Cytogenetic features and prognosis in 496 argentinean patients with primary Myelodysplastic Syndromes

BELLI, CAROLINA; CORREA, WALTER A; BENGIÓ, RAQUEL; GIUNTA, MARIO; BENASAYAG, SILVIA; CAMPESTRI, REINALDO; PENCHASKY, DIANA; AGRA, MARCELA; CRISP, RENÉ; FANTL, DOROTEA; PRATES, M VIRGINIA; LARRIPA, IRENE

London

Congreso; 16th Congress of the European Hematology Association; 2011

European Hematology Association

Background: Myelodysplastic Syndromes (MDS) include a group of heterogeneous hematological disorders with variable risk of evolution to Acute Myeloid Leukemia (AML) and short survival. Around 40-50% of patients show abnormal karyotype at diagnosis. Recently, some isolated deletions have been related with a favorable outcome in MDS (i.e. 9q-, 11q-, 12p-) and Breems et al., 2008, proposed that monosomal karyotypes (MK) are an indicator of poor prognosis in AML. Aims: To characterize the cytogenetic profile, to test its prognostic value and to evaluate cytogenetic groups of risk in the Argentinean MDS population. Methods: This is a multicenter retrospective study of 496 primary Argentinean patients with primary MDS evaluated from 1984 to 2010 (including 239 patients from the Pilot Study and from the MDS Registry sponsored by the Argentinean Society of Hematology). Refractory cytopenia was defined according to Valent et al, 2007 and patients were classified following FAB and WHO criteria. The median age was 69 (17-93) years with a male/female ratio of 1.3. During the follow-up (mean: 26 months), 111 (22.4%) evolve to AML and 222 (44.7%) died. Results: Gender, percentage of bone marrow blast, hemoglobin level, platelets count, number of cytopenias, LDH level and red blood cell transfusion requirements, FAB and WHO classification, IPSS and WPSS prognostic systems were significant predictive variables for prognosis (Kaplan-Meier and Long-Rank test, p<.001). Patients with normal karyotype (n=289, 58%, median survival: 51 months) had better outcome than those with cytogenetic alterations (n=207, 42%, 26 months, p<.001). Among abnormal karyotypes, 137 (66%) showed deletions and/or monosomies, 124 (59%) involved, at least, one chromosome #5, #7, #8 and/or #20. The most common cytogenetic aberrations were: -5/5q- (22% among cases with abnormal karyotype), -7/7q- (15%), +8 (21%), 20q- (9%) and –Y (8%). Karyotypes were divided according to IPSS (p<.001) into Good (n=334, 67%, median survival: 48 months), Intermediate (n=102, 21%, 32 months) and Poor (n=124, 12%, 15 months). In order to find the prognostic value of certain cytogenetic findings, karyotypes were divided as follows: normal, low risk alterations (n=45, 9%, median survival: 43 months), karyotypes with isolated deletions (n=20, 4%, 50 months), trisomy 8 (n=25, 5%, 25 months), other intermediate findings (n=54, 11%, 28 months), chromosome 7 alterations (n=19, 4%, 15 months), MK (n=30, 6%, 16 months) and other complex karyotypes (n=15, 3%, 18 months). No significant differences were observed among MK and other Poor cytogenetic findings (median survival: 15 months, p=.592). Patients with isolated deletions showed a similar behavior than Good cytogenetic findings (p=.437) and a borderline better outcome than the rest of the Intermediate ones (p=.07). An intermediate prognosis was observed when karyotypes included a deletion + other alteration (n=13, 3%, 31 months, p=.523). Conclusions: Cytogenetic findings had a clear impact in our population. Results in the present series, the largest in Latin America, suggest that MK are indicators of poor prognosis whilst the presence of an isolated deletion (not including 7q-) would be a good cytogenetic finding. However, the wide spectrum of low frequency aberrations stresses the importance of large study groups.