{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T04:07:24Z","timestamp":1791086844500,"version":"4.1.0"},"reference-count":54,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"9","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCO"],"published-print":{"date-parts":[[1999,9]]},"abstract":"<jats:p> PURPOSE: To evaluate the efficacy and safety of the combination of topotecan and cytarabine in patients with myelodysplastic syndromes (MDSs) and chronic myelomonocytic leukemia (CMML). <\/jats:p><jats:p> PATIENTS AND METHODS: Fifty-nine patients with MDSs and 27 with CMML were enrolled. They were either previously untreated (66%) or had received only biologic agents (14%) or chemotherapy with or without biologic agents (20%). Treatment consisted of topotecan 1.25 mg\/m<jats:sup>2<\/jats:sup> by continuous intravenous infusion daily for 5 days and cytarabine 1.0 g\/m<jats:sup>2<\/jats:sup> by infusion over 2 hours daily for 5 days. Prophylaxis included antibacterial, antifungal, and antiviral agents. At a median follow-up of 7 months, all 86 patients were assessable for response and toxicity. <\/jats:p><jats:p> RESULTS: Complete remission (CR) was observed in 48 patients (56%; 61% with MDSs, 44% with CMML; P = .15). Similar CR rates were observed for patients with good-risk and poor-risk MDS (70% and 56%, respectively). The treatment effectively induced CR in patients with a poor-prognosis karyotype involving chromosomes 5 and 7 (CR, 71%) and secondary MDSs (CR, 72%). Fifty-four patients received one induction course, 25 patients received two, and the rest received more than two. The median number of continuation courses was two. The median overall duration of CR was 34 weeks (50 weeks for MDSs and 33 weeks for CMML). The median survival was 60 weeks for MDS and 44 weeks for CMML patients. CR and survival durations were longer in patients with refractory anemia with excess blasts (RAEB). Grade 3 or 4 mucositis or diarrhea was observed in three patients each. Fever was observed in 63%, and infections in 49% of patients. Six patients (7%) died during induction therapy. <\/jats:p><jats:p> CONCLUSION: Topotecan and cytarabine induced high CR rates in unselected patients with MDSs and CMML, particularly among patients with poor-prognosis cytogenetics and secondary MDSs. Topotecan-cytarabine is an active induction regimen in MDS and CMML patients, is well tolerated, and is associated with a low mortality rate. <\/jats:p>","DOI":"10.1200\/jco.1999.17.9.2819","type":"journal-article","created":{"date-parts":[[2017,2,24]],"date-time":"2017-02-24T06:05:40Z","timestamp":1487916340000},"page":"2819-2819","source":"Crossref","is-referenced-by-count":112,"title":["Topotecan and Cytarabine Is an Active Combination Regimen in Myelodysplastic Syndromes and Chronic Myelomonocytic Leukemia"],"prefix":"10.1200","volume":"17","author":[{"given":"Miloslav","family":"Beran","sequence":"first","affiliation":[{"name":"From the Departments of Leukemia and Molecular Hematology, and Division of Laboratory Medicine, The University of Texas M.D. Anderson Cancer Center, Houston, TX; and Department of Hematology, Singapore General Hospital, Singapore."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elihu","family":"Estey","sequence":"additional","affiliation":[{"name":"From the Departments of Leukemia and Molecular Hematology, and Division of Laboratory Medicine, The University of Texas M.D. Anderson Cancer Center, Houston, TX; and Department of Hematology, Singapore General Hospital, Singapore."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"O'Brien","sequence":"additional","affiliation":[{"name":"From the Departments of Leukemia and Molecular Hematology, and Division of Laboratory Medicine, The University of Texas M.D. Anderson Cancer Center, Houston, TX; and Department of Hematology, Singapore General Hospital, Singapore."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge","family":"Cortes","sequence":"additional","affiliation":[{"name":"From the Departments of Leukemia and Molecular Hematology, and Division of Laboratory Medicine, The University of Texas M.D. Anderson Cancer Center, Houston, TX; and Department of Hematology, Singapore General Hospital, Singapore."