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Survival of essential thrombocytemia (ET) patients during the first 10 years of their disease is similar to that of the general population. While it is well known that alkylating agents (given alone or sequentially) increase the risk of transformation into an acute myeloid leukemia, the specific role of different therapies on the development of secondary malignancies (SM) in ET patients is still under investigation.

To retrospectively evaluate the role of different treatments on the development of SM in a large cohort of ET patients followed over a 30-year period.

Data from a series of 1026 ET patients diagnosed between 1980 and 2000,  and followed at 11 Hematology Centers of the Lazio region in Central Italy, were collected. The median age at ET diagnosis was 62 years (range 17-93); there were 392 males, 634 females; the median follow-up of the entire population is 6.2 years (range 0.1–32). Among the whole population, 39% of patients carried the JAK2V617F mutation, while 27% were wild type; for 34% of cases, this datum is missing. With regard to adjunctive risk factors (smoke, diabetes, hypertension, dyslipidemia), 64% of patients presented at least one risk factor (42%, 1; 22% >1); 28% of patients did not present adjunctive risk factors and for 8% of cases this datum is missing. Smoke was present in 25% of cases, hypertension in 43%, diabetes in 7%, dyslipidemia in 15%. Sixty three of the 1026 patients (6%) developed 64 SM during the follow-up, after a median time of 50 months (range 2-158) from diagnosis. The observed SM were grouped as follows: genito-urinary 15, breast 14, non-melanoma skin cancer 5, lung 11, gastro-intestinal 8, hematologic 5, thyroid 3, central nervous system 1, soft tissue 1 and unknown 1.

Taking into consideration the different treatment approaches, we divided our population into 5 different groups: group 0, untreated patients; group 1, patients treated with hydroxiurea (HU) alone or in combination/sequentially with interpheron α (IFN)/anagrelide (ANA); group 2, patients treated with alkylating agents (ALK) alone or in combination/sequentially with IFN/ANA; group 3, patients treated with ALK+HU sequentially; group 4, patients treated with ANA and/or IFN only.

With regard to the exposure time to drugs, a statistically significant difference was found between the groups HU vs ALK (p=0.036), HU vs ALK+HU (p=0.006) and ALK+HU vs ANA/IFN (p=0.006). No differences were found for the groups HU vs ANA/IFN, ALK vs ALK+HU, ALK vs ANA/IFN. In univariate analysis, the following variables were considered: gender, age, different therapeutic approaches, exposure time, presence of adjunctive risk factors. A statistically significant difference was found only for gender (M vs F: p=0.035) and age (>60 years vs <60years: p=0.0001). In multivariate analysis, a statistically significant difference was maintained for both gender and age [gender HR1.7 (CI 95% 1.037-2.818) p 0.035; age HR 4.190 (CI 95% 2.308-7.607) p=0.0001)]. 

 

In our series of 1026 ET patients followed over a 30-year period, the different therapies administered, comprising HU and ALK, do not appear to have impacted on the development of SM. A similar prevalence of SM was observed also in untreated patients. The only two variables which showed a statistical significance were male gender and age >60 years.