Karyotype complements the International Prognostic Scoring System for primary myelofibrosis

The International Prognostic Scoring System (IPSS) for primary myelofibrosis (PMF) is based on five independent predictors of inferior survival: age > 65 yr, hemoglobin < 10 g/dL, leukocyte count > 25 x 10(9)/L, circulating blasts >= 1%, and presence of constitutional symptoms. The presence of 0, 1, 2, and >= 3 adverse factors defines low, intermediate-1, intermediate-2, and high risk disease, respectively. We examined the additional prognostic relevance of karyotype. World Health Organization criteria were used for PMF diagnosis. Only patients with bone marrow cytogenetic studies at the time or within 1 yr of diagnosis and a minimum of 20 evaluable metaphases were considered. Cytogenetic findings were categorized as 'normal' vs. 'abnormal' or 'favorable' (normal or with sole abnormalities of 13q- or 20q-) vs. 'unfavorable' (all other abnormalities). A total of 109 patients were studied (median age 63 yr). Numbers of patients in the above-listed four IPSS risk groups were 26, 31, 28, and 24, respectively. Cytogenetic results were abnormal in 33% of the patients and unfavorable in 21%. At a median follow-up of 35 months, 45 (41%) deaths were recorded. 'Unfavorable' (P = 0.008) but not 'abnormal' (P = 0.19) karyotype predicted shortened survival and its significance remained on multivariable analysis that included the IPSS or other prognostic tools as covariates. JAK2V617F, detected in 63 (58%) patients, was inconsequential to survival. In PMF, specific cytogenetic abnormalities and not the mere presence of an abnormal karyotype provide important prognostic information that is not accounted for by the IPSS or other established risk factors.