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles A.","family":"Koller","sequence":"additional","affiliation":[{"name":"From the Departments of Leukemia and Molecular Hematology, and Division of Laboratory Medicine, The University of Texas M.D. Anderson Cancer Center, Houston, TX; and Department of Hematology, Singapore General Hospital, Singapore."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francis J.","family":"Giles","sequence":"additional","affiliation":[{"name":"From the Departments of Leukemia and Molecular Hematology, and Division of Laboratory Medicine, The University of Texas M.D. Anderson Cancer Center, Houston, TX; and Department of Hematology, Singapore General Hospital, Singapore."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"Kornblau","sequence":"additional","affiliation":[{"name":"From the Departments of Leukemia and Molecular Hematology, and Division of Laboratory Medicine, The University of Texas M.D. Anderson Cancer Center, Houston, TX; and Department of Hematology, Singapore General Hospital, Singapore."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Andreeff","sequence":"additional","affiliation":[{"name":"From the Departments of Leukemia and Molecular Hematology, and Division of Laboratory Medicine, The University of Texas M.D. Anderson Cancer Center, Houston, TX; and Department of Hematology, Singapore General Hospital, Singapore."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norbert","family":"Vey","sequence":"additional","affiliation":[{"name":"From the Departments of Leukemia and Molecular Hematology, and Division of Laboratory Medicine, The University of Texas M.D. Anderson Cancer Center, Houston, TX; and Department of Hematology, Singapore General Hospital, Singapore."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sherry R.","family":"Pierce","sequence":"additional","affiliation":[{"name":"From the Departments of Leukemia and Molecular Hematology, and Division of Laboratory Medicine, The University of Texas M.D. Anderson Cancer Center, Houston, TX; and Department of Hematology, Singapore General Hospital, Singapore."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimberly","family":"Hayes","sequence":"additional","affiliation":[{"name":"From the Departments of Leukemia and Molecular Hematology, and Division of Laboratory Medicine, The University of Texas M.D. Anderson Cancer Center, Houston, TX; and Department of Hematology, Singapore General Hospital, Singapore."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gee Chuan","family":"Wong","sequence":"additional","affiliation":[{"name":"From the Departments of Leukemia and Molecular Hematology, and Division of Laboratory Medicine, The University of Texas M.D. Anderson Cancer Center, Houston, TX; and Department of Hematology, Singapore General Hospital, Singapore."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Keating","sequence":"additional","affiliation":[{"name":"From the Departments of Leukemia and Molecular Hematology, and Division of Laboratory Medicine, The University of Texas M.D. Anderson Cancer Center, Houston, TX; and Department of Hematology, Singapore General Hospital, Singapore."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hagop","family":"Kantarjian","sequence":"additional","affiliation":[{"name":"From the Departments of Leukemia and Molecular Hematology, and Division of Laboratory Medicine, The University of Texas M.D. Anderson Cancer Center, Houston, TX; and Department of Hematology, Singapore General Hospital, Singapore."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"233","reference":[{"key":"R1-2819","unstructured":"Bennett  JM: Classification of the myelodysplastic syndromes.  Clin Haematol 15:909,1986-923,"},{"key":"R2-2819","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.1982.tb08475.x"},{"key":"R3-2819","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.1992.tb06430.x"},{"key":"R4-2819","unstructured":"Aul  C,  Gattermann  N,  Germing  U, et al: Risk assessment in primary myelodysplastic syndromes: Validation of the D\u00fcsseldorf score.  