Trial reportThe New England journal of medicine2016
TP53 and Decitabine in Acute Myeloid Leukemia and Myelodysplastic Syndromes.
5 registry-linked trialsOpen access · bronzeAbstract readClinical Trial
In one paragraph
Trial report in The New England journal of medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 5 registered trials, which are not on this map. Cited by 469 papers, 3 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
469citing papers in PubMed, 3 pooled it
65.5field-weighted citation impact, top 1% of its field
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Genomic Predictors of Decitabine Response in AML/MDS
Decitabine and Arsenic Trioxide(ATO) in the Treatment of Myelodysplasic Syndrome
Decitabine,Cytarabine(Ara-C) and Arsenic Trioxide(ATO) in the Treatment of Acute Myeloid Leukemia With p53 Mutations
Decitabine for COVID-19 Pneumonia-ARDS Treatment: DART Trial
Precision Therapy Versus Standard Therapy in Acute Myeloid Leukaemia and Myelodysplastic Syndrome in Elderly
Who cites it
469 citing papers in PubMed, 3 syntheses or guidelines pooled it, 779 citations in OpenAlex.
- The effects of adding decitabine to conditioning regimen for patients with acute myeloid leukemia or myelodysplastic syndrome undergoing allogeneic hematopoietic stem cell transplantation: a systematic review and meta-analysis.Annals of hematology · 2025Pooled it
- Treatment outcomes for newly diagnosed, treatment-naïve TP53-mutated acute myeloid leukemia: a systematic review and meta-analysis.Journal of hematology & oncology · 2023Pooled it
- Targeting p53 pathways: mechanisms, structures, and advances in therapy.Signal transduction and targeted therapy · 2023Pooled it
- A Phase 1b/2 Study of TP-0903 and Decitabine Targeting Mutant TP53 and/or Complex Karyotype in Patients with Untreated Acute Myeloid Leukemia ≥Age 60 Years.Cancer research communications · 2025Trial
- Impact of TP53 Mutation Status in Elderly AML Patients When Adding All-Trans Retinoic Acid or Valproic Acid to Decitabine.European journal of haematology · 2025Trial
- Venetoclax plus D-CAG (decitabine, cytarabine, aclarubicin, G-CSF) for elderly or unfit patients with newly diagnosed acute myeloid leukemia: a multicenter, prospective study.Annals of hematology · 2024Trial
- A multicenter phase 2 clinical trial of low-dose subcutaneous decitabine in myelofibrosis.Blood advances · 2024Trial
- Phase 2 study of epigenetic priming with decitabine followed by cytarabine for acute myeloid leukemia in older patients.American journal of hematology · 2024Trial
- Spliceosome mutations are associated with clinical response in a phase 1b/2 study of the PLK1 inhibitor onvansertib in combination with decitabine in relapsed or refractory acute myeloid leukemia.Annals of hematology · 2023Trial
- Trial
- A Multicenter Phase 2 Clinical Trial of 10-Day Decitabine, Dose-Escalated Donor Lymphocyte Infusion, and Ruxolitinib for Relapsed Acute Myeloid Leukemia and Myelodysplastic Syndromes after Allogeneic Hematopoietic Cell Transplantation.Transplantation and cellular therapy · 2023Trial
- Clinical Trials Assessing Hypomethylating Agents Combined with Other Therapies: Causes for Failure and Potential Solutions.Clinical cancer research : an official journal of the American Association for Cancer Research · 2021Trial
- Decitabine induces cell differentiation and growth inhibition accompanied by upregulation of microRNA-143 and MS4A3 in the myelodysplastic syndromes-derived leukemic cell line MDS-L.Oncology letters · 2026Article
- Article
- Myelodysplastic Syndromes: 2026 Update on Diagnosis, Risk-Stratification and Management.American journal of hematology · 2026Review
- Choice of hypomethylating agent for newly diagnosed TP53-mutant acute myeloid Leukemia: a COMMAND registry study.Leukemia · 2026Article
- Synthetic lethality in TP53-mutant acute myeloid leukemia.Blood advances · 2026Article
- Acute Myeloid Leukemia Patients with High-Risk Karyotypes Benefit from Decitabine in Combination with Modified CAG.Biochemical genetics · 2026Article
- Making large language models reliable data science programming copilots for biomedical research.Nature biomedical engineering · 2026Article
- Real-World Management of HMA-Related Myelosuppression During MDS Treatment in the Canadian Landscape.Current oncology (Toronto, Ont.) · 2026Review
409 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
39 authors at 4 institutions in 1 country.
John S Welch *the Department of Internal Medicine, Division of Oncology (J.S.W., L.D.W., G.L.U., A.G., M.H.T., I.P., R.R., T.A.F., K.E.S.-G., R.V., S.T.O., C.N.A., A.F.C., M.A.S., M.A.J., S.E.H., K.L., M.R.J., M.J.W., P.W., D.C.L., J.F.D., T.J.L.), and the Division of Biostatistics (J.D.B.), and the Department of Pathology and Immunology (E.J.D., B.T., Y.-S.L.), Washington University School of Medicine, and McDonnell Genome Institute, Washington University in St. Louis (A.A.P., C.A.M., C.C.F., M.O., R.S.F., R.K.W., L.D.W., T.J.L.) - both in St. Louis; the Departments of Internal Medicine (A.H., N.K., M.J.S., W.S.) and Pharmacy (R.W.K.), University of Chicago, Chicago; and the Department of Internal Medicine (T.A.G.), Massachusetts General Hospital, Boston.
