Erythrocyte Macrocytosis is A Rather Common, Apparently Uneventful Yet Unexplained Finding in Gist Imatinib (I) Chronic Therapy.

9045 Background: Anemia is an adverse effect related to I therapy both in chronic myeloid leukaemia and in GISTs. Since bone marrow function can be assumed to be unimpaired in GISTs, other anemia causes should be taken in account: 1) gastrointestinal loss (both iron and blood), 2) nutritional deficit (vitamin B12 and folate) and 3) drug assumption. Since we observed an increase in erythrocyte mean corpuscular volume (MCV) during I therapy, we investigated incidence and possible causes of this phenomenon in our prospectively collected series. Methods: Since January 2002 35 consecutive patients affected by advanced GISTs were treated with I starting at 400 mg once a day to be increased to twice a day in case of progressive disease. Laboratory tests were collected before treatment and regularly thereafter with a monthly basis. Only patients with a six month or longer follow-up were included into the analysis. Results: Before therapy hemoglobin (Hb) was lower than 120 g/l in 7/33 (21%) pts (a G0 toxicity according to Common Toxicity Criteria 3.0). Two pts had beta-thalassemia trait (MCV lower than 70 fl). White-cell and platelet counts were in the normal range. During I therapy we observed in 1/33 (3%) pts a G1 anemia, but 5 pts experienced a 20 g/l decrease in Hb (G0). Most notable in 14/33 (42%) an increased MCV was observed always beyond upper normal value (98 fl). Erythrocyte macrocytosis could not be explained on either vitamin deficit base (vitamin B12 and folate within the normal value) or GIST site of origin (gastric vs. enteric). Conclusions: Although anemia requiring I interruption is a rare event, a progressive MCV increase seems to be a rather common side effect of this chronic therapy. To date, the functional level at which imatinib exerts its antiproliferative effect on normal hematopoietic stem cell has not been clarified (Bortolovic K, Blood 2004;103:523). Therefore, we suggest to monitor this “asymptomatic” toxicity adding vitamin supplements without stopping imatinib. No significant financial relationships to disclose.