Impact of adjunct cytogenetic abnormalities for prognostic stratification in patients with myelodysplastic syndrome and deletion 5q

Mallo, Mar; Cervera, José; Schanz, Julie; Such, Esperanza; Garcia‐Manero, Guillermo; Luño, Elisa; Steidl, Christian; Espinet, Blanca; Vallespı́, Teresa; Germing, Ulrich; Blum, Sabine; Ohyashiki, Kazuma; Grau, Juan J.; Pfeilstöcker, Michael; Hernández, Jesús M.; Noesslinger, Thomas; Giagounidis, Aristoteles; Aul, Carlo; Calasanz, Marı́a José; Martín, Manuel Ángel Franco; Valent, Peter; Collado, Rosa; Haferlach, Claudia; Fonatsch, Christa; Lübbert, Michael; Stauder, Reinhard; Hildebrandt, Barbara; Krieger, O.; Pedro, Carme; Arenillas, Leonor; Sanz, Miguel Á.; Valencia, Ana; Florensa, Lourdes; Sanz, G F; Haase, Detlef; Solé, Françesc

doi:10.1038/leu.2010.231

Cited by 107 publications

(94 citation statements)

References 26 publications

(35 reference statements)

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“…5,6 (4) The presence of more than one additional chromosomal aberration is associated with an increased risk of progression. This is in line with the only large study evaluating progression features in patients affected with del(5q) that was recently presented by Mallo et al 16 This study focused primarily on cytogenetic features, comprising 541 patients with different French-American-British subtypes of MDS, including patients with medullary blasts of up to 20% with or without additional chromosomal abnormalities. Chromosomal complexity, platelet count and percentage of marrow blast were the most important factors predictive for the risk of AML progression in that study.…”

Section: Discussionsupporting

confidence: 70%

Survival, prognostic factors and rates of leukemic transformation in 381 untreated patients with MDS and del(5q): A multicenter study

et al. 2012

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Myelodysplastic syndromes (MDS) with del(5q) are considered to have a benign course of the disease. In order to address the issue of the propensity of those patients to progress to acute myeloid leukemia (AML), data on 381 untreated patients with MDS and del(5q) characterized by low or intermediate I International Prognostic Scoring System (IPSS) risk score were collected from nine centers and registries. Median survival of the entire group was 74 months. Transfusion-dependent patients had a median survival of 44 months vs 97 months for transfusion-independent patients (Po0.0001). Transfusion need at diagnosis was the most important patient characteristic for survival. Of the 381 patients, 48 (12.6%) progressed to AML. The cumulative progression rate calculated using the Kaplan --Meier method was 4.9% at 2 years and 17.6% at 5 years. Factors associated with the risk of AML transformation were high-risk World Health Organization adapted Prognostic Scoring System (WPSS) score, marrow blast count 45% and red-cell transfusion dependency at diagnosis. In conclusion, patients with MDS and del(5q) are facing a considerable risk of AML transformation. More detailed cytogenetic and molecular studies may help to identify the patients at risk of progression.

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Section: Discussionsupporting

confidence: 70%

Survival, prognostic factors and rates of leukemic transformation in 381 untreated patients with MDS and del(5q): A multicenter study

et al. 2012

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“…A recent cooperative study revealed that patients with one defect in addition to del(5q) presented an OS similar and a risk of AML transformation higher than those of patients with del(5q) alone [44]. Intriguingly, a current SNP-A report showed that deletions involving the centromeric or telomeric extremes of 5q are associated with a more aggressive disease phenotype and additional chromosomal lesions [45].…”