Leukemia 8:1906,1994-1913,"},{"key":"R5-2819","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V74.1.395.395"},{"key":"R6-2819","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.1985.tb07329.x"},{"key":"R7-2819","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.1987.tb06138.x"},{"key":"R8-2819","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.1985.tb04063.x"},{"key":"R9-2819","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V67.6.1765.1765"},{"key":"R10-2819","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(19871215)60:12<3029::AID-CNCR2820601229>3.0.CO;2-4"},{"key":"R11-2819","unstructured":"Morel  P,  Hebbar  M,  Lai  JL, et al: Cytogenetic analysis has strong independent prognostic value in de novo myelodysplastic syndromes and can be incorporated in a new scoring system: A report on 408 cases.  Leukemia 7:1315,1993-1323,"},{"key":"R12-2819","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V89.6.2079"},{"key":"R13-2819","doi-asserted-by":"crossref","unstructured":"Estey  E,  Keating  M,  Pierce  S, et al: Application of the International Scoring System for Myelodysplasia to M.D.  Anderson patients. Blood 90:2843,1995-2844,","DOI":"10.1182\/blood.V90.7.2843"},{"key":"R14-2819","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.1994.tb06734.x"},{"key":"R15-2819","doi-asserted-by":"publisher","DOI":"10.3109\/10428199309148501"},{"key":"R16-2819","doi-asserted-by":"publisher","DOI":"10.1007\/s00282-997-0041-4"},{"key":"R17-2819","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.1988.6.9.1417"},{"key":"R18-2819","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V78.1.205.205"},{"key":"R19-2819","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(19861101)58:9<2023::AID-CNCR2820580912>3.0.CO;2-H"},{"key":"R21-2819","unstructured":"Greenberg  P,  Taylor  K,  Larson  R, et al: Phase III randomized multicenter trial of G-CSF vs observation for myelodysplastic syndromes (MDS).  Blood 82:196,1993,  (abstr 768)"},{"key":"R22-2819","unstructured":"Schuster  MW,  Thompson  JA,  Larson  R, et al: Randomized trial of subcutaneous granulocyte-macrophage colony stimulating factor (GM-CSF) versus observation in patients with myelodysplastic syndromes or aplastic anemia.  J Clin Oncol 9:205,1990,  (abstr 205)"},{"key":"R23-2819","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.1995.tb08909.x"},{"key":"R24-2819","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.1986.4.12.1857"},{"key":"R25-2819","doi-asserted-by":"publisher","DOI":"10.1007\/BF01697631"},{"key":"R27-2819","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.1996.14.9.2486"},{"key":"R28-2819","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V90.8.2969"},{"key":"R29-2819","doi-asserted-by":"publisher","DOI":"10.3109\/10428199309064263"},{"key":"R30-2819","unstructured":"Armitage  JO,  Dick  FR,  Needleman  SW, et al: Effect of chemotherapy for the dysmyelopoietic syndrome.  Cancer Treat Rep 65:601,1981-605,"},{"key":"R31-2819","doi-asserted-by":"crossref","unstructured":"Mertelsmann  R,  Thaler  HT,  To  L, et al: Morphological classification, response to therapy, and survival in 263 adult patients with acute nonlymphoblastic leukemia.  Blood 56:733,1980-776,","DOI":"10.1182\/blood.V56.5.773.773"},{"key":"R32-2819","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2141.1997.2973114.x"},{"key":"R33-2819","unstructured":"DeWitte  T,  Suciu  S,  Peetermans  M, et al: Intensive chemotherapy for poor prognosis myelodysplasia (MDS) and secondary acute myeloid leukemia (sAML) following MDS of more than 6 months duration: A pilot study by the Leukemia Cooperative Group of the European Organisation for Research and Treatment in Cancer (EORTC-LCG).  Leukemia 9:1805,1995-1811,"},{"key":"R34-2819","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2141.1997.4763281.x"},{"key":"R35-2819","unstructured":"Invernizzi  R,  Pecci  A,  Rossi  G, et al: Idarubicin and cytosine arabinoside in the induction and maintenance therapy of high-risk myelodysplastic syndromes.  Haematologica 82:9,1997-12,"},{"key":"R36-2819","doi-asserted-by":"crossref","unstructured":"Economopoulos  T,  Papageorgiou  E,  Stathakis  N, et al: Treatment of high risk myelodysplastic syndromes with idarubicin and cytosine arabinoside supported by granulocyte-macrophage colony-stimulating factor (GM-CSF).  