3 fold higher in non-responders than responders (P<.05, suggesting that this could be a mechanism of primary resistance. There were no significant differences at relapse in DAC metabolism genes, and no DCK mutations were detected. Global methylation measured by the LINE1 assay was lower at relapse than at diagnosis (P<.05. On average, the methylation of 10 genes was lower at relapse (16.1% compared to diagnosis (18.1% (P<.05. MCAM analysis showed decreased methylation of an average of 4.5% (range 0.6%-9.7% of the genes at relapse. By contrast, new cytogenetic changes were found in 20% of patients. CONCLUSION: Pharmacological mechanisms are involved in primary resistance to DAC, whereas hypomethylation does not prevent a relapse for patients with DAC treatment.

  18. Anemia as the Main Manifestation of Myelodysplastic Syndromes.

    Science.gov (United States)

    Santini, Valeria

    2015-10-01

    Myelodysplastic syndromes (MDS) are a constellation of different diseases sharing anemia in the great majority of cases, and this cytopenia defines these pathologies and their most dramatic clinical manifestations. Anemia in MDS is due to ineffective erythropoiesis, with a high degree of apoptosis of marrow erythroid progenitors. These progenitors show distinctive dysplastic features that consent diagnosis, and are recognizable and differentiated, although not easily, from other morphologic alterations present in other types of anemia. Reaching the diagnosis of MDS in a macrocytic anemia and alleviating the symptoms of anemia are therefore an essential objective of the treating physician. In this work, the signs and symptoms of anemia in MDS, as well as its peculiar pathophysiology, are discussed. Erythopoietic stimulating agents (ESAs) are providing the best treatment for anemic MDS patients, but their use is still not approved by health agencies. While still waiting for this waiver, their clinical use is widespread and their effectivness is well known, as well as the dismal prognosis of patients who do not respond to ESAs and require transfusions. MDS with del5q constitute a unique model of anemia whose complex pathophysiology has been clarified at least partially, defining its link to ribosomal alterations likewise what observed in hereditary anemias like Blackfan Diamond anemia. Lenalidomide is the agent that has shown striking and specific erythropoietic activity in del5q MDS, and the basis of this response is starting to be understood. Several new agents are under evaluation for ESA refractory/relapsed MDS patients, targeting different putative mechanisms of ineffective erythropoiesis, and are here reviewed.

  19. Expansion of effector memory regulatory T cells represents a novel prognostic factor in lower risk myelodysplastic syndrome.

    Science.gov (United States)

    Mailloux, Adam W; Sugimori, Chiharu; Komrokji, Rami S; Yang, Lili; Maciejewski, Jaroslaw P; Sekeres, Mikkael A; Paquette, Ronald; Loughran, Thomas P; List, Alan F; Epling-Burnette, Pearlie K

    2012-09-15

    Myelodysplastic syndromes are premalignant diseases characterized by cytopenias, myeloid dysplasia, immune dysregulation with association to autoimmunity, and variable risk for acute myeloid leukemia transformation. Studies of FOXP3(+) regulatory T cells (Tregs) indicate that the number and/or activation state may influence cancer progression in these patients. Focusing on patients with a lower risk for leukemia transformation, 18 (34.6%) of 52 patients studied displayed an altered Treg compartment compared with age-matched controls. Delineation of unique Treg subsets revealed that an increase in the absolute number of CD4(+)FOXP3(+)CD25(+)CD127(low)CD45RA(-)CD27(-) Tregs (effector memory Tregs [Treg(EM)]) was significantly associated with anemia (p = 0.046), reduced hemoglobin (p = 0.038), and blast counts ≥5% (p = 0.006). In healthy donors, this Treg(EM) population constitutes only 2% of all Tregs (one to six Tregs per microliter) in peripheral blood but, when isolated, exhibit greater suppressive activity in vitro. With a median follow-up of 3.1 y (range 2.7-4.9 y) from sample acquisition, increased numbers of Treg(EM) cells proved to have independent prognostic importance in survival estimates, suggesting that enumeration of this Treg subset may be a more reliable indicator of immunological escape than FOXP3(+) T cells as a whole. Based on multivariate analyses, Treg(EM) impacted survival independently from myeloblast characteristics, cytopenias, karyotype, and comorbidities. Based on these findings, Treg(EM) cell expansion may be synonymous with human Treg activation and indicate microenvironmental changes conducive to transformation in myelodysplastic syndromes.

  20. Safety and efficacy of romiplostim in patients with lower-risk myelodysplastic syndrome and thrombocytopenia.

    NARCIS (Netherlands)

    Kantarjian, H.; Fenaux, P.; Sekeres, M.A.; Becker, P.S.; Boruchov, A.; Bowen, D.; Hellstrom-Lindberg, E.; Larson, R.A.; Lyons, R.M.; Muus, P.; Shammo, J.; Siegel, R.; Hu, K.; Franklin, J.; Berger, D.P.

    2010-01-01

    PURPOSE: To assess the safety and efficacy of romiplostim, a peptibody that increases platelet production, for treatment of thrombocytopenic patients with myelodysplastic syndromes (MDS). PATIENTS AND METHODS: Eligible patients had lower-risk MDS (International Prognostic Scoring System low or inter

  1. Tumor suppressor microRNAs are downregulated in myelodysplastic syndrome with spliceosome mutations

    DEFF Research Database (Denmark)

    Aslan, Derya; Garde, Christian; Nygaard, Mette Katrine;

    2016-01-01

    Spliceosome mutations are frequently observed in patients with myelodysplastic syndromes (MDS). However, it is largely unknown how these mutations contribute to the disease. MicroRNAs (miRNAs) are small noncoding RNAs, which have been implicated in most human cancers due to their role in post...

  2. Darbepoetin alpha for the treatment of anaemia in low-intermediate risk myelodysplastic syndromes

    DEFF Research Database (Denmark)

    Musto, Pellegrino; Lanza, Francesco; Balleari, Enrico;

    2005-01-01

    Thirty-seven anaemic subjects with low-to-intermediate risk myelodysplastic syndrome (MDS) received the highly glycosylated, long-acting erythropoiesis-stimulating molecule darbepoetin-alpha (DPO) at the single, weekly dose of 150 microg s.c. for at least 12 weeks. Fifteen patients (40.5%) achiev...

  3. Hyperfibrotic myelodysplastic syndrome: a report of three cases from north India

    Directory of Open Access Journals (Sweden)

    Prasenjit Das

    2009-06-01

    Full Text Available Extensive fibrosis in myelodysplastic syndromes (MDS is distinctly infrequent. Herein, we report three rare cases of hyperfibrotic MDS. This entity should be classified separately in the chronic myeloproliferative disease (CMPD-MDS group due to variable clinical presentation and poor prognosis.

  4. Reduced expression of FLIPSHORT in bone marrow of low risk myelodysplastic syndrome

    NARCIS (Netherlands)

    Campos, Paula de Melo; Traina, Fabiola; Santos Duarte, Adriana da Silva; Lorand-Metze, Irene; Costa, Fernando F.; Saad, Sara T. O.

    2007-01-01

    Apoptosis is dysregulated in patients with myelodysplastic syndrome (MDS) and acute myelogenous leukaemia (AML). FLIP (FLICE (FAS-associated death-domain-like IL-1 beta-converting enzyme)-inhibitory protein) has been described as an anti-apoptotic protein. Here, we characterize the expression level

  5. Fatal bacteremia by neisseria cinerea in a woman with myelodysplastic syndrome: a case report.

    Science.gov (United States)

    Zhu, Xiaofei; Li, Min; Cao, Huiling; Yang, Xuewen

    2015-01-01

    Neisseria cinerea has been rarely found in blood cultures. In this study, we are reporting a case of a Myelodysplastic Syndrome (MDS) patient in whose blood Neisseria cinerea was found and led a fatal consequence. This case will call our attentions to the uncommon pathogens in the pathogenicity of end-stage patients.

  6. Fatal bacteremia by neisseria cinerea in a woman with myelodysplastic syndrome: a case report

    OpenAIRE

    Zhu, Xiaofei; Li, Min; Cao, Huiling; Yang, Xuewen

    2015-01-01

    Neisseria cinerea has been rarely found in blood cultures. In this study, we are reporting a case of a Myelodysplastic Syndrome (MDS) patient in whose blood Neisseria cinerea was found and led a fatal consequence. This case will call our attentions to the uncommon pathogens in the pathogenicity of end-stage patients.

  7. Practical recommendations on the use of lenalidomide in the management of myelodysplastic syndromes.

    NARCIS (Netherlands)

    Giagounidis, A.; Fenaux, P.; Mufti, G.J.; Muus, P.; Platzbecker, U.; Sanz, G.; Cripe, L.; Lilienfeld-Toal, M. von; Wells, R.A.

    2008-01-01

    Lenalidomide, an oral immunomodulatory agent, has received approval in the USA from the Food and Drug Administration (FDA) for the management of myelodysplastic syndromes (MDS) classified by the International Prognostic Scoring System (IPSS) as low risk or intermediate-1 risk and with a deletion 5q

  8. Longitudinal Analysis of DNA Methylation in CD34+ Hematopoietic Progenitors in Myelodysplastic Syndrome

    DEFF Research Database (Denmark)

    Wong, Yan Fung; Micklem, Chris N; Taguchi, Masataka

    2014-01-01

    Myelodysplastic syndrome (MDS) is a disorder of hematopoietic stem cells (HSCs) that is often treated with DNA methyltransferase 1 (DNMT1) inhibitors (5-azacytidine [AZA], 5-aza-2'-deoxycytidine), suggesting a role for DNA methylation in disease progression. How DNMT inhibition retards disease pr...

  9. Genomic array as compared to karyotyping in myelodysplastic syndromes in a prospective clinical trial

    NARCIS (Netherlands)

    Stevens-Kroef, Marian J; Olde Weghuis, Daniel; ElIdrissi-Zaynoun, Najat; van der Reijden, Bert; Cremers, Eline M P; Alhan, Canan; Westers, Theresia M; Visser-Wisselaar, Heleen A; Chitu, Dana A; Cunha, Sonia M; Vellenga, Edo; Klein, Saskia K; Wijermans, Pierre; de Greef, Georgine E; Schaafsma, M Ron; Muus, Petra; Ossenkoppele, Gert J; van de Loosdrecht, Arjan A; Jansen, Joop H

    2017-01-01

    Karyotyping is considered as the gold standard in the genetic subclassification of myelodysplastic syndrome (MDS). Oligo/SNP-based genomic array profiling is a high-resolution tool that also enables genome wide analysis. We compared karyotyping with oligo/SNP-based array profiling in 104 MDS patient

  10. Clinical management of gastrointestinal disturbances in patients with myelodysplastic syndromes receiving iron chelation treatment with deferasirox

    NARCIS (Netherlands)

    Nolte, F.; Angelucci, E.; Beris, P.; Macwhannell, A.; Selleslag, D.; Schumann, C.; Xicoy, B.; Almeida, A.; Guerci-Bresler, A.; Sliwa, T.; Muus, P.; Porter, J.; Hofmann, W.K.

    2011-01-01

    Myelodysplastic syndromes are characterized by ineffective hematopoiesis resulting in peripheral cytopenias. The majority of patients is dependent on regular transfusions of packed red blood cells leading to a secondary iron overload which might result in organ damage. Therefore, sufficient iron che

  11. Hematologic responses to deferasirox therapy in transfusion-dependent patients with myelodysplastic syndromes

    Science.gov (United States)

    Gattermann, Norbert; Finelli, Carlo; Della Porta, Matteo; Fenaux, Pierre; Stadler, Michael; Guerci-Bresler, Agnes; Schmid, Mathias; Taylor, Kerry; Vassilieff, Dominique; Habr, Dany; Marcellari, Andrea; Roubert, Bernard; Rose, Christian

    2012-01-01

    Background Reductions in transfusion requirements/improvements in hematologic parameters have been associated with iron chelation therapy in transfusion-dependent patients, including those with myelodysplastic syndromes; data on there reductions/improvements have been limited to case reports and small studies. Design and Methods To explore this observation in a large population of patients, we report a post-hoc analysis evaluating hematologic response to deferasirox in a cohort of iron-overloaded patients with myelodysplastic syndromes enrolled in the Evaluation of Patients’ Iron Chelation with Exjade® (EPIC) study using International Working Group 2006 criteria. Results Two-hundred and forty-seven, 100 and 50 patients without concomitant medication for myelodysplastic syndromes were eligible for analysis of erythroid, platelet and neutrophil responses, respectively. Erythroid, platelet and neutrophil responses were observed in 21.5% (53/247), 13.0% (13/100) and 22.0% (11/50) of the patients after a median of 109, 169 and 226 days, respectively. Median serum ferritin reductions were greater in hematologic responders compared with non-responders at end of study, although these differences were not statistically significant. A reduction in labile plasma iron to less than 0.4 μmol/L was observed from week 12 onwards; this change did not differ between hematologic responders and non-responders. Conclusions This analysis suggests that deferasirox treatment for up to 1 year could lead to improvement in hematologic parameters in some patients with myelodysplastic syndromes. PMID:22419577

  12. Immunophenotypic analysis of erythroid dysplasia in myelodysplastic syndromes. A report from the IMDSFlow working group

    Science.gov (United States)

    Westers, Theresia M.; Cremers, Eline M.P.; Oelschlaegel, Uta; Johansson, Ulrika; Bettelheim, Peter; Matarraz, Sergio; Orfao, Alberto; Moshaver, Bijan; Brodersen, Lisa Eidenschink; Loken, Michael R.; Wells, Denise A.; Subirá, Dolores; Cullen, Matthew; te Marvelde, Jeroen G.; van der Velden, Vincent H.J.; Preijers, Frank W.M.B.; Chu, Sung-Chao; Feuillard, Jean; Guérin, Estelle; Psarra, Katherina; Porwit, Anna; Saft, Leonie; Ireland, Robin; Milne, Timothy; Béné, Marie C.; Witte, Birgit I.; Della Porta, Matteo G.; Kern, Wolfgang; van de Loosdrecht, Arjan A.

    2017-01-01

    Current recommendations for diagnosing myelodysplastic syndromes endorse flow cytometry as an informative tool. Most flow cytometry protocols focus on the analysis of progenitor cells and the evaluation of the maturing myelomonocytic lineage. However, one of the most frequently observed features of myelodysplastic syndromes is anemia, which may be associated with dyserythropoiesis. Therefore, analysis of changes in flow cytometry features of nucleated erythroid cells may complement current flow cytometry tools. The multicenter study within the IMDSFlow Working Group, reported herein, focused on defining flow cytometry parameters that enable discrimination of dyserythropoiesis associated with myelodysplastic syndromes from non-clonal cytopenias. Data from a learning cohort were compared between myelodysplasia and controls, and results were validated in a separate cohort. The learning cohort comprised 245 myelodysplasia cases, 290 pathological, and 142 normal controls; the validation cohort comprised 129 myelodysplasia cases, 153 pathological, and 49 normal controls. Multivariate logistic regression analysis performed in the learning cohort revealed that analysis of expression of CD36 and CD71 (expressed as coefficient of variation), in combination with CD71 fluorescence intensity and the percentage of CD117+ erythroid progenitors provided the best discrimination between myelodysplastic syndromes and non-clonal cytopenias (specificity 90%; 95% confidence interval: 84–94%). The high specificity of this marker set was confirmed in the validation cohort (92%; 95% confidence interval: 86–97%). This erythroid flow cytometry marker combination may improve the evaluation of cytopenic cases with suspected myelodysplasia, particularly when combined with flow cytometry assessment of the myelomonocytic lineage. PMID:27758818

  13. Clinical study of CAG regimen combined Decitabine in treatment of elderly patients with moderate and high risk myelodysplastic syndrome and acute myeloid leukemia%地西他滨联合小剂量化疗治疗老年中高危骨髓增生异常综合征及急性髓系白血病的临床观察

    Institute of Scientific and Technical Information of China (English)

    徐瑜; 沙颖豪; 谢彦晖

    2013-01-01

    Objective To observe the clinical efficacy and adverse events of treatment for elderly patients with moderate and high-risk myelodysplastic syndrome (MDS) and acute myelocytic leukemia (AMD with Decitabine (25mg/d, d1-3) combined with CAG (G-CSF300ug/d, d4-13; aclarubicin10mg/d, d4,6,8,10,12; Ara-C25mg/d, d4-13) regimen. Methods Decitabine combined with CAG regimen were used to treat 10 elderly patients with MDS and AML. The outcome was evaluated after 1 course of treatment. Results For ten patients, 3/10(30%) achieved completely remission (CR), 4/10 (40%) marrow completely remission (mCR), 1/10 (10%) partial remission (PR). The overall response rate was 80%. Most patients can withstand adverse reactions occurred mainly for the arrest of bone marrow. Conclusion In older patients, medium and high-risk MDS and AML treated with Decitabine combined with CAG regimen is safe and effective.%目的 观察地西他滨联合CAG方案治疗老年中高危MDS及AML的临床疗效及不良反应.方法 应用地西他滨联合CAG方案治疗MDS及AML患者10例.1个疗程后评估疗效.结果 10例患者,其中3例获得完全缓解(CR) 30%,4例为部分缓解(PR) 10%,1例获得骨髓缓解(mCR)40%.总有效率为80%.大多数患者出现了可以耐受的不良反应,主要表现为骨髓抑制.结论 地西他滨联合CAG方案治疗中高危MDS和老年AML有较好的疗效和安全性.

  14. CAG方案治疗中高危骨髓增生异常综合征和急性髓系白血病疗效观察%Clinical observation of the efficacy of CAG regimen for the treatment of intermediate or high risk myelodysplastic syndrome and acute myeloid leukemia

    Institute of Scientific and Technical Information of China (English)

    侯先锋; 刘琼; 苏贵珍; 孙海英

    2014-01-01

    Objective To observe the efficacy and adverse reactions of CAG regimen ( cytarabine and aclarubicin in combination with granulocyte colony -stimulating factor ) for treatment of intermediate or high risk myelodysplastic syn-drome (MDS) and acute myeloid leukemia (AML).Methods Twenty-eight MDS patients and twenty AML patients received CAG regimen .Then, the resulting efficacy was evaluated after one course of treatment , in which those with posi-tive response was given another course of treatment .Results MDS patients presented 53%of clinical effectiveness , in-cluding 15 cases (53%) with completely remission (CR).AML patients presented 65%of clinical effectiveness, inclu-ding 10 cases (50%) with CR and 3 cases (15%) with partial remission (PR).Most patients reported slight/mild ad-verse events, mainly myelosuppression , which was tolerable .Conclusion CAG regimen is safe and effective to treat in-termediate or high risk MDS and AML with poor prognosis , and its long-term efficacy requires further observation .%目的:观察阿糖胞苷、阿克拉霉素和粒细胞集落刺激因子联合方案( CAG方案)治疗中、高危骨髓增生异常综合征( MDS)和初治急性髓系白血病( AML)的临床疗效及不良反应。方法应用CAG方案治疗中高危MDS 28例和AML 20例,完成1个疗程后评估疗效,治疗失败患者退出观察,有效者继续接受1个疗程治疗,并进行评估。结果28例MDS临床总有效率53%,其中完全缓解15例(53%),部分缓解0例。 AML临床总有效13例(65%),其中完全缓解10例(50%),部分缓解3例(15%)。大部分患者出现了可以耐受的轻微不良反应,主要表现为骨髓抑制。结论 CAG治疗中、高危MDS和预后差的AML安全有效,长期疗效需进一步观察。

  15. Clinical observation of HAG regimen in remission inductive treatment for elderly patients with acute myeloid leukemia and myelodysplastic syndrome%HAG预激化疗作为诱导缓解方案治疗老年人急性髓系白血病和骨髓增生异常综合征的临床观察

    Institute of Scientific and Technical Information of China (English)

    王剑利; 何爱丽; 张王刚; 杨云; 古流芳; 孔颖

    2011-01-01

    Objective To observe the efficacy of HAG regimen in remission inductive treatment for elderly patients with acute myeloid leukemia (AML) and myelodysplastic syndrome-refractory anemia with excess blasts (MDS-RAEB). Methods The clinical features of 21 cases with AML and 9 cases with MDSRAEB (≥60 year old) treated with HA-G regimen in remission induction were retrospectively analyzed,including the complete remission (CR) rate, efficiency rate as well as their toxicities. Results In 21 elderly patients with AML treated with HAG regimen, the efficiency rate was 66.7 % (14/21), CR rate 47.6 % (10/21).In 9 elderly patients with MDS-RAEB, the CR rate was 55.6 % (5/9). The main toxicity of HA-G regimen was infections secondary to hematopoiesis suppression after chemotherapy. All patients were well tolerated to adjusted regimen. Conclusion The HA-G regimen is much effective in remission induction for elderly patients with AML and MDS-RAEB.%目的 观察HAG预激化疗作为诱导缓解方案在治疗老年急性髓系白血病(AML)和骨髓增生异常综合征-难治性贫血伴原始细胞增多型(MDS-RAEB)患者中的疗效.方法 对应用HAG预激方案治疗的21例AML和9例MDS-RAEB患者(≥60岁)的临床资料进行回顾性总结,包括疾病完全缓解(CR)率、有效率以及不良反应.结果 21例老年AML患者中,HAG诱导缓解的有效率为66.7%(14/21),其中CR率为47.6%(10/21);9例老年MDS-RAEB患者中,CR率为55.6%(5/9):HAG预激化疗的主要不良反应为因骨髓抑制继发的感染,调整化疗方案后所有患者均能耐受.结论 HAG预激化疗作为诱导缓解方案适用于老年AML和MDS-RAEB患者.

  16. Characterization of defective megakaryocytic development in patients with myelodysplastic syndromes.

    Science.gov (United States)

    Hofmann, W K; Kalina, U; Wagner, S; Seipelt, G; Ries, C; Hoelzer, D; Ottmann, O G

    1999-03-01

    Megakaryocytic differentiation of progenitor cells was investigated in nine patients with low-risk myelodysplastic syndromes (MDS) (eight refractor anemia [RA] and one RA with ringed sideroblasts [RARS] and five patients with high-risk MDS (two RA with excess of blasts [RAEB] and three RAEB in transformation [RAEB-T]). Bone marrow-derived CD34+ cells were enriched to a purity of 87% +/- 2% (mean +/- SEM) and assayed in short-term suspension cultures in the presence of 10 ng/mL of PEGylated recombinant human megakaryocyte (MK) growth and development factor (PEG-rHuMGDF) and in addition to 50 ng/mL stem cell factor and 10 ng/mL interleukin-3. Cells of the megakaryocytic lineage were identified by flow cytometric analysis of CD42b (GP1b) and mature MKs by morphologic criteria. Transcription of c-mpl receptor-specific mRNA in the CD34+ cells of these patients was investigated by full-length reverse transcriptase polymerase chain reaction of the p form of c-mpl as well as of the alternative splice product c-mpl k. CD34+ cells from seven healthy bone marrow donors served as controls. Differentiation along the MK pathway was stimulated in five patients with RA. C-mpl mRNA was expressed in the CD34+ cells in all cases. In three low-risk patients the capacity for in vitro MK growth was absent or minimal even though mRNA for c-mpl receptor was detected in the CD34+ cells of this group as well. In patients with high-risk MDS, PEG-rHuMGDF stimulated in vitro MK growth from CD34+ cells in only one of five cases. As in the patients with low-risk MDS, c-mpl mRNA for both c-mpl p and c-mpl k splicing products was detected. These results indicate that the in vitro response to stimulation with c-mpl ligand discriminates between two groups of patients with low-risk MDS and that the observed defect in megakaryocytic development is unrelated to the level of c-mpl expression in both low-risk and high-risk MDS.

  17. Hypermethylation of the VTRNA1-3 Promoter is Associated with Poor Outcome in Lower Risk Myelodysplastic Syndrome Patients

    DEFF Research Database (Denmark)

    Helbo, Alexandra Søgaard; Treppendahl, Marianne; Aslan, Derya

    2015-01-01

    Myelodysplastic syndrome (MDS) is a heterogeneous group of clonal hematopoietic disorders. MDS is frequently associated with deletions on chromosome 5q as well as aberrant DNA methylation patterns including hypermethylation of key tumor suppressors. We have previously shown that hypermethylation ...

  18. Megakaryocytic dysfunction in myelodysplastic syndromes and idiopathic thrombocytopenic purpura is in part due to different forms of cell death

    NARCIS (Netherlands)

    Houwerzijl, E. J.; Blom, N. R.; van der Want, J. J. L.; Vellenga, E.; de Wolf, J. T. M.

    2006-01-01

    Platelet production requires compartmentalized caspase activation within megakaryocytes. This eventually results in platelet release in conjunction with apoptosis of the remaining megakaryocyte. Recent studies have indicated that in low-risk myelodysplastic syndromes (MDS) and idiopathic thrombocyto

  19. A calcium- and calpain-dependent pathway determines the response to lenalidomide in myelodysplastic syndromes.

    Science.gov (United States)

    Fang, Jing; Liu, Xiaona; Bolanos, Lyndsey; Barker, Brenden; Rigolino, Carmela; Cortelezzi, Agostino; Oliva, Esther N; Cuzzola, Maria; Grimes, H Leighton; Fontanillo, Celia; Komurov, Kakajan; MacBeth, Kyle; Starczynowski, Daniel T

    2016-07-01

    Despite the high response rates of individuals with myelodysplastic syndrome (MDS) with deletion of chromosome 5q (del(5q)) to treatment with lenalidomide (LEN) and the recent identification of cereblon (CRBN) as the molecular target of LEN, the cellular mechanism by which LEN eliminates MDS clones remains elusive. Here we performed an RNA interference screen to delineate gene regulatory networks that mediate LEN responsiveness in an MDS cell line, MDSL. We identified GPR68, which encodes a G-protein-coupled receptor that has been implicated in calcium metabolism, as the top candidate gene for modulating sensitivity to LEN. LEN induced GPR68 expression via IKAROS family zinc finger 1 (IKZF1), resulting in increased cytosolic calcium levels and activation of a calcium-dependent calpain, CAPN1, which were requisite steps for induction of apoptosis in MDS cells and in acute myeloid leukemia (AML) cells. In contrast, deletion of GPR68 or inhibition of calcium and calpain activation suppressed LEN-induced cytotoxicity. Moreover, expression of calpastatin (CAST), an endogenous CAPN1 inhibitor that is encoded by a gene (CAST) deleted in del(5q) MDS, correlated with LEN responsiveness in patients with del(5q) MDS. Depletion of CAST restored responsiveness of LEN-resistant non-del(5q) MDS cells and AML cells, providing an explanation for the superior responses of patients with del(5q) MDS to LEN treatment. Our study describes a cellular mechanism by which LEN, acting through CRBN and IKZF1, has cytotoxic effects in MDS and AML that depend on a calcium- and calpain-dependent pathway.

  20. Sustained disease-free survival achieved with withdrawal of immunosuppression after rapid relapse of myelodysplastic syndrome following myeloablative allogeneic hematopoietic transplantation: a case report

    Directory of Open Access Journals (Sweden)

    Hamilton Betty K

    2013-01-01

    Full Text Available Abstract Introduction Relapse after allogeneic hematopoietic stem cell transplantation in patients with myelodysplasia is a challenging problem with limited treatment options. Attempts to induce a graft-versus-leukemia effect have been used with limited success. In patients with myelodysplasia, sustained complete remissions have generally been limited to patients with long-term remission after transplant and those with low numbers of marrow blasts. Case presentation We report the case of a 41-year-old Caucasian woman with relapsed myelodysplastic syndrome and a high blast percentage six months after undergoing an allogeneic transplant who achieved a sustained complete remission after withdrawal of immunosuppression alone. Conclusion This case highlights the importance of a reasonable period of observation after withdrawing immunosuppression to induce graft-versus-leukemia, and the potential effectiveness of that approach.

  1. Epigenetic approaches in the treatment of myelodysplastic syndromes: clinical utility of azacitidine

    Directory of Open Access Journals (Sweden)

    Steven E McCormack

    2010-07-01

    Full Text Available Steven E McCormack, Erica D WarlickDepartment of Medicine, Division of Hematology, Oncology, and Transplantation, University of Minnesota, Minneapolis, Minnesota, USAAbstract: Myelodysplastic syndromes (MDS are a varied group of diseases leading to ­significant morbidity and mortality. Therapy of MDS has been difficult, with supportive cares used to ameliorate symptoms, and hematopoietic stem cell transplantation the only curative option. Agents, such as the cytidine analog azacitidine, exert an effect on DNA methyltransferase leading to a reduction in DNA methylation, a process thought to be key to the pathogenesis of MDS. Recently, azacitidine has been shown to prolong survival and improve quality of life in patients with MDS, while maintaining a favorable adverse effect profile. This review highlights the scientific rationale for the use of azacitidine in addition to its application in current clinical practice for patients with MDS.Keywords: hypomethylation, epigenetics, myelodysplastic syndromes, azacitidine

  2. Targeted re-sequencing analysis of 25 genes commonly mutated in myeloid disorders in del(5q) myelodysplastic syndromes

    Science.gov (United States)

    Fernandez-Mercado, Marta; Burns, Adam; Pellagatti, Andrea; Giagounidis, Aristoteles; Germing, Ulrich; Agirre, Xabier; Prosper, Felipe; Aul, Carlo; Killick, Sally; Wainscoat, James S.; Schuh, Anna; Boultwood, Jacqueline

    2013-01-01

    Interstitial deletion of chromosome 5q is the most common chromosomal abnormality in myelodysplastic syndromes. The catalogue of genes involved in the molecular pathogenesis of myelodysplastic syndromes is rapidly expanding and next-generation sequencing technology allows detection of these mutations at great depth. Here we describe the design, validation and application of a targeted next-generation sequencing approach to simultaneously screen 25 genes mutated in myeloid malignancies. We used this method alongside single nucleotide polymorphism-array technology to characterize the mutational and cytogenetic profile of 43 cases of early or advanced del(5q) myelodysplastic syndromes. A total of 29 mutations were detected in our cohort. Overall, 45% of early and 66.7% of advanced cases had at least one mutation. Genes with the highest mutation frequency among advanced cases were TP53 and ASXL1 (25% of patients each). These showed a lower mutation frequency in cases of 5q- syndrome (4.5% and 13.6%, respectively), suggesting a role in disease progression in del(5q) myelodysplastic syndromes. Fifty-two percent of mutations identified were in genes involved in epigenetic regulation (ASXL1, TET2, DNMT3A and JAK2). Six mutations had allele frequencies <20%, likely below the detection limit of traditional sequencing methods. Genomic array data showed that cases of advanced del(5q) myelodysplastic syndrome had a complex background of cytogenetic aberrations, often encompassing genes involved in myeloid disorders. Our study is the first to investigate the molecular pathogenesis of early and advanced del(5q) myelodysplastic syndromes using next-generation sequencing technology on a large panel of genes frequently mutated in myeloid malignancies, further illuminating the molecular landscape of del(5q) myelodysplastic syndromes. PMID:23831921

  3. Diagnostic utility of flow cytometry in low-grade myelodysplastic syndromes: a prospective validation study

    Science.gov (United States)

    Ogata, Kiyoyuki; Della Porta, Matteo G.; Malcovati, Luca; Picone, Cristina; Yokose, Norio; Matsuda, Akira; Yamashita, Taishi; Tamura, Hideto; Tsukada, Junichi; Dan, Kazuo

    2009-01-01

    Background The diagnosis of myelodysplastic syndromes is not always straightforward when patients lack specific diagnostic markers, such as blast excess, karyotype abnormality, and ringed sideroblasts. Design and Methods We designed a flow cytometry protocol applicable in many laboratories and verified its diagnostic utility in patients without those diagnostic markers. The cardinal parameters, analyzable from one cell aliquot, were myeloblasts (%), B-cell progenitors (%), myeloblast CD45 expression, and channel number of side scatter where the maximum number of granulocytes occurs. The adjunctive parameters were CD11b, CD15, and CD56 expression (%) on myeloblasts. Marrow samples from 106 control patients with cytopenia and 134 low-grade myelodysplastic syndromes patients, including 81 lacking both ringed sideroblasts and cytogenetic aberrations, were prospectively analyzed in Japan and Italy. Results Data outside the predetermined reference range in 2 or more parameters (multiple abnormalities) were common in myelodysplastic syndromes patients. In those lacking ringed sideroblasts and cytogenetic aberrations, multiple abnormalities were observed in 8/26 Japanese (30.8%) and 37/55 Italians (67.3%) when the cardinal parameters alone were considered, and in 17/26 Japanese (65.4%) and 42/47 Italians (89.4%) when all parameters were taken into account. Multiple abnormalities were rare in controls. When data from all parameters were used, the diagnostic sensitivities were 65% and 89%, specificities were 98% and 90%, and likelihood ratios were 28.1 and 8.5 for the Japanese and Italian cohorts, respectively. Conclusions This protocol can be used in the diagnostic work-up of low-grade myelodysplastic syndromes patients who lack specific diagnostic markers, although further improvement in diagnostic power is desirable. PMID:19546439

  4. Acute Fibrinous and Organizing Pneumonia with Myelodysplastic Syndrome: Corticosteroid Monotherapy Led to Successful Ventilator Weaning

    OpenAIRE

    Yamamoto, Mari; Murata, Kengo; Kiriu, Takahiro; Kouzai, Yasuji; Takamori, Mikio

    2016-01-01

    A 62-year-old man with myelodysplastic syndrome (MDS) presented to our hospital with a high fever. Although treatment with broad-spectrum antibiotics was initiated, his respiratory status worsened to the point that he required mechanical ventilation. However, he was successfully treated with a corticosteroid without immunosuppression. Sequential transbronchial lung biopsies revealed abundant fibrin exudate in the alveolar spaces, which was subsequently replaced by fibroblasts, showing that ac...

  5. Aloimmunity against HLA class I antigens in patients with myelodysplastic syndrome and aplastic anemia

    OpenAIRE

    2005-01-01

    Myelodysplastic syndrome (MDS) and aplastic anemia (AA) are two of the hematological disorders which present peripheral cytopenias, with extensive clinical manifestations that vary from slight anemia to severe pancytopenia; the latter requiring continuous transfusional reposition of red cell (RC) and platelet concentrates (PC), which can induce aloimunization in patients. Such patients can develop a post-transfusional refractory state, rendering further transfusions unviable. The objective of...

  6. Reproducibility of the World Health Organization 2008 criteria for myelodysplastic syndromes

    Science.gov (United States)

    Senent, Leonor; Arenillas, Leonor; Luño, Elisa; Ruiz, Juan C.; Sanz, Guillermo; Florensa, Lourdes

    2013-01-01

    The reproducibility of the World Health Organization 2008 classification for myelodysplastic syndromes is uncertain and its assessment was the major aim of this study. The different peripheral blood and bone marrow variables required for an adequate morphological classification were blindly evaluated by four cytomorphologists in samples from 50 patients with myelodysplastic syndromes. The degree of agreement among observers was calculated using intraclass correlation coefficient and the generalized kappa statistic for multiple raters. The degree of agreement for the percentages of blasts in bone marrow and peripheral blood, ring sideroblasts in bone marrow, and erythroid, granulocytic and megakaryocytic dysplastic cells was strong (P<0.001 in all instances). After stratifying the percentages according to the categories required for the assignment of World Health Organization subtypes, the degree of agreement was not statistically significant for cases with 5-9% blasts in bone marrow (P=0.07), 0.1-1% blasts in peripheral blood (P=0.47), or percentage of erythroid dysplastic cells (P=0.49). Finally, the interobserver concordance for World Health Organization-defined subtypes showed a moderate overall agreement (P<0.001), the reproducibility being lower for cases with refractory anemia with excess of blasts type 1 (P=0.05) and refractory anemia with ring sideroblasts (P=0.09). In conclusion, the reproducibility of the World Health Organization 2008 classification for myelodysplastic syndromes is acceptable but the defining criteria for blast cells and features of erythroid dysplasia need to be refined. PMID:23065505

  7. Complex karyotype newly defined: the strongest prognostic factor in advanced childhood myelodysplastic syndrome.

    Science.gov (United States)

    Göhring, Gudrun; Michalova, Kyra; Beverloo, H Berna; Betts, David; Harbott, Jochen; Haas, Oskar A; Kerndrup, Gitte; Sainati, Laura; Bergstraesser, Eva; Hasle, Henrik; Stary, Jan; Trebo, Monika; van den Heuvel-Eibrink, Marry M; Zecca, Marco; van Wering, Elisabeth R; Fischer, Alexandra; Noellke, Peter; Strahm, Brigitte; Locatelli, Franco; Niemeyer, Charlotte M; Schlegelberger, Brigitte

    2010-11-11

    To identify cytogenetic risk factors predicting outcome in children with advanced myelodysplastic syndrome, overall survival of 192 children prospectively enrolled in European Working Group of Myelodysplastic Syndrome in Childhood studies was evaluated with regard to karyotypic complexity. Structurally complex constitutes a new definition of complex karyotype characterized by more than or equal to 3 chromosomal aberrations, including at least one structural aberration. Five-year overall survival in patients with more than or equal to 3 clonal aberrations, which were not structurally complex, did not differ from that observed in patients with normal karyotype. Cox regression analysis revealed the presence of a monosomal and structurally complex karyotype to be strongly associated with poor prognosis (hazard ratio = 4.6, P < .01). Notably, a structurally complex karyotype without a monosomy was associated with a very short 2-year overall survival probability of only 14% (hazard ratio = 14.5; P < .01). The presence of a structurally complex karyotype was the strongest independent prognostic marker predicting poor outcome in children with advanced myelodysplastic syndrome.

  8. Abnormalities of chromosome 17 in myelodysplastic syndromes: Incidence and biological significance

    Directory of Open Access Journals (Sweden)

    Marisavljević Dragomir

    2004-01-01

    Full Text Available Cytogenetic analysis has proven to be a mandatory part of the diagnosis of myelodysplastic syndromes (MDS as well as a major indicator for predicting clinical course and outcome. Aside from the 5q-syndrome, no specific clinico-cytogenetic entity has been reported. To determine the incidence and clinical significance of acquired abnormalities of chromosome 17 in adult primary MDS, we reviewed the cytogenetic features of 271 patients detected at our institution during a 10-year period. Clonal cytogenetic abnormalities were identified in 109 cases. Among them, abnormalities of chromosome 17 were identified in 13 patients (11.9%. Five patients had „single" defects, while in eight patients abnormalities of chromosome 17 were associated with other chromosomal rearrangements („complex" defects. After chromosomes 5,7,8 and 1, abnormalities of chromosome 17 were the most frequent chromosomal rearrangements in our patients with MDS. Following „single" defects of chromosome 17 were identified: del(17(pl2 in two cases, and i(17(q10, del(17(q21;q23 and del(17(ql2;q22 in one case each. Two patients with del(17p, one with RAEB-t and the other one with CMML, had an aggressive course of the disease with accelerated leukemic transformation and short survival. Patient with i(17q had RARS subtype and died soon after diagnosis, while other two cases with interstitial deletions of the long arm of chromosome 17 had RAEB subtype and stable, no progressive course of the disease. Among „complex" karyotypes with abnormalities of chromosome 17 we identified der(l 7 in four, monosomy 17 in two, and del(17p and i(17q in one case each. Most of these patients transformed to acute leukemia and had very short survival. The results of this study suggest that abnormalities of chromosome 17 are frequent finding in MDS. Loss of genetic material in 17p, both in „single" and „complex" defects, seems to be closely related to poor prognosis of MDS patients.

