Patients

Patients who were included in the study met the following criteria: evidence of microangiopathic hemolytic anemia, including schistocytes on peripheral blood smear, thrombocytopenia (< 150 G/L), increased lactate dehydrogenase levels (> Upper limit of normal), low serum haptoglobin < normal and/or renal TMA proven by kidney biopsy. Only one of these criteria could be missing. The diagnosis was retained by the team which took charge of the patient with discontinuation of treatment with gemcitabine. Patients with a TMA attributed to an uncontrolled cancer, as defined by erythroblastosis, metastatic bone marrow infiltration, impaired general condition, and low-cumulative dose gemcitabine (< 5000 mg/m²) were excluded [11–13]. Patients treated with another chemotherapy concomitantly with gemcitabine were excluded. Patients with a positive shiga-toxin or ADAMTS13 activity < 10% were also excluded.

Patients were treated with eculizumab according to the regimen previously reported [14]. It consisted generally in 4 weekly infusions 900 mg IV. In responders, a maintenance treatment was started every 2 weeks at week 5, 1200 mg. The number of infusions was left at the discretion of the practitioner.

Hematological and renal responses were evaluated, based on data that were systematically extracted from the clinical record. Hematological response was defined by normalization of hematologic values (a normal platelet count and lactate dehydrogenase level) as previously described [14]. The transfusion needs were calculated over a period going from the admission of the patient to the end of the treatment with eculizumab. Renal response was considered as complete if serum creatinine level returned to baseline and as partial if serum creatinine level decreased by 15% or more.

Acute renal injury (AKI) was assessed according to KDIGO classification 2012. To make possible the comparison between the two groups, we chose to use the CKD-EPI formula for the estimation of the eGFR (glomerular filtration rate), despite we are aware of the limits in the context of AKI. The eGFR of dialysed patients was estimated at 0 ml/min.

We compared patients with G-TMA treated with eculizumab with a control cohort of patients who did not receive eculizumab treatment. Using the French national network, 14 patients were selected using criteria of G-TMA described above without eculizumab therapy. Patients were matched by age and baseline renal function.

This study was approved by the institutional review board of Rouen University Hospital in accordance with the Declaration of Helsinki, and the French Data Protection Authority (“Commission Nationale Informatique et Libertés,” CNIL, authorization n°911,539, and “Comité consultatif sur le traitement de l’information en matière de recherche dans le domaine de la santé,” CCTIRS, authorization n°11.537, Paris, France).