Prognostic Impact of Additional Chromosomal Aberrations (ACA) to 5q- in Patients with primary Myelodysplastic Syndrome.
Authors: Mallo Maria del Mar , Cervera José , Schanz Julie , Espinet Blanca , Such Esperanza , Luño Elisa , Steidl Christian , Martín María Luisa , Germing Ulrich , Grau Javier , Pfeilstoecker Michael , Hernández Jesús M , Noesslinger Thomas , Calasanz M.a José , Valent Peter , Collado Rosa , Fonatsch Christa , Bureo Encarna , Lübbert Michael , Ríos Rafael , Stauder Reinhard , Arranz Eva , Hildebrandt Barbara , Slovak Marilyn L. , Cigudosa Juan , Eclache Virginie , Krieger Otto , Pedro Carmen , Salido Marta , Arenillas Leonor , Sanz Guillermo , Sanz Miguel A. , Valencia Ana , Florensa Lourdes , Haase Detlef , Solé Francesc 
Published: April 2020

Deletion of the long arm of chromosome 5 is the most frequent chromosomal abnormality in MDS (10–15% of MDS cases). Patients with del(5q), particularly those with the ‘5q-syndrome’ have a much better prognosis than other MDS subtypes. Although the presence of additional chromosome abnormalities (ACA), apart from 5q-, has been suggested to negatively influence this favourable outcome, the exact prognostic impact of ACA remains unknown. The aim of the present study was to analyse the prognostic value of ACA in a large series of patients with MDS with 5q- abnormality, treated with supportive care.

Three-hundred and five MDS patients with del(5q) were selected from a 3128 cases database that included 1004 patients from the Spanish Haematological Cytogenetics Working Group (GCECGH) (Solé et al., 2005) and 2124 patients from the German-Austrian MDS Study Group (Haase et al., 2007). Patients were separated into two groups: group A (n=204), all del(5q) cases as a single anomaly and group B (n=101) with additional cytogenetic anomalies. Patients in Group B were subdivided according to:

the number of additional anomalies (1 to 3 5 anomalies); and the type of additional cytogenetic aberrations: chromosomes 1 and 3, monosomy 7, 7q-, trisomy 8, trisomy 11, trisomy 13, 12p-, involvement of chromosome 17, -18/18q-, 20q-, trisomy 21, loss of X/Y chromosome, and unrelated clones.

The series includes 90 males (29.5%) and 215 females (70.5%) with a median age of 66 years (range: 3–92 yr). Using FAB criteria (n=294): 52% had RA, 9% RARS, 30% RAEB, 8% RAEB-t and 1% CMML. WHO classification was available for 217 patients: 52% had ‘5q- syndrome’, 1% RA, 0% RARS, 2% RCMD, 2% RSCMD, 13% RAEB-1, 20% RAEB-2, 1% CMML, 8% AML and 1% were unclassifiable. Overall, 204 (67%) of the patients presented 5q- isolated, 52 (17%) 5q- with one additional abnormality, 10 (3%), 6 (2%), 7 (2%) and 26 (9%) with 2, 3, 4 and 5 or more additional abnormalities, respectively. Follow-up data were available for 273 patients (89.5%). Median survival was 48 months for all. Median survival for patients with isolated del(5q), with one additional abnormality and with two or more additional abnormalities (complex karyotypes) was 69, 55 and 8 months, respectively (P&lt;0.0001). However, no statistical differences were found between patients with isolated del(5q) and patients with only one additional abnormality (P=0.35). Complex karyotypes showed a very adverse outcome. None of the single additional anomalies analysed showed a particular better or worse prognosis. Preliminary results of a multivariate analysis (n=76) showed a highest predictive survival time value for cytogenetics complexity followed by the number of cytopenias and the age.

In conclusion, patients with 5q- associated with two or more additional chromosomal abnormalities have a significantly worse overall survival than patients with isolated 5q- or with only one additional anomaly. Our results do not support the exclusion of patients with one single additional chromosomal abnormality and typical bone marrow features from the ‘5q- syndrome’ WHO category. This work is presented on behalf of the Grupo Cooperativo Español de Citogenética Hematológica (GCECGH), German-Austrian MDS Study Group (GASMSG), International Working Group on MDS Cytogenetics of the MDS Foundation.