  9. Effect of increased-dose decitabine in patients with high-risk myelodysplastic syndrome and acute myeloid leukemia:an analysis of 20 cases%增加地西他滨剂量治疗高危组骨髓增生异常综合征及急性髓系白血病20例分析

    Institute of Scientific and Technical Information of China (English)

    吴倩; 沈益民; 陈峰; 胡晓慧; 金松; 张旭辉; 何广胜; 吴德沛; 孙爱宁; 仇惠英; 金正明; 苗瞄; 唐晓文; 韩悦

    2012-01-01

    Objective To assess the efficacy of increased-dose decitabine for the treatment of patients with high-risk myelodysplastic syndrome and acute myeloid leukemia ( MDS/AML). Methods Twenty consecutive patients with high-risk MDS/AML were enrolled from First Affiliated Hospital of Suzhou Medical University between September 2009 and January 2012 and were treated with a 5-day decitabine intravenous injection (20 mg/m2 ,once daily). Additional dose of decitabine was determined based on the proliferation of marrow, progenitor cell counts and proportion of marrow granulose via bone . marrow aspiration in combination with general conditions and adverse reactions. The relapse and response rates were analyzed after a treatment course. Results Both complete remission (CR) + marrow CR rate and overall response rate were 75% (n =4) in patients with high-risk MBS after the initial treatment course. Patients with AML yielded CR + marrow CR rate and overall response rate of 18. 8% (re =3) and 50% (n =8) Respectively. And these figures were 25% (n =4) and 75% (n. = 3) in those who received initial chemotherapy, 16. 7% (n=2) and41.7% (n, = 12) in relapsed/refractory patients. A 2-year cumulative survival rate of 42% was reported. Conclusion Increased-dose decitabine may be administered in patients with high-risk MDS/AML in a safe fashion. The fact that single treatment course results in high remission rate remains to be explored.%目的 探讨增加地西他滨剂量治疗高危组骨髓增生异常综合征(MDS)及急性髓系白血病(AML)的疗效.方法 收集2009年9月至2012年1月在苏州大学附属第一医院高危组MDS及AML患者20例,静脉滴注地西他滨20 mg/m2,每日1次,连用5d治疗,然后行骨髓检查,根据患者骨髓增生程度、原始细胞数、骨髓小粒饱满情况,结合患者的一般情况、不良反应,酌情增加使用地西他滨,分析治疗1个疗程后缓解率和总反应率.结果 MDS患者1个疗程完全缓解(CR)+骨髓CR为3

  10. 地西他滨联合改良CAG及单倍体相合外周血淋巴细胞回输治疗老年高危恶性血液病%Clinical Efficacy of Decitabine plus Improved CAG Chemotherapy and Haplo-identical Donor Peripheral Lymphocyte Infusion Regimen on Elderly Patients with High Risk Myelodysplastic Syndrome and Acute Myeloid Leukemia

    Institute of Scientific and Technical Information of China (English)

    窦立萍; 靖琙; 王全顺; 梅俊辉; 于力

    2013-01-01

    本研究旨在观察地西他滨联合改良CAG及单倍体相合外周血淋巴细胞回输免疫治疗新方案,作为初治老年高危骨髓增生异常综合征(MDS)和急性髓系白血病(AML)的诱导缓解方案的初步疗效及其不良反应.对2012年4月至2012年7月在本院血液科应用地西他滨联合改良CAG及HLA半相合外周血淋巴细胞回输免疫治疗新方案治疗的5例老年高危MDS和AML患者进行前瞻性研究,观察完全缓解率及副反应.结果表明:5例初治老年患者治疗总有效率100%,4例达到完全缓解,1例患者达到部分缓解.既往无MDS病史患者,中性粒细胞数恢复至0.5×109/L的中位时间为15d,血小板数恢复至20×109/L的中位时间为16 d.主要副作用为IV度骨髓抑制,全部患者治疗中无新发肺部感染等严重并发症.结论:地西他滨联合改良CAG及外周血淋巴细胞回输免疫治疗新方案,治疗老年MDS和AML患者安全有效,值得进一步研究.%This study was aimed to observe the clinical efficacy and adverse effects of decitabine plus improved CAG chemotherapy and haploid-identical donor peripheral lymphocyte infusion regimen on elderly patients with myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML).Five elderly patients with MDS and AML were treated with decitabine plus improved CAG chemotherapy and donor peripheral lymphocyte infusion regimen.Examinations on liver and renal function,electrocardiogram and bone marrow analysis were performed before and after treatment,and adverse effects were observed.The results indicated that after a course of treatment by decitabine plus improved CAG chemotherapy and haplo-identical donor peripheral lymphocyte infusion regimen,the total effective rate was 100%,and 4 patients (80%) achived complete remission,1 patient achived partial remission.The dominant clinical adverse effect was bone marrow depression,the median time of neutrophil >0.5 × 109/L and platelet >20 × 109/L was

  11. Clinical analysis of myelodysplastic syndrome/acute myeloid leuke-mia secondary to malignant tumors in 11 cases%恶性实体瘤继发骨髓增生异常综合征急性髓系白血病11例分析

    Institute of Scientific and Technical Information of China (English)

    李婵娟; 赵海丰; 赵伟鹏; 李倩; 赵智刚; 王晓芳; 于泳; 王亚非; 张翼鷟

    2015-01-01

    Objective:To investigate the etiology, clinical characteristics, and treatment of myelodysplastic syndrome/acute my-eloid leukemia (t-MDS/AML) secondary to malignant tumors. Methods: We retrospectively analyzed 11 patients with t-MDS/AML and investigated the treatment of primary tumors, clinical manifestations, treatment, and survival of t-MDS/AML patients. Results:A total of 11 patients were exposed to cytotoxic chemotherapeutic agents or radiation therapy for their primary tumors. The median laten-cy was 36 months. Common symptoms were fatigue, dyspnea, bleeding, and infection, all of which were related to deficits in hemato-poiesis. Therapeutic regimen included support therapy, immunomodulatory therapy, and chemotherapy. The median overall survival and disease-free survival periods were 28 months and 19 months, respectively, and the overall survival rate for 3 years was 44.4%. Conclu-sion:t-MDS/AML is a serious complication of chemotherapy or radiotherapy for a malignant or nonmalignant condition. The curative effect is limited, and prognosis is poor. Therefore, we should take t-MDS/AML into consideration when making treatment plans for can-cer patients to evaluate treatment benefits and to avoid treatment-related complications.%目的:探讨恶性肿瘤继发骨髓增生异常综合征/急性髓系白血病(t-MDS/AML)的病因、临床特点及治疗策略。方法:对2008年1月至2014年7月在天津医科大学肿瘤医院就诊的11例t-MDS/AML患者的临床资料进行回顾性分析。结果:11例恶性肿瘤患者前期均有不同程度的细胞毒药物、抗代谢药物、含紫杉类药物(和)或放射线治疗史,与t-MDS/AML确诊中位间隔时间为36个月;患者主要表现为乏力、呼吸困难、发热、出血等血细胞减少相关症状;以对症支持治疗,免疫调节治疗及化疗为主,中位OS为28个月,中位DFS为19个月,3年总生存率44.4%。结论:t-MDS/AML继发于

  12. Clinical observation of decitabine treatment for patients with myelodysplastic syndrome and refractory acute myeloid leukemia%地西他滨治疗骨髓增生异常综合征及难治性急性髓系白血病的临床观察

    Institute of Scientific and Technical Information of China (English)

    李菁媛; 周敏; 冉启杰; 罗晓静; 徐彪; 谢红; 王军; 张新华

    2013-01-01

    Objective: To evaluate the clinical therapeutic effect and safety of decitabine in the treatment for Myelodysplastic Syndromes(MDS) and refractory acute myeloid leukemia(RAML). Method:12 patients with MDS and refractory AMI were treated with decitabine at a dose of 20 mg·m-2·d-1 for 5 days. The bone marrow smear,blood routine test etc were used to evaluate the efficacy of the treatment. Adverse effect of the decitabine treatment was evaluated by monitoring body temperature,liver and kidney function,and blood routine examination. Result:Of the 12 patients,4 patients achieved complete remission, 1 patient achieved partial remission, and there was another patient achieved hematological improvement. The overall response rate was 50%. The median time to progression was 9.67 months. The transfusion dependency was improved in 7 patients. The incidence rate of grade W bone marrow depression was 33. 33% ,and the incidence rate of infection was 16. 67% (2/14) ,One of the two infected patients died,which indicated that the mortality rate of the treatment by decitabine was 8. 33%. Mild liver injury was observed. Conclusion: Decitabine can effectively treat MDS and refractory AML. The incidence rate of grade Ⅳ bone marrow depression was low,and other systematic toxicities were mild.%目的:探讨地西他滨治疗骨髓增生异常综合征及难治性急性髓系白血病的临床疗效及安全性.方法:接受地西他滨5d治疗方案(地西他滨20 mg· m-2·d-1×5 d)的1 2例患者,应用骨髓细胞学、血常规评价疗效.监测体温、血常规、肝肾功能等观察其不良反应.结果:12例患者中4例获完全缓解,1例部分缓解,1例血液学改善,总有效率50%(6/12).平均无疾病进展时间为9.67个月.7例患者输血依赖状况改善.4例患者出现Ⅳ度骨髓抑制,发生率为33.3%(4/12).2例并发感染,感染率16.67%(2/12),其中1例死亡,化疗相关死亡率8.33%(1/12).其他不良反应可见轻

  13. Bortezomib in Treating Patients With High-Risk Acute Myeloid Leukemia in Remission

    Science.gov (United States)

    2014-10-30

    Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome; Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Promyelocytic Leukemia (M3); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Secondary Acute Myeloid Leukemia

  14. Combination Chemotherapy With or Without PSC 833, Peripheral Stem Cell Transplantation, and/or Interleukin-2 in Treating Patients With Acute Myeloid Leukemia

    Science.gov (United States)

    2013-06-03

    Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; Adult Acute Erythroid Leukemia (M6); Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monoblastic Leukemia and Acute Monocytic Leukemia (M5); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Childhood Acute Basophilic Leukemia; Childhood Acute Eosinophilic Leukemia; Childhood Acute Erythroleukemia (M6); Childhood Acute Megakaryocytic Leukemia (M7); Childhood Acute Minimally Differentiated Myeloid Leukemia (M0); Childhood Acute Monoblastic Leukemia (M5a); Childhood Acute Monoblastic Leukemia and Acute Monocytic Leukemia (M5); Childhood Acute Monocytic Leukemia (M5b); Childhood Acute Myeloblastic Leukemia With Maturation (M2); Childhood Acute Myeloblastic Leukemia Without Maturation (M1); Childhood Acute Myelomonocytic Leukemia (M4); Childhood Myelodysplastic Syndromes; de Novo Myelodysplastic Syndromes; Untreated Adult Acute Myeloid Leukemia; Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies

  15. Regulation and Function of TIFAB in Myelodysplastic Syndrome

    Science.gov (United States)

    2012-06-01

    2004;317:230-234. 7. Lamothe B, Besse A, Campos AD, Webster WK, Wu H, Darnay BG. Site-specific Lys- 63-linked tumor necrosis factor receptor...International Society of Experimental Hematology. Boston, MA. (July 2008). New Investigator Session. Editorial Board 2012- Leukemia 2012- PLoS One

  16. Clinical observation of feasibility and efficacy of decitabine bridge therapy followed by allogeneic hematopoietic stem cell transplantation in patients with myelodysplastic syndrome and acute myeloid leukemia%地西他滨桥接异基因造血干细胞移植治疗骨髓增生异常综合征和急性髓样白血病的临床可行性和疗效研究

    Institute of Scientific and Technical Information of China (English)

    吴倩; 何广胜; 吴德沛; 孙爱宁; 仇惠英; 金正明; 苗瞄; 唐晓文; 韩悦

    2013-01-01

    Objective: To investigate the feasibility and efficacy of DAC (decitabine) bridge therapy followed by allo-HSCT (allogeneic hematopoietic stem cell transplantation) in patients with MDS (myelodysplastic syndrome) and AML (acute myeloid leukemia). Methods: Seven patients with MDS and 12 patients with AML received DAC bridge therapy followed by allo-HSCT. Results: With DAC bridge therapy, 4 MDS patients achieved complete remission/marrow complete remission and 3 remained stable disease before allo-HSCT. After successful engraftment attained in all the seven MDS patients, six survived without disease, one received donor lymphocyte infusion and obtained complete remission after relapse and eventually died of pneumonia. Of 12 AML patients, 6 achieved complete remission after DAC bridge therapy; 5 survived without disease, one still survived but having disease, and 6 had died. The rates of acute and chronic CVHD were 31.6% and 21.1%, respectively. The two-year overall survival rate and the two-year cumulative recurrence rate were 57.9% and 36.2% after allo-HSCT, respectively. The two-year cumulative recurrence-free rate was 23.6% after allo-HSCT. Conclusion: DAC regimen can be safely and efficiently administrated to bridge time to allo-HSCT in patients with MDS/AML.%目的:探讨地西他滨(decitabine,DAC)作为骨髓增生异常综合征(myelodysplastic syndrome,MDS)和急性髓样白血病(acute myeloid leukemia,AML)患者行异基因造血干细胞移植(allogeneic hematopoietic stem cell transplantation,allo-HSCT)之前的桥接治疗的可行性和疗效.方法:对7例MDS患者和12例AML患者以DAC作为allo-HSCT之前的桥接治疗.结果:DAC桥接治疗后,7例MDS患者中,4例获得完全缓解(complete remission,CR) /mCR (marrow CR),3例为疾病稳定(stable disease,SD),之后行allo-HSCT成功,目前6例为无病生存,1例在复发后接受供者淋巴细胞输注(donor lymphocyte infusion,DLI)后达CR,后死于肺部感染;12例AML患者中,6例在DAC

  17. 地西他滨联合化疗治疗难治复发急性髓系白血病及骨髓增生异常综合征转化白血病的效果观察%Clinical effects of decitabine combined with chemotherapy in the treatment of patients with refractory and relapsed acute myeloid leukemia and myelodysplastic syndrome transformed leukemia

    Institute of Scientific and Technical Information of China (English)

    韩波; 王朝晖; 邵纬; 王九河; 洪青; 范传波; 刘俊玲; 田猛; 王海霞

    2014-01-01

    目的 探讨地西他滨联合化疗治疗难治复发急性髓系白血病(AML)及骨髓增生异常综合征(MDS)转化AML的临床效果.方法 选取2013年2月至2014年3月住院治疗的难治复发AML患者19例及MDS转化AML患者4例,所有患者给予地西他滨联合CAG方案进行治疗,评估患者治疗效果及不良反应.结果 经过1个疗程治疗后,14例(60.9%)完全缓解,2例(8.7%)部分缓解,7例(30.4%)无效,总有效率69.6%,不同染色体核型患者临床治疗效果差异具有统计学意义(P<0.05).23例患者出现不同程度的骨髓抑制,其中Ⅰ~Ⅱ级中性粒细胞减少2例,Ⅲ~Ⅳ级21例,中性粒细胞减少中位时间13 d;Ⅲ~Ⅳ级贫血23例;Ⅲ~Ⅳ级血小板减少23例,血小板减少中位时间16d.Ⅰ~Ⅱ级出血20例,Ⅲ~Ⅳ级3例.Ⅰ~Ⅱ级胃肠道反应1例.Ⅰ~Ⅱ级肝功能异常1例.所有患者随访至2014年3月31日,生存20例,死亡3例,中位总生存期3.1个月,1年累积生存率86%.结论 地西他滨联合化疗治疗难治复发AML及MDS转化白血病的临床缓解率高,不良反应少;染色体核型可能是影响治疗效果的重要因素.%Objective To investigate the clinical effects of decitabine combined with chemotherapy in the treatment of patients with refractory and relapsed acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) transformed leukemia.Methods 19 patients with refractory and relapsed AML and 4 cases of patients with MDS transformed AML were enrolled from February 2013 to March 2014.All cases were treated with decitabine combined with CAG regimen.The clinical effects and adverse reactions were evaluated.Results After a course of treatment,14 cases (60.9 %) were complete remission,2 cases (8.7 %) were parrtial remission,7 cases (30.4 %) were non-remission,and the total efficiency rate was 69.6 %.The differences of clinical outcomes among different karyotypes were statistically significant (P < 0.05).There were

  18. Clinical, hematological, and cytogenetic profile of adult myelodysplastic syndrome in a tertiary care center

    Science.gov (United States)

    Narayanan, Santhosh

    2017-01-01

    Background Myelodysplastic syndrome (MDS), a disorder of clonal hematopoiesis, is an important clinical entity, but most of the studies available are conducted among the Western population. Its etiological factors and clinicohematological profile in the Indian population are quite diverse. The information regarding its prognostic factors and cytogenetics is very scarce. Objectives (1) To assess the clinicohematological profile, cytogenetics, prognostic factors, and outcome of MDS and (2) to study its progression to acute myeloid leukemia (AML) in the selected patients over the study period. Methods A prospective observational study was performed with patients from Department of Medicine and Hematology, Government Medical College, Kozhikode, who were diagnosed with MDS within the study period (from 1 January 2014 to 31 July 2015). Secondary causes of dysplasia were excluded. In possible cases, the international prognostic scoring system was followed. These patients were followed up for an additional 6 months to assess the progression of MDS to AML based on symptoms, signs, hemogram, or repeat peripheral smear/bone marrow studies. Results Of the 60 patients, 73% were aged >60 years. Disease was common in males, with a male:female ratio of 7:3. Thirty-five percent of the patients were working in agricultural and allied fields and had pesticide exposure. Patients with prior radiation exposure had significant association with adverse outcome. Fatigue was the prominent symptom and was reported by 90% of the patients. Blasts were >5% in peripheral smear; bone marrow cytopenia and dysplasia at the time of diagnosis had significant association with risk of transforming to AML. Refractory anemia (RA), observed in 22 patients, was the most common type of MDS. Most of the patients with RA with excess blasts type-1 and RA with excess blasts type-2 transformed to AML, and the association was statistically significant. Deletion of short arm of fifth chromosome (5q deletion) was

  19. Clinical, hematological, and cytogenetic profile of adult myelodysplastic syndrome in a tertiary care center

    Directory of Open Access Journals (Sweden)

    Narayanan S

    2017-02-01

    Full Text Available Santhosh Narayanan Department of Medicine, Government Medical College, Kozhikode, Kerala, India Background: Myelodysplastic syndrome (MDS, a disorder of clonal hematopoiesis, is an important clinical entity, but most of the studies available are conducted among the Western population. Its etiological factors and clinicohematological profile in the Indian population are quite diverse. The information regarding its prognostic factors and cytogenetics is very scarce.Objectives: (1 To assess the clinicohematological profile, cytogenetics, prognostic factors, and outcome of MDS and (2 to study its progression to acute myeloid leukemia (AML in the selected patients over the study period.Methods: A prospective observational study was performed with patients from Department of Medicine and Hematology, Government Medical College, Kozhikode, who were diagnosed with MDS within the study period (from 1 January 2014 to 31 July 2015. Secondary causes of dysplasia were excluded. In possible cases, the international prognostic scoring system was followed. These patients were followed up for an additional 6 months to assess the progression of MDS to AML based on symptoms, signs, hemogram, or repeat peripheral smear/bone marrow studies.Results: Of the 60 patients, 73% were aged >60 years. Disease was common in males, with a male:female ratio of 7:3. Thirty-five percent of the patients were working in agricultural and allied fields and had pesticide exposure. Patients with prior radiation exposure had significant association with adverse outcome. Fatigue was the prominent symptom and was reported by 90% of the patients. Blasts were >5% in peripheral smear; bone marrow cytopenia and dysplasia at the time of diagnosis had significant association with risk of transforming to AML. Refractory anemia (RA, observed in 22 patients, was the most common type of MDS. Most of the patients with RA with excess blasts type-1 and RA with excess blasts type-2 transformed to AML

  20. Initial fluconazole prophylaxis may not be required in adults with acute leukemia or myelodysplastic/myeloproliferative disorders after reduced intensity conditioning peripheral blood stem cell allogeneic transplantation.

    Science.gov (United States)

    Brissot, Eolia; Cahu, Xavier; Guillaume, Thierry; Delaunay, Jacques; Ayari, Sameh; Peterlin, Pierre; Le Bourgeois, Amandine; Harousseau, Jean-Luc; Milpied, Noel; Bene, Marie-Christine; Moreau, Philippe; Mohty, Mohamad; Chevallier, Patrice

    2015-04-01

    In the myeloablative transplant setting, the early use of fluconazole prophylaxis provides a benefit in overall survival. Recent changes in transplantation practices, including the use of peripheral blood stem cells (PBSC) and/or reduced intensity conditioning (RIC) regimen may have favorably impacted the epidemiology of invasive fungal infections (IFI) after allogeneic stem cell transplantation (allo-SCT). Yet, the impact of removing fluconazole prophylaxis after RIC PBSC allotransplant is ill known. Here, a retrospective analysis was performed comparing patients who received fluconazole as antifungal prophylaxis (n = 53) or not (n = 56) after allo-SCT for acute leukemia or myelodysplastic/myeloproliferative syndrome. Sixteen IFI were documented (14 %) at a median time of 103 days after transplantation, including eight before day +100, at a similar rate, whether the patients received fluconazole prophylaxis (13 %) or not (16 %). IFI were due mainly to Aspergillus species (87 %), and only two Candida-related IFI (13 %) were documented in the non-fluconazole group before day +100. The incidences of IFI (overall, before or after day +100) as well as 3-year overall and disease-free survival, non-relapse mortality, or acute and chronic graft-versus-host disease (GVHD) were similar between both groups. In conclusion, this study suggests that fluconazole may not be required at the initial phase of RIC allo-SCT using PBSC. This result has to be confirmed prospectively while Aspergillus prophylaxis should be discussed in this particular setting.

  1. Multicentric study underlining the interest of adding CD5, CD7 and CD56 expression assessment to the flow cytometric Ogata score in myelodysplastic syndromes and myelodysplastic/myeloproliferative neoplasms.

    Science.gov (United States)

    Bardet, Valérie; Wagner-Ballon, Orianne; Guy, Julien; Morvan, Céline; Debord, Camille; Trimoreau, Franck; Benayoun, Emmanuel; Chapuis, Nicolas; Freynet, Nicolas; Rossi, Cédric; Mathis, Stéphanie; Gourin, Marie-Pierre; Toma, Andréa; Béné, Marie C; Feuillard, Jean; Guérin, Estelle

    2015-04-01

    Although numerous recent publications have demonstrated interest in multiparameter flow cytometry in the investigation of myelodysplastic disorders, it is perceived by many laboratory hematologists as difficult and expensive, requiring a high level of expertise. We report a multicentric open real-life study aimed at evaluating the added value of the technically simple flow cytometry score described by the Ogata group for the diagnosis of myelodysplastic syndromes. A total of 652 patients were recruited prospectively in four different centers: 346 myelodysplastic syndromes, 53 myelodysplastic/myeloproliferative neoplasms, and 253 controls. The Ogata score was assessed using CD45 and CD34 staining, with the addition of CD10 and CD19. Moreover, labeling of CD5, CD7 and CD56 for the evaluation of myeloid progenitors and monocytes was tested on a subset of 294 patients. On the whole series, the specificity of Ogata score reached 89%. Respective sensitivities were 54% for low-risk myelodysplastic syndromes, 68% and 84% for type 1 and type 2 refractory anemia with excess of blasts, and 72% for myelodysplastic/myeloproliferative neoplasms. CD5 expression was poorly informative. When adding CD56 or CD7 labeling to the Ogata score, sensitivity rose to 66% for low-risk myelodysplastic syndromes, to 89% for myelodysplastic/myeloproliferative neoplasms and to 97% for refractory anemia with excess of blasts. This large multicenter study confirms the feasibility of Ogata scoring in routine flow cytometry diagnosis but highlights its poor sensitivity in low-risk myelodysplastic syndromes. The addition of CD7 and CD56 in flow cytometry panels improves the sensitivity but more sophisticated panels would be more informative. Copyright© Ferrata Storti Foundation.

  2. 地西他滨治疗骨髓增生异常综合征和急性髓系白血病的临床观察%Clinical Observation of Decitabine-Treating Patients with Myelodysplastic Syndrome and Acute Myeloid Leukemia

    Institute of Scientific and Technical Information of China (English)

    杨华; 朱海燕; 姜孟孟; 王全顺; 韩晓萍; 黄文荣; 靖彧; 王书红; 张松松

    2013-01-01

    This study was purposed to investigate the clinical efficiencies and adverse reactions of treating the myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) by using decitabine. The clinical data of 12 MDS and AML patients treated with decitabine were analyzed retrospectively. Among 12 patients there were 1 case of MDS-RA, 2 cases of MDS-RAEB-Ⅰ , 3 cases of MDS-RAEB- Ⅱ , 2 cases of AML-M4, 2 cases of AML-M5, 1 case of AML-M6 and 1 case of AML-M0. In decitabine chemotherapy program for 5 days (n = 8), decitabine 20 mg/ (m2 · d) × 5 days was applied, 4 weeks for 1 cycle; in program for 3 days (n = 2), decitabine 15 mg / m2, once 8 h for 3 days, 6 weeks for 1 cycle; another program (n = 2), decitabine 20 mg/ (m2 · d) every other day for 5 times. For 1 patient achieved complete remission (CR) after treatment with decitbine, ID4 gene methylated level was detected by MS-PCR and ML-PCR before and after treatment. The results showed that 2 cases achieved CR, 1 case partial remission, 5 cases stable disease, 1 case progress of disease and 3 cases died. Disease control rate was 66. 67% (8/ 12), the effective rate 25% (3/12). The average survival time was (11.5 ±2.1) months. 1 -year OS rate was 40% , 2-year OS rate was 16. 7%. MS-PCR detection showed that the decitabine could significantly reduce the ID4 gene methylation level. It is concluded that decitabine can stablize disease status of MDS patients, reduce blood transfusion dependence and improve the life quality of patients, and even some patients who transformed from MDS to leukemia achieved CR after treatment with decitabine. Decitabine can reduce the ID4 gene methylation level. The main adverse reaction of decitabine was myelosuppression, infection and so on. So the blood transfusions, antibiotics and other supportive treatments for these patients are needed. Most of patients well tolerate the adverse effects of decitabine after active symptomatic and supportive treatment. The efficacy and survival

  3. Myeloid cell differentiation arrest by miR-125b-1 in myelodysplasic syndrome and acute myeloid leukemia with the t(2;11)(p21;q23) translocation

    NARCIS (Netherlands)

    M. Bousquet (Marina); C. Quelen (Cathy); R. Rosati (Roberto); V.M.D. Mas; R.L. Starza (Roberta); C. Bastard (Christian); E. Lippert (Eric); P. Talmant (Pascaline); M. Lafage-Pochitaloff (Marina); D. Leroux (Dominique); C. Gervais (Carine); F. Viguié (Franck); J.L. Lai; C. Terre (Christine); H.B. Beverloo (Berna); C. Sambani (Costantina); A. Hagemeijer (Anne); P. Marynen (Peter); G. Delsol (Georges); N. Dastugue (Nicole); C. Mecucci (Cristina); P. Brousset (Pierre)

    2008-01-01

    textabstractMost chromosomal translocations in myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) involve oncogenes that are either up-regulated or form part of new chimeric genes. The t(2;11)(p21;q23) translocation has been cloned in 19 cases of MDS and AML. In addition to this, we ha

  4. Síndromes mielodisplásicas: protocolo de exclusão Myelodysplastic syndrome: diagnostic protocol

    Directory of Open Access Journals (Sweden)

    Silvia Maria M. Magalhães

    2004-12-01

    heterogeneous clinical and laboratorial presentations, which result in progressive bone marrow failure and evolve to acute leukemia. Anemia is a common symptom. In elderly patients, it is not attributed to the normal aging process and the cause is identified in most cases. The presence of cytopenias associated with bone marrow dysplastic disorders may also be due to secondary and reversible non clonal disorders. Cytogenetic abnormalities found in a proportion of patients with myelodysplastic syndromes may be helpful in the differential diagnosis and to evaluate the prognosis. Ancillary laboratory tests to show clonality are not usually available. The diagnosis of myelodysplastic syndromes is, therefore, made by exclusion, sometimes helped by the passage of time. Considering the proposed multistep myelodysplastic syndrome pathogenesis, patients at the lowest grade, presenting minimal dysplastic features may be difficult to diagnose. Vitamin B12 and/or folate deficiency, recent exposure to heavy metals and recent cytotoxic or growth factor therapy should be considered absolute exclusion factors precluding the definite diagnosis. Alcohol use, chronic inflammatory states, auto-immune disorders, chronic liver or kidney diseases, hormonal disorders and viral infections including HIV must be ruled out or interpreted with caution. Some diseases of the pluripotential stem cells must also be distinguished from myelodysplastic syndromes. Exclusion of paroxysmal nocturnal hemoglobinuria and aplastic anemia may be difficult in the less common hypocellular myelodysplastic syndromes. Dysplastic abnormalities of the bone marrow, therefore, do not in themselves establish a diagnosis of myelodysplasia and a protocol of exclusion should be carried out.

  5. Durable Hematological and Major Cytogenetic Response in a Patient with Isolated 20q Deletion Myelodysplastic Syndrome Treated with Lenalidomide

    Directory of Open Access Journals (Sweden)

    Bagi Jana

    2014-01-01

    Full Text Available Myelodysplastic syndrome (MDS is a clonal bone marrow disorder characterized by ineffective hematopoiesis. It is characterized by peripheral blood cytopenia and significant risk of progression to acute myeloid leukemia result. Deletion of the long arm of chromosome 20 (20q deletion is present in 3–7% of patients with MDS. Lenalidomide is an immunomodulatory agent with antiangiogenic activity. It is FDA approved for the treatment of anemia in patients with low or int-1 risk MDS with chromosome 5q deletion with or without additional cytogenetic abnormalities. Study of lenalidomide in patients with MDS without 5q deletion but other karyotypic abnormalities demonstrated meaningful activity in transfusion dependent patients; however, response of patients with isolated 20q deletion to lenalidomide is not known. We are reporting a patient with 20q deletion MDS treated with lenalidomide after he failed to respond to azacytidine; to our knowledge this is the first report of a patient with isolated 20q deletion treated with lenalidomide.

  6. Translocation (6;15(q12;q15: A Novel Mutation in a Patient with Therapy-Related Myelodysplastic Syndrome

    Directory of Open Access Journals (Sweden)

    Saba F. Ali

    2015-01-01

    Full Text Available Most myelodysplastic syndromes (MDS present with loss or gain of chromosomal material and less commonly show translocations as a sole abnormality. In addition, certain translocations are more commonly seen in MDS than others, but to our knowledge, the presence of t(6;15 has not been reported in MDS, specifically therapy-related MDS (t-MDS cases. Patients with t-MDS, a group of heterogeneous stem cell related disorders resulting as a latent complication of cytotoxic and/or radiation therapy, generally tend to have a poorer prognosis than de novo MDS. We present a unique case of a patient who initially presented with acute myeloid leukemia (AML with a normal karyotype and FLT3-ITD and NPM1 mutations. The patient was successfully treated with chemotherapy and an autologous bone marrow transplant but subsequently developed a new FLT3-ITD negative t-MDS with a unique translocation, t(6;15(q12;q15, three years after transplant. To our knowledge, this unique sole translocation has never been reported in MDS or t-MDS and given her successful response to treatment and remission, presence of this translocation may have some prognostic value.

  7. Hypermethylation of the VTRNA1-3 Promoter is Associated with Poor Outcome in Lower Risk Myelodysplastic Syndrome Patients

    Directory of Open Access Journals (Sweden)

    Alexandra Søgaard Helbo

    2015-10-01

    Full Text Available Myelodysplastic syndrome (MDS is a heterogeneous group of clonal hematopoietic disorders. MDS is frequently associated with deletions on chromosome 5q as well as aberrant DNA methylation patterns including hypermethylation of key tumor suppressors. We have previously shown that hypermethylation and silencing of the non-coding RNA VTRNA2-1 are correlated with poor outcomes in acute myeloid leukemia patients. In this study, we find that VTRNA1-2 and VTRNA1-3, both located on chromosome 5q, can be regulated and silenced by promoter DNA methylation, and that the hypomethylating agent 5-aza-2-deoxycytidine causes reactivation these genes. In normal hematopoiesis, we find that vault RNAs (vtRNAs show differential methylation between various hematopoietic cell populations, indicating that allele-specific methylation events may occur during hematopoiesis. In addition, we show that VTRNA1-3 promoter hypermethylation is frequent in lower risk MDS patients and is associated with a decreased overall survival.

  8. Significance of genome-wide analysis of copy number alterations and UPD in myelodysplastic syndromes using combined CGH - SNP arrays.

    Science.gov (United States)

    Ahmad, Ausaf; Iqbal, M Anwar

    2012-01-01

    Genetic information is an extremely valuable data source in characterizing the personal nature of cancer. Chromosome instability is a hallmark of most cancer cells. Chromosomal abnormalities are correlated with poor prognosis, disease classification, risk stratification, and treatment selection. Copy number alterations (CNAs) are an important molecular signature in cancer initiation, development, and progression. Recent application of whole-genome tools to characterize normal and cancer genomes provides the powerful molecular cytogenetic means to enumerate the multiple somatic, genetic and epigenetic alterations that occur in cancer. Combined array comparative genomic hybridization (aCGH) with single nucleotide polymorphism (SNP) array is a useful technique allowing detection of CNAs and loss of heterozygosity (LOH) or uni-parental disomy (UPD) together in a single experiment. It also provides allelic information on deletions, duplications, and amplifications. UPD can result in an abnormal phenotype when the chromosomes involved are imprinted. Myelodysplastic syndromes (MDS) are the most common clonal stem cell hematologic malignancy characterized by ineffective hematopoiesis, which leads to rapid progression into acute myeloid leukemia. UPD that occurs without concurrent changes in the gene copy number is a common chromosomal defect in hematologic malignancies, especially in MDS. Approximately 40-50% of MDS patients do not have karyotypic abnormalities that are detectable using classical metaphase cytogenetic techniques (MC) because of inherent limitations of MC, low resolution and the requirement of having dividing cells. In this review, we highlight advances in the clinical application of microarray technology in MDS and discuss the clinical potential of microarray.

  9. Pre-transplant weight loss predicts inferior outcome after allogeneic stem cell transplantation in patients with myelodysplastic syndrome.

    Science.gov (United States)

    Radujkovic, Aleksandar; Becker, Natalia; Benner, Axel; Penack, Olaf; Platzbecker, Uwe; Stölzel, Friedrich; Bornhäuser, Martin; Hegenbart, Ute; Ho, Anthony D; Dreger, Peter; Luft, Thomas

    2015-10-27

    Allogeneic stem cell transplantation (alloSCT) represents a curative therapeutic option for patients with myelodysplastic syndrome (MDS), but relapse and non-relapse mortality (NRM) limit treatment efficacy. Based on our previous observation in acute myeloid leukemia we investigated the impact of pre-transplant weight loss on post-transplant outcome in MDS patients. A total of 111 patients diagnosed with MDS according to WHO criteria transplanted between 2000 and 2012 in three different transplant centers were included into the analysis. Data on weight loss were collected from medical records prior to conditioning therapy and 3-6 months earlier. Patient, disease and transplant characteristics did not differ between patients with weight loss (2-5%, n = 17; > 5%, n = 17) and those without (n = 77). In a mixed effect model, weight loss was associated with higher risk MDS (p = 0.046). In multivariable analyses, pre-transplant weight loss exceeding 5% was associated with a higher incidence of relapse (p transplant weight loss of 2-5% and > 5% were independent predictors of worse disease-free (p = 0.023 and p transplantation. Prospective studies addressing pre-transplant nutritional interventions are highly warranted.

  10. [Methylation of FHIT gene promoter region in DNA from plasma of patients with myelodysplastic syndromes and demethylating effect of decitabine].

    Science.gov (United States)

    Deng, Yin-Fen; Zhang, Lei; Zhang, Xiu-Qun; Hu, Ming-Qiu; Dai, Dan; Zhang, Xue-Zhong; Xu, Yan-Li

    2012-10-01

    This study was aimed to detect the methylation status of FHIT gene promoter region in the DNA from plasma of patients with myelodysplastic syndrome (MDS), and to investigate the demethylating effect of decitabine. Methylation-specific PCR method was used to detect the methylation status of FHIT gene promoter region in the DNA from plasma of 4 patients with MDS before and after treatment with decitabine plus semis CAG therapy (among them, 1 case of newly diagnosed MDS, 3 cases progressed into acute leukemia). The results indicated that 3 cases were found to have an increased methylation in the promoter region. After treatment with decitabine plus semis CAG, increased methylation was reversed in 2 cases. In 4 cases, 2 cases displayed clinical response. It is concluded that FHIT gene hypermethylation is associated with MDS pathogenesis. Decitabine has demethylating effect on the FHIT gene hypermethylation of plasma from MDS patients. Detecting the methylation status of FHIT gene in DNA from plasma may play a role in MDS auxiliary diagnosis or prognosis.

  11. Síndromes mielodisplásicas e mielodisplásicas/mieloproliferativas Myelodysplastic syndromes and diseases with myelodysplastic and myeloproliferative features

    Directory of Open Access Journals (Sweden)

    José Vassallo

    2009-08-01

    Full Text Available As síndromes mielodisplásicas (SMD representam um grupo heterogêneo de doenças hematológicas caracterizadas por hematopoese ineficaz e risco aumentado de evolução para leucemia mieloide aguda. Neste artigo educativo são apresentados aspectos gerais da sua fisiopatologia, diagnóstico, apresentação histopatológica e seu papel no diagnóstico diferencial, classificação e estratificação prognóstica. Ressalta-se a importância da avaliação clínica e laboratorial, que inclui avaliação do sangue periférico e medula óssea: morfologia - aspirado medular e biópsia óssea -, citogenética, imunofenotipagem, além de dados evolutivos. O diagnóstico definitivo, em especial nos casos de baixo risco, deve considerar a exclusão de causas não clonais que podem, através de alterações dismielopoéticas reativas, simular a mielodisplasia, tais como infecções virais, principalmente pelo HIV. A nova classificação revisada da Organização Mundial da Saúde (OMS-2008 é apresentada e discutida.Myelodysplastic syndromes (MDS represent a heterogeneous group of hematologic disorders characterized by ineffective hematopoiesis and an increased risk of developing acute myeloid leukemia. In this educational article the general aspects of the physiopathology, diagnosis, and histopathological features of MDS and their role in differential diagnosis, classification and prognostic categorization are presented. The importance of clinical and laboratory evaluations, including peripheral blood and bone marrow analyses, including morphology - aspirate and core biopsy, cytogenetics, immunophenotype and careful serial follow-up is emphasized. Definite diagnosis of MDS, especially in low-risk subtypes, should consider the exclusion of disorders with reactive bone marrow alterations, such as viral infections for example HIV. The new revised World Health Organization (WHO-2008 classification is presented and discussed.

