Refined cytogenetic-risk categorization for overall and leukemia-free survival in primary myelofibrosis: a single center study of 433 patients

D Caramazza, K H Begna, N Gangat, R Vaidya, S Siragusa, D L Van Dyke, C Hanson, A Pardanani, A Tefferi, D Caramazza, K H Begna, N Gangat, R Vaidya, S Siragusa, D L Van Dyke, C Hanson, A Pardanani, A Tefferi

Abstract

We have previously identified sole +9, 13q- or 20q-, as 'favorable' and sole +8 or complex karyotype as 'unfavorable' cytogenetic abnormalities in primary myelofibrosis (PMF). In this study of 433 PMF patients, we describe additional sole abnormalities with favorable (chromosome 1 translocations/duplications) or unfavorable (-7/7q-) prognosis and also show that other sole or two abnormalities that do not include i(17q), -5/5q-, 12p-, inv(3) or 11q23 rearrangement are prognostically aligned with normal karyotype, which is prognostically favorable. These findings were incorporated into a refined two-tired cytogenetic-risk stratification: unfavorable and favorable karyotype. The respective 5-year survival rates were 8 and 51% (hazard ratio (HR): 3.1, 95% confidence interval (CI): 2.2-4.3; P<0.0001). Multivariable analysis confirmed the International Prognostic Scoring System (IPSS)-independent prognostic value of cytogenetic-risk categorization and also identified thrombocytopenia (platelets <100 × 10(9)/l) as another independent predictor of inferior survival (P<0.0001). A similar multivariable analysis showed that karyotype (P=0.001) and platelet count (P=0.04), but not IPSS (P=0.27), predicted leukemia-free survival; the 5-year leukemic transformation rates for unfavorable versus favorable karyotype were 46 and 7% (HR: 5.5, 95% CI: 2.5-12.0; P<0.0001). This study provides the rationale and necessary details for incorporating cytogenetic findings and platelet count in future prognostic models for PMF.

Figures

Figure 1
Figure 1
Survival data of patients with primary myelofibrosis stratified by the International Prognostic Scoring System.
Figure 2
Figure 2
Survival data of patients with primary myelofibrosis stratified by specific cytogenetic categories.
Figure 3
Figure 3
Survival data of patients with primary myelofibrosis stratified by two-tired cytogenetic-risk categorization: unfavorable (complex karyotype or sole or two abnormalities that include +8, −7/7q-, i(17q), inv(3), −5/5q-, 12p- or 11q23 rearrangement) and favorable (all other scenarios including normal karyotype).
Figure 4
Figure 4
Leukemia-free survival data of patients with primary myelofibrosis stratified by two-tired cytogenetic-risk categorization: unfavorable (complex karyotype or sole or two abnormalities that include +8, −7/7q-, i(17q), inv(3), −5/5q-, 12p- or 11q23 rearrangement) and favorable (all other scenarios including normal karyotype).

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