The significance of conventional cytogenetic analysis and the pattern of clonal evolution in patients with primary or secondary myelofibrosis (MF) are not well defined. In a cohort of 371 MF patients managed at the MD Anderson Cancer Center between 09/76 and 04/07, 337 (91%) had an adequate conventional cytogenetic study at the time of presentation. Seventy-eight percent had primary MF, 11% had post-PV MF, and 11% had post-ET MF. The patient characteristics (median and range) were: age 63 years (24–86); male 60%; previous therapy with radiation or alkylating agents 6%; hemoglobin 10.0 g/dL (6.2–16.0), transfusion-dependent 33%; white blood cell count 10.4 x 10^9/L (1.3–171.0), circulating blasts 1% (0–17); platelet count 203 x 10^9/L (1–1958); spleen size 6cm below LCM (0–30); performance status ≥2 in 6%. The median survival from presentation was 34 months, with a median follow-up of 39 months for the survivors. Conventional cytogenetic analysis performed at presentation (n = 337) demonstrated: 63% diploid; 9% deletion 20q; 7% abnormality (abn) of chromosome 5 or 7 or ≥3 abn (5/7/CPX); 5% deletion 13q; 5% translocations; 3% isolated trisomy 8; 3% abn of chromosome 17 (abn17); 2% trisomy 9; 3% other abn. The survival of patients with standard-risk cytogenetic abnormalities was similar to patients with normal diploid karyotypes (median survival [mOS] 34 months), and included deletion 20q (mOS 53 months), deletion 13q (mOS 52 months), translocations (mOS 61 months), isolated trisomy 8 (mOS 30 months), and trisomy 9 (no deaths at median 50 months). Among the standard-risk cytogenetic categories, the co-existence of an additional abnormality not affecting chromosomes 5, 7 or 17 had no significant impact on survival (p>0.50). The median survival by cytogenetic risk were: standard-risk (diploid or favorable cytogenetic findings), 40 months; high-risk (5/7/CPX), 15 months; very high-risk (abn17), 5 months [p<0.0001]. The Lille score (Blood 88:1013) had prognostic significance in standard cytogenetic risk patients, but had no effect on survival among high and very high cytogenetic risk patients. Clonal evolution (CE) was ranked according to the baseline cytogenetic risk categories, and occurred in 44 (28%) of 158 evaluable patients at a median of 17 months. Of these, one occurred at the development of blast phase, and two were already in the very high risk cytogenetic category. The impact of CE on survival was assessed in the remaining 41 patients (44 events). The median post-CE survivals were: new standard risk clone (11%), 31 months; standard risk abn in existing clone (50%), 21 months; 5/7/CPX abn (20%), 18 months; abn17 (18%), 12 months. We conclude that the conventional cytogenetic findings at presentation and the pattern of clonal evolution predict survival independent of established prognostic models. The occurrence of chromosome 17 abn at presentation and during the disease course identifies very high risk patients with a median survival of 12 months or less.

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