  12. MYELODYSPLASTIC/MYELOPROLIFERATIVE DISEASES

    Directory of Open Access Journals (Sweden)

    I. N. Subortseva

    2016-01-01

    Full Text Available Chronic myeloid malignancies that have characteristics of both the myelodysplastic and myeloproliferative disorders allocated to myelodysplastic/myeloproliferative diseases (MDS/MPD group in 2008 World Health Organization classification. This group includes chronic myelomonocytic leukemia, juvenile myelomonocytic leukemia, atypical chronic myeloid leukemia, refractory anemia with ringed sideroblasts and thrombocytosis (RARS-T and unclassified MDS/MPD. Except RARS-T diseases in this group have similar molecular characteristics and clinical manifestations, which require the study of biology, specific molecular markers, morphological features and a clearer definition of nosology. This review provides information on international guidelines for the diagnosis and treatment of MDS/MPD.

  13. [Successful treatment with azacitidine for myelodysplastic syndrome with large vessel vasculitis].

    Science.gov (United States)

    Mishima, Mai; Makita, Masanori; Sando, Yasuhisa; Yamamoto, Yoshikazu; Shiote, Yasuhiro; Hara, Yoshitaka; Yamamoto, Kazuhiko; Imajo, Kenji

    2015-01-01

    Paraneoplastic inflammation of the large vessels is a rare complication of myelodysplastic syndrome (MDS), and patients with MDS and systemic vasculitis have a poor prognosis. We present a 66-year-old male with MDS and large vessel vasculitis treated with azacitidine. Azacitidine administration improved his clinical symptoms, high fever and thickening of the arterial wall, and he achieved a complete bone marrow remission. However, 1 year later he showed progression of MDS. For MDS with vasculitis, intensive therapy, the same as that given to the high-risk group, should be considered and azacitidine administration may represent an efficacious treatment.

  14. Transient myelodysplastic syndrome in X-linked agammaglobulinemia with a novel Btk mutation.

    Science.gov (United States)

    Narula, Gaurav; Currimbhoy, Zinet

    2008-12-01

    X-linked agammaglobulinemia (XLA) is a rare disorder in which recurrent infections occur due to low serum globulins and circulating B lymphocytes caused by a mutation in the Bruton tyrosine kinase (Btk) gene. While myelodysplastic syndrome (MDS) associated with low B lymphocyte counts has been described, clonal cytogenetic abnormalities in confirmed cases of XLA have never been reported. We describe a case of XLA with a novel Btk mutation who also had a persistent clonal population in the bone marrow with abnormal cytogenetics in multiple chromosomes that resolved 1(1/2) years after treatment with IVIG, mimicking a picture of transient MDS.

  15. Necrotizing fasciitis in two patients with myelodysplastic syndrome treated with azacitidine.

    Science.gov (United States)

    Lai, Shiue-Wei; Huang, Tzu-Chuan; Ye, Ren-Hua; Wu, Yi-Ying

    2015-03-01

    Azacitidine is a novel agent for treating myelodysplastic syndromes (MDS). It has a relatively safe toxicity profile with very few reported skin toxicities. Patients with MDS were prone to get severe infections, especially via respiratory tract, urinary system, and bloodstream. However, necrotizing fasciitis (NF) is a relatively rare event in patients with MDS, and it is hard to diagnose early. Here, we report two MDS cases that developed NF in lower extremities while receiving azacitidine treatment. One of them survives after emergent fasciotomy along with the administration of broad-spectrum antibiotics and intravenous immunoglobulin.

  16. Clinical activity of azacitidine in patients who relapse after allogeneic stem cell transplantation for acute myeloid leukemia

    DEFF Research Database (Denmark)

    Craddock, Charles; Labopin, Myriam; Robin, Marie

    2016-01-01

    Disease relapse is the most common cause of treatment failure after allogeneic stem cell transplantation for acute myeloid leukemia and myelodysplastic syndromes, yet treatment options for such patients remain extremely limited. Azacitidine is an important new therapy in high-risk myelodysplastic...... syndromes and acute myeloid leukemia but its role in patients who relapse post allograft has not been defined. We studied the tolerability and activity of azacitidine in 181 patients who relapsed after an allograft for acute myeloid leukemia (n=116) or myelodysplastic syndromes (n=65). Sixty-nine patients...... conclude that azacitidine represents an important new therapy in selected patients with acute myeloid leukemia/myelodysplastic syndromes who relapse after allogeneic stem cell transplantation. Prospective studies to confirm optimal treatment options in this challenging patient population are required....

  17. A study of high-dose lenalidomide induction and low-dose lenalidomide maintenance therapy for patients with hypomethylating agent refractory myelodysplastic syndrome.

    Science.gov (United States)

    Cherian, Mathew A; Tibes, Raoul; Gao, Feng; Fletcher, Theresa; Fiala, Mark; Uy, Geoffrey L; Westervelt, Peter; Jacoby, Meagan A; Cashen, Amanda F; Stockerl-Goldstein, Keith; DiPersio, John F; Vij, Ravi

    2016-11-01

    Myelodysplastic syndromes (MDS) are clonal hematopoietic disorders characterized by bone marrow failure which frequently progress to acute myeloid leukemia. Patients who fail to respond to, or progress on first-line DNA hypomethylating agents (HMA) have a poor prognosis. Conventionally dosed lenalidomide has activity in 5q-MDS. In other subtypes, it may reduce RBC transfusion requirements but does not result in cytogenetic responses. We previously reported that high-dose lenalidomide induction (50 mg/day) results in complete remissions in a high fraction of patients. We, therefore, conducted a Phase 2 trial of the same regimen in MDS refractory to HMA. Marrow complete remissions were seen in 33% of patients and hematological improvement in 8% of patients. Significant infections complicated more than 50% of cases. Future trials to explore alternative dosing schedules of high-dose lenalidomide to increase efficacy while decreasing toxicity are warranted.

  18. 联合化疗方案治疗中、高危骨髓增生异常综合征及急性髓系白血病的疗效分析%Treatment in Middle and High Risk Myelodysplastic Syndrome and Acute Myeloid Leukemia

    Institute of Scientific and Technical Information of China (English)

    魏蓉; 张燕香

    2012-01-01

    目的 探讨阿糖胞苷(AraC)、去甲氧柔红霉素(IDA)和粒细胞集落刺激因子(G-CSF)联合方案(CIG方案),治疗中、高危骨髓增生异常综合征(MDS)和难治、复发、老年初治以及继发于MDS的急性髓系白血病(AML)的临床疗效及不良反应.方法 选择2004年4月至2010年3月,在本院住院的AML和MDS患者中,符合本研究纳入标准和排除标准的34例患者为研究对象.将其随机分为治疗组(n=16)和对照组(n=18)(本研究遵循的程序符合本院人体试验委员会所制定的伦理学标准,得到该伦理会批准,分组征得受试对象本人的知情同意,并与之签订临床研究知情同意书).治疗组共16例采用CIG方案治疗,其中包括3例MDS和13例AML患者;对照组共18例采用米托蒽醌(mitoxantrone)联合AraC方案(MA方案),其中包括2例MDS转化为AML和16例AML患者.完成1个疗程后评估疗效,治疗失败患者则退出观察,有效患者再接受1个疗程治疗.随访分析患者总体生存期(OS),评判CIG方案的疗效.结果 治疗组16例患者中,完全缓解(CR)为9例(56.25%),部分缓解(PR)为4例(25%),未缓解(NR)为2例(12.5%),死亡为1例(6.25%),总有效率达81.25%.其中,第1个疗程达CR患者为6例,第2个疗程达CR为3例.治疗组中位OS为26个月.对照组18例患者中CR为8例(44.44%),PR为4例(22.22%),NR为3例(16.67%),死亡为3例(16.67%),总有效率为66.67%.其中,第1个疗程达CR为4例,第2个疗程达CR为2例.中位OS为20个月.结论 在高危MDS和难治、复发、老年AML患者治疗中,CIG方案较MA方案更为有效,且不良反应发生率较低,长期疗效较好.%Objective To investigate the clinical efficacy and adverse reactions of the CIG regimen,which composed of cytosine arabinoside (AraC),idarubicin (IDA) and granulocyte colony-stimulating factor (G-CSF),in middle and high risk myelodysplastic syndrome (MDS),previously untreated elderly acute myeloid leukemia (AML

  19. Therapeutic efficacies of decitabine application prior to hematopoietic cell transplantation in patients with myelodysplastic syndrome and acute myeloid leukemia%含地西他滨方案桥接异基因造血干细胞移植治疗MDS/AML的效果评估

    Institute of Scientific and Technical Information of China (English)

    周进; 王婧; 刘辉; 郑慧菲; 马玲; 王攀峰; 颜霜; 吴德沛; 傅琤琤

    2015-01-01

    Objective To explore the therapeutic efficacies of decitabine application prior to hematopoietic cell transplantation (HSCY) in patients with myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML).Methods Retrospective reviews were conducted for 46 patients with MDS (n =14) and AML (n =32) on a therapy of decitabine prior to allo-HSCT between September 2009 and February 2013.Results In MDS patients,complete remission (CR,n =10),partial remission (PR,n =2) and stable disease (SD,n =1) were achieved prior to HSCT.And the remission rate of one course was 10/14.After decitabine dosing,17/32 patients achieved CR in 32 with AML and the remission rate of one course was 53.1% (17/32) and effective rate of one course (CR + PR) achieves 78.1% (25/32).Successful engraftment was attained in all MDS patients and 12/14 patients survived disease-free and one died of pneumonia after relapse.And 28 patients with AML attained successful engraftment after using decitabine prior to allo-HSCT and there were 20 disease-free survivors.Ten patients died and another lived with tumor.The incidences of acute and chronic graft-versus-host disease (GVHD) among evaluable patients were 4.3% (2/26) and 23.9% (11/46) respectively.After a median follow-up of 8 months for survivors,the treatment-related mortality was 23.9% (11/46).The 30-month disease-free survival (DFS) rate was 53.1% and 30-month overall survival rate after decitabine dosing 61.9%.Conclusion Thus decitabine is an effective therapy during bridge time to HSCT in patients with MDS and AML.%目的 观察骨髓增生异常综合征(MDS)及复发难治性急性髓系白血病(AML)患者造血干细胞移植前选择含地西他滨方案诱导或巩固作为过渡治疗的临床疗效,以期降低肿瘤负荷,控制疾病并为寻找供体赢取时间.方法 回顾性分析苏州大学附属第一医院2009年9月至2013年2月期间在异基因造血干细胞移植前采用地西他滨单药

  20. 高危骨髓增生异常综合征及急性髓系白血病治疗方案选择研究%Effects of Idarubicin and cytosine arabinoside on high-risk myelodysplastic syndromes and acute myeloid leukemia

    Institute of Scientific and Technical Information of China (English)

    刘惠; 刘鸿; 吴玉红; 王化泉; 邢莉民; 关晶; 王珺; 李丽娟; 付蓉; 邵宗鸿; 阮二宝; 王晓明; 王国锦; 梁勇; 瞿文; 宋嘉

    2009-01-01

    Objective To compare the therapeutic and side effects of idarubicin (IDA) with those of daunorubicin(DNR) in combination with cytosine arabinoside (CA) on high-risk myelodysplastic syndromes and acute myeloid leukemia (AML).Methods 29 patients(18 patients with AML,11 patients with high-risk MDS or AMI7MDS)were treated with IDA(12mg/m~2)for 3d and CA(150mg/m~2)for 7d(IA arm) and 26 patients with AML with DNR(45mg/m~2 )for 3d and CA( 150mg/m~2)for 7d( DA arm)as induction and consolidation therapies. Results (1) For AML patients, the effective rates( CR + PR) were 83. 3% in IA arm and 53. 8% in DA arm( P = 0.042); For patients with higher white blood cell count (≥30×10~9/L) ,the effective rates were 81. 3% in IA arm and 25% in DA arm (P =0.009) ;For elder patients ( ≥ 65y) , the effective rates were 66. 7% in IA arm and 0% in DA arm (P = 0.045);(2) Treatment with IA could also offer significant advantages to high-risk MDS or AML/MDS patients with higher effective rates(83.3%) which was similar to that of AML patients by IA(72.7%). Age and Hyperleukocytosis(≥30 ×10~9/L)could not affect the effective rates in IA arm;(3) The main toxicity of IA was longer myelosuppression with lower WBC below 4 ×10~9/L which was averagely up to (24.1 7.7)d. Hemorrhage, nausea, vomit, hepatic and renal dysfunction and heart toxicity occurred unfrequently. Con-clusion IA was superior to DA as induction and consolidation therapies for AML and also effective for high-risk MDS or MDS-develeped AML. Age and hyperleukocytosis could not affect the effects of IA. IA can be the first therapy choice for the patients with AML and high-risk MDS.%目的 评价IA方案[去甲氧柔红霉素(IDA)+阿糖胞苷(Ara-C)]和DA方案[柔红霉素(DNR)+Ara-C]治疗高危骨髓增生异常综合征(MDs)、急性髓系白血病(AML)及MDS转AML患者的疗效和不良反应.方法 应用IA方案治疗2005年2月至2008年10月天津医科大学总医院血液肿瘤科收治的AML18

  1. An update on the safety and efficacy of decitabine in the treatment of myelodysplastic syndromes

    Directory of Open Access Journals (Sweden)

    Jacqueline S Garcia

    2010-02-01

    Full Text Available Jacqueline S Garcia1, Nitin Jain1, Lucy A Godley1,21Section of Hematology/Oncology, Department of Medicine, The University of Chicago, Chicago, IL, USA; 2Cancer Research Center, The University of Chicago, Chicago, IL, USAAbstract: Myelodysplastic syndromes (MDS are clonal bone marrow malignancies characterized by peripheral cytopenias and dysplastic changes in the bone marrow with various clinical features. Patients with MDS, in particular those with intermediate-2 (Int-2 and high-risk disease, have a poor prognosis. The mainstay of treatment includes cytoxic chemotherapy and supportive care. Over the last decade, promising results from studies focusing on hypomethylating agents, such as decitabine (5-aza-deoxycytidine and 5-azacitidine, have led to the expansion of the therapeutic arsenal for MDS. This review presents the current data available on the clinical efficacy and safety profile for decitabine as a treatment for MDS. Although not fully understood, decitabine’s antitumor activity may involve its ability to induce hypomethylation and reactivation of genes responsible for cellular differentiation, stimulate an immune response, induce DNA damage/apoptotic response pathways, and/or augment stem cell renewal. Future studies that use epigenetic therapies that combine hypomethylating agents with histone deacetylase inhibitors (HDACi and head-to-head comparison studies of decitabine and 5-azacitidine will provide valuable pre-clinical and clinical data, enhancing our understanding of these drugs.Keywords: decitabine, 5-aza-deoxycytidine, 5-azacitidine, myelodysplastic syndromes

  2. The proliferation index of specific bone marrow cell compartments from myelodysplastic syndromes is associated with the diagnostic and patient outcome.

    Directory of Open Access Journals (Sweden)

    Sergio Matarraz

    Full Text Available Myelodysplastic syndromes (MDS are clonal stem cell disorders which frequently show a hypercellular dysplastic bone marrow (BM associated with inefficient hematopoiesis and peripheral cytopenias due to increased apoptosis and maturation blockades. Currently, little is known about the role of cell proliferation in compensating for the BM failure syndrome and in determining patient outcome. Here, we analyzed the proliferation index (PI of different compartments of BM hematopoietic cells in 106 MDS patients compared to both normal/reactive BM (n = 94 and acute myeloid leukemia (AML; n = 30 cases using multiparameter flow cytometry. Our results show abnormally increased overall BM proliferation profiles in MDS which significantly differ between early/low-risk and advanced/high-risk cases. Early/low-risk patients showed increased proliferation of non-lymphoid CD34(+ precursors, maturing neutrophils and nucleated red blood cells (NRBC, while the PI of these compartments of BM precursors progressively fell below normal values towards AML levels in advanced/high-risk MDS. Decreased proliferation of non-lymphoid CD34(+ and NRBC precursors was significantly associated with adverse disease features, shorter overall survival (OS and transformation to AML, both in the whole series and when low- and high-risk MDS patients were separately considered, the PI of NRBC emerging as the most powerful independent predictor for OS and progression to AML. In conclusion, assessment of the PI of NRBC, and potentially also of other compartments of BM precursors (e.g.: myeloid CD34(+ HPC, could significantly contribute to a better management of MDS.

  3. The Proliferation Index of Specific Bone Marrow Cell Compartments from Myelodysplastic Syndromes Is Associated with the Diagnostic and Patient Outcome

    Science.gov (United States)

    Matarraz, Sergio; Teodosio, Cristina; Fernandez, Carlos; Albors, Manuel; Jara-Acevedo, María; López, Antonio; Gonzalez-Gonzalez, María; Gutierrez, María Laura; Flores-Montero, Juan; Cerveró, Carlos; Pizarro-Perea, Marlies; Garrastazul, María Paz; Caballero, Gonzalo; Gutierrez, Oliver; Mendez, Guy Daniel; González-Silva, Manuel; Laranjeira, Paula; Orfao, Alberto

    2012-01-01

    Myelodysplastic syndromes (MDS) are clonal stem cell disorders which frequently show a hypercellular dysplastic bone marrow (BM) associated with inefficient hematopoiesis and peripheral cytopenias due to increased apoptosis and maturation blockades. Currently, little is known about the role of cell proliferation in compensating for the BM failure syndrome and in determining patient outcome. Here, we analyzed the proliferation index (PI) of different compartments of BM hematopoietic cells in 106 MDS patients compared to both normal/reactive BM (n = 94) and acute myeloid leukemia (AML; n = 30 cases) using multiparameter flow cytometry. Our results show abnormally increased overall BM proliferation profiles in MDS which significantly differ between early/low-risk and advanced/high-risk cases. Early/low-risk patients showed increased proliferation of non-lymphoid CD34+ precursors, maturing neutrophils and nucleated red blood cells (NRBC), while the PI of these compartments of BM precursors progressively fell below normal values towards AML levels in advanced/high-risk MDS. Decreased proliferation of non-lymphoid CD34+ and NRBC precursors was significantly associated with adverse disease features, shorter overall survival (OS) and transformation to AML, both in the whole series and when low- and high-risk MDS patients were separately considered, the PI of NRBC emerging as the most powerful independent predictor for OS and progression to AML. In conclusion, assessment of the PI of NRBC, and potentially also of other compartments of BM precursors (e.g.: myeloid CD34+ HPC), could significantly contribute to a better management of MDS. PMID:22952954

  4. p53 protein expression independently predicts outcome in patients with lower-risk myelodysplastic syndromes with del(5q)

    NARCIS (Netherlands)

    Saft, L.; Karimi, M.; Ghaderi, M.; Matolcsy, A.; Mufti, G.J.; Kulasekararaj, A.; Gohring, G.; Giagounidis, A.; Selleslag, D.; Muus, P.; Sanz, G.; Mittelman, M.; Bowen, D.; Porwit, A.; Fu, T.; Backstrom, J.; Fenaux, P.; MacBeth, K.J.; Hellstrom-Lindberg, E.

    2014-01-01

    Del(5q) myelodysplastic syndromes defined by the International Prognostic Scoring System as low- or intermediate-1-risk (lower-risk) are considered to have an indolent course; however, recent data have identified a subgroup of these patients with more aggressive disease and poorer outcomes. Using de

  5. Label-free imaging and identification of typical cells of acute myeloid leukaemia and myelodysplastic syndrome by Raman microspectroscopy

    NARCIS (Netherlands)

    Vanna, R.; Ronchi, P.; Lenferink, A.T.M.; Terstappen, L.W.M.M.; Tresoldi, C.; Morasso, C.; Mehn, D.; Bedoni, M.; Ciceri, F.; Otto, C.; Gramatica, F.

    2015-01-01

    In clinical practice, the diagnosis and classification of acute myeloid leukaemia (AML) and myelodysplastic syndrome (MDS) start from the manual examination of stained smears of bone marrow (BM) and peripheral blood (PB) by using an optical microscope. This step is subjective and scarcely reproducib

  6. Bilateral lung 99mTc-MDP uptake on the bone scintigraphy in the myelodysplastic syndromes (MDS).

    Science.gov (United States)

    Mogharrabi, Mehdi; Javadi, Hamid; Assadi, Majid

    2013-05-01

    We report a case of myelodysplastic syndrome (MDS) with unusual abnormal 99mTc-MDP activity throughout both lungs on whole-body bone scan. To explain the pancytopenia, bone marrow examination was carried out which showed hypocellularity in addition to large abnormal megakaryocytes indicating myelodysplastic changes. His whole-body bone scan showed increased 99mTc-MDP activity in both lungs, kidneys, and also along the proximal two thirds of the femora. It was concluded that lung uptake in addition to skeletal uptake on scintigraphic bone scanning should be kept in mind in patients with MDS.

  7. Immune-mediated complications in patients with myelodysplastic syndromes--clinical and cytogenetic features.

    Science.gov (United States)

    Billström, R; Johansson, H; Johansson, B; Mitelman, F

    1995-07-01

    It has been recognized in recent years that some patients with myelodysplastic syndromes (MDS) develop immune-mediated complications (IMC), but little is known about the correlations to MDS-specific disease features. In a retrospective study of 82 MDS patients, we identified 10 (12%) with IMC (group A) and compared them to the remaining 72 cases (group B). Group A consisted of 5 patients with biopsy-verified skin vasculitis and 1 case each with temporal arteritis/polymyalgia rheumatica, necrotising panniculitis, Hashimoto's thyroiditis, autoimmune thrombocytopenia, and Sweet's syndrome. Survival times, sex ratio and distribution of MDS subtypes were similar in the two groups. The patients in group A were younger than those in group B (median 66 vs. 76 years, p aberrations, were also observed to be more common in group A (3/9 vs. 8/53). The results indicate that IMC preferentially develop in patients with secondary MDS, in younger MDS cases, and in patients with cytogenetic abnormalities.

  8. Terson syndrome and leukemia: a case report

    Directory of Open Access Journals (Sweden)

    Lorenzi U

    2014-04-01

    Full Text Available Umberto Lorenzi, Elisa Buschini, Antonio Fea, Federica Machetta, Federico Maria GrignoloOphthalmic Section, Department of Clinical Pathophysiology, University of Turin, Turin, Italy Abstarct: Terson syndrome is defined as intraocular hemorrhage associated with intracranial bleeding. This syndrome can occur in the event of intracranial hemorrhage or elevated intracranial pressure. To our knowledge, it has never been associated with chronic myeloid leukemia. A 45-year-old woman suffering from chronic myeloid leukemia was referred to our clinic with Terson syndrome after intracranial bleeding. We followed this patient for a year, performing visual acuity assessment, fundus examination, color retinography, and A-scan and B-scan ultrasonography. At presentation, her best-corrected visual acuity on the right was 20/63 and on the left was 20/320. In the right eye, retinoscopy showed blurring of the optic margins surrounded by retinal and preretinal hemorrhages, preretinal fibrosis of the optic disc along the vascular arcades, and perivascular retinal infiltrates. In the left eye, the optic disc was surrounded by retinal and preretinal hemorrhages, and massive fibrosis with hard exudates and severe preretinal hemorrhage were observed at the posterior pole. Roth spots and many circular hemorrhages were noted at the periphery of the retina. A-scan and B-scan ultrasonography did not show intraocular leukemic infiltration. The clinical picture remained stable over the following 12 months. In this patient, we observed the ophthalmoscopic features of chronic myeloid leukemia, but also coexistence of features typical of Terson syndrome. To our knowledge, no similar cases have been reported previously.Keywords: retinal disease, chronic myeloid leukemia, eye hemorrhage, intracranial hemorrhage

  9. Mutations in the gene for the granulocyte colony-stimulating-factor receptor in patients with acute myeloid leukemia preceded by severe congenital neutropenia

    NARCIS (Netherlands)

    F. Dong (Fan); R.K. Brynes; N. Tidow; K. Welte (Karl); B. Löwenberg (Bob); I.P. Touw (Ivo)

    1995-01-01

    textabstractBACKGROUND. In severe congenital neutropenia the maturation of myeloid progenitor cells is arrested. The myelodysplastic syndrome and acute myeloid leukemia develop in some patients with severe congenital neutropenia. Abnormalities in the signal-transduction

  10. Very late recurrences of leukemia: why does leukemia awake after many years of dormancy?

    Science.gov (United States)

    Norkin, Maxim; Uberti, Joseph P; Schiffer, Charles A

    2011-02-01

    We report a heterogeneous group of very late recurrences of leukemia occurring more than 10 years after initial treatment including 2 cases of childhood acute lymphoblastic leukemia (ALL) which recurred after more than 20 years of remission, 2 cases of donor cell leukemia which developed more than 10 years after allograft for acute myeloid leukemia (AML) and high risk myelodysplastic syndrome (MDS) and 2 cases of chronic myeloid leukemia (CML) relapsing 13 and 17 years after allograft. Case descriptions are followed by a discussion regarding possible mechanisms leading to leukemia recurrence and a review of the literature. Copyright © 2010 Elsevier Ltd. All rights reserved.

  11. [Lenalidomide treatment in myelodysplastic syndrome with 5q deletion--Czech MDS group experience].

    Science.gov (United States)

    Jonášová, Anna; Červinek, Libor; Bělohlávková, Petra; Čermák, Jaroslav; Beličková, Monika; Rohoň, Petr; Černá, Olga; Hochová, Ivana; Šišková, Magda; Kačmářová, Karla; Janoušová, Eva

    2015-12-01

    Myelodysplastic syndrome (MDS) is a common hematological disease in patients over sixty. Despite intensive research, the therapy of this heterogeneous blood disease is complicated. In recent years, two new therapeutic approaches have been proposed: immunomodulation and demethylation therapy. Immunomodulation therapy with lenalidomide represents a meaningful advance in the treatment of anemic patients, specifically those with 5q- aberrations. As much as 60-70% of patients respond and achieve transfusion independence. We present the initial lenalidomide experience of the Czech MDS group. We analyze Czech MDS register data of 34 (31 female; 3 male; median age 69 years) chronically transfused low risk MDS patients with 5q- aberration treated by lenalidomide. Twenty-seven (79.4%) patients were diagnosed with 5q- syndrome, 5 patients with refractory anemia with multilineage dysplasia, 1 patient with refractory anemia with excess of blasts 1, and 1 patient with myelodysplastic/myeloproliferative unclassified. Response, as represented by achieving complete transfusion independence, was achieved in 91% of patients. A true 5q- syndrome diagnosis in most our patients may be responsible for such a high response rate. Complete cytogenetic response was reached in 15% of patients and partial cytogenetic response in 67%, within a median time of 12 months. TP53 mutation was detected in 15% (3 from 18 tested) and 2 of these patients progressed to higher grade MDS. The majority of patients tolerated lenalidomide very well. Based on this albeit small study, we present our findings of high lenalidomide efficacy as well as the basic principles and problems of lenalidomide therapy.

  12. Spliceosome mutations exhibit specific associations with epigenetic modifiers and proto-oncogenes mutated in myelodysplastic syndrome.

    Science.gov (United States)

    Mian, Syed A; Smith, Alexander E; Kulasekararaj, Austin G; Kizilors, Aytug; Mohamedali, Azim M; Lea, Nicholas C; Mitsopoulos, Konstantinos; Ford, Kevin; Nasser, Erick; Seidl, Thomas; Mufti, Ghulam J

    2013-07-01

    The recent identification of acquired mutations in key components of the spliceosome machinery strongly implicates abnormalities of mRNA splicing in the pathogenesis of myelodysplastic syndromes. However, questions remain as to how these aberrations functionally combine with the growing list of mutations in genes involved in epigenetic modification and cell signaling/transcription regulation identified in these diseases. In this study, amplicon sequencing was used to perform a mutation screen in 154 myelodysplastic syndrome patients using a 22-gene panel, including commonly mutated spliceosome components (SF3B1, SRSF2, U2AF1, ZRSR2), and a further 18 genes known to be mutated in myeloid cancers. Sequencing of the 22-gene panel revealed that 76% (n=117) of the patients had mutations in at least one of the genes, with 38% (n=59) having splicing gene mutations and 49% (n=75) patients harboring more than one gene mutation. Interestingly, single and specific epigenetic modifier mutations tended to coexist with SF3B1 and SRSF2 mutations (P<0.03). Furthermore, mutations in SF3B1 and SRSF2 were mutually exclusive to TP53 mutations both at diagnosis and at the time of disease transformation. Moreover, mutations in FLT3, NRAS, RUNX1, CCBL and C-KIT were more likely to co-occur with splicing factor mutations generally (P<0.02), and SRSF2 mutants in particular (P<0.003) and were significantly associated with disease transformation (P<0.02). SF3B1 and TP53 mutations had varying impacts on overall survival with hazard ratios of 0.2 (P<0.03, 95% CI, 0.1-0.8) and 2.1 (P<0.04, 95% CI, 1.1-4.4), respectively. Moreover, patients with splicing factor mutations alone had a better overall survival than those with epigenetic modifier mutations, or cell signaling/transcription regulator mutations with and without coexisting mutations of splicing factor genes, with worsening prognosis (P<0.001). These findings suggest that splicing factor mutations are maintained throughout disease

  13. BURDEN OF ABNORMAL HEMATOPOIETIC CLONE IN PATIENTS WITH MYELODYSPLASTIC SYNDROMES

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Objective To investigate the role of the burden of abnormal hematopoietic clone in the development of myelodys plastic syndromes (MDS).Methods The ratio of the bone marrow cells with abnormal chromosomes to the total counted bone marrow cells was regarded as the index of MDS clone burden. The disease severity related parameters including white blood cell count, hemoglobin, platelet count, lactate dehydrogenase level, bone marrow blast, myeloid differentiation index, micromegakaryocyte, transfusion, interleukin-2, tumor necrosis factor ( TNF), CD4 + and CD8 + T cells of MDS patients were assayed, and the correlations between those parameters and MDS clone burden were also analyzed.Results The clone burden of MDS patients was 67.4% ± 36. 2%. MDS clone burden positively correlated with bone marrow blasts (r=0.483, P<0.05), negatively with hemoglobin level (r=-0.445, P<0.05). The number of blasts, hemoglobin, and erythrocytes in high clone burden (>50%) and low clone burden (≤50%) groups were 7.78%±5.51% and 3.45%±3.34%, 56.06±14. 28 g/L and 76.40±24.44 g/L, (1.82±0.48)×1012/L and (2. 32±0.66)×1012/L, respectively (all P <0.05). CD4 + T lymphocytes of MDS patients and normal controls were (0. 274±0.719)×109/L and (0.455±0.206)×109/L, respectively (P<0.05). CD8 ± T lymphocytes of MDS patients and normal controls were (0.240±0.150)×109/L and (0.305 ±0.145)×109/L, respectively. The serum level of interleukin-2 of MDS patients (6.29±3.58 ng/mL) was significantly higher than normal control (3.11±1.40ng/mL, P<0.05). The serum level of TNF of MDS patients and normal control group were 2.42±1.79 ng/mL and 1.68 ±0.69 ng/mL, respectively. The ratio of CD4 to CD8 was higher in high clone burden MDS patients (1.90 ±0.52) than that in low clone burden patients (0.97±0.44, P<0.05).Conclusion The quantitive clonal karyotype abnormalities and deficient T cell immunity are important parameters for evaluating MDS severity and predicting its

  14. Inflammatory arthritis in patients with myelodysplastic syndromes: a multicenter retrospective study and literature review of 68 cases.

    Science.gov (United States)

    Mekinian, Arsène; Braun, Thorsten; Decaux, Olivier; Falgarone, Géraldine; Toussirot, Eric; Raffray, Loic; Omouri, Mohamed; Gombert, Bruno; De Wazieres, Benoit; Buchdaul, Anne-Laure; Ziza, Jean-Marc; Launay, David; Denis, Guillaume; Madaule, Serge; Rose, Christian; Grignano, Eric; Fenaux, Pierre; Fain, Olivier

    2014-01-01

    We describe the characteristics and outcome of inflammatory arthritis in patients with myelodysplastic syndrome (MDS) in a French multicenter retrospective study. Twenty-two patients with MDS (median age, 77.5 yr [interquartile range, 69-81]; 10 women) were included. Inflammatory arthritis presented as polyarthritis in 17 cases (77%) and with symmetric involvement in 15 cases (68%). At diagnosis, the median disease activity score 28 based on C-reactive protein (DAS28-CRP) was 4.5 [2-6.5]. Two patients had anti-citrullinated protein antibodies (ACPAs), and 1 had radiologic erosions. The median time between the diagnoses of arthritis and MDS was 10 months [6-42], with a median articular symptom duration of 3 months [2-8]. The diagnosis of both diseases was concomitant in 6 cases (27%); arthritis preceded MDS in 12 cases (55%), and occurred after MDS in 4 (18%). While the number of swollen and tender joints significantly decreased during follow-up, as did the median DAS28-CRP (from 4.3 [3.8-4.6] at baseline to 2.9 [1.75-3.3]; p 20 mg/L) in 8 patients (42%). Nevertheless, radiographic progression and new ACPA positivity were not observed during a median follow-up of 29 months [9-76]. While most of the patients were treated with steroids (n = 16) for arthritis, additional treatment was administered in only 4 patients (hydroxychloroquine, n = 2; sulfasalazine [Salazopyrin] and etanercept, n = 1, respectively). Eleven patients died during follow-up from acute myeloid leukemia (n = 5); infections (n = 3); or cerebral bleeding, cardiorespiratory failure, or undetermined cause (n = 1, respectively). Inflammatory arthritis associated with MDS can have various presentations and is often seronegative and nonerosive. Steroids alone are the most common treatment in MDS-associated arthritis, but that treatment is insufficient to control arthritis. Steroid-sparing strategies need to be identified.

  15. Cytokine expression patterns and mesenchymal stem cell karyotypes from the bone marrow microenvironment of patients with myelodysplastic syndromes

    Energy Technology Data Exchange (ETDEWEB)

    Xiong, H.; Yang, X.Y.; Han, J.; Wang, Q.; Zou, Z.L. [Department of Hematology, Shanghai Clinical Research Center, Chinese Academy of Sciences, Shanghai Xuhui District Central Hospital, Shanghai (China)

    2015-01-20

    The purpose of this study was to explore cytokine expression patterns and cytogenetic abnormalities of mesenchymal stem cells (MSCs) from the bone marrow microenvironment of Chinese patients with myelodysplastic syndromes (MDS). Bone marrow samples were obtained from 30 cases of MDS (MDS group) and 30 healthy donors (control group). The expression pattern of cytokines was detected by customized protein array. The karyotypes of MSCs were analyzed using fluorescence in situ hybridization. Compared with the control group, leukemia inhibitory factor, stem cell factor (SCF), stromal cell-derived factor (SDF-1), bone morphogenetic protein 4, hematopoietic stem cell (HSC) stimulating factor, and transforming growth factor-β in the MDS group were significantly downregulated (P<0.05), while interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), and programmed death ligand (B7-H1) were significantly upregulated (P<0.05). For chromosome abnormality analysis, the detection rate of abnormal karyotypes (+8, -8, -20, 20q-, -Y, -7, 5q-) was 30% in the MDS group and 0% in the control group. In conclusion, the up- and downregulated expression of these cytokines might play a key role in the pathogenesis of MDS. Among them, SCF and SDF-1 may play roles in the apoptosis of HSCs in MDS; and IFN-γ, TNF-α, and B7-H1 may be associated with apoptosis of bone marrow cells in MDS. In addition, the abnormal karyotypes might be actively involved in the pathogenesis of MDS. Further studies are required to determine the role of abnormal karyotypes in the occurrence and development of MDS.

  16. Increased expression of HERG K(+) channels contributes to myelodysplastic syndrome progression and displays correlation with prognosis stratification.

    Science.gov (United States)

    Lu, Li; Du, Wen; Liu, Wei; Guo, Dongmei; He, Xiaoqi; Li, Huiyu

    2016-12-01

    Human ether-a-go-go-related gene (HERG) K(+) channels are shown to be aberrantly expressed in a variety of cancer cells where they play roles in contributing to cancer progression. Myelodysplastic syndromes (MDS) are a group of clinical heterogeneous disorders characterized by bone marrow failure and dysplasia of blood cells. However, the involvement of HERG K(+) channels in MDS development is poorly understood. The expression of HERG K(+) channels in untreated MDS, acute myeloid leukemia (AML) patients and the control group was detected by flow cytometry. The roles of HERG K(+) channels in regulation of SKM-1 cell proliferation, apoptosis, and cell cycle were determined by CCK-8 assay and flow cytometry, respectively. We found that expression of HERG K(+) channels in MDS patients was significantly higher than controls and was lower than AML. Percentage of HERG K(+) channels on CD34+CD38- cells gradually increased from controls to high-grade MDS subtypes. And HERG K(+) channel levels showed an ascending tendency from low-risk to high-risk MDS group. In addition, the CCK-8 assay, apoptosis and cell cycle analysis were performed and showed that blockage of HERG K(+) channels decreased the proliferation of MDS cells but rarely had effects on cell apoptosis and cell cycle distribution. Our study demonstrated that HERG K(+) channels might be a potential tumor marker of MDS. These channels were likely to contribute to MDS progression and were helpful for predicting prognosis of MDS. Inhibition of HERG K(+) channels might be a novel therapeutic measure for MDS.

  17. Cost-effectiveness of azacitidine compared with low-doses of chemotherapy (LDC in myelodysplastic syndrome (MDS

    Directory of Open Access Journals (Sweden)

    Myrna Candelaria-Hernández

    2017-05-01

    Full Text Available Introduction: Myelodysplastic syndrome (MDS comprises a group of clonal hematological disorders, characterized by ineffective hematopoiesis and progressive bone marrow failure. It increases the risk of transformation to acute myeloid leukemia (AML. Therapeutic benefit should include overall survival increase (OS, hematological improvement, transfusion dependence and time to progression to AML decrease. Objective: Assess, from a Mexican health-care perspective, the cost-effectiveness of azacitidine compared with low-doses of chemotherapy (LDC plus best supportive care (BSC for the treatment of adult patients with intermediate- 2 and high-risk MDS, who are not eligible for hematopoietic stem-cell transplantation. We developed a cost-effectiveness survival analysis model of three stages: MDS, AML, and death. OS and costs are extrapolated beyond three-year time horizon. Discount rate of 5% was applied. To estimate the model cycle probability transition to mortality state, survival curves were constructed for each treatment arm using individual patient-level data from Study AZA-001. Unitary costs are from public price list, and profiles for the management of MDS and AML were collected separately using a structured questionnaire. Probabilistic sensitivity analyses (PSA were conducted by simultaneously sampling from estimated probability distributions of model parameters. Results: Overall survival was projected to increase by 72.26 weeks with azacitidine. Incremental expected total costs for azacitidine compared to LDC was MXN$68,045. However, the cost of the drug therapy was lower with azacitidine. The incremental cost-effectiveness ratio (ICER for azacitidine compared to LDC was MXN$48,932 per life-year gained (LYG. PSA showed that azacitidine was a highly cost-effective option in 96.49% of the simulated cases in MXN$180,000/LYG willingness-to-pay. Conclusions: Compared with LDC, azacitidine represents a cost-effective treatment alternative in

  18. Survival benefits with transplantation in secondary AML evolving from myelodysplastic syndrome with hypomethylating treatment failure.

