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Impact of carfilzomib-based desensitization on heart transplantation of sensitized candidates
- Source :
- The Journal of Heart and Lung Transplantation. 40:595-603
- Publication Year :
- 2021
- Publisher :
- Elsevier BV, 2021.
-
Abstract
- Background Allosensitization in heart transplant candidates is associated with longer transplant wait times and post-transplant complications. We summarize our experience with desensitization using carfilzomib , an irreversible proteasome inhibitor that causes plasma cell apoptosis . Methods One cycle of desensitization consisted of plasmapheresis and carfilzomib 20 mg/m 2 on days 1, 2, 8, 9, 15, and 16 with intravenous immune globulin 2 g/kg after carfilzomib on day 16. Patients underwent repeat cycles as indicated. We compare calculated panel-reactive antibody (cPRA) for neat combined Class I and II IgG and C1q pre- and post-treatment using a cutoff for cPRA entry of ≥ 4000 and 500 MFI, respectively. Results From June 2013 to October 2019, 9 patients underwent 20 cycles of carfilzomib-based desensitization. Each cycle resulted in an average cPRA decrease of 24% (95% CI: 6-42) for IgG and 36% (95% CI: 17-55) for C1q. From treatment start to finish, mean cPRA fell from 76% to 40% (p = 0.01) for IgG and 56% to 4% (p = 0.017) for C1q. Six of 9 patients have been transplanted with 5 of the transplanted hearts crossing preoperative donor-specific antibodies. During a median follow-up of 35.1 months, all transplanted patients have survived with only 1 occurrence of treated rejection. Side effects of desensitization included acute kidney injury (67%) and thrombocytopenia (33%) with all episodes self-resolving. Conclusions A carfilzomib-based desensitization strategy among heart transplant candidates reduces the level of HLA antibodies and complement binding , facilitates successful transplantation, and is associated with excellent outcomes at 3 years.
- Subjects :
- Adult
Graft Rejection
Male
Pulmonary and Respiratory Medicine
medicine.medical_specialty
medicine.medical_treatment
Plasma Cells
Urology
030204 cardiovascular system & hematology
030230 surgery
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
medicine
Humans
Aged
Retrospective Studies
Desensitization (medicine)
Heart transplantation
Transplantation
biology
business.industry
Acute kidney injury
Middle Aged
medicine.disease
Carfilzomib
Tissue Donors
chemistry
Desensitization, Immunologic
biology.protein
Proteasome inhibitor
Heart Transplantation
Female
Surgery
Plasmapheresis
Antibody
Cardiology and Cardiovascular Medicine
business
Oligopeptides
Follow-Up Studies
medicine.drug
Subjects
Details
- ISSN :
- 10532498
- Volume :
- 40
- Database :
- OpenAIRE
- Journal :
- The Journal of Heart and Lung Transplantation
- Accession number :
- edsair.doi.dedup.....942caac031e8d5d1fbd40c1118e2e313