Complex, Not Monosomal, Karyotype Is the Cytogenetic Marker of Poorest Prognosis in Patients With Primary Myelodysplastic Syndrome

Valcárcel, David; Ademà, Vera; Solé, Françesc; Ortega, Margarita; Nomdedeu, Benet; Sanz, Guillermo; Luño, Elisa; Cañizo, Consuelo del; Serna, Javier de la; Ardanaz, Maite; Marco, Víctor; Collado, Rosa; Grau, Javier; Montoro, María Julia; Mallo, Mar; Vallespı́, Teresa

doi:10.1200/jco.2012.41.6073

Cited by 62 publications

(72 citation statements)

References 15 publications

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“…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]. Others have suggested that prognosis was related more with the complexity of karyotype rather than MK [15] and the possibility remains that these observations might be influenced by specific therapy [16].…”

Section: Resultssupporting

confidence: 88%

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

et al. 2013

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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.

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Section: Resultssupporting

confidence: 88%

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

et al. 2013

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“…In line with our findings, recent studies have questioned the relative importance of MK in MDS and secondary AML (sAML) as compared with burden of cytogenetic complexity. [18][19][20][21][22][23] IPSS-R cytogenetic classification predicted OS more efficiently than IPSS cytogenetic classification, a finding consistent with those of a larger series of MDS/sAML patients who underwent HCT 10 ( Table 6), suggesting that IPSS-R cytogenetic classification may indeed refine prognosis not only in untreated patients but also after HCT. In addition, IPSS-R cytogenetic classification as a five-group score, but not MK, was predictive of increased CIR, possibly as a result of the additional impact of 3q21q26 and del 7q found within non-MK (60% in each case).…”

Section: Discussionsupporting

confidence: 80%

Specific abnormalities versus number of abnormalities and cytogenetic scoring systems for outcome prediction after allogeneic hematopoietic SCT for myelodysplastic syndromes

Kelaïdi

Tzannou

Baltadakis

et al. 2014

Bone Marrow Transplant

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Newer cytogenetic scoring systems for myelodysplastic syndromes (MDSs), like cytogenetic stratification of the revised international prognostic scoring system (IPSS-R) or monosomal karyotype, may also improve outcome prediction after hematopoietic SCT (HCT). We compared the prognostic value of specific cytogenetic abnormalities, IPSS-R karyotype and monosomal karyotype for HCT outcome in 98 patients with MDS and AML post MDS. Higher-risk IPSS-R karyotype, 3q21q26 and transformation to AML before HCT were associated with increased cumulative incidence of relapse (CIR), whereas OS was adversely influenced by del 5q/−5, abnormalities of chromosomes 11 and 17 and cytogenetic IPSS-R very poor category. Karyotype with ⩽ 2 abnormalities and no abnormalities of chromosomes 3, 5, 7, 11 and 17 was an independent prognostic factor of lower CIR (hazard ratio (HR) = 0.2, P = 0.01) and longer OS (HR = 0.5, P = 0.03). In conclusion, some specific cytogenetic abnormalities and high cytogenetic complexity, as reflected by IPSS-R very poor karyotype, rather than monosomal karyotype, were associated with higher CIR and shorter OS after HCT. Conversely, results were encouraging in patients lacking those abnormalities, who may be very good candidates for HCT.

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“…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. 18 Overall, monosomal karyotype does not appear to define a specific MDS subtype; further study is needed to determine its impact on prognosis independent of other cytogenetic and molecular genetic risk features.…”

Section: Cytogenetics Mutation Analysis and Flow Cytometry Immunophementioning

confidence: 99%

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

Arber

Hasserjian

2015

Hematology

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A revision to the 4th edition of the WHO Classification of myelodysplastic syndromes (MDSs), originally published in 2008, is expected in mid-2016. Based on recommendations of a Clinical Advisory Committee, the revision will aim to incorporate new discoveries in MDS that impact existing disease categories. Although the basic diagnostic principles of the WHO classification remain unchanged, several changes to the classification are proposed. All revisions are considered preliminary until the actual publication of the monograph and online document. Proposals for change include abandoning the routine use of "refractory anemia/cytopenia" in the various disease names, including the prognostic significance of gene mutations in MDS, revising the diagnostic criteria for MDS entities with ring sideroblasts based on the detection of SF3B1 mutations, modifying the cytogenetic criteria for MDS with isolated del(5q), reclassifying most cases of the erythroid/myeloid type of acute erythroleukemia, and recognizing the familial link in some cases of MDS. This review will provide details of the major proposed changes as well as rationale for the revisions. Learning Objective• Understand proposed changes to the WHO classification of myelodysplastic syndromes

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Complex, Not Monosomal, Karyotype Is the Cytogenetic Marker of Poorest Prognosis in Patients With Primary Myelodysplastic Syndrome

Abstract: After accounting for karyotype complexity, MK was not associated with OS or evolution to AML. In conclusion, these results demonstrate that the prognostic value of MK in MDS is not independent and is mainly the result of its strong association with number of chromosomal abnormalities.

Cited by 62 publications

References 15 publications

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

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

Specific abnormalities versus number of abnormalities and cytogenetic scoring systems for outcome prediction after allogeneic hematopoietic SCT for myelodysplastic syndromes

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

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