THE PREVALENCE OF LEG ULCERS IN PATIENTS WITH MYELOPROLIFERATIVE DISORDERS TREATED WITH HYDROXYUREA

Background:

Leg ulcers (LU) represent a common adverse side effect of long-term hydroxyurea (HU) therapy, which is often neglected.

Aims:

To describe the prevalence of LU in patients with myeloproliferative disorders (MPD) treated with HU and association of LU with chronic venous insufficiency (CVI) and presence of JAK-2 (V617F) mutation.

Methods:

70 patients aged 39 to 89 years, 33 (47%) women and 37 (53%) men treated with HU for MPD (polycytemia vera 34 (49%), essential thrombocythemia 14 (20%), primary myelofibrosis 20 (29%), MPD unspecified 2 (2%). The average duration of HU therapy was 6.66 years with the average HU dose of 2325.8g per patient. JAK-2 (V617F) mutation was examined in 45 (64%) patients; positive results were found in 31 (69%) cases. All patients were assessed using the CEAP classification of CVI, including ultrasonography of lower limb veins.

Results:

CVI symptoms were found in 51 (73%) patients, 35 (50%) of them had both lower limbs affected.  LU developed in 16 (23%) patients during the period of HU treatment.  In 11(69%) of them LU was associated with CVI, while in 6(38%) cases the ulcer affected the leg without CVI.  (1 patient with ulcers of both legs had only one limb with CVI). 19 patients without CVI were followed for 19-870 (median 367) weeks and LU developed in 3 (15.8%) of them. 51 patients with CVI were followed for 20-933 (median 318) weeks and LU developed in 12 (23.6%) of them; the difference was not significant (P=0.4828). The time to LU development was 10 to 547 (mean 233) weeks and 196 to 845 (mean 409) weeks in patients with CVI and without CVI, respectively; the difference was not significant (p=0.1495). The mean cumulative dose of HU administered before LU development was 1848 (55 – 4817) g and 3831 (1635-8648) g in patients with CVI and in patients without CVI, respectively; the difference was not significant (p= 0.1931). The mean duration of HU therapy till LU development was 257 (10-846) weeks in 7 patients with JAK-2 mutation and 313 (197-535) weeks in 3 patients without JAK-2 mutation. The mean cumulative dose of HU administered was 2238 (57-8648) g and 3243 (1083-7011) g in patients with JAK-2 mutation and in patients without mutation, respectively. 2 (18%) ulcers healed within 18 and 33 weeks during HU therapy. In 15 cases HU therapy was stopped due to non-healing ulcers and an alternative therapy was administered. 14 (93%) ulcers disappeared after discontinuation of HU therapy, 1 patient died shortly after HU suspension. The average time from HU discontinuation to healing of LU were 30 (8-73) weeks and 44 (5-121) weeks in ulcers associated and non-associated with CVI, respectively; the difference was not significant (p=0.5035). The average time of healing was 47 (8-121) weeks and 9 (5-13) weeks in patients with JAK-2 mutation and in patients without JAK-2 mutation, respectively.

Summary / Conclusion:

LU is a common complication associated with HU therapy; its negative impact on quality of life is significant. The ulcers occur more frequently in patients with CVI and JAK-2 mutation; however their prevalence in patients without CVI is not negligible. The role of HU in development of LU is substantial and the discontinuation of HU therapy is required in most patients.

Keywords: Hydroxyurea, Myeloproliferative disorder, Side effects

Abstrakta v časopise Haematologica 2013, Suppl1

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