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

Abstract

Cytogenetic classification by the revised international prognostic scoring system (IPSS-R) and the prognostic value of monosomal karyotype (MK) were assessed in 783 patients with primary myelodysplastic syndromes (MDS). At 22 months median follow-up, 562 (72%) deaths were recorded. Percentages of patients with IPSS-R "very good," "good," "intermediate," "poor," and "very poor" cytogenetic categories was 5, 63, 18, 4, and 10%, respectively. The corresponding median survivals were 21, 40, 24, 18, and 6.5 IntroductionAcquired genetic lesions are frequently present in myelodysplastic syndromes (MDS) [1], with cytogenetic abnormalities noted in approximately 45% of patients at diagnosis [2]. Allogeneic stem cell transplant is potentially curative in MDS, but its utility is limited by the relatively high incidence of treatment-related mortality and morbidity [3]. Accurate prediction of shortened survival is essential for therapeutic decision-making. Median survival in MDS ranges from 6 to 60 months and is predicted by one of several prognostic scoring systems: the International Prognostic Scoring System (IPSS) [4] and its recent revision (IPSS-R) [5], the World Health Organization (WHO) classification-based prognostic scoring system (WPSS) [6], and the M.D. 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]. In the current study, we used a large cohort of MDS patients seen at the Mayo Clinic, to examine the performance of IPSS-R-based cytogenetic risk stratification and clarify the additional prognostic value of MK.

IPSS‐R in 555 Taiwanese patients with primary MDS: Integration of monosomal karyotype can better risk‐stratify the patients

“…It was also possible that some unfavorable molecular alterations not detectable by chromosomal analysis were present in this group of patients and influence their survival. Similarly, Gangat et al [17] could not find the prognostic superiority of IPSS-R very good karyotype in a study of 783 patients with primary MDS and the prognosis among very good, intermediate, and poor cytogenetic categories seemed not different. In addition to AML [16], presence of MK was recently found to be a poor prognostic factor in MDS [18,19].…”

“…In addition to AML [16], presence of MK was recently found to be a poor prognostic factor in MDS [18,19]. Patnaik et al [18] showed that MK could further identify a prognostically worse group in 127 patients with complex karyotype and Gangat et al [17] demonstrated MK adversely affected survival in both poor and very poor karyotype groups. In this study, we further showed that MK was significantly associated with shorter LFS and OS in the patients with IPSS-R poor and very poor cytogenetics as well as IPSS-R high and very high risk groups.…”

Mutations of myelodysplastic syndromes (MDS): An update

“…A Clinical Advisory Committee of ~100 hematologists, pathologists and cytogeneticists from all over the world has proposed incorporation of recent knowledge on cytogenetic and gene mutations detected in MDS [135]. In the proposed classification, MK is not considered as a specific MDS-subtype because of its controversial risk in presence or absence of CK [130,162]. Although the five-tier IPSS-R classification has incorporated most MK in the 'very poor' risk-group [9], further study is needed to determine its impact on prognosis independent of other cytogenetic and molecular mutations.…”

Reclassifying myelodysplastic syndromes: what's where in the new WHO and why

“…Monosomal karyotype is associated with high-risk MDS and adverse prognosis in some studies. 16 However, other studies have found that there is no significance of monosomal karyotype after accounting for complex karyotype (Ն3 or Ն5 independent abnormalities). 17 The new IPSS-R 5-group cytogenetic classification appears to account for most monosomal karyotype cases in its "very poor" risk group.…”