Citations 23
A clinical measure of DNA methylation predicts outcome in de novo acute myeloid leukemia
Luskin, Marlise R. , Gimotty, Phyllis A. , Smith, Catherine , Loren, Alison W. , Harrison, Jenna , Sun, Zhuoxin , Tallman, Martin S. , Paietta, Elisabeth , Litzow, Mark R. , Melnick, Ari , Levine, Ross L. , Fernández, Hugo F. , Luger, Selina M. , Wertheim, Gerald , Luskin, Marlise R , Figueroa, María E. , Carroll, Martin P , Master, Stephen R. , Melnick, Ari
JCI Insight | June 15, 2016 | Volume: 1 | Issue: 9 | Pages: No page available
BACKGROUND. Variable response to chemotherapy in acute myeloid leukemia (AML) represents a major treatment challenge. Clinical and genetic features incompletely predict outcome. The value of clinical epigenetic assays for risk classification has not been extensively explored. We assess the prognostic implications of a clinical assay for multilocus DNA methylation on adult patients with de novo AML. METHODS. We performed multilocus DNA methylation assessment using xMELP on samples and calculated a methylation statistic (M-score) for 166 patients from UPENN with de novo AML who received induction chemotherapy. The association of M-score with complete remission (CR) and overall survival (OS) was evaluated. The optimal M-score cut-point for identifying groups with differing survival was used to define a binary M-score classifier. This classifier was validated in an independent cohort of 383 patients from the Eastern Cooperative Oncology Group Trial 1900 (E1900; NCT00049517). RESULTS. A higher mean M-score was associated with death and failure to achieve CR. Multivariable analysis confirmed that a higher M-score was associated with death ( P = 0.011) and failure to achieve CR ( P = 0.034). Median survival was 26.6 months versus 10.6 months for low and high M-score groups. The ability of the M-score to perform as a classifier was confirmed in patients ≤ 60 years with intermediate cytogenetics and patients who achieved CR, as well as in the E1900 validation cohort. CONCLUSION. The M-score represents a valid binary prognostic classifier for patients with de novo AML. The xMELP assay and associated M-score can be used for prognosis and should be further investigated for clinical decision making in AML patients.
Better leukemia-free and overall survival in AML in first remission following cyclophosphamide in combination with busulfan compared with TBI
Copelan, Edward A. , Hamilton, Betty K. , Avalos, Belinda R. , Ahn, Kwang Woo , Bolwell, Brian J., Zhu, Xiaochun , Aljurf, Mahmoud , Bredeson, Christopher , Cahn, Jean‐Yves , Costa, Luciano J. , Hale, Gregory A., Halter, Joerg , Inamoto, Yoshihiro , Kamble, Rammurti T., Litzow, Mark R. , Loren, Alison W. , Marks, David I. , Olavarría, Eduardo, Sabloff, Mitchell , Seftel, Matthew D. , Schouten, Harry C. , Üstün, Celalettin , Waller, Edmund K. , Weisdorf, Daniel J. , Wirk, Baldeep , Horowitz, Mary M. , Arora, Mukta , Cortes, Jörge E. , Kalaycio, Matt, Saber, Wael , Halter, Jörg , Besien, Koen van , Lima, Marcos de , Gale, Robert Peter , Hamadani, Mehdi , Roy, Vivek , Savani, Bipin N. , Szer, Jeff , Maziarz, Richard Thomas , Waller, Edmund K , Weisdorf, Dan , Cortes, Jorge , Costa, Luciano J , Sabloff, Mitchell
Blood | September 25, 2013 | Volume: 122 | Issue: 24 | Pages: 3863-3870
Key Points In combination with cyclophosphamide, intravenous busulfan is associated with better leukemia-free and overall survival in AML than TBI.
Serum 2-hydroxyglutarate levels predict isocitrate dehydrogenase mutations and clinical outcome in acute myeloid leukemia
Propert, Kathleen J., Loren, Alison W. , Paietta, Elisabeth , Sun, Zhuoxin , Levine, Ross L. , Straley, Kimberly, Yen, Katharine , Patel, Jay P., Agresta, Samuel , Abdel‐Wahab, Omar , Perl, Alexander E. , Litzow, Mark R. , Rowe, Jacob M. , Fernández, Hugo F. , Margolis, David J. , Tallman, Martin S. , Luger, Selina M. , DiNardo, Courtney D. , Lazarus, Hillard M. , Carroll, Martin P , Abdel-Wahab, Omar
Blood | May 3, 2013 | Volume: 121 | Issue: 24 | Pages: 4917-4924
Key Points Serum 2HG analysis by LC-MS can accurately identify patients with AML with and without IDH mutations. Oncometabolite testing of serum 2HG is indicated as a diagnostic, prognostic, and therapeutic monitoring tool in AML.