Overview
Thrombotic microangiopathies (TMA) are defined as a triad combining mechanical hemolytic anemia, peripheral thrombocytopenia and ischemic organ damage.
Mitomycin C is an alkylating agent used as chemotherapy in adenocarcinomas of the breast, lung, pancreas, rectum and anal carcinoma. Mitomycin-C-induced TMA (m-TMA) is a potentially serious complication of chemotherapy: its estimated incidence ranges from 4 to 15% and its mortality exceeds 70%, with an estimated median survival of 2 months. This can also be responsible for kidney failure, sometimes requiring hemodialysis. The time to onset of m-TMA varies from one week to 15 months after the last infusion and is believed to depend on the cumulative dose of mitomycin C.
Eculizumab is a monoclonal antibody that binds to complement protein C5, blocking activation of the terminal complement pathway and formation of the membrane attack complex. This therapy has significantly changed the prognosis of patients with atypical hemolytic uremic syndrome (HUS), a disease in which complement activation plays a central role in TMA. Recently, a retrospective study suggested efficacy of eculizumab in TMA induced by gemcitabine, another chemotherapy, with normalization of platelets and LDH in 83% of patients, and partial or complete renal recovery in 67% and 17% of patients. These results provided arguments in favor of a potential benefit of complement-targeted therapies in TMA induced by certain chemotherapies. However, data on eculizumab in m-TMA remain extremely limited to date.
The objective of this study is to describe the clinical, biological and histological presentation of patients with m-TMA and their evolution after treatment with or without eculizumab.
Eligibility
Inclusion Criteria:
- Adult patients (>=18 years)
- Having received treatment with mitomycin C (regardless of the method of administration and indication) between 01/01/1990 and 12/31/2023
- and having developed a picture of thrombotic microangiopathy attributed to mitomycin
C:
- biological: defined as: thrombocytopenia <150G/L and mechanical hemolytic anemia (at least 3 out of 4 criteria: hemoglobin < 12g/dL, presence of schistocytes in blood smear, LDH > 1N, collapsed haptoglobin (< lower limit of the limit of laboratory normal)
- or renal: pathological diagnosis of thrombotic microangiopathy on renal biopsy
- having received or not treatment for the episode of microangiopathy, including or not
complement inhibitors (Eculizumab).
- Subject not opposing, after information, the reuse of their data for the purposes of this research
Exclusion Criteria:
- Subject having expressed opposition to participating in the study
- Test for positive Shiga toxin
- ADAMST13 activity <10%
- Thrombotic microangiopathy attributed to metastatic cancer (infiltration of bone marrow or circulating erythroblasts)
- Impossibility of providing the subject with informed information (difficulties in understanding the subject, etc.)
- Subject under judicial protection
- Subject under guardianship or curatorship