Risk Stratification for Survival and Leukemic Transformation in Essential Thrombocythemia: A Single Institutional Study of 605 Patients.

Abstract

Background It is widely recognized that advanced age and prior thrombosis predict recurrent thrombosis in essential thrombocythemia (ET) and are used to risk-stratify patients. However, the paucity of large sample size and long-term follow-up has limited the development of similar prognostic models for survival and leukemic transformation (LT). Methods Data was abstracted from the medical records of a consecutive cohort of patients with WHO-defined ET seen at the Mayo Clinic. Cox proportional hazards was used to determine the impact of clinical and laboratory variables on survival and LT. Overall survival and leukemia-free survival was estimated by Kaplan-Meier plots. Results i. Patient characteristics and outcome The study cohort included 605 patients of which 399 (66%) were females (median age, 57 years; range 5–91). Median follow-up was 84 months (range; 0–424). During this period, 155 patients (26%) have died and LT was documented in 20 patients (3.3%) occurring at a median of 138 months (range; 23–422) from ET diagnosis. ii. Prognostic variables for overall survival Univariate analysis of parameters at diagnosis identified age ≥ 60 years, hemoglobin less than normal (defined as < 12 g/dL in females and < 13.5 g/dL in males), leukocyte count ≥ 15 x 109/L, tobacco use, diabetes mellitus, thrombosis, male sex, and the absence of microvascular symptoms as independent predictors of inferior survival. All of the above except the last two (i.e. male sex and the absence of microvascular symptoms) sustained their prognostic significance on multivariate analysis. Based on the first three prognostic variables: age, hemoglobin level, and leukocyte count, we constructed a prognostic model for survival: low-risk (none of the risk factors), intermediate-risk (1of 3 risk factors), and high-risk (≥ 2 risk factors). The respective median survivals were 278, 200, and 111 months (p<0.0001; Figure 1) iii. Prognostic variables for leukemic transformation On univariate analysis of parameters at ET diagnosis, LT was significantly associated with platelet count ≥ 1000 x 109/L, hemoglobin less than normal, and exposure to P-32. However, on multivariate analysis, only hemoglobin less than normal and platelet count ≥ 1000 x 109/L maintained independent prognostic value. Accordingly, we utilized these two variables, to construct a prognostic model for LT: low-risk (none of the risk factors), intermediate-risk (1 risk factor), and high-risk (both risk factors). Only 1 of the 239 patients (0.4%) in the low-risk group vs. 14 of the 289 (4.8%) in the intermediate-risk and 5 of the 77 (6.5%) in the high-risk group underwent LT (p=0.0009; Figure 2). Conclusion The current study provides clinician-friendly prognostic models for both survival and LT in ET. Figure 1 Figure 1. Figure 2 Figure 2.

Long‐term follow‐up of 386 consecutive patients with essential thrombocythemia: Safety of cytoreductive therapy

“…An increased number of leukocytes (higher than 15 3 10 9 /L) was a relevant marker of worse outcome in patients with ET, confirming prior reports which recognized the prognostic relevance of leucocytosis on survival in PV [29] and ET [30] patients. These observations suggest that leucocytosis might be an indicator of a biologically more aggressive disease, and might identify a cohort of patients at higher risk of complications and disease progression.…”

Polycythemia vera and essential thrombocythemia: 2019 update on diagnosis, risk‐stratification and management

“…There are, to date, no controlled studies that implicate either hydroxyurea or busulfan as being leukemogenic in either ET or PV. Similarly, the 2 largest noncontrolled studies in ET 84 and PV 70 do not support the concern that leukemia might arise from the use of hydroxyurea and there is additional evidence to that effect from long-term studies of patients receiving hydroxyurea for sickle cell disease. 85 The evidence for busulfan leukemogenicity in the context of treatment for PV or ET is equally weak and inappropriately extrapolated from older patients with advanced phase disease and exposed to multiple cytoreductive drugs.…”

Leukaemic transformation of Philadelphia chromosome‐negative myeloproliferative neoplasms: are Asian patients different?

“…Many studies have also been performed to elucidate risk factors of LT in these patients. Old age, duration of disease, treatment with alkylating agents, combination chemotherapy and evolution to MF have been shown to be risk factors for LT. 2,3,5,21 The role of HU as a leukaemogenic drug is debatable with studies showing conflicting results. 2,4,22 HU was used as primary treatment in 18 of 22 patients.…”

“…6,7 Many studies signify the role of treatment modalities used during the myeloproliferative phase to be an important factor influencing the propensity to develop acute leukaemia. 2,3,5 Most of the cases reported transformation to acute myeloid leukaemia, with only few case reports of transformation to bilineage forms. 8,9 Complex cytogenetic abnormalities are commonly found in the leukaemic cells and many poor prognostic abnormalities are described.…”