Coalescence of the German-Austrian and IMRAW Cytogenetic MDS Databases: Modification of Patient Risk Groups.
Authors: Steidl Christian , Schanz Julie , Le Beau Michelle M. , Bennett John M. , Germing Ulrich , Greenberg Peter L. , Haase Detlef 
Published: April 2020

Abstract
Introduction The International Prognostic Scoring System (IPSS) for evaluating prognosis in myelodysplastic syndromes (MDS) has been the standard for risk assessment in this disease for the past ten years. Based on a patient cohort comprising 816 primary MDS patients from the IMRAW, a refined bone marrow cytogenetic classification system was introduced. Recently, the GACMSG published cytogenetic data including 1155 primary MDS patients treated with supportive care only. Coalescence of these two large databases offered the opportunity to analyze the cytogenetic data jointly and to propose a modified cytogenetic risk stratification system. Patients and Methods 1971 patients with karyotype and survival data originating from the IMRAW and the GACMSG cohorts were included in this study. The collectives comprised patients with primary MDS treated with supportive care, only allowing short courses of low dose oral chemotherapy or hemopoietic growth factors. By reviewing the ISCN karyotypes, the patients were grouped into cytogenetic categories defined by median survival (MS) (Haase et al, Blood in press). The categories comprised karyotypes with the respective abnormality alone or in combination with one additional anomaly. Karyotypes with 3, or more than 3 abnormalities were considered separate categories. Results We found 15 cytogenetic categories each comprising 10 or more patients. These categories could be combined into 4 prognostic groups according to the MS: Group 1 (MS&gt;3 years): normal karyotype, del(5q), del(12p), del(20q), +21, −Y, −X; Group 2 (1.5–3 years): +1/+1q/t(1q), add(3q)/inv(3q)/del(3q)/t(3q), +8, del(11q); Group 3 (1–1.5 years): 3 anomalies, −7, del(7q); Group 4 (MS&lt;1 year): &gt;3 anomalies. Further stratification of these categories led to a system with 4 distinct risk strata (number of patients): good (1374), int-1 (160), int-2 (99), and poor (166). Only 172 patients (9% of all patients) could not be classified according to this system. Survival analysis of these 4 groups showed distinct MS (Log-rank test: p&lt;0.0001): good, 50 months; int-1, 24 months; int-2, 15 months; poor, 6 months. When combining the non-classified patients into one group MS was 31 months. When comparing this new classification system with the original system defined by the IPSS, 66 formerly intermediate risk patients shifted into the good risk group and 114 poor risk patients into the intermediate risk group. Discussion Combined examination of the two databases introduces 7 new cytogenetic categories with distinct survival times as compared to the IPSS; Group 1: del(12p), +21, −X; Group 2: +1/+1q/t(1q), add(3q)/inv(3q)/del(3q)/t(3q), del(11q); Group 3: 3 anomalies. Based on previously published data, the proposed system combines non-complex karyotypes in one category and distinguishes karyotypes with 3 or more than 3 abnormalities. With respect to future refined integrative scoring in MDS we present an approach that distinguishes groups of intermediate risk and a heterogeneous group of as yet unclassified rare cases harboring uncertain prognoses. In the latter cases, risk assessment should be based on other prognostic parameters rather than assigning an intermediate risk to this group. This new cytogenetic risk stratification system needs to be validated and tested using multivariate approaches.