Allegra A Petti *the Department of Internal Medicine, Division of Oncology (J.S.W., L.D.W., G.L.U., A.G., M.H.T., I.P., R.R., T.A.F., K.E.S.-G., R.V., S.T.O., C.N.A., A.F.C., M.A.S., M.A.J., S.E.H., K.L., M.R.J., M.J.W., P.W., D.C.L., J.F.D., T.J.L.), and the Division of Biostatistics (J.D.B.), and the Department of Pathology and Immunology (E.J.D., B.T., Y.-S.L.), Washington University School of Medicine, and McDonnell Genome Institute, Washington University in St. Louis (A.A.P., C.A.M., C.C.F., M.O., R.S.F., R.K.W., L.D.W., T.J.L.) - both in St. Louis; the Departments of Internal Medicine (A.H., N.K., M.J.S., W.S.) and Pharmacy (R.W.K.), University of Chicago, Chicago; and the Department of Internal Medicine (T.A.G.), Massachusetts General Hospital, Boston.
Christopher A Millerthe Department of Internal Medicine, Division of Oncology (J.S.W., L.D.W., G.L.U., A.G., M.H.T., I.P., R.R., T.A.F., K.E.S.-G., R.V., S.T.O., C.N.A., A.F.C., M.A.S., M.A.J., S.E.H., K.L., M.R.J., M.J.W., P.W., D.C.L., J.F.D., T.J.L.), and the Division of Biostatistics (J.D.B.), and the Department of Pathology and Immunology (E.J.D., B.T., Y.-S.L.), Washington University School of Medicine, and McDonnell Genome Institute, Washington University in St. Louis (A.A.P., C.A.M., C.C.F., M.O., R.S.F., R.K.W., L.D.W., T.J.L.) - both in St. Louis; the Departments of Internal Medicine (A.H., N.K., M.J.S., W.S.) and Pharmacy (R.W.K.), University of Chicago, Chicago; and the Department of Internal Medicine (T.A.G.), Massachusetts General Hospital, Boston.
Catrina C Fronickthe Department of Internal Medicine, Division of Oncology (J.S.W., L.D.W., G.L.U., A.G., M.H.T., I.P., R.R., T.A.F., K.E.S.-G., R.V., S.T.O., C.N.A., A.F.C., M.A.S., M.A.J., S.E.H., K.L., M.R.J., M.J.W., P.W., D.C.L., J.F.D., T.J.L.), and the Division of Biostatistics (J.D.B.), and the Department of Pathology and Immunology (E.J.D., B.T., Y.-S.L.), Washington University School of Medicine, and McDonnell Genome Institute, Washington University in St. Louis (A.A.P., C.A.M., C.C.F., M.O., R.S.F., R.K.W., L.D.W., T.J.L.) - both in St. Louis; the Departments of Internal Medicine (A.H., N.K., M.J.S., W.S.) and Pharmacy (R.W.K.), University of Chicago, Chicago; and the Department of Internal Medicine (T.A.G.), Massachusetts General Hospital, Boston.
Michelle O'Laughlinthe Department of Internal Medicine, Division of Oncology (J.S.W., L.D.W., G.L.U., A.G., M.H.T., I.P., R.R., T.A.F., K.E.S.-G., R.V., S.T.O., C.N.A., A.F.C., M.A.S., M.A.J., S.E.H., K.L., M.R.J., M.J.W., P.W., D.C.L., J.F.D., T.J.L.), and the Division of Biostatistics (J.D.B.), and the Department of Pathology and Immunology (E.J.D., B.T., Y.-S.L.), Washington University School of Medicine, and McDonnell Genome Institute, Washington University in St. Louis (A.A.P., C.A.M., C.C.F., M.O., R.S.F., R.K.W., L.D.W., T.J.L.) - both in St. Louis; the Departments of Internal Medicine (A.H., N.K., M.J.S., W.S.) and Pharmacy (R.W.K.), University of Chicago, Chicago; and the Department of Internal Medicine (T.A.G.), Massachusetts General Hospital, Boston.
Robert S Fultonthe Department of Internal Medicine, Division of Oncology (J.S.W., L.D.W., G.L.U., A.G., M.H.T., I.P., R.R., T.A.F., K.E.S.-G., R.V., S.T.O., C.N.A., A.F.C., M.A.S., M.A.J., S.E.H., K.L., M.R.J., M.J.W., P.W., D.C.L., J.F.D., T.J.L.), and the Division of Biostatistics (J.D.B.), and the Department of Pathology and Immunology (E.J.D., B.T., Y.-S.L.), Washington University School of Medicine, and McDonnell Genome Institute, Washington University in St. Louis (A.A.P., C.A.M., C.C.F., M.O., R.S.F., R.K.W., L.D.W., T.J.L.) - both in St. Louis; the Departments of Internal Medicine (A.H., N.K., M.J.S., W.S.) and Pharmacy (R.W.K.), University of Chicago, Chicago; and the Department of Internal Medicine (T.A.G.), Massachusetts General Hospital, Boston.
Richard K Wilsonthe Department of Internal Medicine, Division of Oncology (J.S.W., L.D.W., G.L.U., A.G., M.H.T., I.P., R.R., T.A.F., K.E.S.-G., R.V., S.T.O., C.N.A., A.F.C., M.A.S., M.A.J., S.E.H., K.L., M.R.J., M.J.W., P.W., D.C.L., J.F.D., T.J.L.), and the Division of Biostatistics (J.D.B.), and the Department of Pathology and Immunology (E.J.D., B.T., Y.-S.L.), Washington University School of Medicine, and McDonnell Genome Institute, Washington University in St. Louis (A.A.P., C.A.M., C.C.F., M.O., R.S.F., R.K.W., L.D.W., T.J.L.) - both in St. Louis; the Departments of Internal Medicine (A.H., N.K., M.J.S., W.S.) and Pharmacy (R.W.K.), University of Chicago, Chicago; and the Department of Internal Medicine (T.A.G.), Massachusetts General Hospital, Boston.
