High-dose cytosine arabinoside-induced cutaneous reactions

High-dose cytosine arabinoside (HDAC) is being used increasingly to treat haematological malignancies. The therapy is associated with various non-haematological negative side-effects, frequently involving the skin.

Our aim was to evaluate the actual occurrence of adverse skin reactions to HDAC over the 10-year period from 1989 to 1999.

One hundred and seventy-two subjects, 118 with acute myelogenous leukaemia and 54 with acute lymphoblastic leukaemia, between 16 and 71 years of age were treated with 226 post-remission consolidation regimens with HDAC (54 subjects underwent two cycles of treatment). Treatment was combined with standard doses of other cytotoxic drugs. A prospective study of the skin changes was then performed.

The overall incidence of cutaneous reactions was almost 53%, with rashes occurring in 72.7% and 40.6% of subjects who received total doses of 30 and 24 g/m2, respectively. In the group of subjects who received a second cycle of treatment not all of those who experienced exanthema after the first cycle (44.4%) experienced this reaction after the second cycle (only 33.3%). The most commonly observed reactions were morbilliform eruptions on the trunk and extremities and acral erythema, although severe reactions with swelling and generalized urticaria developed in some cases.

HDAC-induced cutaneous reactions in 53% of subjects. The skin changes were found to be dose related and most cleared spontaneously without requiring treatment. A clinical grading of cutaneous toxicity has been proposed to allow better comparison of cutaneous adverse effects in different reports.