CURRENT CLINICAL INTERESTS
Acute Myeloid Leukemia
CURRENT RESEARCH INTERESTS
Acute Myeloid Leukemia; CD33; Clinical Trials in AML; Immunotherapy of AML; Leukemia Stem Cells; Predictive Modeling
Our research is focused on human acute myeloid leukemia (AML). We are particularly interested in the delineation of the clonal origin of AML, the molecular and phenotypic characterization of AML stem and progenitor cells, and the interaction between AML cells and their environment. An overarching goal of these laboratory-based studies is the development of targeted treatments aimed to eradicate disease-relevant AML cells, with CD33-directed therapies being one important example for our efforts. We are also involved in the early testing of novel drugs and innovative care approaches in patients with AML. Finally, we participate in collaborative projects utilizing large datasets that aim to improve diagnostic and prognostic tools in AML or, together with epidemiologists, study risk factors for the development of this hematological malignancy.
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, Appelbaum FR, Tallman MS, Weiss NS, Larson RA, Estey EH. Shortcomings in the clinical evaluation of new drugs: acute myeloid leukemia as paradigm. Blood 2010;116(14):2420-2428.
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, Appelbaum FR, Estey EH, Bernstein ID. Acute myeloid leukemia stem cells and CD33-targeted immunotherapy. Blood 2012;119(26):6198-6208.
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.
Kung Sutherland MS, Walter RB, Jeffrey SC, Burke PJ, Yu C, Kostner H, Stone I, Ryan MC, Sussman D, Lyon RP, Zeng W, Harrington KH, Klussman K, Westendorf L, Meyer D, Bernstein ID, Senter PD, Benjamin DR, Drachman JG, McEarchern JA. SGN-CD33A: a novel CD33-targeting antibody-drug conjugate utilizing a pyrrolobenzodiazepine dimer is active in models of drug-resistant AML. Blood 2013;122(8):1455-1463.
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; in press.