Jack D Batythe Department of Internal Medicine, Division of Oncology (J.S.W., L.D.W., G.L.U., A.G., M.H.T., I.P., R.R., T.A.F., K.E.S.-G., R.V., S.T.O., C.N.A., A.F.C., M.A.S., M.A.J., S.E.H., K.L., M.R.J., M.J.W., P.W., D.C.L., J.F.D., T.J.L.), and the Division of Biostatistics (J.D.B.), and the Department of Pathology and Immunology (E.J.D., B.T., Y.-S.L.), Washington University School of Medicine, and McDonnell Genome Institute, Washington University in St. Louis (A.A.P., C.A.M., C.C.F., M.O., R.S.F., R.K.W., L.D.W., T.J.L.) - both in St. Louis; the Departments of Internal Medicine (A.H., N.K., M.J.S., W.S.) and Pharmacy (R.W.K.), University of Chicago, Chicago; and the Department of Internal Medicine (T.A.G.), Massachusetts General Hospital, Boston.
Eric J Duncavagethe Department of Internal Medicine, Division of Oncology (J.S.W., L.D.W., G.L.U., A.G., M.H.T., I.P., R.R., T.A.F., K.E.S.-G., R.V., S.T.O., C.N.A., A.F.C., M.A.S., M.A.J., S.E.H., K.L., M.R.J., M.J.W., P.W., D.C.L., J.F.D., T.J.L.), and the Division of Biostatistics (J.D.B.), and the Department of Pathology and Immunology (E.J.D., B.T., Y.-S.L.), Washington University School of Medicine, and McDonnell Genome Institute, Washington University in St. Louis (A.A.P., C.A.M., C.C.F., M.O., R.S.F., R.K.W., L.D.W., T.J.L.) - both in St. Louis; the Departments of Internal Medicine (A.H., N.K., M.J.S., W.S.) and Pharmacy (R.W.K.), University of Chicago, Chicago; and the Department of Internal Medicine (T.A.G.), Massachusetts General Hospital, Boston.
Bevan Tandonthe Department of Internal Medicine, Division of Oncology (J.S.W., L.D.W., G.L.U., A.G., M.H.T., I.P., R.R., T.A.F., K.E.S.-G., R.V., S.T.O., C.N.A., A.F.C., M.A.S., M.A.J., S.E.H., K.L., M.R.J., M.J.W., P.W., D.C.L., J.F.D., T.J.L.), and the Division of Biostatistics (J.D.B.), and the Department of Pathology and Immunology (E.J.D., B.T., Y.-S.L.), Washington University School of Medicine, and McDonnell Genome Institute, Washington University in St. Louis (A.A.P., C.A.M., C.C.F., M.O., R.S.F., R.K.W., L.D.W., T.J.L.) - both in St. Louis; the Departments of Internal Medicine (A.H., N.K., M.J.S., W.S.) and Pharmacy (R.W.K.), University of Chicago, Chicago; and the Department of Internal Medicine (T.A.G.), Massachusetts General Hospital, Boston.
Yi-Shan Leethe Department of Internal Medicine, Division of Oncology (J.S.W., L.D.W., G.L.U., A.G., M.H.T., I.P., R.R., T.A.F., K.E.S.-G., R.V., S.T.O., C.N.A., A.F.C., M.A.S., M.A.J., S.E.H., K.L., M.R.J., M.J.W., P.W., D.C.L., J.F.D., T.J.L.), and the Division of Biostatistics (J.D.B.), and the Department of Pathology and Immunology (E.J.D., B.T., Y.-S.L.), Washington University School of Medicine, and McDonnell Genome Institute, Washington University in St. Louis (A.A.P., C.A.M., C.C.F., M.O., R.S.F., R.K.W., L.D.W., T.J.L.) - both in St. Louis; the Departments of Internal Medicine (A.H., N.K., M.J.S., W.S.) and Pharmacy (R.W.K.), University of Chicago, Chicago; and the Department of Internal Medicine (T.A.G.), Massachusetts General Hospital, Boston.
Lukas D Wartmanthe Department of Internal Medicine, Division of Oncology (J.S.W., L.D.W., G.L.U., A.G., M.H.T., I.P., R.R., T.A.F., K.E.S.-G., R.V., S.T.O., C.N.A., A.F.C., M.A.S., M.A.J., S.E.H., K.L., M.R.J., M.J.W., P.W., D.C.L., J.F.D., T.J.L.), and the Division of Biostatistics (J.D.B.), and the Department of Pathology and Immunology (E.J.D., B.T., Y.-S.L.), Washington University School of Medicine, and McDonnell Genome Institute, Washington University in St. Louis (A.A.P., C.A.M., C.C.F., M.O., R.S.F., R.K.W., L.D.W., T.J.L.) - both in St. Louis; the Departments of Internal Medicine (A.H., N.K., M.J.S., W.S.) and Pharmacy (R.W.K.), University of Chicago, Chicago; and the Department of Internal Medicine (T.A.G.), Massachusetts General Hospital, Boston.
Geoffrey L Uythe Department of Internal Medicine, Division of Oncology (J.S.W., L.D.W., G.L.U., A.G., M.H.T., I.P., R.R., T.A.F., K.E.S.-G., R.V., S.T.O., C.N.A., A.F.C., M.A.S., M.A.J., S.E.H., K.L., M.R.J., M.J.W., P.W., D.C.L., J.F.D., T.J.L.), and the Division of Biostatistics (J.D.B.), and the Department of Pathology and Immunology (E.J.D., B.T., Y.-S.L.), Washington University School of Medicine, and McDonnell Genome Institute, Washington University in St. Louis (A.A.P., C.A.M., C.C.F., M.O., R.S.F., R.K.W., L.D.W., T.J.L.) - both in St. Louis; the Departments of Internal Medicine (A.H., N.K., M.J.S., W.S.) and Pharmacy (R.W.K.), University of Chicago, Chicago; and the Department of Internal Medicine (T.A.G.), Massachusetts General Hospital, Boston.
