Clinical Associations of Cytogenetic Abnormalities in Patients with Primary and Post-Essential Thrombocythemia and Post-Polycythemia Vera Myelofibrosis

Abstract

Introduction: Several studies have evaluated the incidence and clinical relevance of cytogenetic abnormalities in primary myelofibrosis (PMF). However, little is known about the clinical correlation of these abnormalities in patients with post-essential thrombocythemia/polycythemia vera myelofibrosis (PET/PPV-MF).Objective: We aimed to measure the frequency of cytogenetic abnormalities (Abn) and describe their clinical significance in patients with PMF and PET/PPV-MF seen at our center.Methods: We retrospectively reviewed the charts of 1100 patients with MF (766 PMF, 354 PET/PV-MF) who were referred to our institution between 1984 and 2013. Diagnoses were made according to 2008 WHO criteria. Cytogenetic analysis done at the time of referral was reported according to the International System for Human Cytogenetic Nomenclature. Statistical analysis considered parameters at the time of cytogenetic studies. Complex karyotype (CK) was defined as 3 or more unrelated abnormalities (Abn) and monosomal karyotype (MK) was defined as 2 autosomal monosomies or a single monosomy with at least one additional structural abnormality. Fisher's exact, Kruskal-Wallis and Mann-Whitney tests were used for comparisons of categorical and continuous variables, respectively. The Kaplan-Meier analysis with log rank test were used for OS comparisons.Results: Cytogenetic data with > 10 analyzable metaphases were obtained in 981 (89%) patients. Overall, 360 (37%) patients had an abnormal karyotype. Frequency and types of cytogenetic Abn were similar between PMF and PET/PPV-MF (Table 1). Sixty one percent of patients (n=220) had a single Abn, 25% (n=89) had two, and 15% (n=52) had 3 or more Abn, including 6% with MK (n=26). Proportional distribution was similar between PMF and PET/PPV-MF patients.Comparison of patients with one, two, or ≥3 Abn (i.e. CK) revealed that patients with CK were more likely to be anemic (hemoglobin < 10 g/dL, p<0.001) and transfusion dependent (p<0.001) and had higher DIPSS risk scores (p=0.004) than patients with one or two Abn. Among patients with PMF, CK was also associated with thrombocytopenia (p<0.001), while among those with PET/PPV-MF, it was associated with advanced (MF-2, 3) bone marrow fibrosis (p=0.045). Among all patients with one or two Abn, those with Abn in chromosomes 17, 5, or 7 had lower hemoglobin and higher peripheral blood blasts, and were less likely to be JAK2 positive (all p<0.05).Estimated OS was 48 months (range, 43-52) for both patients with PMF and PET/PPV-MF. Among all patients, OS was shorter among those with CK (median 14 months, range 7-21) than in those with one (median 48, range 37-60) or two (median 58, range 43-73) Abn (p=0.000, chi-sq 26.6). Overall median follow up from the time of referral was 29 months (range, 0.5-251) and 61% (n=220) of patients had died. Among all patients, median survival from date of referral was 19 months (range, 0.5-251). During an observation period of 1105 persons-years, progression to AML occurred in 44 (12%) patients after a median time of 13 months (range, 0.5-175). The incidence of AML was higher among those with CK (23% vs 15% vs 13% with CK, two or one Abn, respectively; p=0.014, chi-sq 8.7). Among the known causes of death (in 109 patients), progression of MF/AML was the most common (24%, n=53).Conclusion: The frequency of cytogenetic abnormalities in patients with PMF and PET/PPV-MF and their clinical relevance appear to be similar. Patients with CK have shorter OS and a higher incidence of AML in both PMF and PET/PPV-MF. [Display omitted] DisclosuresCortes:ARIAD: Consultancy, Research Funding; Bristol-Myers Squib: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Teva: Research Funding.