Abstract 655: Hyperdiploidy in plasma cell disorders using multi-parametric flow cytometry (MFC) vs. FISH
Authors: Sidana Surbhi , Tandon Nidhi , Jevremovic Dragan , Ketterling Rhett P. , Dispenzieri Angela , Gertz Morie A. , Buadi Francis K. , Lacy Martha Q. , Morice William , Hanson Curtis A. , Timm Michael , Greipp Patricia , Baughn Linda B. , Dingli David , Hayman Suzanne R. , Gonsalves Wilson I. , Kapoor Prashant , Kyle Robert A. , Leung Nelson , Go Ronald S. , Lust John A. , Rajkumar S.Vincent , Kumar Shaji K. 
Published: August 2018

Abstract
Introduction: Hyperdiploidy on FISH portends a good prognosis in myeloma. We compared hyperdiploidy determined by MFC to that by conventional FISH.
Methods: We studied 1711 patients with plasma cell disorders who had simultaneous FISH and DNA index testing. Monotypic plasma cells in bone marrow are identified by MFC with antibodies to CD19, CD38, CD45, CD138, kappa and lambda; followed by staining by DAPI. DNA index is determined by dividing the measured DNA content of the G0/G1 abnormal plasma cells by the DNA content of the normal G0/G1 plasma cells present. Plasma cells with DNA content index of &lt;0.95 are hypodiploid and G0/G1 DNA content index of &gt;1.05 are considered hyperdiploid.
Results: Distribution DNA index and FISH results are described in Table 1. Sensitivity and specificity of DNA index by hyperdiploidy was 86% and 83%. Cohen's Kappa coefficient for concordance was 0.69. Sensitivity increased to 94% for those with 2 or more trisomies and 97% for 3 or more trisomies. Of the 104 patients with trisomy and non-hyperdiploid DNA index, 62% patients had monosomy (mono) or deletion (del) 13q. Overall, DNA index was lower in patients with mono 13/del 13q (1.01; 0.97-1.11) compared to those without (1.07; 1.0-1.19), p&lt;0.001. After excluding patients with mono 13/del 13q, sensitivity and specificity of hyperdiploidy by DNA index were 92% and 82%, kappa = 0.73.
Hyperdiploidy was seen in 55% of 272 patients with newly diagnosed myeloma. Sensitivity and specificity were 88% and 93%, kappa = 0.78. After median follow-up of 2.3 yrs, those with hyperdiploid DNA index had better progression free survival at 2,3 and 5 years, 62%, 45% and 21% compared to 50%, 33% and 13% in non-hyperdiploid group, p=0.05. Median overall survival (OS) was not reached; estimated 2, 3 and 5 year OS was 83%, 76% and 63% vs. 76%, 64% and 44%, respectively; p=0.08.
Conclusions: DNA index by MFC is a rapid method to determine hyperdiploidy, with potential for replacing trisomy testing by FISH, especially when coupled with monosomy FISH probes.
Hyperdiploid N=768 n/N (%)Diploid N=762 n/N (%)Hypodiploid N=78 n/N (%)P1P2Any trisomy 619/765 (81)96/758(13)8/76 (11)&lt;0.001&lt;0.001One chromosome42587733191429-111362Others12204Two chromosomes8525-Three or more chromosomes492131Any translocation124/744 (17)566/748 (76)53/74 (72)&lt;0.001&lt;0.001t(4;14)106313t(11;14)2240127t(14;16)5325t(14;20)38-t(6;14)8104Unknown partner76524Trisomy + Translocation95/743 (13)60/744 (8)6/74 (8)0.0090.002Monosomy 13/17 or deletion 13q/17p252/759 (33)295/744 (40)54/74 (73)&lt;0.0010.0001Monosomy 13/Deletion 13q208/717 (29)282/718 (39)20/70 (29)Monosomy 17/Deletion 17p70/749 (9)50/735 (7)20/72 (28)P1= three groups; P2= hyperdiploid vs. non-hyperdiploid
Citation Format: Surbhi Sidana, Nidhi Tandon, Dragan Jevremovic, Rhett P. Ketterling, Angela Dispenzieri, Morie A. Gertz, Francis K. Buadi, Martha Q. Lacy, William Morice, Curtis A. Hanson, Michael Timm, Patricia Greipp, Linda B. Baughn, David Dingli, Suzanne R. Hayman, Wilson I. Gonsalves, Prashant Kapoor, Robert A. Kyle, Nelson Leung, Ronald S. Go, John A. Lust, S.Vincent Rajkumar, Shaji K. Kumar. Hyperdiploidy in plasma cell disorders using multi-parametric flow cytometry (MFC) vs. FISH [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 655.