Armin Ghobadithe Department of Internal Medicine, Division of Oncology (J.S.W., L.D.W., G.L.U., A.G., M.H.T., I.P., R.R., T.A.F., K.E.S.-G., R.V., S.T.O., C.N.A., A.F.C., M.A.S., M.A.J., S.E.H., K.L., M.R.J., M.J.W., P.W., D.C.L., J.F.D., T.J.L.), and the Division of Biostatistics (J.D.B.), and the Department of Pathology and Immunology (E.J.D., B.T., Y.-S.L.), Washington University School of Medicine, and McDonnell Genome Institute, Washington University in St. Louis (A.A.P., C.A.M., C.C.F., M.O., R.S.F., R.K.W., L.D.W., T.J.L.) - both in St. Louis; the Departments of Internal Medicine (A.H., N.K., M.J.S., W.S.) and Pharmacy (R.W.K.), University of Chicago, Chicago; and the Department of Internal Medicine (T.A.G.), Massachusetts General Hospital, Boston.
Michael H Tomassonthe Department of Internal Medicine, Division of Oncology (J.S.W., L.D.W., G.L.U., A.G., M.H.T., I.P., R.R., T.A.F., K.E.S.-G., R.V., S.T.O., C.N.A., A.F.C., M.A.S., M.A.J., S.E.H., K.L., M.R.J., M.J.W., P.W., D.C.L., J.F.D., T.J.L.), and the Division of Biostatistics (J.D.B.), and the Department of Pathology and Immunology (E.J.D., B.T., Y.-S.L.), Washington University School of Medicine, and McDonnell Genome Institute, Washington University in St. Louis (A.A.P., C.A.M., C.C.F., M.O., R.S.F., R.K.W., L.D.W., T.J.L.) - both in St. Louis; the Departments of Internal Medicine (A.H., N.K., M.J.S., W.S.) and Pharmacy (R.W.K.), University of Chicago, Chicago; and the Department of Internal Medicine (T.A.G.), Massachusetts General Hospital, Boston.
Iskra Pusicthe Department of Internal Medicine, Division of Oncology (J.S.W., L.D.W., G.L.U., A.G., M.H.T., I.P., R.R., T.A.F., K.E.S.-G., R.V., S.T.O., C.N.A., A.F.C., M.A.S., M.A.J., S.E.H., K.L., M.R.J., M.J.W., P.W., D.C.L., J.F.D., T.J.L.), and the Division of Biostatistics (J.D.B.), and the Department of Pathology and Immunology (E.J.D., B.T., Y.-S.L.), Washington University School of Medicine, and McDonnell Genome Institute, Washington University in St. Louis (A.A.P., C.A.M., C.C.F., M.O., R.S.F., R.K.W., L.D.W., T.J.L.) - both in St. Louis; the Departments of Internal Medicine (A.H., N.K., M.J.S., W.S.) and Pharmacy (R.W.K.), University of Chicago, Chicago; and the Department of Internal Medicine (T.A.G.), Massachusetts General Hospital, Boston.
Rizwan Romeethe Department of Internal Medicine, Division of Oncology (J.S.W., L.D.W., G.L.U., A.G., M.H.T., I.P., R.R., T.A.F., K.E.S.-G., R.V., S.T.O., C.N.A., A.F.C., M.A.S., M.A.J., S.E.H., K.L., M.R.J., M.J.W., P.W., D.C.L., J.F.D., T.J.L.), and the Division of Biostatistics (J.D.B.), and the Department of Pathology and Immunology (E.J.D., B.T., Y.-S.L.), Washington University School of Medicine, and McDonnell Genome Institute, Washington University in St. Louis (A.A.P., C.A.M., C.C.F., M.O., R.S.F., R.K.W., L.D.W., T.J.L.) - both in St. Louis; the Departments of Internal Medicine (A.H., N.K., M.J.S., W.S.) and Pharmacy (R.W.K.), University of Chicago, Chicago; and the Department of Internal Medicine (T.A.G.), Massachusetts General Hospital, Boston.
Todd A Fehnigerthe Department of Internal Medicine, Division of Oncology (J.S.W., L.D.W., G.L.U., A.G., M.H.T., I.P., R.R., T.A.F., K.E.S.-G., R.V., S.T.O., C.N.A., A.F.C., M.A.S., M.A.J., S.E.H., K.L., M.R.J., M.J.W., P.W., D.C.L., J.F.D., T.J.L.), and the Division of Biostatistics (J.D.B.), and the Department of Pathology and Immunology (E.J.D., B.T., Y.-S.L.), Washington University School of Medicine, and McDonnell Genome Institute, Washington University in St. Louis (A.A.P., C.A.M., C.C.F., M.O., R.S.F., R.K.W., L.D.W., T.J.L.) - both in St. Louis; the Departments of Internal Medicine (A.H., N.K., M.J.S., W.S.) and Pharmacy (R.W.K.), University of Chicago, Chicago; and the Department of Internal Medicine (T.A.G.), Massachusetts General Hospital, Boston.
Keith E Stockerl-Goldsteinthe Department of Internal Medicine, Division of Oncology (J.S.W., L.D.W., G.L.U., A.G., M.H.T., I.P., R.R., T.A.F., K.E.S.-G., R.V., S.T.O., C.N.A., A.F.C., M.A.S., M.A.J., S.E.H., K.L., M.R.J., M.J.W., P.W., D.C.L., J.F.D., T.J.L.), and the Division of Biostatistics (J.D.B.), and the Department of Pathology and Immunology (E.J.D., B.T., Y.-S.L.), Washington University School of Medicine, and McDonnell Genome Institute, Washington University in St. Louis (A.A.P., C.A.M., C.C.F., M.O., R.S.F., R.K.W., L.D.W., T.J.L.) - both in St. Louis; the Departments of Internal Medicine (A.H., N.K., M.J.S., W.S.) and Pharmacy (R.W.K.), University of Chicago, Chicago; and the Department of Internal Medicine (T.A.G.), Massachusetts General Hospital, Boston.
