Hemolytic uremic syndrome as a complication of gemcitabine treatment: report of six cases and review of the literature

Hemolytic uremic syndrome is a rare condition during gemcitabine therapy. We report six new cases of hemolytic uremic syndrome related to gemcitabine, three issued from a retrospective study of 136 consecutive patients treated with gemcitabine for which a systematic screening of this side effect has been performed and 29 cases with clinical data available identified in the literature in order to better characterised frequency and clinical presentation of this side effect. In our series, frequency of HUS is 2.2% and is higher than this previously reported (0.015%) or estimated with the data of clinical trials analysed (0.072 %). For 35 cases with clinical data available, the patients were always treated for a local advanced and/or metastatic disease. For our cases and for literature cases, at the time of diagnosis of hemolytic uremic syndrome, mean number of doses received (mean+/-standard deviation. Minimum/maximum)) (personal cases: 26.5+/-6.6. 16/36, literature cases: 21+/-11. 8/54), cumulative dose received (g/m2) (personal cases : 24.5+/-6.3. 16/31.6, literature cases: 21.7+/-12.4. 2.4/54) and duration of treatment (months) (personal cases: 8.2+/-1.9. 5.6/11, literature cases: 8.5+/-4.0. 3/18) are very closed and high individual variations observed for these factors are not consistent with a time and/or dose dependant toxicity. New-onset hypertension or exacerbation of underlying hypertension is the most common clinical manifestation, with mild anemia; thrombocytopenia is inconstant. The degree of severity of renal failure is highly variable. The existence of subacute clinical form with progressive worsening of the symptoms and biological form at the time of diagnosis suggest the interest of a systematic clinical and biological screening of this side effect, before each injection of gemcitabine. Early prognosis is linked to the evolution of hemolytic uremic syndrome and after hemolytic uremic syndrome healing, cancer progression. Treatment include gemcitabine discontinuation, antihypertensive drugs and if necessary fresh frozen plasma. Systematic clinical and biological screening of hemolytic uremic syndrome during gemcitabine therapy should allow to better know this complication, to recognize and treat it earlier with a potential positive impact for patients.