Risk stratification for survival and leukemic transformation in essential thrombocythemia: a single institutional study of 605 patients

Abstract

Unlike the case with thrombosis, prognostic models for survival and leukemic transformation (LT) in essential thrombocythemia (ET) are not available. Among 605 patients with ET seen at our institution and followed for a median of 84 months, 155 died and LT was documented in 20 patients (3.3%). In a multivariable analysis, hemoglobin level below normal (females o120 g/l; males o135 g/l) was identified as an independent risk factor for both inferior survival and LT. Additional risk factors for survival included age X60 years, leukocyte count X15 Â 10 9 /l, smoking, diabetes mellitus and thrombosis. For LT, platelet count X1000 Â 10 9 /l but not cytoreductive therapy was flagged as an additional independent risk factor. In fact, four of the 20 patients (20%) with LT were untreated previously. We used the above information to construct prognostic models that effectively discriminated among low-, intermediate-and high-risk groups with respective median survivals of 278, 200 and 111 months (Po0.0001), and LT rates of 0.4, 4.8 and 6.5% (P ¼ 0.0009) respectively. Presence of JAK2V617F did not impact either survival or LT and mutational frequency was similar among the different risk groups.

Clinico-Hematological Profile and Risk Stratification in Patients with Essential Thrombocythemia: Experience from Pakistan

“…As only 17% were in high risk in one prior USA study (Gangat et al, 2007). Compared with data from developed countries, majority of our patients (57.1%) were in high risk.…”

Polycythemia vera and essential thrombocythemia: 2015 update on diagnosis, risk‐stratification and management

“…In the same study, risk factors for fibrotic transformation included prefibrotic PMF morphology, advanced age, and anemia although the presence of JAK2V617F was associated with a lower risk of fibrotic transformation [52]. Using age 60 years, hemoglobin below normal value and leukocyte count >15 3 10 9 /L, one study demonstrated a median survival of >20 years in the absence of all three risk factors and 9 years in the presence of two of the three risk factors [54].…”

“…There are, to date, no controlled studies that implicate either hydroxyurea or busulfan as being leukemogenic in either ET or PV. Similarly, the two largest non-controlled studies in ET [54] and PV [108] 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 [123]. 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.…”

Interferon-α therapy in bcr-abl-negative myeloproliferative neoplasms

“…[69][70][71][72] By contrast, a leukemogenic potential of hydroxyurea (HU) has not been shown in clinical trials, although there is evidence showing that the sequential use of HU and other cytoreductive drugs (alkylating agents, radioactive phosphorus) increases the risk of AL/MDS. [72][73][74][75] In addition, several retrospective studies did not find an increased risk of AL in PV and ET treated with HU alone, [76][77][78] and similar conclusions were drawn from a recent meta-analysis of HU therapy in sickle cell anemia. 79 Still, very long-term results of prospective studies in HU-treated MPN patients with more than 10 years of follow-up showed a cumulative incidence of AL/MDS of more than 10% beyond 12 years of follow-up, suggesting that the risk of leukemic evolution could be higher than reported earlier in studies with shorter follow-up.…”