Ravi Vijthe Department of Internal Medicine, Division of Oncology (J.S.W., L.D.W., G.L.U., A.G., M.H.T., I.P., R.R., T.A.F., K.E.S.-G., R.V., S.T.O., C.N.A., A.F.C., M.A.S., M.A.J., S.E.H., K.L., M.R.J., M.J.W., P.W., D.C.L., J.F.D., T.J.L.), and the Division of Biostatistics (J.D.B.), and the Department of Pathology and Immunology (E.J.D., B.T., Y.-S.L.), Washington University School of Medicine, and McDonnell Genome Institute, Washington University in St. Louis (A.A.P., C.A.M., C.C.F., M.O., R.S.F., R.K.W., L.D.W., T.J.L.) - both in St. Louis; the Departments of Internal Medicine (A.H., N.K., M.J.S., W.S.) and Pharmacy (R.W.K.), University of Chicago, Chicago; and the Department of Internal Medicine (T.A.G.), Massachusetts General Hospital, Boston.
Stephen T Ohthe Department of Internal Medicine, Division of Oncology (J.S.W., L.D.W., G.L.U., A.G., M.H.T., I.P., R.R., T.A.F., K.E.S.-G., R.V., S.T.O., C.N.A., A.F.C., M.A.S., M.A.J., S.E.H., K.L., M.R.J., M.J.W., P.W., D.C.L., J.F.D., T.J.L.), and the Division of Biostatistics (J.D.B.), and the Department of Pathology and Immunology (E.J.D., B.T., Y.-S.L.), Washington University School of Medicine, and McDonnell Genome Institute, Washington University in St. Louis (A.A.P., C.A.M., C.C.F., M.O., R.S.F., R.K.W., L.D.W., T.J.L.) - both in St. Louis; the Departments of Internal Medicine (A.H., N.K., M.J.S., W.S.) and Pharmacy (R.W.K.), University of Chicago, Chicago; and the Department of Internal Medicine (T.A.G.), Massachusetts General Hospital, Boston.
Camille N Abboudthe Department of Internal Medicine, Division of Oncology (J.S.W., L.D.W., G.L.U., A.G., M.H.T., I.P., R.R., T.A.F., K.E.S.-G., R.V., S.T.O., C.N.A., A.F.C., M.A.S., M.A.J., S.E.H., K.L., M.R.J., M.J.W., P.W., D.C.L., J.F.D., T.J.L.), and the Division of Biostatistics (J.D.B.), and the Department of Pathology and Immunology (E.J.D., B.T., Y.-S.L.), Washington University School of Medicine, and McDonnell Genome Institute, Washington University in St. Louis (A.A.P., C.A.M., C.C.F., M.O., R.S.F., R.K.W., L.D.W., T.J.L.) - both in St. Louis; the Departments of Internal Medicine (A.H., N.K., M.J.S., W.S.) and Pharmacy (R.W.K.), University of Chicago, Chicago; and the Department of Internal Medicine (T.A.G.), Massachusetts General Hospital, Boston.
Amanda F Cashenthe Department of Internal Medicine, Division of Oncology (J.S.W., L.D.W., G.L.U., A.G., M.H.T., I.P., R.R., T.A.F., K.E.S.-G., R.V., S.T.O., C.N.A., A.F.C., M.A.S., M.A.J., S.E.H., K.L., M.R.J., M.J.W., P.W., D.C.L., J.F.D., T.J.L.), and the Division of Biostatistics (J.D.B.), and the Department of Pathology and Immunology (E.J.D., B.T., Y.-S.L.), Washington University School of Medicine, and McDonnell Genome Institute, Washington University in St. Louis (A.A.P., C.A.M., C.C.F., M.O., R.S.F., R.K.W., L.D.W., T.J.L.) - both in St. Louis; the Departments of Internal Medicine (A.H., N.K., M.J.S., W.S.) and Pharmacy (R.W.K.), University of Chicago, Chicago; and the Department of Internal Medicine (T.A.G.), Massachusetts General Hospital, Boston.
Mark A Schroederthe Department of Internal Medicine, Division of Oncology (J.S.W., L.D.W., G.L.U., A.G., M.H.T., I.P., R.R., T.A.F., K.E.S.-G., R.V., S.T.O., C.N.A., A.F.C., M.A.S., M.A.J., S.E.H., K.L., M.R.J., M.J.W., P.W., D.C.L., J.F.D., T.J.L.), and the Division of Biostatistics (J.D.B.), and the Department of Pathology and Immunology (E.J.D., B.T., Y.-S.L.), Washington University School of Medicine, and McDonnell Genome Institute, Washington University in St. Louis (A.A.P., C.A.M., C.C.F., M.O., R.S.F., R.K.W., L.D.W., T.J.L.) - both in St. Louis; the Departments of Internal Medicine (A.H., N.K., M.J.S., W.S.) and Pharmacy (R.W.K.), University of Chicago, Chicago; and the Department of Internal Medicine (T.A.G.), Massachusetts General Hospital, Boston.
Meagan A Jacobythe Department of Internal Medicine, Division of Oncology (J.S.W., L.D.W., G.L.U., A.G., M.H.T., I.P., R.R., T.A.F., K.E.S.-G., R.V., S.T.O., C.N.A., A.F.C., M.A.S., M.A.J., S.E.H., K.L., M.R.J., M.J.W., P.W., D.C.L., J.F.D., T.J.L.), and the Division of Biostatistics (J.D.B.), and the Department of Pathology and Immunology (E.J.D., B.T., Y.-S.L.), Washington University School of Medicine, and McDonnell Genome Institute, Washington University in St. Louis (A.A.P., C.A.M., C.C.F., M.O., R.S.F., R.K.W., L.D.W., T.J.L.) - both in St. Louis; the Departments of Internal Medicine (A.H., N.K., M.J.S., W.S.) and Pharmacy (R.W.K.), University of Chicago, Chicago; and the Department of Internal Medicine (T.A.G.), Massachusetts General Hospital, Boston.
