CURRENT CLINICAL INTERESTS
Acute Myeloid Leukemia
CURRENT RESEARCH INTERESTS
Acute Myeloid Leukemia; Antibody-based Immunotherapy of AML; Clinical Trials in AML; Leukemia Stem Cells; Minimal Residual Disease; Predictive Modeling
My research is focused on human acute myeloid leukemia (AML). I am particularly interested in the preclinical and early clinical development of novel antigen-directed immunotherapies for AML and the delineation of the mechanisms of action and resistance that are clinically relevant for these agents. We are also investigating the molecular and phenotypic characteristics of AML stem and progenitor cells to understand how antigen-directed immunotherapies can be best utilized to eliminate these cells. In clinical studies, I am involved in the conduct of trials testing novel treatments and innovative care approaches for AML patients. Furthermore, in collaborative research, I am taking advantage of large patient datasets to develop and improve diagnostic and prognostic tools in AML.
Walter RB, Raden BW, Kamikura DM, Cooper JA, Bernstein ID. Influence of CD33 expression levels and ITIM-dependent internalization on gemtuzumab ozogamicin-induced cytotoxicity. Blood 2005:105(3):1295-1302.
Walter RB, Gooley TA, van der Velden VHJ, Loken MR, van Dongen JJM, Flowers DA, Bernstein ID, Appelbaum FR. CD33 expression and P-glycoprotein-mediated drug efflux inversely correlate and predict clinical outcome in patients with acute myeloid leukemia treated with gemtuzumab ozogamicin monotherapy. Blood 2007;109(10):4168-4170.
Walter RB, Kantarjian HM, Huang X, Pierce SA, Sun Z, Gundacker HM, Ravandi F, Faderl SH, Tallman MS, Appelbaum FR, Estey EH. The effect of complete remission (CR) and CR with incomplete platelet recovery (CRp) on outcome in acute myeloid leukemia: a combined Eastern Cooperative Oncology Group (ECOG), Southwest Oncology Group (SWOG), and M.D. Anderson Cancer Center study. J Clin Oncol 2010;28(10):1766-1771.
Walter RB, Alonzo TA, Gerbing RB, Ho PA, Smith FO, Raimondi SC, Hirsch BA, Gamis AS, Franklin JL, Hurwitz CA, Loken MR, Meshinchi S. High expression of the very late antigen (VLA)-4 integrin independently predicts reduced risk of relapse and improved outcome in pediatric acute myeloid leukemia: a report from the Children’s Oncology Group. J Clin Oncol 2010;28(17):2831-2838.
Walter RB, Gooley TA, Wood BL, Milano F, Fang M, Sorror ML, Estey EH, Salter AI, Lansverk E, Chien JW, Gopal AK, Appelbaum FR, Pagel JM. Impact of pre-transplant minimal residual disease, as detected by multiparametric flow cytometry, on outcome of myeloablative hematopoietic cell transplantation for acute myeloid leukemia. J Clin Oncol 2011;29(9):1190-1197.
Walter RB, Milano F, Brasky TM, White E. Long-term use of acetaminophen, aspirin, and other non-steroidal anti-inflammatory drugs and risk of hematologic malignancies: results from the prospective VITamins and Lifestyle (VITAL) study. J Clin Oncol 2011;29(17):2424-2431.
Walter RB, Othus M, Borthakur G, Ravandi F, Cortes JE, Pierce SA, Appelbaum FR, Kantarjian HM, Estey EH. Prediction of early death following induction therapy for newly diagnosed acute myeloid leukemia with pretreatment risk scores: a novel paradigm for treatment assignment. J Clin Oncol 2011;29(33):4417-4424.
Walter RB, Othus M, Burnett AK, Löwenberg B, Kantarjian HM, Ossenkoppele GJ, Hills RK, van Montfort KGM, Ravandi F, Evans A, Pierce SR, Appelbaum FR, Estey EH. Significance of FAB subclassification of “acute myeloid leukemia, not otherwise specified” in the 2008 WHO classification: analysis of 5848 newly diagnosed patients. Blood 2013;121(13):2424-2431.
Laszlo GS, Gudgeon CJ, Harrington KH, Dell’Aringa J, Newhall KJ, Means GD, Sinclair AM, Kischel R, Frankel SR, Walter RB. Cellular determinants for preclinical activity of a novel CD33/CD3 bispecific T-cell engager (BiTE) antibody, AMG 330, against human AML. Blood 2014;123(4):554-561.
Walter RB, Laszlo GS, Lionberger JM, Pollard JA, Harrington KH, Gudgeon CJ, Othus M, Rafii S, Meshinchi S, Appelbaum FR, Bernstein ID. Heterogeneity of clonal expansion and maturation-linked mutation acquisition in hematopoietic progenitors in human acute myeloid leukemia. Leukemia 2014;28(10):1969-1977.
Walter RB, Gyurkocza B, Storer BE, Godwin CD, Pagel JM, Buckley SA, Sorror ML, Wood BL, Storb R, Appelbaum FR, Sandmaier BM. Comparison of minimal residual disease as outcome predictor for AML patients in first complete remission undergoing myeloablative or nonmyeloablative allogeneic hematopoietic cell transplantation. Leukemia 2015;29(1):137-144. PMID: 24888275.
Walter RB, Othus M, Burnett AK, Löwenberg B, Kantarjian HM, Ossenkoppele GJ, Hills RK, Ravandi F, Pabst T, Evans A, Pierce SR, Vekemans M-C, Appelbaum FR, Estey EH. Resistance prediction in AML: analysis of 4,601 patients from MRC/NCRI, HOVON/SAKK, SWOG, and MD Anderson Cancer Center. Leukemia 2015;29(2):312-320. PMID: 25113226.
Vaughn JE, Othus M, Powell MA, Gardner KM, Rizzuto DL, Hendrie PC, Becker PS, Pottinger PS, Estey EH, Walter RB. Comparative analysis of resource utilization and safety of outpatient management following intensive AML induction/salvage chemotherapy. JAMA Oncol. 2015;1(8):1120-1127. PMID: 26355382.
Laszlo GS, Gudgeon CJ, Harrington KH, Walter RB. T-cell ligands modulate the cytolytic activity of the CD33/CD3 BiTE antibody construct, AMG 330. Blood Cancer J. 2015;5:e340.
Harrington KH, Gudgeon CJ, Laszlo GS, Newhall KJ, Sinclair AM, Frankel SR, Kischel R, Chen G, Walter RB. The broad anti-AML activity of the CD33/CD3 BiTE antibody construct, AMG 330, is impacted by disease stage and risk. PLoS One. 2015;10:e0135945.
Araki D, Wood BL, Othus M, Radich JP, Halpern AB, Zhou Y, Mielcarek M, Estey EH, Appelbaum FR, Walter RB. Allogeneic hematopoietic cell transplantation for acute myeloid leukemia: is it time to move toward a minimal residual disease-based definition of complete remission. J Clin Oncol. 2016;34(4):329-336.
Zhou Y, Othus M, Araki D, Wood BL, Radich JP, Halpern AB, Mielcarek M, Estey EH, Appelbaum FR, Walter RB. Pre- and post-transplant quantification of measurable (“minimal”) residual disease via multiparameter flow cytometry in adult acute myeloid leukemia. Leukemia. 2016; in press.