New Comprehensive Cytogenetic Scoring System for Primary Myelodysplastic Syndromes (MDS) and Oligoblastic Acute Myeloid Leukemia After MDS Derived From an International Database Merge

Abstract

Purpose The karyotype is a strong independent prognostic factor in myelodysplastic syndromes (MDS). Since the implementation of the International Prognostic Scoring System (IPSS) in 1997, knowledge concerning the prognostic impact of abnormalities has increased substantially. The present study proposes a new and comprehensive cytogenetic scoring system based on an international data collection of 2,902 patients. Patients and Methods Patients were included from the German-Austrian MDS Study Group (n = 1,193), the International MDS Risk Analysis Workshop (n = 816), the Spanish Hematological Cytogenetics Working Group (n = 849), and the International Working Group on MDS Cytogenetics (n = 44) databases. Patients with primary MDS and oligoblastic acute myeloid leukemia (AML) after MDS treated with supportive care only were evaluated for overall survival (OS) and AML evolution. Internal validation by bootstrap analysis and external validation in an independent patient cohort were performed to confirm the results. Results In total, 19 cytogenetic categories were defined, providing clear prognostic classification in 91% of all patients. The abnormalities were classified into five prognostic subgroups (P < .001): very good (median OS, 61 months; hazard ratio [HR], 0.5; n = 81); good (49 months; HR, 1.0 [reference category]; n = 1,809); intermediate (26 months; HR, 1.6; n = 529); poor (16 months; HR, 2.6; n = 148); and very poor (6 months; HR, 4.2; n = 187). The internal and external validations confirmed the results of the score. Conclusion In conclusion, these data should contribute to the ongoing efforts to update the IPSS by refining the cytogenetic risk categories.

Evaluation of revised IPSS cytogenetic risk stratification and prognostic impact of monosomal karyotype in 783 patients with primary myelodysplastic syndromes

“…We cannot explain why our findings are different from those of other investigators [8,13] but we show that our patient cohort behaved as expected when the original IPSS cytogenetic risk stratification was applied [4]. More importantly, we demonstrate the additional value of considering MK as a separate prognostic category, and our observations in this regard are consistent with the adverse prognostic impact of MK in other myeloid malignancies including acute myeloid leukemia and primary myelofibrosis [9,14].…”

“…The IPSS-R classifies cytogenetic information in MDS into five risk groups: "very good" (-Y, del(11q)); "good" (normal, del(5q), del(20q) and del(12p) as sole abnormalities or double abnormalities including del(5q)); "intermediate" (del(7q), 18, 119, i(17q) or any other abnormality not listed in the other risk groups); "poor" (27, inv(3)/t(3q)/del(3q), double abnormalities including 27/del(7q) or complex with three abnormalities); and "very poor" (complex with >3 abnormalities) [8], with corresponding median survivals of 61, 49, 26, 16, and 6 months [8].…”

“…Anderson prognostic model [7]. Each one of these prognostic systems includes karyotype as a prognostic variable.The IPSS-R classifies cytogenetic information in MDS into five risk groups: "very good" (-Y, del(11q)); "good" (normal, del(5q), del(20q) and del(12p) as sole abnormalities or double abnormalities including del(5q)); "intermediate" (del(7q), 18, 119, i(17q) or any other abnormality not listed in the other risk groups); "poor" (27, inv(3)/t(3q)/del(3q), double abnormalities including 27/del(7q) or complex with three abnormalities); and "very poor" (complex with >3 abnormalities) [8], with corresponding median survivals of 61, 49, 26, 16, and 6 months [8].IPSS-R poor and very poor cytogenetic groups include patients with monosomal karyotype (MK), defined as the presence of two or more autosomal monosomies or a single autosomal monosomy in association with other structural abnormalities [9]. We have previously identified MK as an additional adverse risk factor in MDS patients with complex karyotype [10].…”

Clinicopathologic analysis of acute myeloid leukemia arising from chronic myelomonocytic leukemia

“…Cases were stratified according to the UK Medical Research Council 20 karyotype risk grouping for acute myeloid leukemia. The chronic myelomonocytic leukemia karyotypes were also stratified according to the IPSS scoring system, 21 the new Comprehensive Cytogenetic Scoring System (CCSS) for primary myelodysplastic syndrome, 22 and the recently proposed cytogenetic risk stratification system for chronic myelomonocytic leukemia. 23 The CCSS score was also used along with blood counts and bone marrow blast count to classify the chronic myelomonocytic leukemia cases according to the IPSS-R scoring system.…”

Plasma circulating-microRNA profiles are useful for assessing prognosis in patients with cytogenetically normal myelodysplastic syndromes

“…Patients with complex cytogenetic abnormalities, or certain single abnormalities such as þ 8, del(7q), or À 7, are considered to have an intermediate or poor prognosis, whereas patients with other single cytogenetic abnormalities, such as del(5q), del(20q), or -Y, are considered to have a good or very good prognosis. 5 Nevertheless, over half of the patients with myelodysplastic syndromes do not have detectable cytogenetic abnormalities (cytogenetically normal with a diploid karyotype) and are included in the good-prognostic group. 6 This obviously limits the predictive power of the model for patients with myelodysplastic syndromes.…”