Sharon E Heaththe Department of Internal Medicine, Division of Oncology (J.S.W., L.D.W., G.L.U., A.G., M.H.T., I.P., R.R., T.A.F., K.E.S.-G., R.V., S.T.O., C.N.A., A.F.C., M.A.S., M.A.J., S.E.H., K.L., M.R.J., M.J.W., P.W., D.C.L., J.F.D., T.J.L.), and the Division of Biostatistics (J.D.B.), and the Department of Pathology and Immunology (E.J.D., B.T., Y.-S.L.), Washington University School of Medicine, and McDonnell Genome Institute, Washington University in St. Louis (A.A.P., C.A.M., C.C.F., M.O., R.S.F., R.K.W., L.D.W., T.J.L.) - both in St. Louis; the Departments of Internal Medicine (A.H., N.K., M.J.S., W.S.) and Pharmacy (R.W.K.), University of Chicago, Chicago; and the Department of Internal Medicine (T.A.G.), Massachusetts General Hospital, Boston.
Kierstin Luberthe Department of Internal Medicine, Division of Oncology (J.S.W., L.D.W., G.L.U., A.G., M.H.T., I.P., R.R., T.A.F., K.E.S.-G., R.V., S.T.O., C.N.A., A.F.C., M.A.S., M.A.J., S.E.H., K.L., M.R.J., M.J.W., P.W., D.C.L., J.F.D., T.J.L.), and the Division of Biostatistics (J.D.B.), and the Department of Pathology and Immunology (E.J.D., B.T., Y.-S.L.), Washington University School of Medicine, and McDonnell Genome Institute, Washington University in St. Louis (A.A.P., C.A.M., C.C.F., M.O., R.S.F., R.K.W., L.D.W., T.J.L.) - both in St. Louis; the Departments of Internal Medicine (A.H., N.K., M.J.S., W.S.) and Pharmacy (R.W.K.), University of Chicago, Chicago; and the Department of Internal Medicine (T.A.G.), Massachusetts General Hospital, Boston.
Megan R Jankethe Department of Internal Medicine, Division of Oncology (J.S.W., L.D.W., G.L.U., A.G., M.H.T., I.P., R.R., T.A.F., K.E.S.-G., R.V., S.T.O., C.N.A., A.F.C., M.A.S., M.A.J., S.E.H., K.L., M.R.J., M.J.W., P.W., D.C.L., J.F.D., T.J.L.), and the Division of Biostatistics (J.D.B.), and the Department of Pathology and Immunology (E.J.D., B.T., Y.-S.L.), Washington University School of Medicine, and McDonnell Genome Institute, Washington University in St. Louis (A.A.P., C.A.M., C.C.F., M.O., R.S.F., R.K.W., L.D.W., T.J.L.) - both in St. Louis; the Departments of Internal Medicine (A.H., N.K., M.J.S., W.S.) and Pharmacy (R.W.K.), University of Chicago, Chicago; and the Department of Internal Medicine (T.A.G.), Massachusetts General Hospital, Boston.
Andrew Hantelthe Department of Internal Medicine, Division of Oncology (J.S.W., L.D.W., G.L.U., A.G., M.H.T., I.P., R.R., T.A.F., K.E.S.-G., R.V., S.T.O., C.N.A., A.F.C., M.A.S., M.A.J., S.E.H., K.L., M.R.J., M.J.W., P.W., D.C.L., J.F.D., T.J.L.), and the Division of Biostatistics (J.D.B.), and the Department of Pathology and Immunology (E.J.D., B.T., Y.-S.L.), Washington University School of Medicine, and McDonnell Genome Institute, Washington University in St. Louis (A.A.P., C.A.M., C.C.F., M.O., R.S.F., R.K.W., L.D.W., T.J.L.) - both in St. Louis; the Departments of Internal Medicine (A.H., N.K., M.J.S., W.S.) and Pharmacy (R.W.K.), University of Chicago, Chicago; and the Department of Internal Medicine (T.A.G.), Massachusetts General Hospital, Boston.
Niloufer Khanthe Department of Internal Medicine, Division of Oncology (J.S.W., L.D.W., G.L.U., A.G., M.H.T., I.P., R.R., T.A.F., K.E.S.-G., R.V., S.T.O., C.N.A., A.F.C., M.A.S., M.A.J., S.E.H., K.L., M.R.J., M.J.W., P.W., D.C.L., J.F.D., T.J.L.), and the Division of Biostatistics (J.D.B.), and the Department of Pathology and Immunology (E.J.D., B.T., Y.-S.L.), Washington University School of Medicine, and McDonnell Genome Institute, Washington University in St. Louis (A.A.P., C.A.M., C.C.F., M.O., R.S.F., R.K.W., L.D.W., T.J.L.) - both in St. Louis; the Departments of Internal Medicine (A.H., N.K., M.J.S., W.S.) and Pharmacy (R.W.K.), University of Chicago, Chicago; and the Department of Internal Medicine (T.A.G.), Massachusetts General Hospital, Boston.
Madina J Sukhanovathe Department of Internal Medicine, Division of Oncology (J.S.W., L.D.W., G.L.U., A.G., M.H.T., I.P., R.R., T.A.F., K.E.S.-G., R.V., S.T.O., C.N.A., A.F.C., M.A.S., M.A.J., S.E.H., K.L., M.R.J., M.J.W., P.W., D.C.L., J.F.D., T.J.L.), and the Division of Biostatistics (J.D.B.), and the Department of Pathology and Immunology (E.J.D., B.T., Y.-S.L.), Washington University School of Medicine, and McDonnell Genome Institute, Washington University in St. Louis (A.A.P., C.A.M., C.C.F., M.O., R.S.F., R.K.W., L.D.W., T.J.L.) - both in St. Louis; the Departments of Internal Medicine (A.H., N.K., M.J.S., W.S.) and Pharmacy (R.W.K.), University of Chicago, Chicago; and the Department of Internal Medicine (T.A.G.), Massachusetts General Hospital, Boston.