    Science.gov (United States)

    Shin, S-H; Yahng, S-A; Yoon, J-H; Lee, S-E; Cho, B-S; Eom, K-S; Lee, S; Min, C-K; Kim, H-J; Cho, S-G; Kim, D-W; Lee, J-W; Min, W-S; Park, C-W; Kim, Y-J

    2013-05-01

    The prognosis for patients with myelodysplastic syndrome with hypomethylating treatment failure (MDS-HTF) has been known to be poor. However, the clinical outcomes and optimal treatment options for secondary AML evolving from MDS-HTF (sAML/MDS-HTF) are not well known. This retrospective analysis was conducted to evaluate the clinical outcomes and influences of treatment options on survival in 46 consecutive patients with sAML/MDS-HTF. The median OS rates were 1.4 months in the best supportive care group (n=15) and 9.4 months in the active treatment group (n=31). One-year OS rates were 13.3% and 36.8%, respectively (P=0.001). Active treatment (PHTF if the patient is medically fit.

  19. 657del5 mutation of the NBS1 gene in myelodysplastic syndrome

    Directory of Open Access Journals (Sweden)

    Bunjevacki Vera

    2014-01-01

    Full Text Available Myelodysplastic syndromes (MDS are clonal hematologic stem cell disorders with an as yet unknown molecular pathology. Genetic instability has been proposed as a cause of MDS. Mutations in the NBS1 gene, whose product nibrin (p95 is involved in DNA damage repair and cell-cycle control, might be associated with an elevated predisposition to the development of MDS. The aim of the study was to examine truncating 5 bp deletion (657del5, the most frequent NBS1 gene mutation in Slavic populations, in MDS patients. Among 71 MDS patients, we found one case that was heterozygous for the NBS1 657del5 mutation. To the best of our knowledge, this is the first report of a NBS1 mutation in MDS. [Projekat Ministarstva nauke Republike Srbije, br. 175091

  20. Impact of Nagasaki atomic bomb exposure on myelodysplastic syndrome patients who are treated with azacitidine.

    Science.gov (United States)

    Jo, Tatsuro; Horio, Kensuke; Shigematsu, Kazuto

    2015-05-01

    High-dose radiation exposure greatly increases the risk of myelodysplastic syndromes (MDS), however the clinical characteristics of MDS among atomic bomb survivors have not been thoroughly investigated to date. We designed this study to identify these characteristics. We retrospectively evaluated data from 13 atomic bomb survivors with MDS and 15 elderly patients with de novo MDS who were diagnosed between April 2011 and April 2013 at the Nagasaki Genbaku Hospital. All patients were treated with azacitidine (AZA; a hypomethylating agent) and overall survival rates were estimated. No clear difference was observed in the clinical response to AZA between the two groups. However, atomic bomb survivors had a survival disadvantage, independent of their karyotype. Minute genetic alterations caused by exposure to atomic radiation can adversely affect the response to AZA, even 66 years after the exposure. Further studies are required to clarify the mechanisms underlying this phenomenon. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  1. Prognostic factors in de novo myelodysplastic syndrome in young and middle-aged people

    Directory of Open Access Journals (Sweden)

    Наталья Николаевна Климкович

    2015-01-01

    Full Text Available We spent multivariate analysis of clinical and laboratory parameters for the prediction of de-novo myelodysplastic syndromes (MDS patients aged 18-60 years. The results of clinical application of prognostic systems in MDS show that there is a large variability within individual risk groups, especially at low-risk MDS. So now hematologists conduct research aimed at identifying additional adverse risk MDS. This is done so that patients with low-risk MDS embodiments and unfavorable prognosis could benefit from early therapeutic intervention, and not only be clinician monitored until disease progression. We found that additional adverse risk factors for the development of MDS are the expression of CD95 in bone marrow ≤40 % and FLT3≥60 %. The expression level of CD95 in bone marrow cells≤40 % and FLT3≥60 % can be considered as a prognostic marker progression of MDS and time start specific therapy

  2. YKL-40 in allogeneic hematopoietic cell transplantation after AML and myelodysplastic syndrome

    DEFF Research Database (Denmark)

    Kornblit, B; Wang, T; Lee, S J;

    2016-01-01

    YKL-40, also called chitinase-3-like-1 protein, is an inflammatory biomarker that has been associated with disease severity in inflammatory and malignant diseases, including AML, multiple myeloma and lymphomas. The objective of the current study was to assess the prognostic value of pretransplant......, otherwise equal, donors are available.Bone Marrow Transplantation advance online publication, 18 July 2016; doi:10.1038/bmt.2016.192....... recipient and donor plasma YKL-40 concentrations in patients with AML (n=624) or myelodysplastic syndrome (n=157) treated with allogeneic hematopoietic cell transplantation (HCT). In recipients, the plasma YKL-40 concentrations were increased when the HCT-comorbidity index was ⩾5 (P=0.028). There were...

  3. Combining gene mutation with gene expression data improves outcome prediction in myelodysplastic syndromes

    Science.gov (United States)

    Gerstung, Moritz; Pellagatti, Andrea; Malcovati, Luca; Giagounidis, Aristoteles; Porta, Matteo G Della; Jädersten, Martin; Dolatshad, Hamid; Verma, Amit; Cross, Nicholas C. P.; Vyas, Paresh; Killick, Sally; Hellström-Lindberg, Eva; Cazzola, Mario; Papaemmanuil, Elli; Campbell, Peter J.; Boultwood, Jacqueline

    2015-01-01

    Cancer is a genetic disease, but two patients rarely have identical genotypes. Similarly, patients differ in their clinicopathological parameters, but how genotypic and phenotypic heterogeneity are interconnected is not well understood. Here we build statistical models to disentangle the effect of 12 recurrently mutated genes and 4 cytogenetic alterations on gene expression, diagnostic clinical variables and outcome in 124 patients with myelodysplastic syndromes. Overall, one or more genetic lesions correlate with expression levels of ~20% of all genes, explaining 20–65% of observed expression variability. Differential expression patterns vary between mutations and reflect the underlying biology, such as aberrant polycomb repression for ASXL1 and EZH2 mutations or perturbed gene dosage for copy-number changes. In predicting survival, genomic, transcriptomic and diagnostic clinical variables all have utility, with the largest contribution from the transcriptome. Similar observations are made on the TCGA acute myeloid leukaemia cohort, confirming the general trends reported here. PMID:25574665

  4. [Recent advances of studies on abnormal HOX gene in myelodysplastic syndromes and its molecular mechanisms].

    Science.gov (United States)

    Xie, Xin-Yan; Shao, Zong-Hong

    2015-02-01

    HOX gene encodes a group of homeodomain transcription factors which are highly conserved. The caudal-type homeobox (CDX) , ten-eleven translocation (TET) genes and polycomb group (PcG) , trithorax group (TrxG) proteins act as upstream regulators of HOX genes that manipulate the targeted gene expression through genetic and epigenetic mechanisms. The abnormal expression of HOX genes and their fusions contribute to myelodysplastic syndromes (MDS) pathogenesis. Aberrant DNA methylation and NUP98-HOX translocation serve as molecular mediators of dysfunction in MDS which can be used for the evaluation of biology and therapy. This article provides an overview of recent advances of studies on HOX gene and its abnormal molecular mechanisms, as well as potential correlation with MDS.

  5. Myelodysplastic Syndrome Clinically Presenting with the “Classic TTP Pentad”

    Science.gov (United States)

    Polanco Jácome, Evelyn Carolina; Guevara, Elizabeth; Mattoo, Vijay

    2017-01-01

    The clinical presentation of myelodysplastic syndrome (MDS) is not specific. Many patients can be asymptomatic and can be detected only due to an abnormal complete blood cell count (CBC) on routine exam or for other reasons while others can be symptomatic as a consequence of underlying cytopenias. Thrombotic thrombocytopenic purpura (TTP) usually is suspected under the evidence of microangiopathic hemolytic anemia (MAHA) and thrombocytopenia and because it is a life-threatening condition (medical emergency) immediate initiation of plasmapheresis could be life-saving. The following case illustrates an unusual presentation of MDS in a patient who came in to the emergency room with the classic TTP “pentad” of fever, renal involvement, MAHA, mental status changes, and thrombocytopenia. We will focus our discussion in the clinical presentation of this case. PMID:28255478

  6. Splicing factor gene mutations in the myelodysplastic syndromes: impact on disease phenotype and therapeutic applications.

    Science.gov (United States)

    Pellagatti, Andrea; Boultwood, Jacqueline

    2017-01-01

    Splicing factor gene mutations are the most frequent mutations found in patients with the myeloid malignancy myelodysplastic syndrome (MDS), suggesting that spliceosomal dysfunction plays a major role in disease pathogenesis. The aberrantly spliced target genes and deregulated cellular pathways associated with the commonly mutated splicing factor genes in MDS (SF3B1, SRSF2 and U2AF1) are being identified, illuminating the molecular mechanisms underlying MDS. Emerging data from mouse modeling studies indicate that the presence of splicing factor gene mutations can lead to bone marrow hematopoietic stem/myeloid progenitor cell expansion, impaired hematopoiesis and dysplastic differentiation that are hallmarks of MDS. Importantly, recent evidence suggests that spliceosome inhibitors and splicing modulators may have therapeutic value in the treatment of splicing factor mutant myeloid malignancies.

  7. Myelodysplastic Syndrome and Histone Deacetylase Inhibitors: “To Be or Not to Be Acetylated”?

    Directory of Open Access Journals (Sweden)

    Sebastian Stintzing

    2011-01-01

    Full Text Available Myelodysplastic syndrome (MDS represents a heterogeneous group of diseases with clonal proliferation, bone marrow failure and increasing risk of transformation into an acute myeloid leukaemia. Structured guidelines are developed for selective therapy based on prognostic subgroups, age, and performance status. Although many driving forces of disease phenotype and biology are described, the complete and possibly interacting pathogenetic pathways still remain unclear. Epigenetic investigations of cancer and haematologic diseases like MDS give new insights into the pathogenesis of this complex disease. Modifications of DNA or histones via methylation or acetylation lead to gene silencing and altered physiology relevant for MDS. First clinical trials give evidence that patients with MDS could benefit from epigenetic treatment with, for example, DNA methyl transferase inhibitors (DNMTi or histone deacetylase inhibitors (HDACi. Nevertheless, many issues of HDACi remain incompletely understood and pose clinical and translational challenges. In this paper, major aspects of MDS, MDS-associated epigenetics and the potential use of HDACi are discussed.

  8. Differences in Community and Academic Practice Patterns for Newly Diagnosed Myelodysplastic Syndromes (MDS) Patients

    Science.gov (United States)

    Pease, Daniel F.; Ross, Julie A.; Poynter, Jenny N.; Nguyen, Phuong L.; Hirsch, Betsy; Cioc, Adina; Roesler, Michelle A.; Warlick, Erica D.

    2015-01-01

    Purpose The heterogeneous nature of myelodysplastic syndromes (MDS) complicates therapeutic decision making, particularly for newly diagnosed disease. Factors impacting the treatment plan in this early period of disease course are poorly defined. This study determines whether therapeutic choices for newly diagnosed MDS are associated with location of treatment (community or academic), prognostic risk category, and patient age. Methods The Adults in Minnesota with Myelodysplastic Syndromes (AIMMS) database was utilized in this statewide, prospective population-based study conducted by the University of Minnesota (UMN), Mayo Clinic, and Minnesota Department of Health. Adult (age 20+ years) cases of MDS newly diagnosed starting in April 2010 were invited to participate. This analysis includes patients enrolled during the first study year with one-year follow-up data. Treatment choices (supportive, active, and transplant) were stratified by the international prognostic scoring system (IPSS) and the revised-IPSS (IPSS-R), then separated into groups by location of care and age (<65 or 65+ years). Academic-based care was any contact with the UMN and Mayo Clinic; community-based care was all other clinical sites. Results Stratification by IPSS and IPSS-R showed supportive care decreased and active care increased with advancing risk categories (p <0.0001). Comparing treatment setting, community-based care had 77% supportive and 23% active treatment; academic-based care was 36% supportive, 41% active, and 23% transplant (p <0.0001). By age groups, patients <65 years with intermediate, high, or very high risk disease by IPSS-R received 97% active care/transplant, compared to only 52% of patients age 65+. Conclusions Younger patients and those treated at academic centers had a more aggressive treatment approach. Whether these treatment differences convey improved disease control and mortality, and therefore should be extended more frequently to older and community

  9. Myelodysplastic syndromes.

    Science.gov (United States)

    Koeffler, H P

    1996-04-01

    These two issues of the Seminars in Hematology will provide the physician the necessary knowledge to help make sense of this somewhat confusing array of diseases. The subdivisions of MDS reflect the precision of our techniques of dissection, with morphological and histochemical analyses forming the foundation to identify and subdivide MDS. Although steady refinement has occurred over the last half-century, the basic morphologic technique is unchanged. Cytogenetic analysis, which has been possible since the 1960s and 1970s, should be done at least at initial presentation in all patients to provide refinement of diagnosis and prognosis. FISH is not, at this time, useful as a screening technique. Although the 1990s is an era of rapidly growing knowledge and technical abilities in molecular biology, the use of these techniques in MDS is in its infancy. Very few genes have been identified which are altered in MDS, although many must exist. The molecular assays continue to be cumbersome and impractical to use in the clinical laboratory and remain the domain of the research scientist. Nevertheless, in the future, molecular biology will enable the internist to give each individual a clearer diagnosis and prognosis and may even provide targetted therapies of patients with MDS. At this time the center of management is good supportive care. Some patients, however, will benefit from special interventions, which include the use of growth factors, BMT, and in selected patients, aggressive chemotherapy. Induction of differentiation of the abnormal hematopoietic clone remains only a dream, although some of the differentiation agents may have applicability for their ability to induce apoptosis and prevent growth of the MDS clone of cells. Many of the major advances in our knowledge of cancer developed through the study of hematopoietic malignancy. A lot of these advances are due to the ease of obtaining the abnormal cells. MDS provides an excellent model for studying the progression of cells from their normal to preneoplastic and fully transformed states. A lucid understanding of this progression can form the paradigm for basic science to study neoplastic progression, and the molecular biology techniques used for these studies will be the basic tools used by hematologists and oncologists in the future.

  10. Incidence of ATRX mutations in myelodysplastic syndromes, the value of microcytosis.

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    Herbaux, Charles; Duployez, Nicolas; Badens, Catherine; Poret, Nicolas; Gardin, Claude; Decamp, Mathieu; Eclache, Virginie; Daliphard, Sylvie; Murati, Anne; Cony-Makhoul, Pascale; Cheze, Stéphane; Beve, Blandine; Lacoste, Caroline; Prebet, Thomas; Hunault-Berger, Mathilde; Maloisel, Frédéric; Renneville, Aline; Figeac, Martin; Stamatoullas-Bastard, Aspasia; Bastard, Christian; Fenaux, Pierre; Preudhomme, Claude; Rose, Christian

    2015-08-01

    Acquired α-thalassemia myelodysplastic syndrome (MDS) (ATMDS) is an acquired syndrome characterized by a somatic point mutation or splicing defect in the ATRX gene in patients with myeloid disorders, primarily MDS. In a large MDS patient series, the incidence of ATMDS was below 0.5%. But no large series has yet assessed the incidence of ATMDS in microcytic MDS. In this study, we focused on patients with MDS and unexplained microcytosis, which was defined as absence of iron deficiency, inflammatory disease, or history of inherited hemoglobinopathy. Our data confirm the low frequency of ATRX mutations in MDS: 0% in an unselected clinical trial cohort of 80 low risk MDS, 0.2-0.8% in a multicenter registry of 2,980 MDS and 43% of MDS with unexplained microcytosis in this same registry. In addition, we reported four novel mutations of the ATRX gene in ATMDS. This study further determines the frequency of ATRX mutations and highlights the importance of microcytosis to detect ATRX mutations within MDS patients.

  11. Chromothripsis: Basis of a Concurrent Unusual Association between Myelodysplastic Syndrome and Primary Ciliary Dyskinesia

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    Abhinav Agrawal

    2014-01-01

    Full Text Available A 20 year old male was initially diagnosed suffering from Primary ciliary dyskinesia with symptoms of bronchiectasis, severe frontal, maxillary and ethmoid sinus disease. At the age of 20, the patient was also diagnosed with Myelodysplastic syndrome requiring Bone marrow transplant due to the advanced stage at time of presentation. Primary ciliary dyskinesia and Myelodsyplastic syndrome are both rare clinical conditions found in the general population, especially in young adults. This rare combination of disorders has never been reported in literature to the best of the author’s knowledge. The presence of an advanced cancer and a genetic abnormality due to two deletions occurring in two arms of the same chromosome can be explained on the base of chromothripsis. A number of evidences have been published in the literature, about multiple deletions in chromosome 5 and advanced stages of MDS being associated with chromothripsis however this is the first case report on two deletions in chromosome 7 giving rise to two different clinical entities requiring multiple modes of management.

  12. Familial Myelodysplastic/Acute Leukemia Syndromes—Myeloid Neoplasms with Germline Predisposition

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    Baptista, Renata Lyrio Rafael; dos Santos, Anna Cláudia Evangelista; Gutiyama, Luciana Mayumi; Solza, Cristiana; Zalcberg, Ilana Renault

    2017-01-01

    Although most cases of myeloid neoplasms are sporadic, a small subset has been associated with germline mutations. The 2016 revision of the World Health Organization classification included these cases in a myeloid neoplasm group with a predisposing germline mutational background. These patients must have a different management and their families should get genetic counseling. Cases identification and outline of the major known syndromes characteristics will be discussed in this text. PMID:28955657

  13. Síndrome mielodisplásica na infância Myelodysplastic syndromes in childhood

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    Luiz F. Lopes

    2006-09-01

    ,7%. Quanto à evolução clínica dos pacientes encontramos: óbito em 54,8% dos casos, remissão espontânea em 5,4% e 16,1% encontrava-se em tratamento conservador. Infecções em pacientes com SMD e naqueles que sofreram transformação leucêmica foram as causas mais freqüentes de óbito (58,8%. Propomos também neste artigo uma abordagem de diagnóstico em genética e biologia molecular voltada para os casos infantis assim como uma revisão de literatura sobre transplante de medula óssea para os casos pediátricos, além de outros aspectos que diferem da abordagem feita para pacientes adultos.The Brazilian Cooperative Study Group on Pediatric Myelodysplastic Syndromes (GCB-SMD-PED started in January 1997 with the goal of studying under 18-year-old patients with MDS or suspected MDS from all over the country. Some primary or secondary disorders are incorrectly called MDS. Because of this the GCB-SMD-PED is a referral group in the country to review and also to give diagnostic support (morphology, genetics, etc.. Some groups still use the FAB classification but two new classifications for pediatric cases have been published: one from the Sick Children's Hospital, University of Toronto, Canada the "CCC Classification" (category, cytology and cytogenetic, and the WHO pediatric classification by Hasle et al. Our proposal here is to present data from the 173 pediatric cases which were referred to the GCB-SMD-PED from 15 states (41 centers. From 1983 to 1997, 51 pediatric cases were registered as retrospective cases and from January 1998 to February 2003, 122 prospective cases were registered. From these 173 cases, 93 where confirmed as MDS. In 36.5% of them there was a transformation into acute leukemia with 82.3% as AML and 17.7% as ALL. The follow up showed that 54.8% died, 5.4% had spontaneous remission and 16.1% were in treatment with no chemotherapy (just transfusion or conservative approach. Infections were the primary cause of death (58.8%. Additionally, in this

  14. Low-dose decitabine combined with fractional allogeneic hematopoietic stem cell transfusion for treatment of elderly patients with acute myeloid leukemia transformed from myelodysplastic syndrome:a report of 2 cases%小剂量地西他滨联合异基因造血干细胞分次输注治疗老年骨髓增生异常综合征转急性髓性白血病2例报告

    Institute of Scientific and Technical Information of China (English)

    李云双; 陈永升; 聂伟业; 黄琴; 孔祥敬; 尹晓林

    2015-01-01

    Objective To explore the efficay of low-dose decitabine combined with fractional allogeneic hematopoietic stem cell transfusion( micro transplantation) for treatment of elderly patients with acute myeloid leukemia transformed from myelodysplastic syndrome ( MDS-AML) .Methods Two patients diagnosed as MDS-AML were treated with chemotherapy regimen of low-dose decitabine or decitabine combined with CAG(cytosine arabinoside+aclacinomycin) and micro transplantation.The donors were children of patients with human leukocyte antigen semi-matched.Peripheral blood stem cells from the donors were mobilized with granulocyte colony-stimulating factor and then collected. Patients transfused PBSC about 36 hours after the chemotherapy finished.The disease status,platelet levels,survival timeand side effects were observed.Re sults Two cases did not achieve complete response.The survival times of Case 1 and Case 2 were 2 months and 4 months respectively. The platelet level in Case 1 increased remarkably after treatment,and reached to the maximal level of 59 ×109/L.No platelet transfusion was observed in Case 1.In Case 2,the interval of platelet transfusion was prolonged,and the patient was gradually independent on platelet transfusions. No graft-versus-host disease occurred in the two patients.Conclusion For elderly patients with MDS-AML,low-dose decitabine combined with micro transplantation can not cure the disease,but can prolong the survival time,increase the level of platelet and improve the quality of life.%目的 观察小剂量地西他滨联合异基因造血干细胞分次输注(微移植)治疗老年骨髓增生异常综合征转急性髓性白血病( MDS-AML)的疗效. 方法 对2例确诊为MDS-AML患者分别予小剂量地西他滨或地西他滨联合CAG方案(阿糖胞苷+阿克拉霉素)化疗加微移植治疗,供者为人类白细胞抗原半相合的患者子女,采集重组人粒细胞集落刺激因子动员后的供者外周血

  15. Prognostic value of isocitrate dehydrogenase mutations in myelodysplastic syndromes: a retrospective cohort study and meta-analysis.

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    Jie Jin

    Full Text Available Recent genomic sequencing efforts have identified a number of recurrent mutations in myelodysplastic syndromes (MDS that may contribute to disease progression and overall survival, including mutations in isocitrate dehydrogenases 1 and 2 (IDH1 and IDH2.Pretreatment bone marrow (BM samples were acquired from mononuclear cells in 146 adult patients with de novo MDS from January 2006 to June 2013. Polymerase chain reaction (PCR and direct sequencing were performed on exon 4 of IDH1/2 genes and mutation status was correlated with overall survival (OS and leukemia-free survival (LFS. We then performed a meta-analysis combining previously published and current studies to explore the effect of IDH mutations on OS and LFS in MDS.In our study, somatic mutations of either IDH gene were discovered in 11 MDS patients (7.53% and were significantly correlated with poorer OS (P = 0.007. IDH mutations were specifically associated with a poorer OS in the intermediate-1 risk group by the International Prognostic Scoring System (IPSS (P = 0.039. In addition, we discovered decitabine achieved a better therapeutic effect compared to other treatments in IDH mutation-positive patients (P = 0.023. We identified six previous studies of IDH mutations in MDS. A meta-analysis of these studies included 111 MDS patients IDH mutations and 1671 MDS patients with wild-type IDH1/2. The hazard ratios (HRs of OS and LFS for patients with IDH mutations were 1.62 (95% CI, 1.27-2.09 and 2.21 (95% CI, 1.48-3.30, respectively.The results from our study and the meta-analysis provide firm evidence that IDH mutations are significantly associated with poorer clinical outcomes in MDS. Identification of IDH mutations may be pivotal for better risk stratification in MDS patients and improving IPSS score. Additionally, hypomethylating agents may be an effective treatment option for MDS patients with IDH mutations.

  16. Current State of the Art: Management of Higher Risk Myelodysplastic Syndromes.

    Science.gov (United States)

    Komrokji, Rami S

    2016-08-01

    The higher risk myelodysplastic syndrome (MDS) patients, defined by the International Prognostic Scoring System (IPSS) as intermediate-2 or high-risk groups, compromise a third of MDS patients who have an expected survival of less than 1.5 years. Our ability to better define higher risk MDS improved with the proposal of new clinical risk models such as the revised IPSS and by integration of molecular data, including somatic gene mutations. Allogeneic hematopoietic stem-cell transplantation (AHSCT) remains the only curative option. In higher risk MDS patients, proceeding early with AHSCT is associated with maximum survival gain. The decision to pursue AHSCT is individualized according to disease risk, comorbidities, and functional status. The role of therapy before AHSCT remains controversial, and the role of post-AHSCT maintenance is evolving. Hypomethylating agents are the only medications that alter the natural history of the disease. Azacitidine is the only drug reported to improve overall survival in higher risk MDS patients. Appropriate use and assessment of response is key for assuring patients benefit of such limited options. Treatment after failure of hypomethylating agents is an unmet need. The role of detectable somatic gene mutations in prognosis and tailoring therapy continue to emerge.

  17. Automated screening for myelodysplastic syndromes through analysis of complete blood count and cell population data parameters.

    Science.gov (United States)

    Raess, Philipp W; van de Geijn, Gert-Jan M; Njo, Tjin L; Klop, Boudewijn; Sukhachev, Dmitry; Wertheim, Gerald; McAleer, Tom; Master, Stephen R; Bagg, Adam

    2014-04-01

    The diagnosis of myelodysplastic syndromes (MDS) requires a high clinical index of suspicion to prompt bone marrow studies as well as subjective assessment of dysplastic morphology. We sought to determine if data collected by automated hematology analyzers during complete blood count (CBC) analysis might help to identify MDS in a routine clinical setting. We collected CBC parameters (including those for research use only and cell population data) and demographic information in a large (>5,000), unselected sequential cohort of outpatients. The cohort was divided into independent training and test groups to develop and validate a random forest classifier that identifies MDS. The classifier effectively identified MDS and had a receiver operating characteristic area under the curve (AUC) of 0.942. Platelet distribution width and the standard deviation of red blood cell distribution width were the most discriminating variables within the classifier. Additionally, a similar classifier was validated with an additional, independent set of >200 patients from a second institution with an AUC of 0.93. This retrospective study demonstrates the feasibility of identifying MDS in an unselected outpatient population using data routinely collected during CBC analysis with a classifier that has been validated using two independent data sets from different institutions.

  18. Variants of the Mitochondrial Displacement Loop in Patients with Myelodysplastic Syndromes

    Institute of Scientific and Technical Information of China (English)

    Xiaojing Hu; Yaqin Cong; Conggao Xu; Jinbo Feng; Yujie Jiang; Hong Jin

    2008-01-01

    OBJECTIVE Some mtDNA mutations have been detected in patients with myelodysplastic syndromes (MDSs).As the noncoding region of mitochondria,the displacement loop (D-loop)region of mtDNA contains important elements for mtDNA replication and transcription.Variants of the D-loop region were found to be related to the cause of many diseases.The aim of our study was to investigate mutations and single nucleotide polymorphisms in the D-loop region of MDS patients.METHODS The mutations and SNPs in the hypervariable regions of the D-loop were detected by direct sequencing in MDS patients and normal controls.RESULTS Sixty-four SNPs were found in the D-loop region in MDS cases and control group.Among the SNPs,the 16,189 variant (T > C transition) was found to have an increased frequency in the MDS group (P = 0.044).However,no mutations were detected in neither group.CONCLUSION Our data provide evidence for a highly polymorphic D-loop region in patients with MDS,but do not support the presence of mutations in the mitochondrial D-loop region in MDS cases.The mtDNA T16,189C variant,which may be a functional variant,is associated with increased susceptibility to a MDS.

  19. Endothelial Progenitor Cell Dysfunction in Myelodysplastic Syndromes: Possible Contribution of a Defective Vascular Niche to Myelodysplasia

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    Luciana Teofili

    2015-05-01

    Full Text Available We set a model to replicate the vascular bone marrow niche by using endothelial colony forming cells (ECFCs, and we used it to explore the vascular niche function in patients with low-risk myelodysplastic syndromes (MDS. Overall, we investigated 56 patients and we observed higher levels of ECFCs in MDS than in healthy controls; moreover, MDS ECFCs were found variably hypermethylated for p15INK4b DAPK1, CDH1, or SOCS1. MDS ECFCs exhibited a marked adhesive capacity to normal mononuclear cells. When normal CD34+ cells were co-cultured with MDS ECFCs, they generated significant lower amounts of CD11b+ and CD41+ cells than in co-culture with normal ECFCs. At gene expression profile, several genes involved in cell adhesion were upregulated in MDS ECFCs, while several members of the Wingless and int (Wnt pathways were underexpressed. Furthermore, at miRNA expression profile, MDS ECFCs hypo-expressed various miRNAs involved in Wnt pathway regulation. The addition of Wnt3A reduced the expression of intercellular cell adhesion molecule-1 on MDS ECFCs and restored the defective expression of markers of differentiation. Overall, our data demonstrate that in low-risk MDS, ECFCs exhibit various primary abnormalities, including putative MDS signatures, and suggest the possible contribution of the vascular niche dysfunction to myelodysplasia.

  20. TP53 mutations predict decitabine-induced complete responses in patients with myelodysplastic syndromes.

    Science.gov (United States)

    Chang, Chun-Kang; Zhao, You-Shan; Xu, Feng; Guo, Juan; Zhang, Zheng; He, Qi; Wu, Dong; Wu, Ling-Yun; Su, Ji-Ying; Song, Lu-Xi; Xiao, Chao; Li, Xiao

    2017-02-01

    To identify the molecular signatures that predict responses to decitabine (DAC), we examined baseline gene mutations (28 target genes) in 109 myelodysplastic syndrome (MDS) patients at diagnosis. We determined that TP53 mutations predicted complete response (CR), as 10 of 15 patients (66·7%) who possessed TP53 mutations achieved a CR. Univariate and multivariate analyses showed that TP53 mutations are the only molecular signatures predictive of a CR to DAC in MDS. Among the ten patients with TP53 mutations who achieved a CR, nine presented with complex karyotypes due to abnormalities involving chromosome 5 and/or chromosome 7, and eight possessed monosomies. Although TP53 mutations were associated with a higher frequency of CRs, they were not associated with improved survival. Poor outcomes were attributed to early relapses and transformation to acute myeloid leukaemia after CR. Post-DAC therapy patient gene mutation profiles showed that most CR patients exhibited fewer gene mutations after achieving a CR. It seems that suppression of these gene mutations was facilitated by DAC, resulting in a CR. In summary, TP53 mutations might predict decitabine-induced complete responses in patients with MDS. DAC-induced responses may result from partial suppression of malignant clones containing mutated TP53 genes.

  1. Optimal timing of allogeneic hematopoietic stem cell transplantation in patients with myelodysplastic syndrome.

    Science.gov (United States)

    Alessandrino, Emilio Paolo; Porta, Matteo G Della; Malcovati, Luca; Jackson, Christopher H; Pascutto, Cristiana; Bacigalupo, Andrea; Teresa van Lint, Maria; Falda, Michele; Bernardi, Massimo; Onida, Francesco; Guidi, Stefano; Iori, Anna Paola; Cerretti, Raffaella; Marenco, Paola; Pioltelli, Pietro; Angelucci, Emanuele; Oneto, Rosi; Ripamonti, Francesco; Rambaldi, Alessandro; Bosi, Alberto; Cazzola, Mario

    2013-07-01

    Allogeneic hematopoietic stem cell transplantation (HSCT) represents the only curative treatment for patients with myelodysplastic syndrome (MDS), but involves non-negligible morbidity and mortality. Registry studies have shown that advanced disease stage at transplantation is associated with inferior overall survival. To define the optimal timing of allogeneic HSCT, we carried out a decision analysis by studying 660 patients who received best supportive care and 449 subjects who underwent transplantation. Risk assessment was based on both the International Prognostic Scoring System (IPSS) and the World Health Organization classification-based Prognostic Scoring System (WPSS). We used a continuous-time multistate Markov model to describe the natural history of disease and evaluate the effect of allogeneic HSCT on survival. This model estimated life expectancy from diagnosis according to treatment policy at different risk stages. Relative to supportive care, estimated life expectancy increased when transplantation was delayed from the initial stages until progression to intermediate-1 IPSS-risk or to intermediate WPSS-risk stage, and then decreased for higher risks. Modeling decision analysis on WPSS versus IPSS allowed better estimation of the optimal timing of transplantation. These observations indicate that allogeneic HSCT offers optimal survival benefits when the procedure is performed before MDS patients progress to advanced disease stages.

  2. Potential Relationship between Inadequate Response to DNA Damage and Development of Myelodysplastic Syndrome

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    Ting Zhou

    2015-01-01

    Full Text Available Hematopoietic stem cells (HSCs are responsible for the continuous regeneration of all types of blood cells, including themselves. To ensure the functional and genomic integrity of blood tissue, a network of regulatory pathways tightly controls the proliferative status of HSCs. Nevertheless, normal HSC aging is associated with a noticeable decline in regenerative potential and possible changes in other functions. Myelodysplastic syndrome (MDS is an age-associated hematopoietic malignancy, characterized by abnormal blood cell maturation and a high propensity for leukemic transformation. It is furthermore thought to originate in a HSC and to be associated with the accrual of multiple genetic and epigenetic aberrations. This raises the question whether MDS is, in part, related to an inability to adequately cope with DNA damage. Here we discuss the various components of the cellular response to DNA damage. For each component, we evaluate related studies that may shed light on a potential relationship between MDS development and aberrant DNA damage response/repair.

  3. Therapy related myelodysplastic syndrome: A case report and review of literature

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    Smita Sonawane

    2011-01-01

    Full Text Available Therapy related myeloid neoplasm is directly related to previous cytotoxic chemotherapy or radiation therapy. We present a 47-year-old lady who developed therapy related myelodysplastic syndrome (MDS 2.5 years after she received four cycles of chemotherapy and local radiation therapy for carcinoma breast. She presented with bicytopenia with trilineage dyspoiesis in the peripheral blood, bone marrow aspirate and biopsy. Fluorescent in-situ hybridization studies did not reveal any of the common abnormalities associated with MDS. A diagnosis of therapy related MDS was rendered. Different studies have shown that patients treated with alkylating agents and ionizing radiation present as MDS with a latent period of 3-10 years. Our patient developed MDS within 2.5 years of starting chemotherapy and radiotherapy and did not reveal any of the conventional cytogenetic abnormalities. It highlights the importance of simple tests like a complete blood count and peripheral blood smear examination in follow-up of the patients treated with chemotherapy.

  4. Lenalidomide: a brief review of its therapeutic potential in myelodysplastic syndromes

    Science.gov (United States)

    Giagounidis, Aristoteles A N; Germing, Ulrich; Haase, Sabine; Aul, Carlo

    2007-01-01

    Lenalidomide is a novel thalidomide analogue with enhanced immunomodulatory and antiangiogenic action lacking most of the typical thalidomide-associated adverse events. In myelodysplastic syndromes (MDS), it has been used primarily in the IPSS low- and intermediate-1 risk setting. Several trials have demonstrated its potential to lead to both erythroid and cytogenetic responses in these disease groups. In a clinical trial of patients with a del(5q) chromosomal abnormality, lenalidomide treatment resulted in red blood cell (RBC) transfusion independence in 67% of patients. Moreover, 45% of patients achieved a complete cytogenetic remission, and 28% achieved a minor cytogenetic remission. This result was independent of karyotype complexity. Lenalidomide might also induce long-term remissions in del(5q) patients with an elevated medullary blast count. In non-del(5q) patients, 43% of patients with confirmed low- and intermediate-1 risk achieved transfusion independence or a reduction of at least 50% of pre-treatment RBC transfusion levels. Adverse events are common but manageable and include neutropenia and thrombocytopenia, pruritus, rash, diarrhea, and others. Lenalidomide will prove an essential part in the armamentarium of MDS therapeutics. Combination therapies with cytokines, demethylating agents, tyrosine kinase inhibitors, or chemotherapy are being investigated and may show additional benefit in both low- and high risk MDS. PMID:18472976

  5. Lenalidomide for myelodysplastic syndromes with del(5q): how long should it last?

    Science.gov (United States)

    Vozella, Federico; Latagliata, Roberto; Carmosino, Ida; Volpicelli, Paola; Montagna, Chiara; Romano, Angela; Roberto, Amanda; Finsinger, Paola; Mancini, Marco; Breccia, Massimo; Oliva, Esther; Oliva, Esther

    2015-03-01

    Lenalidomide induces in patients with myelodysplastic syndrome (MDS) and del(5q) erythroid and cytogenetic response rates as high as 75% and 50%, respectively. It is still unclear, however, how long lenalidomide treatment should be continued and whether or not the drug could be interrupted. To assess the feasibility of lenalidomide discontinuation, we revised a cohort of 16 low-risk MDS patients with del(5q) treated at our institute in a phase II multicentric Italian study. Among the 12 responding patients, four discontinued lenalidomide while in complete response. All four patients needed during treatment a permanent lenalidomide reduction from 10 to 5 mg/day because of haematological toxicity (three patients) or grade 3 muscular and bone pain (one patient). At lenalidomide discontinuation after 16, 20, 27 and 20 months from the start, respectively, all four patients were in complete hematologic response and three forth in complete cytogenetic response. Three patients are still in response after 36, 30 and 20 months from lenalidomide discontinuation, respectively: The remaining patient relapsed after 20 months, and she is now receiving a new course of lenalidomide. In conclusion, long-lasting remissions are achievable in MDS patients with del(5q) in complete response after lenalidomide discontinuation.

  6. [Clinical analysis in a cohort of 102 patients with myelodysplastic syndrome characterized by erythroid hyperplasia].

