Olga Sala Torra, Megan Othus, David W

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Next-Generation Sequencing in Adult B Cell Acute Lymphoblastic Leukemia Patients Olga Sala Torra, Megan Othus, David W. Williamson, Brent Wood, Ilan Kirsch, Harlan Robins, Lan Beppu, Margaret R. O'Donnell, Stephen J. Forman, Frederick R. Appelbaum, Jerald P. Radich Biology of Blood and Marrow Transplantation Volume 23, Issue 4, Pages 691-696 (April 2017) DOI: 10.1016/j.bbmt.2016.12.639 Copyright © 2017 The American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 1 (A) Comparison of tumor burden measurements obtained by NGS (Y axis) and MFC (X axis) in 61 BM specimens. Diamonds represent the 20 specimens positive both by NGS and MFC. The triangle denotes the single specimen negative by NGS and positive by MFC. Asterisks show 9 samples positive by NGS and negative by MFC. Circles show 31 specimens negative by both methods. NGS is presented as a fraction of the total nucleated cells calculated using the percent of B cells determined by MFC, and MFC as a fraction of total white blood cells. NGS and MFC values of disease burden are highly correlated (R2 = .91, P < .001). (B) A comparison of disease burden in BM and PB. This figure shows 24 cases with a BM positive for ALL, with a time point paired sample from PB. The X-axis displays disease burden in BM as a fraction of nucleated cells, calculated from MFC data. Triangles represent specimens for which NGS analysis of the equivalent PB specimen detected disease, and circles, those BM specimens for which NGS analysis of the concomitant PB specimen was negative for MRD. Of the 9 samples with ALL detected in BM but not in PB, the levels of MRD are very low (~1:104) in 8 cases, suggesting that PB may be able to supplement BM testing in patients with MRD. Biology of Blood and Marrow Transplantation 2017 23, 691-696DOI: (10.1016/j.bbmt.2016.12.639) Copyright © 2017 The American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 2 Comparison of MRD detection in BM and PB in 54 samples. Biology of Blood and Marrow Transplantation 2017 23, 691-696DOI: (10.1016/j.bbmt.2016.12.639) Copyright © 2017 The American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 3 Survival by MRD status. (A) and (B) Show OS and RFS according to MRD status at the time of registration to the protocol mandated second induction. The solid line shows survival for patients with MRD negative by MFC and NGS; ticked line shows survival for patients with MRD positive both by NGS an MFC; and dotted line shows survival for patients with MRD positive by NGS and negative by flow. (C) and (D) Illustrate RFS for patients with MRD negative (solid line) or positive (ticked line) by flow and NGS respectively. Biology of Blood and Marrow Transplantation 2017 23, 691-696DOI: (10.1016/j.bbmt.2016.12.639) Copyright © 2017 The American Society for Blood and Marrow Transplantation Terms and Conditions