Randall W Knoebelthe Department of Internal Medicine, Division of Oncology (J.S.W., L.D.W., G.L.U., A.G., M.H.T., I.P., R.R., T.A.F., K.E.S.-G., R.V., S.T.O., C.N.A., A.F.C., M.A.S., M.A.J., S.E.H., K.L., M.R.J., M.J.W., P.W., D.C.L., J.F.D., T.J.L.), and the Division of Biostatistics (J.D.B.), and the Department of Pathology and Immunology (E.J.D., B.T., Y.-S.L.), Washington University School of Medicine, and McDonnell Genome Institute, Washington University in St. Louis (A.A.P., C.A.M., C.C.F., M.O., R.S.F., R.K.W., L.D.W., T.J.L.) - both in St. Louis; the Departments of Internal Medicine (A.H., N.K., M.J.S., W.S.) and Pharmacy (R.W.K.), University of Chicago, Chicago; and the Department of Internal Medicine (T.A.G.), Massachusetts General Hospital, Boston.
Wendy Stockthe Department of Internal Medicine, Division of Oncology (J.S.W., L.D.W., G.L.U., A.G., M.H.T., I.P., R.R., T.A.F., K.E.S.-G., R.V., S.T.O., C.N.A., A.F.C., M.A.S., M.A.J., S.E.H., K.L., M.R.J., M.J.W., P.W., D.C.L., J.F.D., T.J.L.), and the Division of Biostatistics (J.D.B.), and the Department of Pathology and Immunology (E.J.D., B.T., Y.-S.L.), Washington University School of Medicine, and McDonnell Genome Institute, Washington University in St. Louis (A.A.P., C.A.M., C.C.F., M.O., R.S.F., R.K.W., L.D.W., T.J.L.) - both in St. Louis; the Departments of Internal Medicine (A.H., N.K., M.J.S., W.S.) and Pharmacy (R.W.K.), University of Chicago, Chicago; and the Department of Internal Medicine (T.A.G.), Massachusetts General Hospital, Boston.
Timothy A Graubertthe Department of Internal Medicine, Division of Oncology (J.S.W., L.D.W., G.L.U., A.G., M.H.T., I.P., R.R., T.A.F., K.E.S.-G., R.V., S.T.O., C.N.A., A.F.C., M.A.S., M.A.J., S.E.H., K.L., M.R.J., M.J.W., P.W., D.C.L., J.F.D., T.J.L.), and the Division of Biostatistics (J.D.B.), and the Department of Pathology and Immunology (E.J.D., B.T., Y.-S.L.), Washington University School of Medicine, and McDonnell Genome Institute, Washington University in St. Louis (A.A.P., C.A.M., C.C.F., M.O., R.S.F., R.K.W., L.D.W., T.J.L.) - both in St. Louis; the Departments of Internal Medicine (A.H., N.K., M.J.S., W.S.) and Pharmacy (R.W.K.), University of Chicago, Chicago; and the Department of Internal Medicine (T.A.G.), Massachusetts General Hospital, Boston.
Matthew J Walterthe Department of Internal Medicine, Division of Oncology (J.S.W., L.D.W., G.L.U., A.G., M.H.T., I.P., R.R., T.A.F., K.E.S.-G., R.V., S.T.O., C.N.A., A.F.C., M.A.S., M.A.J., S.E.H., K.L., M.R.J., M.J.W., P.W., D.C.L., J.F.D., T.J.L.), and the Division of Biostatistics (J.D.B.), and the Department of Pathology and Immunology (E.J.D., B.T., Y.-S.L.), Washington University School of Medicine, and McDonnell Genome Institute, Washington University in St. Louis (A.A.P., C.A.M., C.C.F., M.O., R.S.F., R.K.W., L.D.W., T.J.L.) - both in St. Louis; the Departments of Internal Medicine (A.H., N.K., M.J.S., W.S.) and Pharmacy (R.W.K.), University of Chicago, Chicago; and the Department of Internal Medicine (T.A.G.), Massachusetts General Hospital, Boston.
Peter Westerveltthe Department of Internal Medicine, Division of Oncology (J.S.W., L.D.W., G.L.U., A.G., M.H.T., I.P., R.R., T.A.F., K.E.S.-G., R.V., S.T.O., C.N.A., A.F.C., M.A.S., M.A.J., S.E.H., K.L., M.R.J., M.J.W., P.W., D.C.L., J.F.D., T.J.L.), and the Division of Biostatistics (J.D.B.), and the Department of Pathology and Immunology (E.J.D., B.T., Y.-S.L.), Washington University School of Medicine, and McDonnell Genome Institute, Washington University in St. Louis (A.A.P., C.A.M., C.C.F., M.O., R.S.F., R.K.W., L.D.W., T.J.L.) - both in St. Louis; the Departments of Internal Medicine (A.H., N.K., M.J.S., W.S.) and Pharmacy (R.W.K.), University of Chicago, Chicago; and the Department of Internal Medicine (T.A.G.), Massachusetts General Hospital, Boston.
Daniel C Linkthe Department of Internal Medicine, Division of Oncology (J.S.W., L.D.W., G.L.U., A.G., M.H.T., I.P., R.R., T.A.F., K.E.S.-G., R.V., S.T.O., C.N.A., A.F.C., M.A.S., M.A.J., S.E.H., K.L., M.R.J., M.J.W., P.W., D.C.L., J.F.D., T.J.L.), and the Division of Biostatistics (J.D.B.), and the Department of Pathology and Immunology (E.J.D., B.T., Y.-S.L.), Washington University School of Medicine, and McDonnell Genome Institute, Washington University in St. Louis (A.A.P., C.A.M., C.C.F., M.O., R.S.F., R.K.W., L.D.W., T.J.L.) - both in St. Louis; the Departments of Internal Medicine (A.H., N.K., M.J.S., W.S.) and Pharmacy (R.W.K.), University of Chicago, Chicago; and the Department of Internal Medicine (T.A.G.), Massachusetts General Hospital, Boston.