    Science.gov (United States)

    Yu, Y; Sun, A N; Chen, S N; Wang, Q R; Zhang, T T; Wu, D P

    2017-01-01

    Objective: To investigate the clinical and laboratorial characteristics of patients with myelodysplastic syndrome (MDS) and erythroid hyperplasia. Methods: MDS patients whose bone marrow was hypercellular with erythroid lineage more than 50% and blasts account for less than 20% of non-erythroid cells were enrolled in this study. The ratio of mature erythrocytes to nucleated erythrocytes was no more than 20, namely MDS patients with erythroid hyperplasia(MDS-E). The retrospective analysis comprised 102 patients with MDS-E from the First Affiliated Hospital of Suzhou University. Clinical characteristics, karyotype, and the prognostic significance of erythroid hyperplasia were evaluated. Results: A total of 48 MDS-E patients (47.1%) presented a variety of cytogenetic abnormalities. The most frequently involved chromosomes were chromosome 8 (39.5% of all abnormal karyotypes), chromosome 7 (22.9%), followed by chromosome 5 (18.8%), chromosome 1 (16.7%) and chromosome 20 (16.7%). Hemoglobin (Hb) level affected the prognosis by survival analysis. The overall survival (OS) of MDS-E patients with Hb equal or more than 70 g/L was longer than that of patients less than 70 g/L (Phyperplasia in bone marrow did not impact on prognosis (P=0.187). Conclusions: Compared with previous reports of MDS patients, MDS-E patients have higher level of erythroid hyperplasia, more common erythroid dyshematopoiesis, more frequent 8 and 1 chromosome abnormalities. The degree of erythroid hyperplasia is not correlated with prognosis. Allogeneic hematopoietic stem cell transplantation improves the prognosis.

  7. Genetics and epigenetics of myelodysplastic syndromes and response to drug therapy: new insights

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    Saeid Shahrabi

    2016-12-01

    Full Text Available Myelodysplastic syndromes (MDS are a heterogeneous group of hematologic neoplasms ocurring mostly in the elderly. The clinical outcome of MDS patients is still poor despite progress in treatment approaches. About 90% of patients harbor at least one somatic mutation. This review aimed to assess the potential of molecular abnormalities in understanding pathogenesis, prognosis, diagnosis and in guiding choice of proper therapy in MDS patients. Papers related to this topic from 2000 to 2016 in PubMed and Scopus databases were searched and studied. The most common molecular abnormalities were TET2, ASXL1 as well as molecules involved in spliceosome machinery (U2AF1, SRSF2 and SF3B1. Patients with defects in TET2 molecule show better response to treatment with azacitidine. IDH and DNMT3A mutations are associated with a good response to decitabine therapy. In addition, patients with del5q subtype harboring TP53 mutation do not show a good response to lenalidomide therapy. In general, the results of this study show that molecular abnormalities can be associated with the occurrence of a specific morphological phenotype in patients. Therefore, considering the morphology of patients, different gene profiling methods can be selected to choice the most appropriate therapeutic measure in these patients in addition to faster and more cost-effective diagnosis of molecular abnormalities.

  8. [Cold autoimmune hemolytic anemia complicated with relapsed myelodysplastic syndrome after allogeneic hematopoietic cell transplantation].

    Science.gov (United States)

    Okamura, Hiroshi; Nakane, Takahiko; Fujino, Keizo; Koh, Shiro; Yoshimura, Takuro; Nishimoto, Mitsutaka; Hayashi, Yoshiki; Koh, Hideo; Nakao, Yoshitaka; Nakamae, Hirohisa; Hino, Masayuki

    2015-04-01

    Myelodysplastic syndrome (MDS) is known to often be complicated by a range of autoimmune diseases. We herein present a case with MDS complicated by cold autoimmune hemolytic anemia (cold AIHA). The patient was a 51-year-old woman. She was diagnosed with MDS (refractory cytopenia with multilineage dysplasia) in May 2009. In January 2010, she underwent unrelated allogeneic bone marrow transplantation but was re-admitted in October 2010 for treatment of relapsed MDS. Despite daily transfusions of red blood cells, her anemia failed to improve. Her laboratory examinations showed a low haptoglobin level and elevation of indirect bilirubin and LDH. The direct Coombs test was positive at a low and at room temperature and cold agglutinin was negative. After confirming the diagnosis of cold AIHA, all transfusion fluids were warmed but her anemia still failed to improve. In addition to the warmed transfusion fluids, we administered corticosteroids, immunosuppressive agents and high-dose intravenous immunoglobulin infusions. This management strategy ameliorated the patient's hemolytic anemia. To our knowledge, MDS cases complicated by cold AIHA are rare. Our patient thus provides a valuable contribution to medical knowledge.

  9. [Hematologic response predictor factors in adults with myelodysplastic syndromes (SMD) treated with cyclosporin A (CSA)].

    Science.gov (United States)

    Zamora-Pérez, Elia; López-Karpovitch, Xavier

    2015-01-01

    Myelodysplastic syndromes (MDS) are clonal diseases of hematopoietic cells. The International Prognostic Scoring System (IPSS) is the risk scale most employed in MDS. Cyclosporin A (CsA) has been used in the treatment of cytopenias in MDS. To evaluate hematologic response and identify response predictive factors in adults with MDS treated with CsA. Patients with MDS diagnosed according World Health Organization (WHO) classification were recruited from January 1997 to June 2012. All patients were classified with IPSS, IPSS revised (IPSS-R),WHO Prognostic Scoring System (WPSS), and WPSS revised (WPSS-R) risk scales. Cyclosporin A was administered orally at a dose of 5 mg/kg/day. Hematologic response was evaluated following the International Working Group for MDS (2006 version) criteria. Inclusion criteria were met by 32 patients. Median age was 56.5 years, with a median follow-up of 3.1 years. Hematologic response was 56.2% and erythrocyte independence transfusion was found in 42.9% of patients. Age,hemoglobin level, and WPSS at diagnosis were independent predictive factors for CsA response. Survival was longer in responder than in nonresponder CsA patients (p=0.06). Cyclosporin A induced hematologic response in >50% of patients with MDS aged <57 years, with Hb<8 g/dl and low WPSS at diagnosis.

  10. Case Report: Myelodysplastic syndrome- associated myeloid sarcoma: an unusual clinical presentation of a rare disease.

    Science.gov (United States)

    Horvath, Emoke; Demian, Smaranda; Nagy, Elod

    2016-01-01

    Myeloid sarcoma results from the extramedullary homing and proliferation of immature myeloid precursors. We present the timeline, events and diagnostic pitfalls related to a 66 year-old male patient's case, admitted to the Hematology Clinic for pancytopenia, fever, weight loss and fatigue. The severe cytopenia and the few blasts observed in his blood smear indicated a bone marrow biopsy. The bone marrow showed hypercellularity and multilineage dysplasia with the presence of 15% myeloblasts. After the biopsy, he promptly developed paraplegia and nuclear magnetic resonance revealed an epidural tumour which was then resected.In the epidural tumour mass blast-like, round cells were observed with a complex immunophenotype, characterized by myeloperoxidase, CD117, CD15, CD99, leucocyte common antigen positivity and a high Ki-67 proliferation index. Considering the main differential diagnostic issues, the final diagnosis was stated as myelodysplastic syndrome-associated myeloid sarcoma. The prognosis was unfavourable, the bone marrow was quickly invaded by proliferating blast cells, and despite chemotherapy attempts, the patient died.

  11. Decitabine of reduced dosage in Chinese patients with myelodysplastic syndrome: a retrospective analysis.

    Directory of Open Access Journals (Sweden)

    Xiao Li

    Full Text Available Decitabine has been approved for the treatment of all subtypes of myelodysplastic syndrome (MDS. However, the optimal regimen for decitabine treatment is not well established. In this study, an observational, retrospective and multi-center analysis was performed to explore the decitabine schedule for the treatment of MDS. A total of 79 patients received reduced dosage decitabine treatment (15 mg/M2/day intravenously for five consecutive days every four weeks. Fifty-three out of the 79 patients were defined as intermediate-2/high risk by international prognostic scoring system (IPSS risk category. 67.1% of MDS patients achieved treatment response including complete response (CR (n = 23, Partial response (n = 1, marrow CR (mCR with hematological improvement (HI (n = 11, mCR without HI (n = 11 and HI alone (n = 7 with a median of 4 courses (range 1-11. The median overall survival (OS was 18.0 months. The median OS was 22.0, 17.0 and 12.0 months in the patients with CR, those with other response, and those without response, respectively. In addition, this regimen contributed to zero therapy-related death and punctual course delivery, although III or IV grade of cytopenia was frequently observed. In conclusion, the 15 mg/M2/d×5 day decitabine regimen was effective and safe for Chinese MDS patients with IPSS score of 0.5 or higher.

  12. Decitabine treatment could ameliorate primary iron-overload in myelodysplastic syndrome patients.

    Science.gov (United States)

    Shucheng, Gu; Chunkang, Chang; Youshan, Zhao; Juan, Guo; Chengming, Fei; Xi, Zhang; Chao, Xiao; Xiao, Li

    2015-04-01

    In order to research how does hypomethylating agents ameliorate iron metabolism in myelodysplastic syndrome (MDS), we performed methylation-specific, polymerase chain reaction (MSP), bisulfate genomic sequencing polymerase chain reaction (BSP), quantitative real-time PCR and western blot of hemojuvelin (HJV) and ELISA assay for hepcidin before and after demethylating therapy (decitabine) to determine whether the change of HJV methylation status would have an influence on hepcidin expression. Eleven of 22 MDS patients achieved CR or PR according to IWG criteria (50%). HJV mRNA was induced in decitabine responders (p = .006 comparing pre/post decitabine treatment) but not in non-responders (p = .121). Similarly, hepcidin serum expression increased from 320.77 ± 34.8 μg/L to 366.77 ± 21.90 μg/L (p = .012) in responders but did not significantly change in non-responders (p = .058), while no difference of adjusted serum ferritin (ASF) was found. In conclusion, hypermethylation of HJV promoter region could silence the gene expression and demethylating therapy might ameliorate iron-overload through HJV demethylation.

  13. Maintenance treatment with azacytidine for patients with high-risk myelodysplastic syndromes (MDS) or acute myeloid leukaemia following MDS in complete remission after induction chemotherapy

    DEFF Research Database (Denmark)

    Grövdal, Michael; Karimi, Mohsen; Khan, Rasheed

    2010-01-01

    This prospective Phase II study is the first to assess the feasibility and efficacy of maintenance 5-azacytidine for older patients with high-risk myelodysplastic syndrome (MDS), chronic myelomonocytic leukaemia and MDS-acute myeloid leukaemia syndromes in complete remission (CR) after induction...

  14. Cardiac iron overload in chronically transfused patients with thalassemia, sickle cell anemia, or myelodysplastic syndrome.

    Science.gov (United States)

    de Montalembert, Mariane; Ribeil, Jean-Antoine; Brousse, Valentine; Guerci-Bresler, Agnes; Stamatoullas, Aspasia; Vannier, Jean-Pierre; Dumesnil, Cécile; Lahary, Agnès; Touati, Mohamed; Bouabdallah, Krimo; Cavazzana, Marina; Chauzit, Emmanuelle; Baptiste, Amandine; Lefebvre, Thibaud; Puy, Hervé; Elie, Caroline; Karim, Zoubida; Ernst, Olivier; Rose, Christian

    2017-01-01

    The risk and clinical significance of cardiac iron overload due to chronic transfusion varies with the underlying disease. Cardiac iron overload shortens the life expectancy of patients with thalassemia, whereas its effect is unclear in those with myelodysplastic syndromes (MDS). In patients with sickle cell anemia (SCA), iron does not seem to deposit quickly in the heart. Our primary objective was to assess through a multicentric study the prevalence of cardiac iron overload, defined as a cardiovascular magnetic resonance T2*8 ECs in the past year, and age older than 6 years. We included from 9 centers 20 patients with thalassemia, 41 with SCA, and 25 with MDS in 2012-2014. Erythrocytapharesis did not consistently prevent iron overload in patients with SCA. Cardiac iron overload was found in 3 (15%) patients with thalassemia, none with SCA, and 4 (16%) with MDS. The liver iron content (LIC) ranged from 10.4 to 15.2 mg/g dry weight, with no significant differences across groups (P = 0.29). Abnormal T2* was not significantly associated with any of the measures of transfusion or chelation. Ferritin levels showed a strong association with LIC. Non-transferrin-bound iron was high in the thalassemia and MDS groups but low in the SCA group (P<0.001). Hepcidin was low in thalassemia, normal in SCA, and markedly elevated in MDS (P<0.001). Two mechanisms may explain that iron deposition largely spares the heart in SCA: the high level of erythropoiesis recycles the iron and the chronic inflammation retains iron within the macrophages. Thalassemia, in contrast, is characterized by inefficient erythropoiesis, unable to handle free iron. Iron accumulation varies widely in MDS syndromes due to the competing influences of abnormal erythropoiesis, excess iron supply, and inflammation.

  15. Cardiac iron overload in chronically transfused patients with thalassemia, sickle cell anemia, or myelodysplastic syndrome

    Science.gov (United States)

    de Montalembert, Mariane; Ribeil, Jean-Antoine; Brousse, Valentine; Guerci-Bresler, Agnes; Stamatoullas, Aspasia; Vannier, Jean-Pierre; Dumesnil, Cécile; Lahary, Agnès; Touati, Mohamed; Bouabdallah, Krimo; Cavazzana, Marina; Chauzit, Emmanuelle; Baptiste, Amandine; Lefebvre, Thibaud; Puy, Hervé; Elie, Caroline

    2017-01-01

    The risk and clinical significance of cardiac iron overload due to chronic transfusion varies with the underlying disease. Cardiac iron overload shortens the life expectancy of patients with thalassemia, whereas its effect is unclear in those with myelodysplastic syndromes (MDS). In patients with sickle cell anemia (SCA), iron does not seem to deposit quickly in the heart. Our primary objective was to assess through a multicentric study the prevalence of cardiac iron overload, defined as a cardiovascular magnetic resonance T2*8 ECs in the past year, and age older than 6 years. We included from 9 centers 20 patients with thalassemia, 41 with SCA, and 25 with MDS in 2012-2014. Erythrocytapharesis did not consistently prevent iron overload in patients with SCA. Cardiac iron overload was found in 3 (15%) patients with thalassemia, none with SCA, and 4 (16%) with MDS. The liver iron content (LIC) ranged from 10.4 to 15.2 mg/g dry weight, with no significant differences across groups (P = 0.29). Abnormal T2* was not significantly associated with any of the measures of transfusion or chelation. Ferritin levels showed a strong association with LIC. Non-transferrin-bound iron was high in the thalassemia and MDS groups but low in the SCA group (P<0.001). Hepcidin was low in thalassemia, normal in SCA, and markedly elevated in MDS (P<0.001). Two mechanisms may explain that iron deposition largely spares the heart in SCA: the high level of erythropoiesis recycles the iron and the chronic inflammation retains iron within the macrophages. Thalassemia, in contrast, is characterized by inefficient erythropoiesis, unable to handle free iron. Iron accumulation varies widely in MDS syndromes due to the competing influences of abnormal erythropoiesis, excess iron supply, and inflammation. PMID:28257476

  16. Comparison of I-FISH and G-banding for the detection of chromosomal abnormalities during the evolution of myelodysplastic syndrome

    Directory of Open Access Journals (Sweden)

    R.F. Pinheiro

    2009-11-01

    Full Text Available Myelodysplastic syndrome (MDS patients with a normal karyotype constitute a heterogeneous group from a biological standpoint and their outcome is often unpredictable. Interphase fluorescence in situ hybridization (I-FISH studies could increase the rate of detection of abnormalities, but previous reports in the literature have been contradictory. We performed I-FISH and conventional karyotyping (G-banding on 50 MDS patients at diagnosis, after 6 and 12 months or at any time if a transformation to acute myeloid leukemia (AML was detected. Applying a probe-panel targeting the centromere of chromosomes 7 and 8, 5q31, 5p15.2 and 7q31, we observed one case with 5q deletion not identified by G-banding. I-FISH at 6 and 12 months confirmed the karyotype results. Eight cases transformed to AML during follow-up, but no hidden clone was detected by I-FISH in any of them. The inclusion of I-FISH during follow-up of MDS resulted in a small improvement in abnormality detection when compared with conventional G-banding.

  17. WHO classification and WPSS predict posttransplantation outcome in patients with myelodysplastic syndrome: a study from the Gruppo Italiano Trapianto di Midollo Osseo (GITMO).

    Science.gov (United States)

    Alessandrino, Emilio Paolo; Della Porta, Matteo Giovanni; Bacigalupo, Andrea; Van Lint, Maria Teresa; Falda, Michele; Onida, Francesco; Bernardi, Massimo; Iori, Anna Paola; Rambaldi, Alessandro; Cerretti, Raffaella; Marenco, Paola; Pioltelli, Pietro; Malcovati, Luca; Pascutto, Cristiana; Oneto, Rosi; Fanin, Renato; Bosi, Alberto

    2008-08-01

    We evaluated the impact of World Health Organization (WHO) classification and WHO classification-based Prognostic Scoring System (WPSS) on the outcome of patients with myelodysplastic syndrome (MDS) who underwent allogeneic stem cell transplantation (allo-SCT) between 1990 and 2006. Five-year overall survival (OS) was 80% in refractory anemias, 57% in refractory cytopenias, 51% in refractory anemia with excess blasts 1 (RAEB-1), 28% in RAEB-2, and 25% in acute leukemia from MDS (P = .001). Five-year probability of relapse was 9%, 22%, 24%, 56%, and 53%, respectively (P < .001). Five-year transplant-related mortality (TRM) was 14%, 39%, 38%, 34%, and 44%, respectively (P = .24). In multivariate analysis, WHO classification showed a significant effect on OS (P = .017) and probability of relapse (P = .01); transfusion dependency was associated with a reduced OS (P = .01) and increased TRM (P = .037), whereas WPSS showed a prognostic significance on both OS (P = .001) and probability of relapse (P < .001). In patients without excess blasts, multilineage dysplasia and transfusion dependency affected OS (P = .001 and P = .009, respectively), and were associated with an increased TRM (P = .013 and P = .031, respectively). In these patients, WPSS identified 2 groups with different OS and TRM. These data suggest that WHO classification and WPSS have a relevant prognostic value in posttransplantation outcome of MDS patients.

  18. The translocation t(2;11)(p21;q23) without MLL gene rearrangement--a possible marker of good prognosis in myelodysplastic syndrome patients.

    Science.gov (United States)

    Dvorak, Pavel; Lysak, Daniel; Vokurka, Samuel; Michalova, Kyra; Sarova, Iveta; Jonasova, Anna; Hruba, Martina; Rykovska, Anna; Subrt, Ivan

    2014-06-01

    The translocation t(2;11)(p21;q23) is associated with de novo myelodysplastic syndromes (MDS) and has an overall frequency of approximately 1%. The outcome of MDS patients with this translocation is not clear until now, because most of the clinical data addressing the t(2;11)(p21;q23) has been collected without investigating the status of the mixed lineage leukemia (MLL) gene. In this report, we present seven new patients with MDS diagnosis and the t(2;11)(p21;q23) in bone marrow cells; all of them without MLL gene rearrangement. They were found in two databases consisting of 1185 patients of two Czech institutions. These patients tended to be younger and showed a strong male predominance. A cytological and histological assessment of bone marrow at diagnosis revealed only mild MDS with marked dysplasia in megakaryopoiesis. Similar to other primary abnormalities in MDS (e.g. deletion of 11q), the t(2;11)(p21;q23) was frequently associated with deletion of 5q. Our results stress the common clinicopathological features of this entity and indicate that the t(2;11)(p21;q23) may be associated with a good prognosis for MDS patients (median survival 72 months).

  19. Pregnancy associated with myelodysplastic syndrome:one case report%妊娠合并骨髓异常增生综合征1例

    Institute of Scientific and Technical Information of China (English)

    吕小慧; 郭欣; 李佳; 周福兴; 刘朵朵; 刘淑娟; 陈必良

    2016-01-01

    Myelodysplastic syndrome ( MDS) is a group heterogeneous of clonal myeloid disorders derived from hematopoietic stem cells . The pathological manifestations are abnormalities of myeloid cell differentiation and development .The clinical manifestations are ineffective hematopoiesis, refractory cytopenia, hematopoiesis failure and high-risk conversion to acute myeloid leukemia (AML).The treatment of MDS mainly focuses on two points: bone marrow failure and complications as well as AML transformation .For different patients , the natural disease course and prognosis of MDS varies widely and the treatment should be individualized .%骨髓增生异常综合征( MDS)是起源于造血干细胞的一组异质性髓系克隆性疾病,病理学表现为髓系细胞分化及发育异常,临床表现为无效造血、难治性血细胞减少、造血功能衰竭,高风险向急性髓系白血病( AML)转化。 MDS治疗主要集中于两类问题:骨髓衰竭及并发症、AML转化。对于不同的患者而言,MDS患者自然病程和预后的差异性很大,治疗宜个体化。

  20. Molecular matching for Rh and K reduces red blood cell alloimmunisation in patients with myelodysplastic syndrome

    Science.gov (United States)

    Guelsin, Gláucia A.S.; Rodrigues, Camila; Visentainer, Jeane E.L.; de Melo Campos, Paula; Traina, Fabíola; Gilli, Simone C.O.; Saad, Sara T.O.; Castilho, Lilian

    2015-01-01

    Background Matching for Rh and K antigens has been used in an attempt to reduce antibody formation in patients receiving chronic transfusions but an extended phenotype matching including Fya and Jka antigens has also been recommended. The aim of this study was to identify an efficient transfusion protocol of genotype matching for patients with myelodysplastic syndrome (MDS) or chronic myelomonocytic leukaemia. We also examined a possible association of HLA class II alleles with red blood cell (RBC) alloimmunisation. Materials and methods We evaluated 43 patients with MDS undergoing transfusion therapy with and without antibody formation. We investigated antigen-matched RBC units for ABO, D, C, c, E, e, K, Fya, Fyb, Jka, Jkb, S, s, Doa, Dob and Dia on the patients’ samples and on the donor units serologically matched for them based on their ABO, Rh and K phenotypes and presence of antibodies. We also determined the frequencies of HLA-DRB1 alleles in the alloimmunised and non-alloimmunised patients. Results Seventeen of the 43 patients had discrepancies or mismatches for multiple antigens between their genotype-predicted profile and the antigen profile of the units of blood serologically matched for them. We verified that 36.8% of patients had more than one RBC alloantibody and 10.5% of patients had autoantibodies. Although we were able to find a better match for the patients in our extended genotyped/phenotyped units, we verified that matching for Rh and K would be sufficient for most of the patients. We also observed an over-representation of the HLA-DRB1*13 allele in the non-alloimmunised group of patients with MDS. Discussion In our population molecular matching for C, c, E, e, K was able to reduce RBC alloimmunisation in MDS patients. An association of HLA-DRB1*13 and protection from RBC alloimmunisation should be confirmed. PMID:24960644

  1. Lenalidomide induces lipid raft assembly to enhance erythropoietin receptor signaling in myelodysplastic syndrome progenitors.

    Science.gov (United States)

    McGraw, Kathy L; Basiorka, Ashley A; Johnson, Joseph O; Clark, Justine; Caceres, Gisela; Padron, Eric; Heaton, Ruth; Ozawa, Yukiyasu; Wei, Sheng; Sokol, Lubomir; List, Alan F

    2014-01-01

    Anemia remains the principal management challenge for patients with lower risk Myelodysplastic Syndromes (MDS). Despite appropriate cytokine production and cellular receptor display, erythropoietin receptor (EpoR) signaling is impaired. We reported that EpoR signaling is dependent upon receptor localization within lipid raft microdomains, and that disruption of raft integrity abolishes signaling capacity. Here, we show that MDS erythroid progenitors display markedly diminished raft assembly and smaller raft aggregates compared to normal controls (p = 0.005, raft number; p = 0.023, raft size). Because lenalidomide triggers raft coalescence in T-lymphocytes promoting immune synapse formation, we assessed effects of lenalidomide on raft assembly in MDS erythroid precursors and UT7 cells. Lenalidomide treatment rapidly induced lipid raft formation accompanied by EpoR recruitment into raft fractions together with STAT5, JAK2, and Lyn kinase. The JAK2 phosphatase, CD45, a key negative regulator of EpoR signaling, was displaced from raft fractions. Lenalidomide treatment prior to Epo stimulation enhanced both JAK2 and STAT5 phosphorylation in UT7 and primary MDS erythroid progenitors, accompanied by increased STAT5 DNA binding in UT7 cells, and increased erythroid colony forming capacity in both UT7 and primary cells. Raft induction was associated with F-actin polymerization, which was blocked by Rho kinase inhibition. These data indicate that deficient raft integrity impairs EpoR signaling, and provides a novel strategy to enhance EpoR signal fidelity in non-del(5q) MDS.

  2. Chromothripsis Is a Recurrent Genomic Abnormality in High-Risk Myelodysplastic Syndromes

    Science.gov (United States)

    Abáigar, María; Robledo, Cristina; Benito, Rocío; Ramos, Fernando; Díez-Campelo, María; Hermosín, Lourdes; Sánchez-del-Real, Javier; Alonso, Jose M.; Cuello, Rebeca; Megido, Marta; Rodríguez, Juan N.; Martín-Núñez, Guillermo; Aguilar, Carlos; Vargas, Manuel; Martín, Ana A.; García, Juan L.; Kohlmann, Alexander; del Cañizo, M. Consuelo; Hernández-Rivas, Jesús M.

    2016-01-01

    To explore novel genetic abnormalities occurring in myelodysplastic syndromes (MDS) through an integrative study combining array-based comparative genomic hybridization (aCGH) and next-generation sequencing (NGS) in a series of MDS and MDS/myeloproliferative neoplasms (MPN) patients. 301 patients diagnosed with MDS (n = 240) or MDS/MPN (n = 61) were studied at the time of diagnosis. A genome-wide analysis of DNA copy number abnormalities was performed. In addition, a mutational analysis of DNMT3A, TET2, RUNX1, TP53 and BCOR genes was performed by NGS in selected cases. 285 abnormalities were identified in 71 patients (23.6%). Three high-risk MDS cases (1.2%) displayed chromothripsis involving exclusively chromosome 13 and affecting some cancer genes: FLT3, BRCA2 and RB1. All three cases carried TP53 mutations as revealed by NGS. Moreover, in the whole series, the integrative analysis of aCGH and NGS enabled the identification of cryptic recurrent deletions in 2p23.3 (DNMT3A; n = 2.8%), 4q24 (TET2; n = 10%) 17p13 (TP53; n = 8.5%), 21q22 (RUNX1; n = 7%), and Xp11.4 (BCOR; n = 2.8%), while mutations in the non-deleted allele where found only in DNMT3A (n = 1), TET2 (n = 3), and TP53 (n = 4). These cryptic abnormalities were detected mainly in patients with normal (45%) or non-informative (15%) karyotype by conventional cytogenetics, except for those with TP53 deletion and mutation (15%), which had a complex karyotype. In addition to well-known copy number defects, the presence of chromothripsis involving chromosome 13 was a novel recurrent change in high-risk MDS patients. Array CGH analysis revealed the presence of cryptic abnormalities in genomic regions where MDS-related genes, such as TET2, DNMT3A, RUNX1 and BCOR, are located. PMID:27741277

  3. TP53 overexpression is an independent adverse prognostic factor in de novo myelodysplastic syndromes with fibrosis.

    Science.gov (United States)

    Loghavi, Sanam; Al-Ibraheemi, Alyaa; Zuo, Zhuang; Garcia-Manero, Guillermo; Yabe, Mariko; Wang, Sa A; Kantarjian, Hagop M; Yin, Cameron C; Miranda, Roberto N; Luthra, Raja; Medeiros, L Jeffrey; Bueso-Ramos, Carlos E; Khoury, Joseph D

    2015-10-01

    Bone marrow (BM) fibrosis is associated with poor prognosis in patients with de novo myelodysplastic syndromes (MDS). TP53 mutations and TP53 (p53) overexpression in MDS are also associated with poor patient outcomes. The prevalence and significance of TP53 mutations and TP53 overexpression in MDS with fibrosis are unknown. We studied 67 patients with de novo MDS demonstrating moderate to severe reticulin fibrosis (MDS-F). Expression of TP53 was evaluated in BM core biopsy specimens using dual-colour CD34/TP53 immunohistochemistry with computer-assisted image analysis. Mutation analysis was performed using next-generation sequencing, or Sanger sequencing methods. TP53 mutations were present in 47·1% of cases. TP53 mutation was significantly associated with TP53 expression (P = 0·0294). High levels of TP53 expression (3 +  in ≥10% cells) were associated with higher BM blast counts (P = 0·0149); alterations of chromosomes 5 (P = 0·0009) or 7 (P = 0·0141); complex karyotype (P = 0·0002); high- and very-high risk IPSS-R groups (P = 0·009); and TP53 mutations (P = 0·0003). High TP53 expression independently predicted shorter overall survival (OS) by multivariate analysis (P = TP53 by CD34-positive cells was associated with shorter OS and leukaemia-free survival (P = 0·0428). TP53 overexpression is a predictor of poor outcome in patients with MDS-F.

  4. SF3B1 haploinsufficiency leads to formation of ring sideroblasts in myelodysplastic syndromes.

    Science.gov (United States)

    Visconte, Valeria; Rogers, Heesun J; Singh, Jarnail; Barnard, John; Bupathi, Manoj; Traina, Fabiola; McMahon, James; Makishima, Hideki; Szpurka, Hadrian; Jankowska, Anna; Jerez, Andres; Sekeres, Mikkael A; Saunthararajah, Yogen; Advani, Anjali S; Copelan, Edward; Koseki, Haruhiko; Isono, Kyoichi; Padgett, Richard A; Osman, Sami; Koide, Kazunori; O'Keefe, Christine; Maciejewski, Jaroslaw P; Tiu, Ramon V

    2012-10-18

    Whole exome/genome sequencing has been fundamental in the identification of somatic mutations in the spliceosome machinery in myelodysplastic syndromes (MDSs) and other hematologic disorders. SF3B1, splicing factor 3b subunit 1 is mutated in 60%-80% of refractory anemia with ring sideroblasts (RARS) and RARS associated with thrombocytosis (RARS-T), 2 distinct subtypes of MDS and MDS/myeloproliferative neoplasms (MDSs/MPNs). An idiosyncratic feature of RARS/RARS-T is the presence of abnormal sideroblasts characterized by iron overload in the mitochondria, called RS. Based on the high frequency of mutations of SF3B1 in RARS/RARS-T, we investigated the consequences of SF3B1 alterations. Ultrastructurally, SF3B1 mutants showed altered iron distribution characterized by coarse iron deposits compared with wild-type RARS patients by transmission electron microscopy. SF3B1 knockdown experiments in K562 cells resulted in down-regulation of U2-type intron-splicing by RT-PCR. RNA-sequencing analysis of SF3B1 mutants showed differentially used genes relevant in MDS pathogenesis, such as ASXL1, CBL, EZH, and RUNX families. A SF3B pharmacologic inhibitor, meayamycin, induced the formation of RS in healthy BM cells. Further, BM aspirates of Sf3b1 heterozygous knockout mice showed RS by Prussian blue. In conclusion, we report the first experimental evidence of the association between SF3B1 and RS phenotype. Our data suggest that SF3B1 haploinsufficiency leads to RS formation.

  5. Lenalidomide induces lipid raft assembly to enhance erythropoietin receptor signaling in myelodysplastic syndrome progenitors.

    Directory of Open Access Journals (Sweden)

    Kathy L McGraw

    Full Text Available Anemia remains the principal management challenge for patients with lower risk Myelodysplastic Syndromes (MDS. Despite appropriate cytokine production and cellular receptor display, erythropoietin receptor (EpoR signaling is impaired. We reported that EpoR signaling is dependent upon receptor localization within lipid raft microdomains, and that disruption of raft integrity abolishes signaling capacity. Here, we show that MDS erythroid progenitors display markedly diminished raft assembly and smaller raft aggregates compared to normal controls (p = 0.005, raft number; p = 0.023, raft size. Because lenalidomide triggers raft coalescence in T-lymphocytes promoting immune synapse formation, we assessed effects of lenalidomide on raft assembly in MDS erythroid precursors and UT7 cells. Lenalidomide treatment rapidly induced lipid raft formation accompanied by EpoR recruitment into raft fractions together with STAT5, JAK2, and Lyn kinase. The JAK2 phosphatase, CD45, a key negative regulator of EpoR signaling, was displaced from raft fractions. Lenalidomide treatment prior to Epo stimulation enhanced both JAK2 and STAT5 phosphorylation in UT7 and primary MDS erythroid progenitors, accompanied by increased STAT5 DNA binding in UT7 cells, and increased erythroid colony forming capacity in both UT7 and primary cells. Raft induction was associated with F-actin polymerization, which was blocked by Rho kinase inhibition. These data indicate that deficient raft integrity impairs EpoR signaling, and provides a novel strategy to enhance EpoR signal fidelity in non-del(5q MDS.

  6. [Predict response to decitabine in patients with myelodysplastic syndrome and related neoplasms].

    Science.gov (United States)

    Zhao, Y S; Guo, J; Xu, F; Wu, D; Wu, L Y; Song, L L; Xiao, C; Li, X; Chang, C K

    2017-02-14

    Objective: To identify clinical and molecular signatures for predicting response to decitabine (DAC) in patients with myelodysplastic syndrome (MDS) and related neoplasms. Methods: The clinical characteristics of 109 patients with MDS and related neoplasms who were treated with DAC were analyzed retrospectively and the next target sequencing was performed to define recurrently mutated genes in these disease samples, to examine the association of the clinical and molecular signatures with response to DAC treatment. Results: Of 109 MDS and related neoplasms patients, there were 70 males and 39 females, the median age was 61 years old (ranges: 17-85 years old) . According to the international prognostic scoring system (IPSS) , 46 cases were included in the relatively low risk group (low risk and intermediate-1 risk) , 63 in the relative high risk group (intermediate-2 and high risk) . There were 21 cases with complex karyotype, 17 chromosome 7 abnormality and 17 monosomal karyotype. The median courses of DAC treatment was 4 (2-11) . A total of 74 patients achieved response (67.9%) and 30 (27.5%) achieved complete response (CR) . Univariate analysis found that CR was higher in patients with high risk of IPSS, complex karyotypes, monosomal karyotypes, chromosome 7 abnormality, and platelet doubling after one cycle of DAC treatment. Patients with TP53 gene mutation were more likely to receive CR, 10 of 15 patients with TP53 mutations achieved CR. (66.7%) , which was significantly higher than that of the patients without TP53 gene mutation (21.3%) (P=0.001) . Multivariate analysis showed that TP53 gene mutation, platelet doubling after one cycle of DAC treatment and the complex karyotype were independent prognostic factors for CR. Of them, TP53 gene mutation is the strongest predictor (OR=4.39, 95%CI, 1.20-16.06, P=0.026) . Conclusion: TP53 mutation, platelet doubling after one cycle of DAC treatment and complex karyotypes could predict CR to DAC.

  7. Richter Syndrome in Chronic Lymphocytic Leukemia.

    Science.gov (United States)

    Vitale, Candida; Ferrajoli, Alessandra

    2016-02-01

    The term Richter syndrome (RS) indicates the transformation of chronic lymphocytic leukemia (CLL) into an aggressive lymphoma. RS is a rare complication with an aggressive clinical course, bearing an unfavorable prognosis. In the majority of cases, CLL transforms into RS as diffuse large B cell lymphoma (DLBCL), and a clonal relation between the two processes can be found. However, clonally unrelated RS can occur and transformations to other histologies beside DLBCL have been described. Recent data have shed some light on genetic characteristics that can influence and drive the transformation from CLL to RS. This molecular information has not been translated yet into significant treatment advances, and currently the therapy regimens for RS continue to rely on intensive chemotherapy combinations followed by stem cell transplant in suitable candidates. Based on the rapid pace of discoveries in the field of hematological malignancies and on the recent revolution in the therapeutic landscape for CLL and B cell lymphomas, new therapeutic options for RS might be available in the upcoming years.

  8. Developments in the treatment of transfusion-dependent anemia in patients with myelodysplastic syndromes: epidemiology, etiology, genetics, and targeted therapies

    Directory of Open Access Journals (Sweden)

    Raza A

    2014-07-01

    Full Text Available Azra Raza, Nicholas Iverson, Abdullah M AliThe MDS Center, Columbia University, New York, NY, USAAbstract: Myelodysplastic syndromes are malignant hematopoietic stem cell disorders that present with variable cytopenias and predominantly affect the elderly. Treatment options are limited, with allogeneic transplant being the only potentially curative strategy. Recent mutational profiling studies have led to cataloguing of driver and passenger mutations most commonly affecting the epigenetic regulators and genes involved in RNA splicing. Despite improved understanding of the disease biology, these emerging molecular insights have not led to identification of novel therapeutic strategies. Although several drugs approved in the last decade improve the cytopenias, the relief is temporary, most likely due to the sequential activation of clones. Future advances depend upon identification of signaling pathways in dominant clones and targeting these with agents that might be known but need to be matched to suit the needs of individual patients in a longitudinal, dynamic fashion. Myelodysplastic syndromes are ideally suited for the development of such personalized medicine.Keywords: cancer, epigenetics, iron, MDS, myelodysplasia, splicing

  9. Myelodysplastic syndrome and pancytopenia responding to treatment of hyperthyroidism: Peripheral blood and bone marrow analysis before and after antihormonal treatment

    Directory of Open Access Journals (Sweden)

    Akoum Riad

    2007-01-01

    Full Text Available Hematological disorders, especially single lineage abnormalities, have been described in hyperthyroidism. Pancytopenia has been reported, without myelodysplastic syndrome or megaloblastic anemia. We studied the peripheral blood smear and the bone marrow aspiration and biopsy of a 65-year-old lady, who presented with pancytopenia and thyrotoxicosis due to multinodular goiter. She denied ingesting any toxic medication. At diagnosis: WBC: 2500 /ul, platelets count: 58.000/ul, hemoglobin level: 6.5 g/dl. The bone marrow was moderately hyper cellular with moderate myelofibrosis and arrested hematopoiesis. The TSH level was: 0.02 mIU/l (N: 0.25-4, the fT3: 18 pmol/l (N: 4-10, the routine serum immunologic tests were negative. After treatment with single agent neomercazole (carbimazole, complete recovery of the blood cell counts was obtained within one month. The bone marrow aspiration, performed three months after starting therapy, showed normal hematopoiesis. The thyroid function tests returned to normal and no autoimmune reaction was detected on routine serum testing. Persistent response was observed six months later under medical treatment. The patient has refused surgical treatment. Reversible myelodysplastic syndrome may also be part of the changes in blood picture of patients with hyperthyroidism, probably due to direct toxic mechanism.

  10. Fatal Relapse of Myelodysplastic Syndrome in a Patient with HIV/Hepatitis C Coinfection Treated with Simeprevir/Sofosbuvir.

    Science.gov (United States)

    Diejomaoh, Efemena Michael; Gathe, Joseph Clayton; Mayberry, Carl Craig; Clemmons, John Benjamin; Miguel, Bernie; Glombicki, Alan; Daquioag, Benjamin

    2017-01-01

    Registrational studies and observational cohorts clearly suggest sustained virologic response (SVR) rates in HIV-/hepatitis C-coinfected patients are similar to monoinfected patients when utilizing interferon-free regimens, and this can be accomplished with agents that are well tolerated with minimal adverse events. These randomized trials that led to the approval of several of our new direct-acting antiviral agents, however, specifically excluded patients who had significant comorbidities and none to our knowledge accepted patients with a history of cancer. Therefore, the effect of treatment of active hepatitis C in such patients and the effect on preexisting neoplasia are relatively unknown. We prospectively followed a 62-year-old male coinfected with HIV/hepatitis C who had a history of anal squamous cell carcinoma, prostate carcinoma, renal cell carcinoma all clinically cured and a myelodysplastic syndrome that was in remission. The patient achieved an SVR of hepatitis C with simeprevir/sofosbuvir without ribavirin and died shortly thereafter of a fatal relapse of his previously clinically controlled myelodysplastic syndrome.

