Publication Date:
2020-11-05
Description:
Carfilzomib is a critical chemotherapy medication used to treat patients with relapsed or refractory multiple myeloma. Unfortunately, drug-induced atypical hemolytic uremic syndrome (aHUS) has been established as a devastating and unpredictable side-effect of carfilzomib. Loss-of-function mutations in alternative complement pathway regulatory genes, such as complement factor H (CFH) and its related proteins (CFHRs), are the most frequently identified genetic abnormalities seen with aHUS. In our recently published work, two of three patients treated at the University of Rochester Medical Center for carfilzomib-induced aHUS were found to harbor the heterozygousCFHR3-CFHR1deletion, a genetic variant that is generally considered benign, implicating it in development of disease. We sought to further characterize the relationship between the heterozygousCFHR3-CFHR1deletion and development of carfilzomib-induced aHUS by conducting a case-control study. We screened banked frozen peripheral blood mononuclear cell (PBMC) samples from subjects treated with carfilzomib-based regimens at Washington University. Criteria for aHUS case selection were defined as all of the following: elevated LDH, decreased haptoglobin or elevated total bilirubin, evidence of schistocytes on peripheral blood smear, de novo anemia and thrombocytopenia, acute kidney injury, no evidence of infectious diarrhea (if tested), and active carfilzomib treatment at the time of disease. To ensure that controls had adequate exposure to carfilzomib, controls were selected from subjects who received ≥20 treatment cycles. Additional control selection criteria included: age 〉40 years, no evidence of hemolysis (LDH 100 x 109/L), and no chronic or acute kidney disease (creatinine
Print ISSN:
0006-4971
Electronic ISSN:
1528-0020
Topics:
Biology
,
Medicine
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