Leuk Lymphoma 20:385,1996-391,","DOI":"10.1016\/0145-2126(95)00169-7"},{"key":"R37-2819","doi-asserted-by":"publisher","DOI":"10.1016\/S0145-2126(96)00116-6"},{"key":"R38-2819","doi-asserted-by":"crossref","unstructured":"Fenaux  P,  Morel  P,  Rose  C, et al: Prognostic factors in adult de novo myelodysplastic syndromes treated by intensive chemotherapy.  Br J Haematol 77:497,1991-501,","DOI":"10.1111\/j.1365-2141.1991.tb08616.x"},{"key":"R39-2819","unstructured":"Hsiang  Y-H,  Liu  LF: Identification of mammalian DNA topoisomerase I as an intracellular target of the anticancer drug camptothecin.  Cancer Res 48:1722,1988-1726,"},{"key":"R40-2819","unstructured":"Hsiang  Y-H,  Lihou  MG,  Liu  LF: Arrest of replication forks by drug-stabilized topoisomerase I-DNA cleavable complexes as a mechanism of cell killing by camptothecin.  Cancer Res 49:5077,1989-5082,"},{"key":"R41-2819","unstructured":"Zhang  H,  D'Arpa  P,  Liu  LF: A model for tumor cell killing by topoisomerase poisons.  Cancer Cells 2:23,1990-27,"},{"key":"R44-2819","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V81.5.1146.1146"},{"key":"R45-2819","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.1994.12.10.2193"},{"key":"R46-2819","unstructured":"Rowinsky  EK,  Kaufmann  SH,  Baker  SD, et al: A phase I and pharmacological study of topotecan infused over 30 minutes for five days in patients with refractory acute leukemia.  Clin Cancer Res 2:1921,1996-1930,"},{"key":"R47-2819","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V88.7.2473.bloodjournal8872473"},{"key":"R48-2819","doi-asserted-by":"publisher","DOI":"10.3109\/10428199809057611"},{"key":"R49-2819","unstructured":"Ghaddar  HM,  Plunkett  W,  Kantarjian  HM, et al: Long-term results following treatment of newly-diagnosed acute myelogenous leukemia with continuous-infusion high-dose cytosine arabinoside.  Leukemia 8:1269,1994-1274,"},{"key":"R50-2819","unstructured":"Estey  E,  Beran  M,  Pierce  S, et al: All-trans retinoic acid (ATRA) may improve results of chemotherapy in poor prognosis non-APL AML and MDS: A randomized study.  Blood 90:416,1997,  (abstr 1851)"},{"key":"R51-2819","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V93.8.2478"},{"key":"R52-2819","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.1994.12.4.671"},{"key":"R53-2819","doi-asserted-by":"crossref","unstructured":"Estey  E,  Kantarjian  HM,  O'Brien  S, et al: High remission rate, short remission duration in patients with refractory anemia with excess blasts (RAEB) in transformation (RAEB-t) given acute myelogenous leukemia (AML)-type chemotherapy in combination with granulocyte-CSF (G-CFS).  Cytokines Mol Ther 1:21,1995-28,","DOI":"10.1016\/0145-2126(94)90157-0"},{"key":"R55-2819","unstructured":"Crump  M,  Lipton  J,  Hedley  D, et al: A phase I trial of sequential topotecan and etoposide in adult acute myeloid leukemia (AML).  Blood 88:867,1996,  (abstr 867)"},{"key":"R56-2819","unstructured":"Cooper  BW,  Lazarus  HM,  Creger  R, et al: A phase I and pharmacodynamic study of sequential topotecan and etoposide (TE) in adult patients with refractory relapsed acute leukemia (RAL).  J Clin Oncol 15:486,1996,  (abstr 486)"},{"key":"R58-2819","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.1997.15.1.44"},{"key":"R59-2819","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(19820801)50:3<457::AID-CNCR2820500313>3.0.CO;2-K"},{"key":"R60-2819","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198301063080105"}],"container-title":["Journal of Clinical Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascopubs.org\/doi\/pdfdirect\/10.1200\/JCO.1999.17.9.2819","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,5,25]],"date-time":"2022-05-25T21:28:36Z","timestamp":1653514116000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascopubs.org\/doi\/10.1200\/JCO.1999.17.9.2819"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1999,9]]},"references-count":54,"journal-issue":{"issue":"9","published-print":{"date-parts":[[1999,9]]}},"alternative-id":["10.1200\/JCO.1999.17.9.2819"],"URL":"https:\/\/doi.org\/10.1200\/jco.1999.17.9.2819","relation":{},"ISSN":["0732-183X","1527-7755"],"issn-type":[{"value":"0732-183X","type":"print"},{"value":"1527-7755","type":"electronic"}],"subject":[],"published":{"date-parts":[[1999,9]]}}}