  11. Acquired hemoglobin H disease in a patient with aplastic anemia evolving into acute myeloid leukemia

    Directory of Open Access Journals (Sweden)

    Maria Stella Figueiredo

    Full Text Available CONTEXT: The prognosis of severe aplastic anemia has improved since the introduction of bone marrow transplantation and treatment with antithymocyte globulin. In contrast to the success of these protocols, studies with long term follow-up have shown the occurrence of clonal diseases such as paroxysmal nocturnal hemoglobinuria, myelodysplastic syndrome and acute leukemia in aplastic anemia. CASE REPORT: We report the first case of a Brazilian patient with aplastic anemia who developed myelodysplastic syndrome and acute myeloid leukemia showing acquired hemoglobin H and increased fetal hemoglobin.

  12. A randomized study of granulocyte colony-stimulating factor applied during and after chemotherapy in patients with poor risk myelodysplastic syndromes : a report from the HOVON Cooperative Group

    NARCIS (Netherlands)

    Ossenkoppele, GJ; van der Holt, B; Verhoef, GEG; Daenen, SMGJ; Verdonck, LF; Sonneveld, P; Wijermans, PW; van der Lelie, J; van Putten, WLJ; Lowenberg, B

    1999-01-01

    The purpose of this study was to determine the safety and efficacy of filgrastim as an adjunct to induction and consolidation chemotherapy in poor risk patients with myelodysplastic syndrome (MDS). Filgrastim was given both during and after chemotherapy with the objective to accelerate hematopoietic

  13. A randomized phase 3 study of lenalidomide versus placebo in RBC transfusion-dependent patients with Low-/Intermediate-1-risk myelodysplastic syndromes with del5q

    NARCIS (Netherlands)

    Fenaux, P.; Giagounidis, A.; Selleslag, D.; Beyne-Rauzy, O.; Mufti, G.; Mittelman, M.; Muus, P.; Boekhorst, P. Te; Sanz, G.; Del Canizo, C.; Guerci-Bresler, A.; Nilsson, L.; Platzbecker, U.; Lubbert, M.; Quesnel, B.; Cazzola, M.; Ganser, A.; Bowen, D.; Schlegelberger, B.; Aul, C.; Knight, R.; Francis, J.; Fu, T.; Hellstrom-Lindberg, E.

    2011-01-01

    This phase 3, randomized, double-blind study assessed the efficacy and safety of lenalidomide in 205 red blood cell (RBC) transfusion-dependent patients with International Prognostic Scoring System Low-/Intermediate-1-risk del5q31 myelodysplastic syndromes. Patients received lenalidomide 10 mg/day o

  14. Implementation of flow cytometry in the diagnostic work-up of myelodysplastic syndromes in a multicenter approach : Report from the Dutch Working Party on Flow Cytometry in MDS

    NARCIS (Netherlands)

    Westers, Theresia M.; van der Velden, Vincent H. J.; Alhan, Canan; Bekkema, Roelof; Bijkerk, Andre; Brooimans, Rik A.; Cali, Claudia; Drager, Angelika M.; de Haas, Valerie; Homburg, Christa; Kuiper-Kramer, P. (Ellen) A.; Leenders, Marije; Lommerse, Ingrid; Marvelde, Jeroen G. te; van der Molen-Sinke, Joke K.; Moshaver, Bijan; Mulder, Andre B.; Preijers, Frank W. M. B.; Schindhelm, Roger K.; van der Sluijs, Alita; van Wering, Elisabeth R.; Westra, August H.; van de Loosdrecht, Arjan A.; de Jong, A.

    2012-01-01

    Flow cytometry (FC) is recognized as an important tool in the diagnosis of myelodysplastic syndromes (MDS) especially when standard criteria fail. A working group within the Dutch Society of Cytometry aimed to implement FC in the diagnostic work-up of MDS. Hereto, guidelines for data acquisition, an

  15. Recurrent unbalanced whole-arm t(1;10)(q10;p10) in myelodysplastic syndrome: a case report and literature review.

    Science.gov (United States)

    Odish, Omar Ferkad Faraj; Gotoh, Akihiko; Liu, Yi-Chang; Shoji, Nohoko; Kimura, Yukihiko; Kodama, Atsushi; Ohyashiki, Kazuma

    2007-01-15

    We report a patient with myelodysplastic syndrome (refractory anemia) showing the karyotype 46,XY,+1,der(1;10)(q10;p10), resulting in trisomy 1q and monosomy 10q abnormality. This finding suggests that either trisomy of 1q or centromeric connection between chromosomes 1 and 10, rather than the absence of 10q, might be essential toward neoplastic transformation.

  16. Lenalidomide for the Treatment of Low- or Intermediate-1-Risk Myelodysplastic Syndromes Associated with Deletion 5q Cytogenetic Abnormality: An Evidence Review of the NICE Submission from Celgene

    NARCIS (Netherlands)

    H.M. Sluimer-Blommestein (Hedwig); N. Armstrong (Nigel); S. Ryder; S. Deshpande (Sohan); G. Worthy (Gill); C. Noake; R. Riemsma; J. Kleijnen (Jos); J.L. Severens (Hans); M.J. Al (Maiwenn)

    2016-01-01

    textabstractThe National Institute for Health and Care Excellence (NICE) invited the manufacturer of lenalidomide (Celgene) to submit evidence of the clinical and cost effectiveness of the drug for treating adults with myelodysplastic syndromes (MDS) associated with deletion 5q cytogenetic abnormali

  17. Deferasirox is a powerful NF-κB inhibitor in myelodysplastic cells and in leukemia cell lines acting independently from cell iron deprivation by chelation and reactive oxygen species scavenging

    Science.gov (United States)

    Messa, Emanuela; Carturan, Sonia; Maffè, Chiara; Pautasso, Marisa; Bracco, Enrico; Roetto, Antonella; Messa, Francesca; Arruga, Francesca; Defilippi, Ilaria; Rosso, Valentina; Zanone, Chiara; Rotolo, Antonia; Greco, Elisabetta; Pellegrino, Rosa M.; Alberti, Daniele; Saglio, Giuseppe; Cilloni, Daniela

    2010-01-01

    Background Usefulness of iron chelation therapy in myelodysplastic patients is still under debate but many authors suggest its possible role in improving survival of low-risk myelodysplastic patients. Several reports have described an unexpected effect of iron chelators, such as an improvement in hemoglobin levels, in patients affected by myelodysplastic syndromes. Furthermore, the novel chelator deferasirox induces a similar improvement more rapidly. Nuclear factor-κB is a key regulator of many cellular processes and its impaired activity has been described in different myeloid malignancies including myelodysplastic syndromes. Design and Methods We evaluated deferasirox activity on nuclear factor-κB in myelodysplastic syndromes as a possible mechanism involved in hemoglobin improvement during in vivo treatment. Forty peripheral blood samples collected from myelodysplastic syndrome patients were incubated with 50 μM deferasirox for 18h. Results Nuclear factor-κB activity dramatically decreased in samples showing high basal activity as well as in cell lines, whereas no similar behavior was observed with other iron chelators despite a similar reduction in reactive oxygen species levels. Additionally, ferric hydroxyquinoline incubation did not decrease deferasirox activity in K562 cells suggesting the mechanism of action of the drug is independent from cell iron deprivation by chelation. Finally, incubation with both etoposide and deferasirox induced an increase in K562 apoptotic rate. Conclusions Nuclear factor-κB inhibition by deferasirox is not seen from other chelators and is iron and reactive oxygen species scavenging independent. This could explain the hemoglobin improvement after in vivo treatment, such that our hypothesis needs to be validated in further prospective studies. PMID:20534700

  18. Aberrations of chromosome 8 in myelodysplastic syndromes: Clinical and biological significance

    Directory of Open Access Journals (Sweden)

    Marisavljević Dragomir

    2006-01-01

    Full Text Available Introduction: Rearrangements of any single chromosome in human karyotype have been reported in patients with pMDS. Objective: To examine the role of aberrations of chromosome 8 in pathogenesis, clinical presentation and progression of myelodysplastic syndromes. Method: Cytogenetic analysis of bone marrow cells was carried out by direct method and by means of 24- and/or 48-hour unstimulated cell culture. Chromosomes were obtained by modified method of HG-bands. Results: On presentation, 109 out of 271 successfully karyotyped patients (40,2% had abnormal karyotypes. Among them, 22 patients (10.9% had aberrations of chromosome 8. Ten patients had trisomy 8 as "simple" aberration whilst additional three cases had trisomy 8 included in "complex" karyotypes (≥3 chromosomes. Cases with constitutional trisomy 8 mosaicism (CT8M were excluded using the chromosome analyses of PHA-stimulated blood cultures. On the contrary, monosomy (seven patients or deletion of chromosome 8 (two patients were exclusively found in "complex" karyotypes. During prolonged cytogenetic follow-up, trisomy 8 was not recorded in evolving karyotypes. In contrast, trisomy 8 disappeared in two cases during subsequent cytogenetic studies, i.e. 23 and 72 months from diagnosis, accompanied in one patient with complete hematological remission. No difference regarding age, sex, cytopenia, blood and marrow blast count or response to treatment was found between patients with trisomy 8 as the sole aberration compared to those with normal cytogenetics. Median survival of patients with trisomy 8 as the sole aberration was 27 months, as compared to 32 months in patients with normal cytogenetics (p=0.468, whilst median survival of patients with aberrations of chromosome 8 included in "complex" karyotypes was only 4 months. Conclusion: Aberrations of chromosome 8 are common in patients with pMDS. The presence of a clone with trisomy 8 is not always the sign of disease progression or poor

  19. Alterações moleculares em síndrome mielodisplásica Molecular abnormalities in myelodysplastic syndrome

    Directory of Open Access Journals (Sweden)

    Maria de Lourdes L. F. Chauffaille

    2006-09-01

    Full Text Available A síndrome mielodisplásica (SMD representa um grupo heterogêneo de doenças hematopoéticas clonais. As alterações cromossômicas observadas em SMD foram o ponto de partida para uma série de estudos para a caracterização da patogênese molecular nessa doença. A perda de material genético leva à hipótese de inativação de genes supressores tumorais (GST, mas essa teoria não explica o evento inicial desencadeador da vantagem de crescimento das células progenitoras hematopoéticas, estando outros mecanismos envolvidos, dos quais sobressaem a ativação de oncogenes, alteração de vias de sinalização e fatores de transcrição. Mutações de oncogenes, como RAS, P53, PDGF, FLT3 e MLL, dentre outros, podem contribuir para o desenvolvimento da SMD. A mutação em tandem do FLT3 é evento genético tardio no curso da doença e os pacientes portadores da mesma tendem a apresentar prognóstico desfavorável e transformação iminente para leucemia aguda. Tanto aberrações qualitativas como quantitativas de fatores de transcrição induzem o desequilíbrio ou bloqueio de diferenciação da célula hematopoética, que, por sua vez, se traduz em hematopoese ineficaz. Alterações epigenéticas são caracterizadas por metilação de DNA que tem papel no controle da expressão gênica. Hipermetilação e inativação de genes reguladores exercem função no desenvolvimento da doença. SMD de alto risco está associada à elevada prevalência de inativação do gene supressor tumoral p15INK4B por hipermetilação do promotor. Encurtamento do telômero correlaciona-se a cariótipos complexos, indicando instabilidade genômica e pior prognóstico.Myelodysplastic syndrome (MDS is a heterogenous group of clonal hematopoietic disorders. Chromosomal abnormalities detected in this disease were the start to many studies in order to characterize molecular pathogenesis. The loss of genetic material observed in most patients with MDS leads to the

  20. Acute lymphoblastic leukemia in children with Down syndrome

    DEFF Research Database (Denmark)

    Buitenkamp, Trudy D; Izraeli, Shai; Zimmermann, Martin

    2014-01-01

    Children with Down syndrome (DS) have an increased risk of B-cell precursor (BCP) acute lymphoblastic leukemia (ALL). The prognostic factors and outcome of DS-ALL patients treated in contemporary protocols are uncertain. We studied 653 DS-ALL patients enrolled in 16 international trials from 1995...

  1. Secondary Myelodysplastic Syndrome May Happen Same as Paraneoplastic Syndrome in a Period of Time and Prior to The Appearance of Malignancy: A case Study of 6 Patients

    OpenAIRE

    Aznab, Mozaffar; Kavianymoghadam, Kaveh

    2013-01-01

    Myelodysplastic syndrome is a bone marrow failure in which differentiation and maturity do not happen naturally and dysplasia exists in each of 3 cell categories in Bone marrow. Refractory anemia is one of the major complaints with which the patients come to hematology clinics, which in diagnostic considerations lead to MDS as diagnosis. Often there is no recognized reason for this, so it is called “primary MDS”. In practice, we meet some patients who have MDS criteria however we can also fin...

  2. Depletion of cytotoxic T-cells does not protect NUP98-HOXD13 mice from myelodysplastic syndrome but reveals a modest tumor immunosurveillance effect.

    Directory of Open Access Journals (Sweden)

    Sheryl M Gough

    Full Text Available Myelodysplastic syndrome (MDS and aplastic anemia (AA patients both present with symptoms of bone marrow failure. In many AA patients, these features are thought to result from an oligoclonal expansion of cytotoxic T-cells that destroy haematopoietic stem or progenitor cells. This notion is supported by the observation that AA patients respond to immunosuppressive therapy. A fraction of MDS patients also respond well to immunosuppressive therapy suggesting a similar role for cytotoxic T-cells in the etiology of MDS, however the role of cytotoxic T-cells in MDS remains unclear. Mice that express a NUP98-HOXD13 (NHD13 transgene develop a MDS that closely mimics the human condition in terms of dysplasia, ineffective hematopoiesis, and transformation to acute myeloid leukemia (AML. We followed a cohort of NHD13 mice lacking the Rag1 protein (NHD13/Rag1KO to determine if the absence of lymphocytes might 1 delay the onset and/or diminish the severity of the MDS, or 2 effect malignant transformation and survival of the NHD13 mice. No difference was seen in the onset or severity of MDS between the NHD13 and NHD13/Rag1KO mice. However, NHD13/Rag1KO mice had decreased survival and showed a trend toward increased incidence of transformation to AML compared to the NHD13 mice, suggesting protection from AML transformation by a modest immuno-surveillance effect. In the absence of functional Tcrb signaling in the NHD13/Rag1KO T-cell tumors, Pak7 was identified as a potential Tcrb surrogate survival signal.

  3. The clinical efficacy of the patients of acute myeloid leukemia and myelodysplastic syndromes treated with decitabine alone, combined with half or one couse of CAG regimen%地西他滨单药及联合半程和全程CAG方案治疗骨髓增生异常综合征和急性髓系白血病疗效观察

    Institute of Scientific and Technical Information of China (English)

    高苏; 仇惠英; 金正明; 唐晓文; 傅铮铮; 马骁; 韩悦; 陈苏宁; 孙爱宁

    2014-01-01

    Objective To observe the clinical safety and efficacy of decitabine in patients of acute myeloid leukemia and myelodysplastic syndromes (MDS/AML).Methods Totally 79 patients with MDS/AML were divided into three groups:①Treated with decitabine alone (20 mg/m2 for 5 days).② Combination of decitabine with half dose CAG chemotherapy (Acla 20 mg qod × 3 d,Ara-C 10 mg/m2 q12 h×7 d,G-CSF 300 μg/d,the dose of G-CSF adjust to the amount of blood routine).③Combination of decitabine with CAG chemotherapy (Acla 20 mg qod×4 d,Ara-C 10 mg/m2 q12 h× 14 d,G-CSF 300 μg/d,the dose of G-CSF adjust to the amount of blood routine).We observed complete remission (CR) rate,overall response rate (ORR) and overall survival (OS) of the three groups; meanwhile,we analyzed the factors relevant to decitabine efficacy and the prognosis.Results ORR in the three groups were 53.3%,56.5% and 69.2% respectively,with no statistically significant differences (P>0.05).Due to the last follow-up at 2014.04.01,20 patients still survived,45 died,14 were lost to follow-up.The 5-year cumulative survival rate of 79 patients was 25.3%,the 2-year survival were of the three groups were 34.8%,24.8 and 29.2% respectively with no statistically significant differences (P>0.05).Adverse events of infection and bleeding were mainly caused by decitabine.Grade 3 to 4 hematological toxicities were observed in 72 cases with the average time for the lack of granulocytes as 14.8 days.59 patients experienced infectious events,including grade 3 or 4 infections in 14 cases,grade 1 or 2 infections in 45 cases.There were no statistically significant differences (P>0.05) among the three groups in terms of infection rates,bleeding rates,duration of neutrophenia,mean MAP transfusion and mean platelet transfusion.79 patients were safely through bone marrow suppression by anti-infective and supportive treatment without treatment-related deaths.Conclusions Treating MDS/AML with decitabine alone

  4. [Clinical and genetic background of familial myelodysplasia and acute myeloid leukemia].

    Science.gov (United States)

    Király, Péter Attila; Kállay, Krisztián; Marosvári, Dóra; Benyó, Gábor; Szőke, Anita; Csomor, Judit; Bödör, Csaba

    2016-02-21

    Myelodysplastic syndrome and acute myeloid leukaemia are mainly sporadic diseases, however, rare familial cases exist. These disorders are considered rare, but are likely to be more common than currently appreciated, and are characterized by the autosomal dominant mutations of hematopoietic transcription factors. These syndromes have typical phenotypic features and are associated with an increased risk for developing overt malignancy. Currently, four recognized syndromes could be separated: familial acute myeloid leukemia with mutated CEBPA, familial myelodysplastic syndrome/acute myeloid leukemia with mutated GATA2, familial platelet disorder with propensity to myeloid malignancy with RUNX1 mutations, and telomere biology disorders due to mutations of TERC or TERT. Furthermore, there are new, emerging syndromes associated with germline mutations in novel genes including ANKRD26, ETV6, SRP72 or DDX41. This review will discuss the current understanding of the genetic basis and clinical presentation of familial leukemia and myelodysplasia.

  5. Acute pediatric leg compartment syndrome in chronic myeloid leukemia.

    Science.gov (United States)

    Cohen, Eric; Truntzer, Jeremy; Trunzter, Jeremy; Klinge, Steve; Schwartz, Kevin; Schiller, Jonathan

    2014-11-01

    Acute compartment syndrome is an orthopedic surgical emergency and may result in devastating complications in the setting of delayed or missed diagnosis. Compartment syndrome has a variety of causes, including posttraumatic or postoperative swelling, external compression, burns, bleeding disorders, and ischemia-reperfusion injury. Rare cases of pediatric acute compartment syndrome in the setting of acute myeloid leukemia and, even less commonly, chronic myeloid leukemia have been reported. The authors report the first known case of pediatric acute compartment syndrome in a patient without a previously known diagnosis of chronic myeloid leukemia. On initial examination, an 11-year-old boy presented with a 2-week history of progressive left calf pain and swelling after playing soccer. Magnetic resonance imaging scan showed a hematoma in the left superficial posterior compartment. The patient had unrelenting pain, intermittent lateral foot parethesias, and inability to bear weight. Subsequently, he was diagnosed with acute compartment syndrome and underwent fasciotomy and evacuation of a hematoma. Laboratory results showed an abnormal white blood cell count of 440×10(9)/L (normal, 4.4-11×10(9)) and international normalized ratio of 1.3 (normal, 0.8-1.2). Further testing included the BCR-ABL1 fusion gene located on the Philadelphia chromosome, leading to a diagnosis of chronic myeloid leukemia. Monotherapy with imatinib mesylate (Gleevec) was initiated. This report adds another unique case to the growing literature on compartment syndrome in the pediatric population and reinforces the need to consider compartment syndrome, even in unlikely clinical scenarios. Copyright 2014, SLACK Incorporated.

  6. Random-start controlled ovarian stimulation for emergency fertility preservation in a patient with myelodysplastic syndrome: a case report

    Directory of Open Access Journals (Sweden)

    H. Cai

    2016-01-01

    Full Text Available This study reports a case of a gonadotropin-releasing hormone agonist trigger in a young female with myelodysplastic syndrome (MDS who underwent fertility preservation using random-start controlled ovarian stimulation. This method involves the stimulation of the ovary regardless of a patient's menstrual-cycle phase. A review of the related literature is also provided. A 17-year-old patient was diagnosed with MDS and required initiation of peripheral blood stem cell transplantation within a maximum of 3 weeks and was in the luteal phase of the menstrual cycle when the possibility of attempting preservation of fertility was presented to her. She opted for a random-start controlled ovarian stimulation with gonadotropins. With successful hemorrhagic prophylaxis, 17 oocytes were retrieved including 10 mature and 7 immature oocytes. Of the immature oocytes, 3 were successfully matured in vitro and a vitrification protocol was used to freeze the 13 mature oocytes.

  7. Identification of SNP-containing regulatory motifs in the myelodysplastic syndromes model using SNP arrays and gene expression arrays

    Institute of Scientific and Technical Information of China (English)

    Jing Fan; Jennifer G.Dy; Chung-Che Chang; Xiaobo Zhou

    2013-01-01

    Myelodysplastic syndromes have increased in frequency and incidence in the American population,but patient prognosis has not significantly improved over the last decade.Such improvements could be realized if biomarkers for accurate diagnosis and prognostic stratification were successfully identified.In this study,we propose a method that associates two state-of-the-art array technologies-single nucleotide polymorphism (SNP) array and gene expression array-with gene motifs considered transcription factor-binding sites (TFBS).We are particularly interested in SNP-containing motifs introduced by genetic variation and mutation as TFBS.The potential regulation of SNP-containing motifs affects only when certain mutations occur.These motifs can be identified from a group of co-expressed genes with copy number variation.Then,we used a sliding window to identify motif candidates near SNPs on gene sequences.The candidates were filtered by coarse thresholding and fine statistical testing.Using the regression-based LARS-EN algorithm and a level-wise sequence combination procedure,we identified 28 SNP-containing motifs as candidate TFBS.We confirmed 21 of the 28 motifs with ChIP-chip fragments in the TRANSFAC database.Another six motifs were validated by TRANSFAC via searching binding fragments on coregulated genes.The identified motifs and their location genes can be considered potential biomarkers for myelodysplastic syndromes.Thus,our proposed method,a novel strategy for associating two data categories,is capable of integrating information from different sources to identify reliable candidate regulatory SNP-containing motifs introduced by genetic variation and mutation.

  8. Therapy reduction in patients with Down syndrome and myeloid leukemia

    DEFF Research Database (Denmark)

    Uffmann, Madita; Rasche, Mareike; Zimmermann, Martin

    2017-01-01

    Children with myeloid leukemia associated with Down syndrome (ML-DS) have superior outcome compared with non-DS patients, but suffer from higher constitutional cytotoxic drug susceptibility. We analyzed the outcome of 170 pediatric patients with ML-DS enrolled in the prospective, multicenter, open......-label, nonrandomized ML-DS 2006 trial by Nordic Society for Pediatric Hematology and Oncology (NOPHO), Dutch Childhood Oncology Group (DCOG), and Acute Myeloid Leukemia-Berlin-Frankfurt-Münster (AML-BFM) study group. Compared with the historical control arm (reduced-intensity protocol for ML-DS patients from the AML...

  9. The Danish National Acute Leukemia Registry

    DEFF Research Database (Denmark)

    Østgård, Lene Sofie Granfeldt; Nørgaard, Jan Maxwell; Raaschou-Jensen, Klas Kræsten

    2016-01-01

    AIM OF DATABASE: The main aim of the Danish National Acute Leukemia Registry (DNLR) was to obtain information about the epidemiology of the hematologic cancers acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), and myelodysplastic syndrome (MDS). STUDY POPULATION: The registry...... was established in January 2000 by the Danish Acute Leukemia Group and has been expanded over the years. It includes adult AML patients diagnosed in Denmark since 2000, ALL patients diagnosed since 2005, and MDS patients diagnosed since 2010. The coverage of leukemia patients exceeds 99%, and the coverage of MDS...... years. To ensure this high coverage, completeness, and quality of data, linkage to the Danish Civil Registration System and the Danish National Registry of Patients, and several programmed data entry checks are used. CONCLUSION: The completeness and positive predictive values of the leukemia data have...

  10. [Decitabine treatment in myelodysplastic syndromes--results of a compassionate patient program in Israel].

    Science.gov (United States)

    Klepfish, Abraham; Silbershatz, Itay; Lugassy, Gilles; Shimoni, Avichai; Mittelman, Moshe

    2013-10-01

    Hypermethylation of tumor suppressor genes (TSG) has been recognized as an important factor in the pathogenesis of malignancies, including myelodysplastic syndromes (MDS). Decitabine (trade name Dacogen; 5-aza-2'-deoxycytidine) is a cytosine analog which inhibits the enzyme DNA methyltransferase (DNMT), inducing hypomethylation and activates TSG, leading to tumor cell growth inhibition. In clinical trials with hypomethylating agents in advanced MDS, a total response rate of 30-73% has been observed, with a complete response (CR) of 9-37%, partial response (PR] of similar rate and a hematologic improvement (HI] in 20-48% of the patients. We report the results of a national Israeli compassionate program of decitabine administration to patients with advanced MDS. From July 2007 through August 2008, under the joint sponsorship of The Israel Society of Hematology and Blood Transfusions and Janssen, Israel, a compassionate program was conducted. Decitabine was administered to patients with advanced MDS who were not candidates for any other anti-MDS treatment, except for supportive care. The selected regimen was a 5-day intravenous administration of 20 mg/m/d, every 28 days. After the program had been completed, an approval of the institutional Helsinki committees was obtained, and the data were collected in an attempt to evaluate the results of this novel treatment. The standard response criteria, i.e. total response, CR, PR and HI were applied. Toxicity, survival and leukemic transformation rate were also analyzed. Twenty-four patients with advanced MDS participated in the program but evaluable information could be collected only on 17 patients. The median number of therapeutic cycles was two per patient. Twelve patients were transfusion-dependent at program onset, of whom 7 either benefited from reduced transfusion requirements or became transfusion-free. The overall response rate was 26%, with 23% PR and 13% HI. Two patients (13%) demonstrated leukemic transformation

  11. Veliparib and Temozolomide in Treating Patients With Acute Leukemia

    Science.gov (United States)

    2016-12-19

    Accelerated Phase of Disease; Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(8;21); (q22; q22.1); RUNX1-RUNX1T1; Adult Acute Myeloid Leukemia With t(9;11)(p22.3;q23.3); MLLT3-KMT2A; Adult Acute Promyelocytic Leukemia With PML-RARA; Adult B Acute Lymphoblastic Leukemia; Adult B Acute Lymphoblastic Leukemia With t(9;22)(q34.1;q11.2); BCR-ABL1; Adult T Acute Lymphoblastic Leukemia; Alkylating Agent-Related Acute Myeloid Leukemia; Blastic Phase; Chronic Myelomonocytic Leukemia; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Disease; Secondary Acute Myeloid Leukemia; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Myeloid Leukemia

  12. Myelodysplastic and myeloproliferative disorders of childhood

    DEFF Research Database (Denmark)

    Hasle, Henrik

    2016-01-01

    Myelodysplastic syndrome (MDS) and myeloproliferative disorders are rare in children; they are divided into low-grade MDS (refractory cytopenia of childhood [RCC]), advanced MDS (refractory anemia with excess blasts in transformation), and juvenile myelomonocytic leukemia (JMML), each...... with refractory anemia with excess blasts are candidates for HSCT; children age 12 years or older have a higher risk of treatment-related death, and the conditioning regimens should be adjusted accordingly. Unraveling the genetics of JMML has demonstrated that JMML in patients with germ line PTPN11 and CBL...... with different characteristics and management strategies. Underlying genetic predisposition is recognized in an increasing number of patients. Germ line GATA2 mutation is found in 70% of adolescents with MDS and monosomy 7. It is challenging to distinguish RCC from aplastic anemia, inherited bone marrow failure...

  13. Real-world analysis of the Celgene Global Drug Safety database: early discontinuation of lenalidomide in patients with myelodysplastic syndromes due to non-serious rash

    OpenAIRE

    Weiss L; Gary D; Swern AS; Freeman J.; Sugrue MM

    2015-01-01

    Lilia Weiss,1 Dianna Gary,1 Arlene S Swern,2 John Freeman,1 Mary M Sugrue3 1Global Drug Safety, Celgene Corporation, Summit, 2Biometrics, Celgene Corporation, Berkeley Heights, 3Medical Affairs, Celgene Corporation, Summit, NJ, USA Background: Lenalidomide is approved for treating transfusion-dependent anemia due to lower-risk del(5q) myelodysplastic syndromes (MDS). In clinical trials, rash was common, although severe rash was infrequent. To examine rash in patients with MDS treated with l...

  14. The abnormalities of microenvironment in myelodysplastic syndrome%骨髓增生异常综合征中的微环境异常

    Institute of Scientific and Technical Information of China (English)

    钱军; 陈子兴

    2003-01-01

    Myelodysplastic syndrome (MDS) is considered as a preleukemic course, characteristic of hypercellular marrow and pancytopenia. Many studies have demonstrated that defects occur in the heamtopoiet-ic cells from patients with MDS. Recently, many abnormal changes in apoptosis, proliferation, ability of hematopoietic support, cytokine secretion, clonal origin of stromal cells and angiogenesis have also been re-vealed in the bone marrow mieroenvironment of MDS patients.

  15. Decitabine and Midostaurin in Treating Older Patients With Newly Diagnosed Acute Myeloid Leukemia

    Science.gov (United States)

    2016-04-25

    Acute Myeloid Leukemia (AML) With Multilineage Dysplasia Following Myelodysplastic Syndrome, in Adults; AML (Adult) With 11q23 (MLL) Abnormalities; AML (Adult) With Del(5q); AML (Adult) With Inv(16)(p13;q22); AML (Adult) With t(16;16)(p13;q22); AML (Adult) With t(8;21)(q22;q22); Secondary AML (Adult); Untreated AML (Adult)

  16. [Tumor lysis syndrome in a pregnancy complicated with acute lymphoblastic leukemia].

    Science.gov (United States)

    Álvarez-Goris, M P; Sánchez-Zamora, R; Torres-Aguilar, A A; Briones Garduño, J C

    2016-04-01

    Acute leukemia is rare during pregnancy, affects about 1 in 75,000 pregnancies, of all leukemias diagnosed only 28% are acute lymphoblastic leukemia, this is a risk factor to develop spontaneous tumor lysis syndrome, it's a oncologic complication potentially deadly if the prophylactic treatment its avoided. Cases of acute lymphoblastic leukemia associated with pregnancy has been poorly documented in the literature the association of these two entities to pregnancy is the first report published worldwide, so the information is limited.

  17. Azacitidine and Sonidegib or Decitabine in Treating Patients With Myeloid Malignancies

    Science.gov (United States)

    2016-05-25

    Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndrome; Essential Thrombocythemia; Myelodysplastic Syndrome; Myelodysplastic/Myeloproliferative Neoplasm; Polycythemia Vera; Previously Treated Myelodysplastic Syndrome; Primary Myelofibrosis; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  18. Juvenile myelomonocytic leukemia presenting as bilateral breast masses

    Energy Technology Data Exchange (ETDEWEB)

    Edison, Michele N.; Letter, Haley P. [Florida Hospital, Department of Radiology, Orlando, FL (United States); University of Central Florida, College of Medicine, Orlando, FL (United States); O' Dell, M.C. [University of Central Florida, College of Medicine, Orlando, FL (United States); Children' s Hospital of Philadelphia, Pediatric Radiology, Philadelphia, PA (United States); Scherer, Kurt; Williams, Jennifer L. [Florida Hospital, Department of Radiology, Orlando, FL (United States); University of Central Florida, College of Medicine, Orlando, FL (United States); Florida State University, College of Medicine, Tallahassee, FL (United States)

    2017-01-15

    An 8-year-old girl presented with bilateral breast masses and was subsequently diagnosed with juvenile myelomonocytic leukemia. Juvenile myelomonocytic leukemia is a rare myelodysplastic syndrome that typically presents in boys younger than 3 years of age with splenomegaly, lymphadenopathy and skin findings. Bilateral breast masses in a child are rare and, as such, present a diagnostic dilemma due to the relative paucity of cases in the literature. We present a case of granulocytic sarcoma of the breasts in a patient with juvenile myelomonocytic leukemia. The authors hope that increased reporting and research regarding pediatric breast masses will help create awareness for such cases. (orig.)

  19. Obesity and Metabolic Syndrome Among Adult Survivors of Childhood Leukemia.

    Science.gov (United States)

    Gibson, Todd M; Ehrhardt, Matthew J; Ness, Kirsten K

    2016-04-01

    Treatment-related obesity and the metabolic syndrome in adult survivors of childhood acute lymphoblastic leukemia (ALL) are risk factors for cardiovascular disease. Both conditions often begin during therapy. Preventive measures, including dietary counseling and tailored exercise, should be initiated early in the course of survivorship, with referral to specialists to optimize success. However, among adults who develop obesity or the metabolic syndrome and who do not respond to lifestyle therapy, medical intervention may be indicated to manage underlying pathology, such as growth hormone deficiency, or to mitigate risk factors of cardiovascular disease. Because no specific clinical trials have been done in this population to treat metabolic syndrome or its components, clinicians who follow adult survivors of childhood ALL should use the existing American Heart Association/National Heart Lung and Blood Institute Scientific Statement to guide their approach.

  20. Results of a randomized, double-blind study of romiplostim versus placebo in patients with low/intermediate-1–risk myelodysplastic syndrome and thrombocytopenia

    Science.gov (United States)

    Giagounidis, Aristoteles; Mufti, Ghulam J; Fenaux, Pierre; Sekeres, Mikkael A; Szer, Jeffrey; Platzbecker, Uwe; Kuendgen, Andrea; Gaidano, Gianluca; Wiktor-Jedrzejczak, Wieslaw; Hu, Kuolung; Woodard, Paul; Yang, Allen S; Kantarjian, Hagop M

    2014-01-01

    BACKGROUND Thrombocytopenia in patients with myelodysplastic syndrome (MDS) is associated with shortened survival and an increased risk of evolution to acute myeloid leukemia (AML). In this study, the authors evaluated the efficacy of romiplostim in patients who had thrombocytopenia with low-risk/intermediate-1–risk MDS. METHODS Patients who had thrombocytopenia with low-risk/intermediate-1–risk MDS (N = 250) were randomized 2:1 to receive romiplostim or placebo weekly for 58 weeks. RESULTS The primary endpoint— the number of clinically significant bleeding events (CSBEs) per patient—had a hazard ratio for romiplostim:placebo of 0.83 (95% confidence interval, 0.66-1.05; P = .13). CSBEs were reduced significantly in the romiplostim group for patients who had baseline platelet counts ≥20 × 109/L (P < .0001). For patients who had baseline platelet counts <20 × 109/L, there was no difference in the number of CSBEs, but the platelet transfusion rates were higher in the placebo group (P < .0001), which may have affected the overall CSBE results in this group with severe thrombocytopenia. The incidence of bleeding events was reduced significantly in the romiplostim group (relative risk, 0.92), as were protocol-defined platelet transfusions (relative risk, 0.77). Platelet response rates according to 2006 International Working Group criteria were higher for the group that received romiplostim (odds ratio, 15.6). On the basis of interim data, an independent data monitoring committee advised halting study drug because of concerns regarding excess blasts and AML rates with romiplostim (interim hazard ratio, 2.51). At 58 weeks, the AML rates were 6% in the romiplostim group and 4.9% in the placebo group (hazard ratio, 1.20; 95% confidence interval, 0.38-3.84), and the overall survival rates were similar. CONCLUSIONS Romiplostim treatment in patients with low-risk/intermediate-1–risk MDS increased platelet counts and decreased the number of

  1. Copy number neutral loss of heterozygosity at 17p and homozygous mutations of TP53 are associated with complex chromosomal aberrations in patients newly diagnosed with myelodysplastic syndromes.

    Science.gov (United States)

    Svobodova, Karla; Zemanova, Zuzana; Lhotska, Halka; Novakova, Milena; Podskalska, Lucie; Belickova, Monika; Brezinova, Jana; Sarova, Iveta; Izakova, Silvia; Lizcova, Libuse; Berkova, Adela; Siskova, Magda; Jonasova, Anna; Cermak, Jaroslav; Michalova, Kyra

    2016-03-01

    Complex karyotypes are seen in approximately 20% of patients with myelodysplastic syndromes (MDS) and are associated with a high risk of transformation to acute myeloid leukemia and poor outcomes in patients. Copy number neutral loss of heterozygosity (CN-LOH, i.e., both copies of a chromosomal pair or their parts originate from one parent) might contribute to increased genomic instability in the bone-marrow cells of patients with MDS. The pathological potential of CN-LOH, which arises as a clonal aberration in a proportion of somatic cells, consists of tumor suppressor gene and oncogene homozygous mutations. The aim of our study was to evaluate the frequency of CN-LOH at 17p in bone-marrow cells of newly diagnosed MDS patients with complex chromosomal aberrations and to assess its correlation with mutations in the TP53 gene (17p13.1). CN-LOH was detected in 40 chromosomal regions in 21 (29%) of 72 patients analyzed. The changes in 27 of the 40 regions identified were sporadic. The most common finding was CN-LOH of the short arm of chromosome 17, which was detected in 13 (18%) of 72 patients. A mutational analysis confirmed the homozygous mutation of TP53 in all CN-LOH 17p patients, among which two frameshift mutations are not registered in the International Agency for Research on Cancer TP53 Database. CN-LOH 17p correlated with aggressive disease (median overall survival 4 months) and was strongly associated with a complex karyotype in the cohort studied, which might cause rapid disease progression in high-risk MDS. No other CN-LOH region previously recorded in MDS or AML patients (1p, 4q, 7q, 11q, 13q, 19q, 21q) was detected in our cohort of patients with complex karyotype examined at the diagnosis of MDS. The LOH region appeared to be balanced (i.e., with no DNA copy number change) when examined with conventional and molecular cytogenetic methods. Therefore, a microarray that detects single-nucleotide polymorphisms is an ideal method with which to identify and

  2. Two novel RUNX1 mutations in a patient with congenital thrombocytopenia that evolved into a high grade myelodysplastic syndrome

    Directory of Open Access Journals (Sweden)

    Jessica M. Schmit

    2015-01-01

    Full Text Available Here we report two new RUNX1 mutations in one patient with congenital thrombocytopenia that transformed into a high grade myelodysplastic syndrome with myelomonocytic features. The first mutation was a nucleotide base substitution from guanine to adenine within exon 8, resulting in a nonsense mutation in the DNA-binding inhibitory domain of the Runx1 protein. This nonsense mutation is suspected a de novo germline mutation since both parents are negative for the mutation. The second mutation identified was an in-frame six nucleotide base pair insertion in exon 5 of the RUNX1 gene, which is predicted to result in an insertion in the DNA-binding runt homology domain (RHD. This mutation is believed to be a somatic mutation as it was mosaic before allogeneic hematopoietic cell transplantation and disappeared after transplant. As no other genetic mutation was found using genetic screening, it is speculated that the combined effect of these two RUNX1 mutations may have exerted a stronger dominant negative effect than either RUNX1 mutation alone, thus leading to a myeloid malignancy.