Section: Discussionmentioning

confidence: 98%

Validation of the new comprehensive cytogenetic scoring system (NCCSS) on 630 consecutive de novo MDS patients from a single institution

et al. 2013

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This study evaluated whether the NCCSS truly improves the prognostic stratification of 630 consecutive de novo MDS patients and established which cytogenetic grouping [NCCSS or International Prognostic Scoring System (IPSS)], when combined with the WHO classification, best predicted the clinical outcome of myelodysplastic syndromes (MDS). The frequency of chromosomal defects was 53.8%. Clinical parameters, including number of cytopenias, WHO classification, IPSS cytogenetic categories and scores, NCCSS were all relevant for overall survival (OS) and leukemia-free survival (LFS) and were included in six distinct multivariate models compared by the Akaike Information Criterion (AIC). The most effective model to predict OS included the number of cytopenias, the WHO classification and the NCCSS, whereas the model including the number of cytopenias, blast cell percentage and the NCCSS and the model including the number of cytopenias the WHO classification and the NCCSS were almost equally effective to predict LFS. In conclusion, the NCCS (i) improves the prognostic stratification of the good and poor IPSS cytogenetic categories by introducing the very good and the very poor categories; (ii) is still incomplete in establishing the prognostic relevance of rare/double defects, (ii) applied to patients who receive supportive treatment only identifies five different prognostic subgroups, but applied to patients treated with specific therapies reveals only a trend toward a significantly different OS and LFS when patients of the poor and intermediate cytogenetic categories are compared, (iii) combined with the WHO classification is much more effective than the IPSS in predicting MDS clinical outcome. Am. J. Hematol. 88:120-129,

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“…The "5q-syndrome" was first described by Van den Berghe in 1974 with distinct morphologic features which include thrombocytosis, macrocytic anemia, and hypolobulated megakaryocytes, along with minimal dysplasia in the granulomonocytic and erythroid lineages [35]. Among patients with MDS with del(5q), the presence of an additional nonhigh-risk cytogenetic abnormality has not been shown to have an adverse impact on the otherwise favorable prognosis [36]. On the other hand, studies have confirmed that the presence of TP53 mutations confers adverse prognosis to del(5q) patients [37,38].…”

Section: Introductionmentioning

confidence: 99%

Myelodysplastic syndromes: Contemporary review and how we treat

2015

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Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal stem cell disorders with an inherent tendency for leukemic transformation. Diagnosis is currently based on the presence of peripheral blood cytopenias, peripheral blood and bone marrow dysplasia/blasts, and clonal cytogenetic abnormalities. With the advent of next generation sequencing, recurrent somatic mutations in genes involved in epigenetic regulation (TET2, ASXL1, EZH2, DNMT3A, IDH1/2), RNA splicing (SF3B1, SRSF2, U2AF1, ZRSR2), DNA damage response (TP53), transcriptional regulation (RUNX1, BCOR, ETV6) and signal transduction (CBL, NRAS, JAK2) have been identified in MDS. Conventional prognostication is by the revised International prognostic scoring system (IPSS-R) with additional adverse prognosis conferred by presence of ASXL1, EZH2, or TP53 mutations. Currently Food and Drug administration (FDA)-approved drugs for the treatment of MDS are not curative and their effect on survival is limited; they include the hypomethylating agents (HMA) azacitidine and decitabine and lenalidomide for MDS with isolated del(5q). To date, allogeneic stem cell transplant (ASCT) remains the only treatment option for possible cure. Given the current lack of drugs with convincing evidence of favorable effect on survival, we consider ASCT as the treatment of choice for most patients with symptomatic disease, and especially for those with high-risk disease. For nontransplant candidates, participation in clinical trials is preferred over conventional therapy. There is not one right way of treatment for patients who are not candidates for either ASCT or clinical trials and palliative drugs of choice depend on the clinical problem, such as symptomatic anemia (ESAs, danazol, HMA), thrombocytopenia (HMA), or neutropenia (myeloid growth factors). Conversely, there is no controlled evidence to support the use of iron chelating agents in MDS. Going forward, we believe it is time to incorporate mutation information in clinically derived prognostic models in MDS and encourage development of novel drugs with disease-modifying activity.

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Impact of adjunct cytogenetic abnormalities for prognostic stratification in patients with myelodysplastic syndrome and deletion 5q

Cited by 107 publications

References 26 publications

Survival, prognostic factors and rates of leukemic transformation in 381 untreated patients with MDS and del(5q): A multicenter study

Survival, prognostic factors and rates of leukemic transformation in 381 untreated patients with MDS and del(5q): A multicenter study

Validation of the new comprehensive cytogenetic scoring system (NCCSS) on 630 consecutive de novo MDS patients from a single institution

Myelodysplastic syndromes: Contemporary review and how we treat

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