John F DiPersiothe Department of Internal Medicine, Division of Oncology (J.S.W., L.D.W., G.L.U., A.G., M.H.T., I.P., R.R., T.A.F., K.E.S.-G., R.V., S.T.O., C.N.A., A.F.C., M.A.S., M.A.J., S.E.H., K.L., M.R.J., M.J.W., P.W., D.C.L., J.F.D., T.J.L.), and the Division of Biostatistics (J.D.B.), and the Department of Pathology and Immunology (E.J.D., B.T., Y.-S.L.), Washington University School of Medicine, and McDonnell Genome Institute, Washington University in St. Louis (A.A.P., C.A.M., C.C.F., M.O., R.S.F., R.K.W., L.D.W., T.J.L.) - both in St. Louis; the Departments of Internal Medicine (A.H., N.K., M.J.S., W.S.) and Pharmacy (R.W.K.), University of Chicago, Chicago; and the Department of Internal Medicine (T.A.G.), Massachusetts General Hospital, Boston.
Timothy J Leythe Department of Internal Medicine, Division of Oncology (J.S.W., L.D.W., G.L.U., A.G., M.H.T., I.P., R.R., T.A.F., K.E.S.-G., R.V., S.T.O., C.N.A., A.F.C., M.A.S., M.A.J., S.E.H., K.L., M.R.J., M.J.W., P.W., D.C.L., J.F.D., T.J.L.), and the Division of Biostatistics (J.D.B.), and the Department of Pathology and Immunology (E.J.D., B.T., Y.-S.L.), Washington University School of Medicine, and McDonnell Genome Institute, Washington University in St. Louis (A.A.P., C.A.M., C.C.F., M.O., R.S.F., R.K.W., L.D.W., T.J.L.) - both in St. Louis; the Departments of Internal Medicine (A.H., N.K., M.J.S., W.S.) and Pharmacy (R.W.K.), University of Chicago, Chicago; and the Department of Internal Medicine (T.A.G.), Massachusetts General Hospital, Boston.
Washington University in St. Louis · USUniversity of Chicago · USCancer Research And Biostatistics · USMassachusetts General Hospital · US
Funding
Viral VectorP30CA086862 · NCI · UNIVERSITY OF IOWA · PI Douglas Robert Spitz · 2000 to 2026
$70.0MSpecimen Acquistition and Expression ProfilingP01CA101937 · NCI · WASHINGTON UNIVERSITY · PI LEY, TIMOTHY J. · 2003 to 2023
$58.8MTargeting the Bone Marrow Microenvironment In Acute Lymphocytic LeukemiaP50CA171963 · NCI · WASHINGTON UNIVERSITY · PI TODD A FEHNIGER · 2013 to 2026
$31.6MWashington University Paul Calabresi K12 Career Development Award for Clinical OncologyK12CA167540 · NCI · WASHINGTON UNIVERSITY · PI John F. Dipersio, Ramaswamy Govindan · 2012 to 2026
$11.7MMolecular Pathogenesis of Acute Myeloid LeukemiaR35CA197561 · NCI · WASHINGTON UNIVERSITY · PI Timothy J. Ley · 2015 to 2026
$11.0MRETINOIDS IN HEMATOPOIESISR01HL128447 · NHLBI · WASHINGTON UNIVERSITY · PI WELCH, JOHN S · 2016 to 2020
$1.9MHISTONE H3 METHYLATION AND EPIGENOMICS IN ACUTE LEUKEMIAK08CA166229 · NCI · WASHINGTON UNIVERSITY · PI WARTMAN, LUKAS D · 2013 to 2017
$768kNCI NIH HHS K08 CA166229NCI NIH HHS K12 CA167540NCI NIH HHS P01 CA101937NCI NIH HHS P50 CA171963NCI NIH HHS R35 CA197561NHLBI NIH HHS R01 HL128447
Abstract
backgroundThe molecular determinants of clinical responses to decitabine therapy in patients with acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS) are unclear.
methodsWe enrolled 84 adult patients with AML or MDS in a single-institution trial of decitabine to identify somatic mutations and their relationships to clinical responses. Decitabine was administered at a dose of 20 mg per square meter of body-surface area per day for 10 consecutive days in monthly cycles. We performed enhanced exome or gene-panel sequencing in 67 of these patients and serial sequencing at multiple time points to evaluate patterns of mutation clearance in 54 patients. An extension cohort included 32 additional patients who received decitabine in different protocols.
resultsOf the 116 patients, 53 (46%) had bone marrow blast clearance (<5% blasts). Response rates were higher among patients with an unfavorable-risk cytogenetic profile than among patients with an intermediate-risk or favorable-risk cytogenetic profile (29 of 43 patients [67%] vs. 24 of 71 patients [34%], P<0.001) and among patients with TP53 mutations than among patients with wild-type TP53 (21 of 21 [100%] vs. 32 of 78 [41%], P<0.001). Previous studies have consistently shown that patients with an unfavorable-risk cytogenetic profile and TP53 mutations who receive conventional chemotherapy have poor outcomes. However, in this study of 10-day courses of decitabine, neither of these risk factors was associated with a lower rate of overall survival than the rate of survival among study patients with intermediate-risk cytogenetic profiles.
conclusionsPatients with AML and MDS who had cytogenetic abnormalities associated with unfavorable risk, TP53 mutations, or both had favorable clinical responses and robust (but incomplete) mutation clearance after receiving serial 10-day courses of decitabine. Although these responses were not durable, they resulted in rates of overall survival that were similar to those among patients with AML who had an intermediate-risk cytogenetic profile and who also received serial 10-day courses of decitabine. (Funded by the National Cancer Institute and others; ClinicalTrials.gov number, NCT01687400 .).
Indexed as
Mutation5-MethylcytosineAdultAgedAged, 80 and overAntimetabolites, AntineoplasticAzacitidineBiomarkers, TumorBone MarrowDecitabineExomeFemaleHumansLeukemia, Myeloid, AcuteMaleMiddle Aged5-MethylcytosineAntimetabolites, AntineoplasticAzacitidineBiomarkers, TumorDecitabineTP53 protein, humanTumor Suppressor Protein p53
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NCT01687400ClinicalTrials.gov
NCT03377725ClinicalTrials.gov
NCT03381781ClinicalTrials.gov
NCT04482621ClinicalTrials.gov
NCT05025098ClinicalTrials.gov
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