  3. A comparative study of deferasirox and deferiprone in the treatment of iron overload in patients with myelodysplastic syndromes.

    Science.gov (United States)

    Cermak, Jaroslav; Jonasova, Anna; Vondrakova, Jana; Cervinek, Libor; Belohlavkova, Petra; Neuwirtova, Radana

    2013-12-01

    One hundred thirteen patients with myelodysplastic syndromes (MDS) with deferasirox in a daily dose of 10-40 mg/kg (65 patients). Median duration of treatment was 10,9 months for deferiprone and 13,7 months for deferasirox. A substantial reduction of iron stores evaluated as a decrease in serum ferritin of more than 50% of pretreatment level was achieved in 18 patients in deferasirox group (27.7%) but not in any patient treated with deferiprone, The incidence of adverse effects (mostly gastrointestinal symptoms) was similar after administration of both the drugs. The symptoms of deferasirox toxicity were mild and mostly transient and no drug related myelosuppresive effect was observed in contrast to deferiprone where agranulocytosis occurred in 4% of patients and the treatment had to be discontinued due to side effects in 20% of patients. The results confirmed the usefulness of deferasirox as an effective and safe iron chelator in MDS patients and indication of deferiprone as an alternative treatment only in patients with mild or moderate iron overload clearly not indicated for deferasirox.

  4. Quantitative Detection of ID4 Gene Aberrant Methylation in the Differentiation of Myelodysplastic Syndrome from Aplastic Anemia

    Institute of Scientific and Technical Information of China (English)

    Mian-Yang Li; Yuan-Yuan Xu; Hui-Yuan Kang; Xin-Rong Wang; Li Gao; Jian Cen; Wei Wang

    2015-01-01

    Background:The diagnosis of myelodysplastic syndrome (MDS),especially hypoplastic MDS,and MDS with low blast counts or normal karyotype may be problematic.This study characterized ID4 gene methylation in patients with MDS and aplastic anemia (AA).Methods:The methylation status ofID4 was analyzed by bisulfite sequencing polymerase chain reaction (PCR) and quantitative real-time methylation-specific PCR (MethyLight PCR) in 100 patients with MDS and 31 patients with AA.Results:The MDS group had a higher ID4 gene methylation positivity rate (22.22%) and higher methylation levels (0.21 [0-3.79]) than the AA group (P < 0.05).Furthermore,there were significant differences between the hypoplastic MDS and AA groups,the MDS with low blast count and the AA groups,and the MDS with normal karyotype and the AA groups.The combination of genetic and epigenetic markers was used in much more patients with MDS (62.5% [35/56]) than the use of genetic markers only (51.79% [29/56]).Conclusions:These results showed that the detection ofID4 methylation positivity rates and levels could be a useful biomarker for MDS diagnosis.

  5. Sonic Hedgehog Produced by Bone Marrow-Derived Mesenchymal Stromal Cells Supports Cell Survival in Myelodysplastic Syndrome

    Directory of Open Access Journals (Sweden)

    Jixue Zou

    2015-01-01

    Full Text Available The role of marrow microenvironment in the pathogenesis of myelodysplastic syndrome (MDS remains controversial. Therefore, we studied the influence of bone marrow-derived mesenchymal stromal cells (BMSCs from patients with different risk types of MDS on the survival of the MDS cell lines SKM-1 and MUTZ-1. We first demonstrated that the expression of Sonic hedgehog (Shh, smoothened (Smo, and glioma-associated oncogene homolog 1 (Gli1 was increased in MDS patients n=23; the increase in expression was positively correlated with the presence of high-risk factors. The Shh signaling inhibitor, cyclopamine, inhibited high-risk MDS BMSC-induced survival of SKM-1 and MUTZ-1 cells, suggesting a role for Shh signaling in MDS cell survival. Furthermore, cyclopamine-mediated inhibition of Shh signaling in SKM-1 and MUTZ-1 cells resulted in decreased DNMT1 expression and cell survival; however, exogenous Shh peptide had the opposite effect, suggesting that Shh signaling could regulate the expression of DNMT1, thereby modulating cell survival in MDS. In addition, the apoptosis of SKM-1 and MUTZ-1 cell increased significantly when cultured with cyclopamine and a demethylation agent, 5-Aza-2′-deoxycytidine. These findings suggest that Shh signaling from BMSCs is important in the pathogenesis of MDS and could play a role in disease progression by modulating methylation.

  6. Role of chromosome 1 pericentric heterochromatin (1q) in pathogenesis of myelodysplastic syndromes: report of 2 new cases.

    Science.gov (United States)

    Millington, Karmaine; Hudnall, S David; Northup, Jill; Panova, Neli; Velagaleti, Gopalrao

    2008-04-01

    Chromosome 1 pericentromeric heterochromatin (1q) has been shown to play an important role in the pathogenesis of non-Hodgkin lymphoma and multiple myeloma. Myelodysplastic syndrome (MDS) results from marrow failure in two or more cell lineages. Although trisomy 1q has been reported in MDS, it is usually present with additional common abnormalities such as trisomy 8, monosomy 5 or monosomy 7, leading to speculation that 1q abnormalities are mostly secondary events representing clonal evolution. We report two cases of MDS in which consistent involvement of 1q heterochromatin is seen as the primary clonal abnormality. Both patients presented with fatigue and pancytopenia. Based on the published reports and our cases, we propose that the 1q heterochromatin plays a vital role in the pathophysiology of MDS. Abnormalities involving 1q result in aberrant heterochromatin/euchromatin junctions, leading to gene dosage abnormalities. Further studies of 1q abnormalities in MDS might provide specific insights as to the exact role of the excess 1q heterochromatin in the etiology of MDS.

  7. Risk of myelodysplastic syndromes in people exposed to ionizing radiation: a retrospective cohort study of Nagasaki atomic bomb survivors.

    Science.gov (United States)

    Iwanaga, Masako; Hsu, Wan-Ling; Soda, Midori; Takasaki, Yumi; Tawara, Masayuki; Joh, Tatsuro; Amenomori, Tatsuhiko; Yamamura, Masaomi; Yoshida, Yoshiharu; Koba, Takashi; Miyazaki, Yasushi; Matsuo, Tatsuki; Preston, Dale L; Suyama, Akihiko; Kodama, Kazunori; Tomonaga, Masao

    2011-02-01

    The risk of myelodysplastic syndromes (MDS) has not been fully investigated among people exposed to ionizing radiation. We investigate MDS risk and radiation dose-response in Japanese atomic bomb survivors. We conducted a retrospective cohort study by using two databases of Nagasaki atomic bomb survivors: 64,026 people with known exposure distance in the database of Nagasaki University Atomic-Bomb Disease Institute (ABDI) and 22,245 people with estimated radiation dose in the Radiation Effects Research Foundation Life Span Study (LSS). Patients with MDS diagnosed from 1985 to 2004 were identified by record linkage between the cohorts and the Nagasaki Prefecture Cancer Registry. Cox and Poisson regression models were used to estimate relationships between exposure distance or dose and MDS risk. There were 151 patients with MDS in the ABDI cohort and 47 patients with MDS in the LSS cohort. MDS rate increased inversely with exposure distance, with an excess relative risk (ERR) decay per km of 1.2 (95% CI, 0.4 to 3.0; P atomic bomb survivors 40 to 60 years after radiation exposure. Clinicians should perform careful long-term follow-up of irradiated people to detect MDS as early as possible.

  8. Research progress of myelodysplastic syndrome%骨髓增生异常综合征研究进展

    Institute of Scientific and Technical Information of China (English)

    何广胜

    2014-01-01

    骨髓增生异常综合征(myelodysplastic syndromes,MDS)亚克隆在低危组就达到很高比例,驱动基因导致疾病进展.RNA剪接子复合物基因突变与MDS有较高相对特异性,并与疾病临床表现和顸后相关.MDS的难治性血胞减少伴单系病态造血(refractory cytopenia with unilineage dysplasia,RCUD)中各亚型,MDS-U(MDS-unclassified,MDS-U)和MDS-RCMD(MDS-refractory cytopenia with multilineage dysplasia,MDS-RCMD)之间,病态造血、生存率和转白率无显著差异.IPSS的修订版和合并症指数更好地对MDS患者的预后和机体状态做出评价.规则去铁治疗可能改善MDS患者生活质量、生存期.促红细胞生成素早期失败者转白率和生存率均差.去甲化药物中阿扎胞苷可能疗效更佳.

  9. Oral Ezatiostat HCl (TLK199) and Myelodysplastic syndrome: a case report of sustained hematologic response following an abbreviated exposure.

    Science.gov (United States)

    Quddus, Fahd; Clima, Jessica; Seedham, Helen; Sajjad, Ghulam; Galili, Naomi; Raza, Azra

    2010-04-23

    Treatment options for patients with lower risk non-del(5q) myelodysplastic syndromes (MDS) who fail erythroid stimulating agents are restricted to one of the hypomethylating drugs with an expected response rate of approximately 50%. Ezatiostat HCl, an agent with the potential for producing multi-lineage responses in this population is currently in clinical investigation phase. This case report describes a 77 year old male who received less than two cycles of therapy with ezatiostat HCl which had to be aborted due to intolerable side effects, but which produced a sustained normalization of all three blood counts. This trilineage response has now lasted for more than a year. Interestingly, the patient began with a del(5q) abnormality and responded briefly to lenalidomide. Upon relapse of the anemia, a bone marrow showed the disappearance of the del(5q) but the appearance of a new clonal abnormality t(2;3). Given that the patient had a complete cytogenetic response to a truncated exposure to lenalidomide followed by a trilineage response to an even briefer course of ezatiostat HCl suggests a potential role for ezatiostat HCl in del(5q) patients who relapse following lenalidomide.

  10. Downregulation of hTERT: an important As2O3 induced mechanism of apoptosis in myelodysplastic syndrome.

    Directory of Open Access Journals (Sweden)

    Weilai Xu

    Full Text Available Two myelodysplastic syndrome (MDS cell lines, MUTZ-1 and SKM-1 cells, were used to study the effect of arsenic trioxide (As2O3 on hematological malignant cells. As2O3 induced this two cell lines apoptosis via activation of caspase-3/8 and cleavage of poly (ADP-ribose polymerase (PARP, a DNA repair enzyme. As2O3 reduced NF-κB activity, which was important for inducing MUTZ-1 and SKM-1 cells apoptosis. As2O3 also inhibited the activities of hTERT in MUTZ-1 and SKM-1 cells. Moreover, the NF-κB inhibitor, pyrrolidine dithiocarbamate (PDTC, had no effect on caspase-8 activation, although PDTC did inhibit MUTZ-1 and SKM-1 cells proliferation. Incubation of MUTZ-1 cells with a caspase-8 inhibitor failed to block As2O3-induced inhibition of NF-κB activity. Our findings suggest that As2O3 may induce apoptosis in MUTZ-1 and SKM-1 cells by two independent pathways: first, by activation of caspase-3/8 and PARP; and second, by inhibition of NF-κB activity, which results in downregulation of hTERT expression. We conclude that hTERT and NF-κB are important molecular targets in As2O3-induced apoptosis.

  11. Proteome Changes in the Plasma of Myelodysplastic Syndrome Patients with Refractory Anemia with Excess Blasts Subtype 2

    Directory of Open Access Journals (Sweden)

    Pavel Majek

    2014-01-01

    Full Text Available The goal of this study was to explore the plasma proteome of myelodysplastic syndrome (MDS patients with refractory anemia with excess blasts subtype 2 (RAEB-2 in comparison to healthy controls. 20 plasma samples were separated with 2D electrophoresis and statistically processed with Progenesis SameSpots software. 47 significantly differing (P<0.05 spots were observed, and 27 different proteins were identified by nano-LC-MS/MS. Mass spectrometry-based relative label-free quantification showed a 2-fold increase of the leucine-rich alpha-2-glycoprotein (LRAG peptide levels in the RAEB-2 group. Changes in the fragments of the inter-alpha-trypsin inhibitor heavy chain H4 (ITIH4 protein were observed. Western blot analysis showed no differences in albumin and ITIH4 levels, while increased expression was observed for LRAG in the RAEB-2 group. Quantification using ELISA showed decreased plasma level of alpha-2-HS glycoprotein in the RAEB-2 group. In conclusion, this is the first time that alpha-2-HS glycoprotein and LRAG were proposed as new biomarkers of RAEB-2 and advanced MDS, respectively. Alpha-2-HS glycoprotein, a protein involved in the bone marrow development and previously proposed as a MDS biomarker candidate, was significantly decreased in RAEB-2. Increased expression and changes in modification(s were observed for LRAG, a protein involved in granulocytic and neutrophil differentiation, and angiogenesis.

  12. A phase II Open-label Study of the Intravenous Administration of Homoharringtonine in the treatment of Myelodysplastic syndrome

    Science.gov (United States)

    Daver, Naval; Vega-Ruiz, Arturo; Kantarjian, Hagop M.; Estrov, Zeev; Ferrajoli, Alessandra; Kornblau, Steve; Verstovsek, Srdan; Garcia-Manero, Guillermo; Cortes, Jorge E.

    2013-01-01

    Homoharringtonine is an alkaloid inhibitor of protein synthesis with activity in myeloid malignancies. We report a phase II pilot study of homoharringtonine in myelodysplastic syndrome (MDS). Induction consisted of homoharringtonine at 2.5 mg/m2 via continuous infusion for seven days. Maintenance was given every 4 weeks. Nine patients were enrolled: five with refractory anaemia with excess blasts, two with refractory anaemia with excess blasts in transformation, one each with refractory anaemia and chronic myelomonocytic leukaemia, respectively. Median age was 70 years (55–84) and 6 (66%) were male. Per International Prognostic Scoring System (IPSS) two patients were intermediate-1, five intermediate-2 and two high-risk. Median chemotherapy courses were one (1–3). One patient (11%) responded with complete hematologic and cytogenetic remission after one course. Eight patients did not respond (four had stable disease, two progressed to acute leukaemia and two died during induction - from aspergillus pneumonia and intracerebral haemorrhage, respectively). Grade 3/4 myelosuppression seen in 56% (5/9). Serious non-hematologic toxicities included one case of grade 4 left bundle branch heart block and one grade 3 nephrotoxicity. Median time between courses was 42 days (35–72 days). In conclusion homoharringtonine might have clinical activity in some patients with MDS. PMID:23701251

  13. Deferasirox Decreases Liver Iron Concentration in Iron-Overloaded Patients with Myelodysplastic Syndromes, Aplastic Anemia and Other Rare Anemias.

    Science.gov (United States)

    Kohgo, Yutaka; Urabe, Akio; Kilinç, Yurdanur; Agaoglu, Leyla; Warzocha, Krzysztof; Miyamura, Koichi; Lim, Lay Cheng; Glaser, Sabine; Wang, Candace; Wiktor-Jedrzejczak, Wieslaw

    2015-01-01

    Iron overload in transfusion-dependent patients with rare anemias can be managed with chelation therapy. This study evaluated deferasirox efficacy and safety in patients with myelodysplastic syndromes (MDS), aplastic anemia (AA) or other rare anemias. A 1-year, open-label, multicenter, single-arm, phase II trial was performed with deferasirox (10–40 mg/kg/day, based on transfusion frequency and therapeutic goals), including an optional 1-year extension. The primary end point was a change in liver iron concentration (LIC) after 1 year. Secondary end points included changes in efficacy and safety parameters (including ophthalmologic assessments) overall as well as in a Japanese subpopulation. Overall, 102 patients (42 with MDS, 29 with AA and 31 with other rare anemias) were enrolled; 57 continued into the extension. Mean absolute change in LIC was –10.9 mg Fe/g dry weight (d.w.) after 1 year (baseline: 24.5 mg Fe/g d.w.) and –13.5 mg Fe/g d.w. after 2 years. The most common drug-related adverse event was increased serum creatinine (23.5%), predominantly in MDS patients. Four patients had suspected drug-related ophthalmologic abnormalities. Outcomes in Japanese patients were generally consistent with the overall population. Results confirm deferasirox efficacy in patients with rare anemias, including a Japanese subpopulation. The safety profile was consistent with previous studies and ophthalmologic parameters generally agreed with baseline values (EUDRACT 2006-003337-32).

  14. Higher Risk Myelodysplastic Syndromes in Patients with Well-Controlled HIV Infection: Clinical Features, Treatment, and Outcome

    Directory of Open Access Journals (Sweden)

    Bradley T. Williamson

    2016-01-01

    Full Text Available Introduction. In advanced HIV prior to combination antiretroviral therapy (ART, dysplastic marrow changes occurred and resolved with ART. Few reports of myelodysplastic syndromes (MDS in well-controlled HIV exist and management is undefined. Methods. Patients with well-controlled HIV and higher risk MDS were identified; characteristics, treatment, and outcomes were reviewed. Results. Of 292 MDS patients since 1996, 1 (0.3% was HIV-positive. A 56-year-old woman presented with cytopenias. CD4 was 1310 cells/mL and HIV viral load <40 copies/mL. Bone marrow biopsy showed RCMD and karyotype included del(5q and del(7q; IPSS was intermediate-2 risk. She received azacitidine at 75% dose. Cycle 2, at full dose, was complicated by marrow aplasia and possible AML; she elected palliation. Three additional HIV patients with higher risk MDS, aged 56–64, were identified from the literature. All had deletions involving chromosomes 5 and 7. MDS treatment of 2 was not reported and one received palliation; all died of AML. Conclusion. Four higher risk MDS in well-controlled HIV were below the median age of diagnosis for HIV-negative patients; all had adverse karyotype. This is the first report of an HIV patient receiving MDS treatment with azacitidine. Cytopenias were profound and dosing in HIV patients should be considered with caution.

  15. Prognostic value of trisomy 8 as a single anomaly and the influence of additional cytogenetic aberrations in primary myelodysplastic syndromes.

    Science.gov (United States)

    Saumell, Sílvia; Florensa, Lourdes; Luño, Elisa; Sanzo, Carmen; Cañizo, Consuelo; Hernández, Jesus M; Cervera, José; Gallart, Miguel A; Carbonell, Félix; Collado, Rosa; Arenillas, Leonor; Pedro, Carme; Bargay, Joan; Nomdedeu, Benet; Xicoy, Blanca; Vallespí, Teresa; Raya, José M; Belloch, Luis; Sanz, Guillermo F; Solé, Francesc

    2012-11-01

    Trisomy 8 is the most common chromosomal gain in myelodysplastic syndromes (MDS), however, little is known about the features of MDS with isolated trisomy 8 and the influence of additional cytogenetic aberrations. We determined the characteristics and prognostic factors of 72 patients with trisomy 8 as a single anomaly and analysed also the impact of other aberrations added to trisomy 8 in another 62 patients. According to our study, MDS with isolated trisomy 8 was more frequent in men, with more than one cytopenia in most patients (62%) and having about 4% bone marrow blasts. The multivariate analysis demonstrated that platelet count and percentage bone marrow blasts had the strongest impact on overall survival (OS). The median OS for isolated trisomy 8, trisomy 8 plus one aberration (tr8 + 1), plus two (tr8 + 2) and plus three or more aberrations (tr8 + ≥3) was 34·3, 40, 23·4 and 5·8 months, respectively (P < 0·001). Trisomy 8 confers a poorer prognosis than a normal karyotype in MDS patients with ≥5% bone marrow blasts. This study supports the view that MDS with isolated trisomy 8 should be included in the intermediate cytogenetic risk group. © 2012 Blackwell Publishing Ltd.

  16. Analysis of the efficacy of lenalidomide in patients with intermediate-1 risk myelodysplastic syndrome without 5q deletion.

    Science.gov (United States)

    Yang, Yan; Gao, Sujun; Fan, Hongqiong; Lin, Hai; Li, Wei; Wang, Juan

    2013-09-01

    The aim of this study was to evaluate the efficacy and adverse effects of lenalidomide in the treatment of intermediate-1 risk non-5q deletion [non-del (5q)] myelodysplastic syndrome (MDS). A total of 30 patients with MDS were classified through G-banding chromosome karyotype analysis and fluorescence in situ hybridization (FISH). According to the International Prognostic Scoring System scores, among the 30 patients, 23 and seven cases had scores of 0.5 and 1.0, respectively. Lenalidomide (Revlimid(®)), 10 mg/day) was administered for 21 days every 28 days. All 30 cases were treated with lenalidomide for at least three cycles, including 20 cases with four cycles. The patients did not require erythropoietin, cyclosporine or iron chelation treatments. Statistical analysis was performed using SPSS statistical software version 13.0, and comparisons among groups were conducted using a t-test. The efficacy of lenalidomide was demonstrated in patients with intermediate-1 risk non-del (5q) MDS. Peripheral blood cell counts were improved following treatment, and absolute neutrophil, haemoglobin and platelet counts increased following 2-4 cycles of treatment. All patients became stable having undergone three cycles of treatment; however, 17 patients with chromosomal abnormalities had no cytogenetic response to the treatment, as confirmed through the FISH test. Patients with intermediate-1 risk non-del (5q) MDS treated with lenalidomide did not achieve complete haematological remission, although they demonstrated haematological improvement.

  17. Efficacy and safety of extended dosing schedules of CC-486 (oral azacitidine) in patients with lower-risk myelodysplastic syndromes

    Science.gov (United States)

    Garcia-Manero, G; Gore, S D; Kambhampati, S; Scott, B; Tefferi, A; Cogle, C R; Edenfield, W J; Hetzer, J; Kumar, K; Laille, E; Shi, T; MacBeth, K J; Skikne, B

    2016-01-01

    CC-486, the oral formulation of azacitidine (AZA), is an epigenetic modifier and DNA methyltransferase inhibitor in clinical development for treatment of hematologic malignancies. CC-486 administered for 7 days per 28-day treatment cycle was evaluated in a phase 1 dose-finding study. AZA has a short plasma half-life and DNA incorporation is S-phase-restricted; extending CC-486 exposure may increase the number of AZA-affected diseased target cells and maximize therapeutic effects. Patients with lower-risk myelodysplastic syndromes (MDS) received 300 mg CC-486 once daily for 14 days (n=28) or 21 days (n=27) of repeated 28-day cycles. Median patient age was 72 years (range 31–87) and 75% of patients had International Prognostic Scoring System Intermediate-1 risk MDS. Median number of CC-486 treatment cycles was 7 (range 2–24) for the 14-day dosing schedule and 6 (1–24) for the 21-day schedule. Overall response (complete or partial remission, red blood cell (RBC) or platelet transfusion independence (TI), or hematologic improvement) (International Working Group 2006) was attained by 36% of patients receiving 14-day dosing and 41% receiving 21-day dosing. RBC TI rates were similar with both dosing schedules (31% and 38%, respectively). CC-486 was generally well-tolerated. Extended dosing schedules of oral CC-486 may provide effective long-term treatment for patients with lower-risk MDS. PMID:26442612

  18. Case Report: Myelodysplastic syndrome- associated myeloid sarcoma: an unusual clinical presentation of a rare disease [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Emoke Horvath

    2016-02-01

    Full Text Available Myeloid sarcoma results from the extramedullary homing and proliferation of immature myeloid precursors. We present the timeline, events and diagnostic pitfalls related to a 66 year-old male patient’s case, admitted to the Hematology Clinic for pancytopenia, fever, weight loss and fatigue. The severe cytopenia and the few blasts observed in his blood smear indicated a bone marrow biopsy. The bone marrow showed hypercellularity and multilineage dysplasia with the presence of 15% myeloblasts. After the biopsy, he promptly developed paraplegia and nuclear magnetic resonance revealed an epidural tumour which was then resected.In the epidural tumour mass blast-like, round cells were observed with a complex immunophenotype, characterized by myeloperoxidase, CD117, CD15, CD99, leucocyte common antigen positivity and a high Ki-67 proliferation index. Considering the main differential diagnostic issues, the final diagnosis was stated as myelodysplastic syndrome-associated myeloid sarcoma. The prognosis was unfavourable, the bone marrow was quickly invaded by proliferating blast cells, and despite chemotherapy attempts, the patient died.

  19. Development of myeloma and secondary myelodysplastic syndrome from a common clone.

    Science.gov (United States)

    Schmetzer, H M; Mittermüller, J; Duell, T; Wilmanns, W

    1998-01-01

    We report the case of a 49-year-old woman who presented with a monoclonally IgG kappa expressing myeloma since October 1989. Four years later, after 24 cycles of Melphalan-containing chemotherapy, bone marrow (BM) cells of the patient cytologically revealed myelodysplastic changes for the first time. Cytogenetic examination of the BM obtained in January 1994 showed two clonally aberrant main lines. Each of them represented one of the hematological neoplastic diseases. The quantitatively major clone (MDS-clone) showed a deletion of the long arm of chromosome 7, typical for secondary myeloid disorders. The other clone (myeloma (MM) clone) was characterized by a reciprocal translocation between the short arm of chromosome 8, band q24, a region known to contain the c-myc gene, and the long arm of chromosome 2, band p12, where the Ig kappa gene is located. An unusual finding, however, was that an abnormality of the long arm of chromosome 16 could be detected in both obviously unrelated clones. In the further course of the disease, the MDS and MM clones could be detected, both of them showing cytogenetically a clonal evolution characterized by additional clonal abnormalities. Our data stress the significance of cytogenetics in detecting typical clonal abnormalities in different malignant hematological disorders and in detecting "clonal evolution" as an indicator of the progress of the disease. Moreover, our data suggest that MM and MDS may arise from a common stem cell, which may be characterized by a clonal cytogenetic abnormality.

  20. The Role of U2AF1 Mutations in the Pathogenesis of Myelodysplastic Syndromes

    Science.gov (United States)

    2014-10-01

    effect has been previously reported in acute myeloid leukemia (AML) patient samples with U2AF1 mutations . To prioritize altered junctions for...hematopoiesis and pre-mRNA splicing observed in patients with U2AF1 mutations . This study also identifies changes in gene isoform expression unique to U2AF1...making it one of the most commonly mutated genes in MDS. Overall, mutations in spliceosome genes occur in up to 57% of patients with MDS, further

  1. Therapeutic trial of intensified conditioning regimen with high-dose cytosine arabinoside, cyclophosphamide and either total body irradiation or busulfan followed by allogeneic bone marrow transplantation for myelodysplastic syndrome in children

    Energy Technology Data Exchange (ETDEWEB)

    Nagatoshi, Yoshihisa; Okamura, Jun; Ikuno, Yoshiko; Akamatsu, Minoru; Tasaka, Hideko [National Kyushu Cancer Center, Fukuoka (Japan)

    1997-04-01

    Ten children with myelodysplastic syndrome underwent an allogeneic bone marrow transplantation (BMT) with an intensified conditioning regimen. The median age of the patients was 8 years (range 2-10), and included 6 males and 4 females. The subtype of the disease was refractory anemia (RA) in 4, RA with excess blasts (RAEB) in 4, RAEB in transformation (RAEB-T) in 1, and juvenile chronic myelogenous leukemia (JCML) in 1. All patients were conditioned with high-dose cytosine arabinoside (12000 mg/m{sup 2}), cyclophosphamide (120 mg/kg) and either total body irradiation (10-13.2 Gy) or busulfan (16 mg/kg or 560 mg/m{sup 2}). Cyclosporine A and/or methotrexate were used for the prophylaxis of graft-versus-host disease (GVHD). Engraftment was prompt in all but one patient. Severe acute GVHD (grade 3) (n=1), interstitial pneumonitis (n=1) and veno-occlusive disease of the liver (n=1) occurred. The disease relapsed in one patient with RAEB-T. Seven of the 10 patients were alive and disease free 2-74 months after BMT. The disease-free survival rate at 4 years was 69{+-}15%. All surviving patients were in the full performance status. The examined children with MDS tolerated this intensified conditioning regimen well. (author)

  2. Williams syndrome and mature B-Leukemia: A random association?

    Science.gov (United States)

    Decimi, Valentina; Fazio, Grazia; Dell'Acqua, Fabiola; Maitz, Silvia; Galbiati, Marta; Rizzari, Carmelo; Biondi, Andrea; Cazzaniga, Giovanni; Selicorni, Angelo

    2016-12-01

    Williams syndrome (WBS) is a rare neurodevelopmental disorder with specific phenotypic characteristics and cardiac abnormalities, but is not considered as a cancer predisposing condition. However, in rare cases, malignancies have been described in patients with WBS, with hematologic cancer (mainly Burkitt Lymphoma and Acute Lymphoblastic Leukemia) as the most represented. We report here the case of a boy with WS and B-NHL. This is the unique case within the large cohort of patients (n = 117) followed in our institution for long time (mean clinical follow-up, 13 years). We herewith propose that the BCL7B gene, located in the chromosomal region commonly deleted in Williams syndrome, could potentially have a role in this particular association.

  3. Comparison of Intensive Chemotherapy and Hypomethylating Agents before Allogeneic Stem Cell Transplantation for Advanced Myelodysplastic Syndromes: A Study of the Myelodysplastic Syndrome Subcommittee of the Chronic Malignancies Working Party of the European Society for Blood and Marrow Transplant Research.

    Science.gov (United States)

    Potter, Victoria T; Iacobelli, Simona; van Biezen, Anja; Maertens, Johann; Bourhis, Jean-Henri; Passweg, Jakob R; Yakhoub-Agha, Ibrahim; Tabrizi, Reza; Bay, Jacques-Olivier; Chevallier, Patrice; Chalandon, Yves; Huynh, Anne; Cahn, Jean Yves; Ljungman, Per; Craddock, Charles; Lenhoff, Stig; Russell, N H; Fegueux, Nathalie; Socié, Gerard; Benedetto, Bruno; Meijer, Ellen; Mufti, G J; de Witte, Theo; Robin, Marie; Kröger, Nicolaus

    2016-09-01

    The European Society for Blood and Marrow Transplant Research data set was used to retrospectively analyze the outcomes of hypomethylating therapy (HMA) compared with those of conventional chemotherapy (CC) before hematopoietic stem cell transplantation (HSCT) in 209 patients with advanced myelodysplastic syndromes. Median follow-up was 22.1 months and the median age of the group was 57.6 years with 37% of the population older than > 60 years. The majority of patients (59%) received reduced-intensity conditioning and 34% and 27% had intermediate-2 and high international prognostic scoring system (IPSS) scores. At time of HSCT, 32% of patients did not achieve complete remission (CR) and 13% had primary refractory disease. On univariate analysis, outcomes at 3 years were not significantly different between HMA and CC for overall survival (OS), relapse-free survival (RFS), cumulative incidence of relapse (CIR), and nonrelapse mortality (NRM): OS (42% versus 35%), RFS (29% versus 31%), CIR (45% versus 40%), and NRM (26% versus 28%). Comparing characteristics of the groups, there were more patients < 55 years old, more patients in CR (68% versus 32%), and fewer patients with primary refractory disease in the CC group than in the HMA group (10% versus 19%, P < .001). Patients with primary refractory disease had worse outcomes than those in CR with regard to OS (hazard ratio [HR], 2.42; 95% confidence interval [CI], 1.41 to 4.13; P = .001), RFS (HR, 2.27; 95% CI, 1.37 to 3.76; P = .001), and NRM (HR, 2.49; 95% CI, 1.18 to 5.26; P = .016). In addition, an adverse effect of IPSS-R cytogenetic risk group was evident for RFS. In summary, outcomes after HSCT are similar for patients receiving HMA compared with those receiving CC, despite the higher proportion of patients with primary refractory disease in the HMA group.

  4. An analysis of the demographic profile, clinical manifestations, investigations and outcome of paediatric myelodysplastic syndrome: A single centre, cross-sectional study

    Directory of Open Access Journals (Sweden)

    Appaji Lingegowda

    2015-09-01

    Full Text Available Purpose: Pediatric myelodysplastic syndrome (MDS is a relatively rare entity, with distinct clinical features and more aggressive course than its adult counterpart. The aim of this study was to analyze the incidence of pediatric myelodysplastic syndrome at a tertiary cancer care center in southern India along with clinical manifestations, investigations and outcome.Methods: On retrospective analysis of 1094 cases of pediatric hematological malignancies over a five-year period from September 2009 to August 2014, a total of seven cases of pediatric myelodysplastic syndrome were identified. Presenting complaints, physical examination, investigations including haemogram, biochemistry, bone marrow examination and cytogenetics were reviewed. The diagnosis of MDS was made if there was dysplasia in at least 10% of cells in two or more cell lineages. All patients were risk stratified using the revised IPSS. Results: Out of 1094 cases of pediatric hematological malignancies presenting at our institute within the study period, there were only seven cases of pediatric MDS with an incidence of 0.65%. There were no genetic predispositions nor any cases of therapy related MDS. The most common presentation was with fever and all patients had significant splenomegaly. All patients had anemia (Median-6.2 gm / dL with elevated WBC counts (Median-30,900 / uL and thrombocytopenia (Median-50,000 / uL. The marrow cytogenetics was normal in five patients. Most patients fell into the high and very high-risk category of the revised IPSS, with only two patients of low risk. All seven patients were given only supportive care but one progressed to AML for which he was treated with remission induction. Only two patients were alive at the time of analysis and median survival was 9 months. Conclusion: Pediatric MDS is a rare disease with a short clinical history, aggressive course and generally poor outcomes as compared to the adult variant. A hematopoietic stem cell

  5. Therapy-related myelodysplastic syndrome and acute myeloid leukemia in patients with chronic lymphocytic leukemia treated with fludarabine and cyclophosphamide.

    Science.gov (United States)

    Colović, M; Suvajdžić, N; Janković, G; Tomin, D; Colović, N; Fekete, M Denčić; Palibrk, V

    2011-08-01

    We retrospectively studied four cases of t-MDS/AML among 210 (1.9%) consecutive patients with CLL treated at a single center with fludarabine and cyclophosphamide (FC) either as the first- or second-line therapy. The median follow-up of the whole cohort of patients was 46months (range: 7-60). Two of these patients (2/130, 1.7%) had been treated with FC only, and two more (2/80, 2.3%) with CHOP and CHOP+FND, respectively, prior to FC. The median age was 61.5years (range: 49-71); three were male. They developed t-MDS/AML after a median latency period of 41months (range: 7-56) from the FC completion. Chromosomal aberrations with an adverse prognostic impact were present in the karyotype of all four patients, including abnormalities of chromosome 5 in three of them, and a rare chromosomal translocation in one patient. Median survival after t-MDS/AML diagnosis was 4months (range: 2-8). Although the agents administered prior to FC make it difficult to assess the risk of t-MDS/AML attributable to FC, this report might be a valuable addition to the literature.

  6. Response to recombinant erythropoietin alpha, without the adjunct of granulocyte-colony stimulating factor, is associated with a longer survival in patients with transfusion-dependent myelodysplastic syndromes.

    Science.gov (United States)

    Musto, Pellegrino; Villani, Oreste; Martorelli, Maria Carmen; Pietrantuono, Giuseppe; Guariglia, Roberto; Mansueto, Giovanna; D'Auria, Fiorella; Grieco, Vitina; Bianchino, Gabriella; Sparano, Anna; Zonno, Antonia; Lerose, Rosa; Sanpaolo, Grazia; Falcone, Antonietta

    2010-08-01

    This was a retrospective, comparative study focused on the extended follow-up of 192 transfusion-dependent patients with myelodysplastic syndromes treated (n. 83) or not treated (n. 109) with recombinant erythropoietin alpha (r-EPO) as single agent during the course of their disease. The results supported the safety of this treatment in the long term and also showed a significant survival advantage (median 52 months vs. 31 months, p<0.0095) in responding patients as compared to non-responding ones or to subjects never treated with r-EPO. At multivariate analysis, response to r-EPO maintained an independent prognostic value on OS.

  7. Mutations in the gene for the granulocyte colony-stimulating-factor receptor in patients with acute myeloid leukemia preceded by severe congenital neutropenia

    NARCIS (Netherlands)

    F. Dong (Fan); R.K. Brynes; N. Tidow; K. Welte (Karl); B. Löwenberg (Bob); I.P. Touw (Ivo)

    1995-01-01

    textabstractIn severe congenital neutropenia the maturation of myeloid progenitor cells is arrested. The myelodysplastic syndrome and acute myeloid leukemia develop in some patients with severe congenital neutropenia. Abnormalities in the signal-transduction pathways for granulocyte colony-stimulati

  8. Normal karyotype is a poor prognostic factor in myeloid leukemia of Down syndrome: A retrospective, international study

    NARCIS (Netherlands)

    M. Blink (Marjolein); M. Zimmermann (Martin); C. von Neuhoff (Christine); D. Reinhardt (Dirk); V. de Haas (Valerie); H. Hasle (Henrik); M.M. O'Brien (Maureen); B. Stark (Batia); J. Tandonnet (Julie); A. Pession (Andrea); K. Tousovska (Katerina); T.H.F. Cheuk; K. Kudo (Kazuko); T. Taga (Takashi); J.E. Rubnitz (Jeffrey); I. Haltrich (Iren); W. Balwierz (Walentyna); R. Pieters (Rob); E. Forestier (Erik); B. Johansson (Bert); M.M. van den Heuvel-Eibrink (Marry); C.M. Zwaan (Christian Michel)

    2014-01-01

    textabstractMyeloid leukemia of Down syndrome has a better prognosis than sporadic pediatric acute myeloid leukemia. Most cases of myeloid leukemia of Down syndrome are characterized by additional cytogenetic changes besides the constitutional trisomy 21, but their potential prognostic impact is not

  9. Prognostic relevance of morphological classification models for myelodysplastic syndromes in an era of the revised International Prognostic Scoring System.

    Science.gov (United States)

    van Spronsen, Margot F; Ossenkoppele, Gert J; Westers, Theresia M; van de Loosdrecht, Arjan A

    2016-03-01

    Numerous morphological classification models have been developed to organise the heterogeneous spectrum of myelodysplastic syndromes (MDS). While the 2008 update of the World Health Organisation (WHO) is the current standard, the publication of the revised International Prognostic Scoring System (IPSS-R) has illustrated the need for supplemental prognostic information. The aim of this study was to investigate whether morphological classification models for MDS - of both the French-American-British (FAB) group and WHO - provide reliable criteria for their classification into homogeneous and clinically relevant categories with prognostic relevance beyond the IPSS-R. We reclassified 238 MDS patients using each of the FAB, WHO 2001 and WHO 2008 criteria and studied classification categories in terms of clinical, haematological and cytogenetic features. Subsequently, we calculated prognostic scores using the IPSS-R and investigated whether the morphological classification models had significantly prognostic value in patients stratified by the IPSS-R and vice versa. By adopting the FAB, WHO 2001 and WHO 2008 classifications, MDS patients were organised into homogeneous categories with intrinsic prognostic information. However, whereas the morphological classification models showed no prognostic value beyond the IPSS-R, the IPSS-R had significant prognostic value beyond the FAB, WHO 2001 and WHO 2008 classifications. Even though morphological classification models for MDS might be clinically relevant from a prognostic point of view, their relevance in terms of risk stratification is evidently limited in light of the IPSS-R. Therefore, we suggest to stop the use of morphological classification models for MDS for risk stratification in routine clinical practice.

  10. Oxidative stress levels are correlated with P15 and P16 gene promoter methylation in myelodysplastic syndrome patients.

    Science.gov (United States)

    Gonçalves, Ana Cristina; Cortesão, Emília; Oliveiros, Barbara; Alves, Vera; Espadana, Ana Isabel; Rito, Luís; Magalhães, Emília; Pereira, Sónia; Pereira, Amélia; Costa, José Manuel Nascimento; Mota-Vieira, Luisa; Sarmento-Ribeiro, Ana Bela

    2016-08-01

    Oxidative stress and abnormal DNA methylation have been implicated in some types of cancer, namely in myelodysplastic syndromes (MDS). Since both mechanisms are observed in MDS patients, we analyzed the correlation of intracellular levels of peroxides, superoxide anion, and glutathione (GSH), as well as ratios of peroxides/GSH and superoxide/GSH, with the methylation status of P15 and P16 gene promoters in bone marrow leukocytes from MDS patients. Compared to controls, these patients had lower GSH content, higher peroxide levels, peroxides/GSH and superoxide/GSH ratios, as well as higher methylation frequency of P15 and P16 gene promoters. Moreover, patients with methylated P15 gene had higher oxidative stress levels than patients without methylation (peroxides: 460 ± 42 MIF vs 229 ± 25 MIF, p = 0.001; superoxide: 383 ± 48 MIF vs 243 ± 17 MIF, p = 0.022; peroxides/GSH: 2.50 ± 0.08 vs 1.04 ± 0.34, p levels as well as peroxides/GSH ratio than patients without methylation. Interestingly, oxidative stress levels allow the discrimination of patients without methylation from ones with methylated P15, methylated P16, or at least one methylated (P15 or P16) promoter. Taken together, these findings support the hypothesis that oxidative stress is correlated with P15 and P16 hypermethylation.

  11. Large-vessel thrombosis in intestinal Beh(c)et's disease complicated with myelodysplastic syndrome and trisomy 8

    Institute of Scientific and Technical Information of China (English)

    Huang-Chi Chen; Ying-Ming Chiu

    2012-01-01

    Beh(c)et's disease is characterized by recurrent oral ulcers,genital ulcers,uveitis and skin lesions.Myelodysplastic syndrome (MDS) is characterized by problems due to ineffective hematopoiesis.Several studies have identified a relationship between MDS and Beh(c)et's disease,especially intestinal Beh(c)et's disease.Trisomy 8 seems to play an important role in these disorders as well.The present case was a 24-year-old woman who had a huge tonsil ulcer with initial symptoms of odynophagia and intermittent fever.We also noted folliculitis on her upper back.Five days later,she began to experience diarrhea and abdominal pain.Abdominal computed tomography and subsequent surgery revealed ileum perforation and enterocolitis with multiple ulcers.Later,she was admitted again for a vulvar suppurative ulcer and suspicious Bartholin's cyst infection.The patient's clinical presentations met the criteria for Beh(c)et's disease.Six months after the bowel perforation event,we noted the development of pancytopenia in a routine laboratory examination.All the examinations led to the diagnosis of MDS with trisomy 8.The most unusual finding was that multiple large vessel thrombi developed during follow-up.Previous studies have suggested that trisomy 8 in MDS leads to concurrent intestinal Beh(c)et's disease.Moreover,the inflammatory and immune genes related to thrombus formation are overexpressed in cases of MDS with trisomy 8.Trisomy 8 must play a role in thrombosis.Further studies are needed to help clarify the pathophysiology and pathogenesis of these disorders.

  12. Identification of gene expression-based prognostic markers in the hematopoietic stem cells of patients with myelodysplastic syndromes.

    Science.gov (United States)

    Pellagatti, Andrea; Benner, Axel; Mills, Ken I; Cazzola, Mario; Giagounidis, Aristoteles; Perry, Janet; Malcovati, Luca; Della Porta, Matteo G; Jädersten, Martin; Verma, Amit; McDonald, Emma-Jane; Killick, Sally; Hellström-Lindberg, Eva; Bullinger, Lars; Wainscoat, James S; Boultwood, Jacqueline

    2013-10-01

    The diagnosis of patients with myelodysplastic syndromes (MDS) is largely dependent on morphologic examination of bone marrow aspirates. Several criteria that form the basis of the classifications and scoring systems most commonly used in clinical practice are affected by operator-dependent variation. To identify standardized molecular markers that would allow prediction of prognosis, we have used gene expression profiling (GEP) data on CD34+ cells from patients with MDS to determine the relationship between gene expression levels and prognosis. GEP data on CD34+ cells from 125 patients with MDS with a minimum 12-month follow-up since date of bone marrow sample collection were included in this study. Supervised principal components and lasso penalized Cox proportional hazards regression (Coxnet) were used for the analysis. We identified several genes, the expression of which was significantly associated with survival of patients with MDS, including LEF1, CDH1, WT1, and MN1. The Coxnet predictor, based on expression data on 20 genes, outperformed other predictors, including one that additionally used clinical information. Our Coxnet gene signature based on CD34+ cells significantly identified a separation of patients with good or bad prognosis in an independent GEP data set based on unsorted bone marrow mononuclear cells, demonstrating that our signature is robust and may be applicable to bone marrow cells without the need to isolate CD34+ cells. We present a new, valuable GEP-based signature for assessing prognosis in MDS. GEP-based signatures correlating with clinical outcome may significantly contribute to a refined risk classification of MDS.

  13. Label-free imaging and identification of typical cells of acute myeloid leukaemia and myelodysplastic syndrome by Raman microspectroscopy.

    Science.gov (United States)

    Vanna, R; Ronchi, P; Lenferink, A T M; Tresoldi, C; Morasso, C; Mehn, D; Bedoni, M; Picciolini, S; Terstappen, L W M M; Ciceri, F; Otto, C; Gramatica, F

    2015-02-21

    In clinical practice, the diagnosis and classification of acute myeloid leukaemia (AML) and myelodysplastic syndrome (MDS) start from the manual examination of stained smears of bone marrow (BM) and peripheral blood (PB) by using an optical microscope. This step is subjective and scarcely reproducible. Therefore, the development of subjective and potentially automatable methods for the recognition of typical AML/MDS cells is necessary. Here we have used Raman spectroscopy for distinguishing myeloblasts, promyelocytes, abnormal promyelocytes and erhytroblasts, which have to be counted for a correct diagnosis and morphological classification of AML and MDS. BM samples from patients affected by four different AML subtypes, mostly characterized by the presence of the four subpopulations selected for this study, were analyzed. First, each cell was scanned by acquiring 4096 spectra, thus obtaining Raman images which demonstrate an accurate description of morphological features characteristic of each subpopulation. Raman imaging coupled with hierarchical cluster analysis permitted the automatic discrimination and localization of the nucleus, the cytoplasm, myeloperoxidase containing granules and haemoglobin. Second, the averaged Raman fingerprint of each cell was analysed by multivariate analysis (principal component analysis and linear discriminant analysis) in order to study the typical vibrational features of each subpopulation and also for the automatic recognition of cells. The leave-one-out cross validation of a Raman-based classification model demonstrated the correct classification of myeloblasts, promyelocytes (normal/abnormal) and erhytroblasts with an accuracy of 100%. Normal and abnormal promyelocytes were distinguished with 95% accuracy. The overall classification accuracy considering the four subpopulations was 98%. This proof-of-concept study shows that Raman micro-spectroscopy could be a valid approach for developing label-free, objective and automatic

  14. The Danish National Acute Leukemia Registry

    DEFF Research Database (Denmark)

    Østgård, Lene Sofie Granfeldt; Nørgaard, Jan Maxwell; Raaschou-Jensen, Klas Kræsten;

    2016-01-01

    AIM OF DATABASE: The main aim of the Danish National Acute Leukemia Registry (DNLR) was to obtain information about the epidemiology of the hematologic cancers acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), and myelodysplastic syndrome (MDS). STUDY POPULATION: The registry...... patients is currently 90%. MAIN VARIABLES AND DESCRIPTIVE DATA: Approximately, 250 AML patients, 25 ALL patients, and 230 MDS patients are registered in the DNLR every year. In January 2015, the registry included detailed patient characteristics, disease characteristics, treatment characteristics...... years. To ensure this high coverage, completeness, and quality of data, linkage to the Danish Civil Registration System and the Danish National Registry of Patients, and several programmed data entry checks are used. CONCLUSION: The completeness and positive predictive values of the leukemia data have...

  15. Managing myelodysplastic symptoms in elderly patients

    Directory of Open Access Journals (Sweden)

    R Ria

    2009-10-01

    Full Text Available R Ria, M Moschetta, A Reale, G Mangialardi, A Castrovilli, A Vacca, F DammaccoDepartment of Biomedical Sciences and Human Oncology, Section of Internal Medicine and Clinical Oncology, University of Bari Medical School, Bari, ItalyAbstract: Most patients with myelodysplastic syndromes (MDS are elderly (median age range 65 to 70 years; as a consequence, the incidence and prevalence of these diseases are rising as the population ages. Physicians are often uncertain about how to identify patients who may benefit from specific treatment strategies. The International Prognostic Scoring System is a widely used tool to assess the risk of transformation to leukemia and to guide treatment decisions, but it fails to take into account many aspects of treating elderly patients, including comorbid illnesses, secondary causes of MDS, prior therapy for MDS, and other age-related health, functional, cognitive, and social problems that affect the outcome and managing of myelodysplastic symptoms. Patients with low-risk disease traditionally have been given only best supportive care, but evidence is increasing that treatment with novel non-conventional drugs such as lenalidomide or methyltransferase inhibitors may influence the natural history of the disease and should be used in conjunction with supportive-care measures. Supportive care of these patients could also be improved in order to enhance their quality of life and functional performance. Elderly patients commonly have multiple medical problems and use medications to deal with these. In addition, they are more likely to have more than one health care provider. These factors all increase the risk of drug interactions and the consequent treatment of toxicities. Manifestations of common toxicities or illnesses may be more subtle in the elderly, owing to age-associated functional deficits in multiple organ systems. Particularly important to the elderly MDS patient is the age-related decline in normal bone

  16. High frequency of BTG1 deletions in acute lymphoblastic leukemia in children with down syndrome

    DEFF Research Database (Denmark)

    Lundin, Catarina; Hjorth, Lars; Behrendtz, Mikael

    2012-01-01

    Previous cytogenetic studies of myeloid and acute lymphoblastic leukemias in children with Down syndrome (ML-DS and DS-ALL) have revealed significant differences in abnormality patterns between such cases and acute leukemias in general. Also, certain molecular genetic aberrations characterize DS...

  17. Extensive myocardial infiltration by hemopoietic precursors in a patient with myelodysplastic syndrome

    Directory of Open Access Journals (Sweden)

    Harding Sheila R

    2006-09-01

    Full Text Available Abstract Background Although myocardial infiltration with leukemic blasts is a known finding in patients with acute leukemia, this phenomenon in myelodysplasia is not reported in the literature. Cardiac symptoms in patients with myelodysplasia are often due to anemia and may be due to iron overload and side effects of therapy. Case presentation Herein we report the first case of neoplastic infiltration of the heart with associated myocardial necrosis in a patient with myelodysplasia. It was associated with unicellular and multifocal geographic areas of necrosis in the left ventricle and the interventricular septum. It is likely that cardiac compromise in our patient was due to a combination of restrictive cardiomyopathy due to leukemic infiltration, concomitant anemia, cardiac dilatation, conduction blocks and myocardial necrosis. Myocardial necrosis was most likely due to a combination of ischemic damage secondary to anemia and prolonged hypotension and extensive leukemic infiltration. Markedly rapid decrease in ejection fraction from 66% to 33% also suggests the role of ischemia, since leukemic infiltration is not expected to cause this degree of systolic dysfunction over a 24-hour period. The diagnosis was not suspected during life due to concomitant signs and symptoms of anemia, pulmonary infections, and pericardial and pleural effusions. The patient succumbed to cardiac failure. Conclusion Hemopoietic cell infiltration was not considered in the differential diagnosis and contributed to this patient's morbidity and mortality. This case highlights the clinical importance of considering myocardial infiltration in patients with myelodysplasia and cardiac symptoms.

  18. Cytogenetic follow-up by karyotyping and fluorescence in situ hybridization: implications for monitoring patients with myelodysplastic syndrome and deletion 5q treated with lenalidomide

    Science.gov (United States)

    Göhring, Gudrun; Giagounidis, Aristoteles; Büsche, Guntram; Hofmann, Winfried; Kreipe, Hans Heinrich; Fenaux, Pierre; Hellström-Lindberg, Eva; Schlegelberger, Brigitte

    2011-01-01

    In patients with low and intermediate risk myelodysplastic syndrome and deletion 5q (del(5q)) treated with lenalidomide, monitoring of cytogenetic response is mandatory, since patients without cytogenetic response have a significantly increased risk of progression. Therefore, we have reviewed cytogenetic data of 302 patients. Patients were analyzed by karyotyping and fluorescence in situ hybridization. In 85 patients, del(5q) was only detected by karyotyping. In 8 patients undergoing karyotypic evolution, the del(5q) and additional chromosomal aberrations were only detected by karyotyping. In 3 patients, del(5q) was only detected by fluorescence in situ hybridization, but not by karyotyping due to a low number of metaphases. Karyotyping was significantly more sensitive than fluorescence in situ hybridization in detecting the del(5q) clone. In conclusion, to optimize therapy control of myelodysplastic syndrome patients with del(5q) treated with lenalidomide and to identify cytogenetic non-response or progression as early as possible, fluorescence in situ hybridization alone is inadequate for evaluation. Karyotyping must be performed to optimally evaluate response. (clinicaltrials.gov identifier: NCT01099267 and NCT00179621) PMID:21109690

  19. Diretrizes para diagnóstico morfológico em síndromes mielodisplásicas Guidelines for morphological diagnosis of myelodysplastic syndromes

    Directory of Open Access Journals (Sweden)

    Lígia Niero-Melo

    2006-09-01

    Full Text Available As síndromes mielodisplásicas são reconhecidas como doenças que se originam nas células-tronco da medula óssea e que requerem avaliação sistemática e criteriosa de sangue periférico e medula óssea para seu correto diagnóstico. O objetivo deste relato é estabelecer os critérios morfológicos (cito-histológicos como parâmetros para o diagnóstico de SMD em amostras de sangue periférico e medula óssea, com especial direcionamento aos hematologistas e patologistas clínicos que exercem a hematologia laboratorial na sua rotina de trabalho. Os principais achados morfológicos são listados no final deste relato, na forma de "check-list", objetivando a sistematização sobre estes achados.Myelodysplastic syndromes require both thorougly and systematic blood smear and bone marrow examinations. The main goal of this report is to establish criteria of the morphological ( cyto-histological features, as parameters for the diagnosis of myelodysplastic syndromes ( MDS from peripheral blood smears and bone marrow samples, with especial address to hematology and pathology practitioners. The main features are listed ( checklist at the end of this report, in order to synthesize them.

  20. Mutations in the gene for the granulocyte colony-stimulating-factor receptor in patients with acute myeloid leukemia preceded by severe congenital neutropenia

    OpenAIRE

    1995-01-01

    textabstractBACKGROUND. In severe congenital neutropenia the maturation of myeloid progenitor cells is arrested. The myelodysplastic syndrome and acute myeloid leukemia develop in some patients with severe congenital neutropenia. Abnormalities in the signal-transduction pathways for granulocyte colony-stimulating factor (G-CSF) may play a part in the progression to acute myeloid leukemia. METHODS. We isolated genomic DNA and RNA from hematopoietic cells obtained from two patients with acute m...

  1. Serum iron metabolism and erythropoiesis in patients with myelodysplastic syndrome not receiving RBC transfusions

    OpenAIRE

    Cui, Rui; Gale, Robert Peter; Zhu, Guoqing; Xu, Zefeng; Qin, Tiejun; Zhang, Yue; Huang, Gang; Li, Bing; Fang, Liwei; Zhang, Hongli; Pan, Lijuan; Hu, Naibo; Qu, Shiqiang; Xiao, Zhijian

    2014-01-01

    Dysregulation of hepcidin, a key iron regulating hormone, is important in the pathogenesis of iron overload in patients with myelodysplatic syndrome (MDS). However, most studies of hepcidin levels are complicated by concomitant RBC transfusions. To evaluate the relationship between iron metabolism and erythropoiesis, we measured serum levels of hepcidin, growth-differentiation factor-15 (GDF15) and other markers of erythropoiesis in 107 subjects with MDS not receiving RBC transfusions. Patien...

  2. The value of fludarabine in addition to ARA-C and G-CSF in the treatment of patients with high-risk myelodysplastic syndromes and AML in elderly patients.

    NARCIS (Netherlands)

    Ossenkoppele, G.J.; Graveland, W.J.; Sonneveld, P.; Daenen, S.M.G.J.; Biesma, D.H.; Verdonck, L.F.; Schaafsma, M.R.; Westveer, P.H.; Peters, G.J.; Noordhuis, P.; Muus, P.; Selleslag, D.; Holt, B. van der; Delforge, M.; Lowenberg, B.; Verhoef, G.E.

    2004-01-01

    Fludarabine in addition to cytosine-arabinoside (ARA-C) increases the accumulation of ARA-C-5'-triphosphate (ARA-CTP), which is responsible for the cytotoxic effect in leukemic blasts. In a randomized phase 3 trial, patients with high-risk myelodysplastic syndrome (MDS) (n = 91) or elderly patients

  3. The value of fludarabine in addition to ARA-C and G-CSF in the treatment of patients with high-risk myelodysplastic syndromes and AML in elderly patients

    NARCIS (Netherlands)

    Ossenkoppele, GJ; Graveland, WJ; Sonneveld, P; Daenen, SMGJ; Biesma, DH; Verdonck, LF; Schaafsma, R; Westveer, PHM; Peters, F; Noordhuis, P; Muus, P; van der Holt, R; Delforge, M; Lowenberg, B; Verhoef, GEG

    2004-01-01

    Fludarabine in addition to cytosine-arabinoside (ARA-C) increases the accumulation of ARA-C-5'-triphosphate (ARA-CTP), which is responsible for the cytotoxic effect in leukemic blasts. In a randomized phase 3 trial, patients with high-risk myelodysplastic syndrome (MDS) (n = 91) or elderly patient's

  4. Outcomes in RBC transfusion-dependent patients with Low-/Intermediate-1-risk myelodysplastic syndromes with isolated deletion 5q treated with lenalidomide: A subset analysis from the MDS-004 study

    NARCIS (Netherlands)

    A. Giagounidis (Aristoteles); G.J. Mufti (Ghulam); M. Mittelman (Moshe); G. Sanz (Guillermo); U. Platzbecker (Uwe); P. Muus (P.); D. Selleslag; O. Beyne-Rauzy (Odile); P.A.W. te Boekhorst (Peter); C. del Cañizo (Consuelo); A. Guerci-Bresler (Agnes); L. Nilsson (Lars); M. Lübbert (Michael); B. Quesnel (Bruno); A. Ganser (Arnold); D. Bowen (David); B. Schlegelberger (Brigitte); G. Göhring (Gudrun); T. Fu (Tommy); B. Benettaib (Bouchra); E. Hellström-Lindberg (Eva); P. Fenaux (Pierre)

    2014-01-01

    textabstractObjective: A subset analysis of the randomised, phase 3, MDS-004 study to evaluate outcomes in patients with International Prognostic Scoring System (IPSS)-defined Low-/Intermediate (Int)-1-risk myelodysplastic syndromes (MDS) with isolated del(5q). Methods: Patients received lenalidomid

  5. Validation of the revised international prognostic scoring system (IPSS-R) in patients with lower-risk myelodysplastic syndromes: a report from the prospective European LeukaemiaNet MDS (EUMDS) registry

    NARCIS (Netherlands)

    Swart, L. de; Smith, A.; Johnston, T.W.; Haase, D.; Droste, J.; Fenaux, P.; Symeonidis, A.; Sanz, G.; Hellstrom-Lindberg, E.; Cermak, J.; Germing, U.; Stauder, R.; Georgescu, O.; MacKenzie, M.; Malcovati, L.; Holm, M.S.; Almeida, A.M.; Madry, K.; Slama, B.; Guerci-Bresler, A.; Sanhes, L.; Beyne-Rauzy, O.; Luno, E.; Bowen, D.; Witte, T.J. de

    2015-01-01

    Baseline characteristics, disease-management and outcome of 1000 lower-risk myelodysplastic syndrome (MDS) patients within the European LeukaemiaNet MDS (EUMDS) Registry are described in conjunction with the validation of the revised International Prognostic Scoring System (IPSS-R). The EUMDS regist

  6. Platelet doubling after the first azacitidine cycle is a promising predictor for response in myelodysplastic syndromes (MDS), chronic myelomonocytic leukaemia (CMML) and acute myeloid leukaemia (AML) patients in the Dutch azacitidine compassionate named patient programme

    NARCIS (Netherlands)

    van der Helm, Lieke H.; Alhan, Canan; Wijermans, Pierre W.; Kooy, Marinus van Marwijk; Schaafsma, Ron; Biemond, Bart J.; Beeker, Aart; Hoogendoorn, Mels; van Rees, Bastiaan P.; de Weerdt, Okke; Wegman, Jurgen; Libourel, Ward J.; Luykx-de Bakker, Sylvia A.; Minnema, Monique C.; Brouwer, Rolf E.; Boer, Fransien Croon-de; Eefting, Matthijs; Jie, Kon-Siong G.; de Loosdrecht, Arjan A. van; Koedam, Jan; Veeger, Nic J. G. M.; Vellenga, Edo; Huls, Gerwin

    2011-01-01

    The efficacy of azacitidine in the treatment of high-risk myelodysplastic syndromes (MDS), chronic myelomonocytic leukaemia (CMML) and acute myeloid leukaemia (AML) (20-30% blasts) has been demonstrated. To investigate the efficacy of azacitidine in daily clinical practice and to identify predictors

  7. Chronic myeloid leukemia in case of Klinefelter syndrome

    Directory of Open Access Journals (Sweden)

    Vasundhara Chennuri

    2014-01-01

    Full Text Available Klinefelter syndrome (KS is a sex chromosome disorder and has been reported to be associated with increased risk for malignancies. We report a 22-year-old male patient who was diagnosed to have chronic myeloid leukemia in chronic phase. Bone marrow cytogenetic examination revealed karyotype 47, XXY, t (9; 22(q34, q11 suggestive of KS with presence of Philadelphia chromosome. The patient was treated with oral imatinib mesylate (400 mg/day. Complete hematological response was achieved after 2 months of therapy. The bcr-abl/abl transcript percentage measured from peripheral blood at baseline, 1 and 2 years after imatinib were 97%, 1.99%, 0.007%, respectively. He remains in complete hematological and major molecular remission after 2 years of continued imatinib therapy.

  8. Miller-Fisher syndrome associated with chronic lymphocytic leukemia

    Directory of Open Access Journals (Sweden)

    Aki Zeynep

    2008-01-01

    Full Text Available Chronic lymphocytic leukemia (CLL is a frequent hematological malignancy, with meningeal or peripheral nerve infiltrations being the most commonly encountered neurological complications. In this report, we describe a CLL patient with Miller-Fisher syndrome (MFS who responded to immune modulation with plasmapheresis. A 47-year-old man diagnosed as B-cell CLL admitted with neutropenic fever. He complained of diplopia and numbness of both arms. Neurological examination revealed a bilateral external ophthalmoplegia, dysphagia, dysarthria, mild shoulder girdle muscle weakness and gait ataxia, accompanied by absent tendon reflexes. Nerve conduction studies were indicative of a predominantly axonal sensori-motor peripheral neuropathy. This association of CLL with MFS had not been previously reported in the literature.

  9. Epidemiology of childhood leukemia in the presence and absence of Down syndrome.

    Science.gov (United States)

    Mezei, Gabor; Sudan, Madhuri; Izraeli, Shai; Kheifets, Leeka

    2014-10-01

    Down syndrome (DS) is a common congenital anomaly, and children with DS have a substantially higher risk of leukemia. Although understanding of genetic and epigenetic changes of childhood leukemia has improved, the causes of childhood leukemia and the potential role of environmental exposures in leukemogenesis remain largely unknown. Although many epidemiologic studies have examined a variety of environmental exposures, ionizing radiation remains the only generally accepted environmental risk factor for childhood leukemia. Among suspected risk factors, infections, exposure to pesticides, and extremely low frequency magnetic fields are notable. While there are well-defined differences between leukemia in children with and without DS, studies of risk factors for leukemia among DS children are generally consistent with trends seen among non-DS (NDS) children. We provide background on DS epidemiology and review the similarities and differences in biological and epidemiologic features of leukemia in children with and without DS. We propose that both acute lymphoblastic and acute myeloblastic leukemia among DS children can serve as an informative model for development of childhood leukemia. Further, the high rates of leukemia among DS children make it possible to study this disease using a cohort approach, a powerful method that is unfeasible in the general population due to the rarity of childhood leukemia.

  10. Treatment Options for Myelodysplastic/Myeloproliferative Neoplasms

    Science.gov (United States)

    ... Treatment Myelodysplastic/ Myeloproliferative Neoplasms Treatment Myelodysplastic/ Myeloproliferative Neoplasms Treatment (PDQ®)–Patient Version General Information About Myelodysplastic/ Myeloproliferative ...

  11. Guillain-Barré syndrome in a child with acute lymphoblastic leukemia.

    Science.gov (United States)

    Aral, Y Z; Gursel, T; Ozturk, G; Serdaroglu, A

    2001-01-01

    A 4-year-old boy with acute lymphoblastic leukemia receiving maintenance treatment developed quadriparesis, facial palsy, difficulty in swallowing, and hypertension following a respiratory infection and candida septicemia. Examination of the cerebrospinal fluid was normal initially but later showed albuminocytologic dissociation, the characteristic finding of Guillain-Barré syndrome. Complete recovery occurred after treatment with intravenous immunoglobulin. Differential diagnosis of Guillain-Barré syndrome from vincristine toxicity in patients with leukemia and possible association with the infections are discussed.

  12. [A case of mediastinal growing teratoma syndrome with acute megakaryoblastic leukemia].

    Science.gov (United States)

    Hayashi, Masachika; Igarashi, Natsue; Fujimori, Fumio; Kuriyama, Hideyuki; Ebe, Yusuke; Nishibori, Takeaki; Sato, Kazuhiro; Hosaka, Yasuko; Yamato, Yasushi; Togashi, Kenichi; Yano, Toshio

    2014-07-01

    We report a case of a 38-year-old man who was diagnosed with a mediastinal germ cell tumor. After induction chemotherapy, the tumor marker levels normalized, but the tumor itself continued to grow. Surgical resection was performed successfully, but the patient developed acute megakaryoblastic leukemia 6 months later, and induction and consolidation therapies failed to achieve remission. Leukemia cells invaded the central nervous system following hematopoietic stem cell transplantation, and the patient died 5 months after being diagnosed with leukemia. This very rare case of a mediastinal germ cell tumor met the criteria for "growing teratoma syndrome", against a background of acute megakaryoblastic leukemia.

  13. Maintenance treatment with azacytidine for patients with high-risk myelodysplastic syndromes (MDS) or acute myeloid leukaemia following MDS in complete remission after induction chemotherapy

    DEFF Research Database (Denmark)

    Grövdal, Michael; Karimi, Mohsen; Khan, Rasheed

    2010-01-01

    This prospective Phase II study is the first to assess the feasibility and efficacy of maintenance 5-azacytidine for older patients with high-risk myelodysplastic syndrome (MDS), chronic myelomonocytic leukaemia and MDS-acute myeloid leukaemia syndromes in complete remission (CR) after induction...... and 24 months post CR. Twenty-four (40%) patients achieved CR after induction chemotherapy and 23 started maintenance treatment with azacytidine. Median CR duration was 13.5 months, >24 months in 17% of the patients, and 18-30.5 months in the four patients with trisomy 8. CR duration was not associated......-IV thrombocytopenia and neutropenia occurred after 9.5 and 30% of the cycles, respectively, while haemoglobin levels increased during treatment. 5-azacytidine treatment is safe, feasible and may be of benefit in a subset of patients....

  14. Case report of isochromosome 17q in acute myeloid leukemia with myelodysplasia-related changes after treatment with a hypomethylating agent.

    Science.gov (United States)

    Sousa, J C; Germano, R T; Castro, C C M; Magalhaes, S M M; Pinheiro, R F

    2012-08-06

    Isochromosome 17q is a relatively common karyotypic abnormality in medulloblastoma, gastric, bladder, and breast cancers. In myeloid disorders, it is observed during disease progression and evolution to acute myeloid leukemia in Philadelphia-positive chronic myeloid leukemia. It has been reported in rare cases of myelodysplastic syndrome, with an incidence of 0.4-1.57%. Two new agents have been approved for treatment of myelodysplastic syndrome/chronic myelomonocytic leukemia. These are the hypomethylating agents, 5-azacytidine and decitabine, recommended by consensus guidelines for high-risk myelodysplastic syndrome patients not eligible for hematopoietic stem cell transplantation. We present a case of chronic myelomonocytic leukemia with normal cytogenetics at diagnosis treated with decitabine (with good response); however, the patient evolved to acute myeloid leukemia with i(17q) shortly after suspending treatment. To the best of our knowledge, this is the first report of acute myeloid leukemia with myelodysplasia-related changes with i(17q) after the use of a hypomethylating agent.

  15. Leukemia

    Science.gov (United States)

    Leukemia is cancer of the white blood cells. White blood cells help your body fight infection. Your blood cells form in your bone marrow. In leukemia, the bone marrow produces abnormal white blood cells. ...

  16. Computerized texture analysis of atypical immature myeloid precursors in patients with myelodysplastic syndromes: an entity between blasts and promyelocytes

    Directory of Open Access Journals (Sweden)

    Lorand-Metze Irene GH

    2011-09-01

    Full Text Available Abstract Background Bone marrow (BM blast count is an essential parameter for classification and prognosis of myelodysplastic syndromes (MDS. However, a high degree of cell atypias in bone marrow hemopoietic cells may be found in this group of clonal disorders, making it difficult to quantify precisely myeloblasts, and to distinguish them from promyelocytes and atypical immature myeloid precursors. Our aim was to investigate whether computerized image analysis of routine cytology would help to characterize these cells. Methods In May-Grünwald-Giemsa stained BM smears of 30 newly diagnosed MDS patients and 19 cases of normal BM, nuclei of blasts and promyelocytes were digitalized and interactively segmented. The morphological classification of the cells was done by consensus of two observers. Immature granulocytic precursors, which could not be clearly classified either as blasts or promyelocytes, were called "atypic myeloid precursors". Nuclear morphometry and texture features derived from the co-occurrence matrix and fractal dimension (FD were calculated. Results In normal BM, when compared to myeloblasts, nuclei of promyelocytes showed significant increase in perimeter and local texture homogeneity and a decrease in form factor, chromatin gray levels, Haralick's entropy, inertia, energy, contrast, diagonal moment, cluster prominence, the fractal dimension according to Minkowski and its goodness-of-fit. Compared to normal myeloblast nuclei, the chromatin texture of MDS myeloblasts revealed higher local homogeneity and goodness-of-fit of the FD, but lower values of entropy, contrast, diagonal moment, and fractal dimension. The same differences were found between nuclei of normal promyelocytes and those of MDS. Nuclei of atypical myeloid precursors showed intermediate characteristics between those of blasts and promyelocytes according to the quantitative features (perimeter, form factor, gray level and its standard deviation, but were similar to

  17. 阿扎胞苷在骨髓增生异常综合征应用的研究进展%Advances of azacitidine in myelodysplastic syndromes

    Institute of Scientific and Technical Information of China (English)

    谢丽丽

    2015-01-01

    In recent years,researches on the mechanisms of methylation and demethylation treatment strategies have brought new ideas for treatment of myelodysplastic syndrome (MDS).Azacitidine and decitabine were approved by United States Food and Drug Administration(FDA) for the treatment of MDS.Chinese researchers have a preliminary understanding of the clinical applications of decitabine after 5 years exploration.Azacitidine can improve the quality of life of high-risk patients with MDS,and prolong overall survival (OS) and the median time of acute myeloid leukemia(AML) transformation,especially in high-risk MDS patients over 65 years old compared with decitabine.Azacitidine maintenance therapy after hematopoietic stem cell transplantation(HSCT) can delay the recurrence.In addition,application of low-dose azacitidine for low-risk MDS patients is still in exploring.Azacitidine has been combined with other novel agents such as histone deacetylase (HDAC) inhibitors,lenalidomide and infliximab monoclonal antibody are very promising in clinical researches.However,azacitidine has not been approved by China Food and Drug Administration (CFDA) and lacks clinical experience.This article reviews literatures on exploring optimal dose,efficacy of different subtypes of MDS and prospects of azacitidine combination therapy.%近年来,对甲基化机制研究与去甲基化治疗策略为骨髓增生异常综合征(MDS)临床治疗带来新思路,美国食品药品监督管理局(FDA)已经批准药物包括阿扎胞苷与地西他滨应用于临床.国内对于地西他滨经过近5年的研究认识已经初具临床经验.目前,相关研究结果显示阿扎胞苷可提高高危MDS患者生存质量,显著延长其总生存(OS)期与向急性髓细胞白血病(AML)转化的时间.与采用地西他滨治疗相比,在年龄≥65岁的高危老年MDS患者中疗效更为显著.阿扎胞苷应用于造血干细胞移植(HSCT)后维持治疗可延缓MDS患者复发.此外,低剂量阿扎

  18. Second Malignant Neoplasms After Treatment of Childhood Acute Lymphoblastic Leukemia

    DEFF Research Database (Denmark)

    Schmiegelow, K.; Levinsen, Mette Frandsen; Attarbaschi, Andishe

    2013-01-01

    PURPOSE: Second malignant neoplasms (SMNs) after diagnosis of childhood acute lymphoblastic leukemia (ALL) are rare events. PATIENTS AND METHODS: We analyzed data on risk factors and outcomes of 642 children with SMNs occurring after treatment for ALL from 18 collaborative study groups between 1980...... and 2007. RESULTS: Acute myeloid leukemia (AML; n = 186), myelodysplastic syndrome (MDS; n = 69), and nonmeningioma brain tumor (n = 116) were the most common types of SMNs and had the poorest outcome (5-year survival rate, 18.1% ± 2.9%, 31.1% ± 6.2%, and 18.3% ± 3.8%, respectively). Five-year survival...

  19. Clinical analysis of 12 cases of pediatric myelodysplastic syndrome%儿童骨髓增生异常综合征12例

    Institute of Scientific and Technical Information of China (English)

    林巍; 张莉; 廉红云; 张蕊; 苏雁; 金玲; 杨骏; 朱光华; 姜锦

    2015-01-01

    目的 回顾性分析儿童骨髓增生异常综合征(MDS)患儿的临床特点、实验室检查、治疗及转归资料,了解儿童MDS疾病发生、发展特点,为进一步规范诊断治疗提供依据.方法 回顾性分析2012年1月至2013年12月首都医科大学附属北京儿童医院血液肿瘤中心收治的12例MDS患儿的临床表现、实验室检查、治疗及疾病转归资料.结果 共收集病例12例,中位年龄9(4 ~14)岁;男7例,女5例.临床资料:12例患儿病史平均2个月(0.5~5.0个月),临床表现为贫血10例(83.3%)、出血4例(33.3%)、肝脾大3例(25.0%)、发热2例(16.7%)、特殊皮疹2例(16.7%).实验室检查:血常规二系(75.0%)或三系(25.0%)减低,以血小板、血红蛋白减少为著;骨髓以增生活跃为主(11/12例,91.7%),三系均出现病态造血6例(50.0%)、二系病态造血5例(41.7%);抗碱血红蛋白中位数0.120 0(0.030 0 ~0.197 6),高于正常;小巨核细胞>0.30者8例(66.7%,0.05~0.88);异常染色体6例(占50.0%).病例均临床观察超过1年.3例找到合适供者行造血干细胞移植,后1例死于移植并发症、2例存活.7例仅予支持治疗:3例进展为急性髓细胞白血病,后予以化疗治疗(1例化疗后因合并重症感染死亡、2例存活),转化白血病中位时间为7个月;另4例目前带病存活.2例失访.结论 儿童MDS起病较急、病程较短、进展快、白血病转化率高.血常规以血细胞减少为主;骨髓虽增生活跃,但病态造血明显伴抗碱血红蛋白升高、小巨核细胞比例升高;造血干细胞移植可能为有效的治疗手段.%Objective To summarize the characteristics of pediatric myelodysplastic syndrome (MDS),and provide the basis for further standardize diagnosis and treatment,through retrospective collection of children's myelodysplastic syndrome clinical features,laboratory tests,treatment and outcome data.Methods Twelve children diagnosed as MDS in Hematology

  20. Radioimmunotherapy for treatment of acute myeloid leukaemia and myelodysplastic syndrome. Conceptual chances

    Energy Technology Data Exchange (ETDEWEB)

    Buchmann, I.; Helisch, A.; Bartenstein, P. [Klinik und Poliklinik fuer Nuklearmedizin, Universitaetsklinikum Mainz (Germany); Meyer, R.G.; Herr, W. [III. Medizinische Klinik und Poliklinik (Haematologie), Universitaetsklinikum Mainz (Germany)

    2005-07-01

    The prognosis of patients with acute myeloid leukaemia (AML) has improved considerably by introduction of aggressive consolidation chemotherapy and haematopoietic stem cell transplantation (SCT). Nevertheless, only 20-30% of patients with AML achieve long-term disease-free survival after SCT. The most common cause of treatment failure is relapse. Additionally, mortality rates are significantly increased by therapy-related causes such as toxicity of chemotherapy and complications of SCT. Including radioimmunotherapies in the treatment of AML and myelodyplastic syndrome (MDS) allows for the achievement of a pronounced antileukaemic effect for the reduction of relapse rates on the one hand. On the other hand, no increase of acute toxicity and later complications should be induced. These effects are important for the primary reduction of tumour cells as well as for the myelblative conditioning before SCT. This paper provides a systematic and critical review of the currently used radionuclides and immunoconjugates for the treatment of AML and MDS and summarizes the literature on primary tumour cell reductive radioimmunotherapies on the one hand and conditioning radioimmunotherapies before SCT on the other hand. (orig.)