Long-Term Success of Treatment for Cardiac Transplant AMR May Depend Upon Suppressing Class II Donor Specific Antibodies
1Dept of Medicine, California Pacific Medical Center, San Francisco, CA
2Dept of Medicine, Kaiser Permanente, Santa Clara, CA.
Meeting: 2018 American Transplant Congress
Abstract number: B38
Keywords: Antibodies, Graft failure, Heart transplant patients, Plasmapheresis
Session Information
Session Name: Poster Session B: Heart and VADs: All Topics
Session Type: Poster Session
Date: Sunday, June 3, 2018
Session Time: 6:00pm-7:00pm
Presentation Time: 6:00pm-7:00pm
Location: Hall 4EF
Antibody mediated rejection (AMR) in cardiac transplant (tspt) patients (pts) is primarily mediated by donor specific antibodies (DSAs) and associated with reduced long-term graft survival. Treatment options are poorly understood and standardized.
Methods: We reviewed the records of 56 heart tspt pts referred for immunotherapy, from 1/08-6/17, to treat AMR. Median age of pts was 51 years (yrs) (19-73 yrs old); 34 pts (61%) were male. Pts presented with symptoms of CHF, systolic and/or diastolic dysfunction (syst/diast dysf), and decreased EF. 48 pts (86%) had endomyocardial biopsy c/w AMR, and 53 pts (95%) had circulating DSAs. All pts were DSA and T-cell crossmatch negative at transplant. Median time from transplantation to AMR was bimodal: 2.4 yrs (0.4-5.3 yrs) for 33 pts (59%); 9.6 yrs (6.1-15.9 yrs) for 23 pts (41%).
Treatment: All pts received immunotherapy (IT) protocol: plasma exchange (TPE) QOD (or 3X/week) for 4-6 treatments (txs), followed by IVIG (1 gm/kg/day X 2 days). 47 pts (84%) received high dose IV corticosteroids. Serial DSA measurements were obtained after each pharmacologic intervention. For refractory AMR, 43 pts (77%) received weekly rituximab (2-4 doses), and 26 pts (46%) received twice-weekly bortezomib (4 doses).
Results: 56 pts received 107 courses of TPE (1-5 courses/pt), each followed by post-TPE IVIG. 44 pts (79%) had moderate improvement in allograft function; 37 pts (66%) showed substantial improvement in syst/diast dysf and EF. 30 pts (54%) had significant reduction or elimination of class I and II DSAs, and resolution of AMR with 1 course of IT tx. 26 pts (46%) required a minimum of 2 courses of IT tx for AMR, of which 12 pts (21%) had refractory AMR requiring 3-5 courses of IT tx. The most common DSAs present in refractory AMR included class II DQ2-9, DR4-8, and DR52-53. Pts with refractory AMR received monthly IVIG, and intermittent courses of TPE and bortezomib. Over a mean follow-up of 3.9 yrs (0.3-6.7) from time of AMR, 14/56 (25%) cardiac tspt AMR pts lost their allografts, whereas over a mean follow-up of 5.7 yrs (0.4-10.1), only 5/57 (9%) renal tspt AMR pts lost their allograft (p<0.04); both groups received similar protocols for AMR.
Conclusion: TPE tx, IVIG, rituximab, and bortezomib are useful treatment modalities for cardiac transplant pts with AMR. Suppressing refractory class II DQ and DR DSAs may be critical for durable allograft rescue.
CITATION INFORMATION: Hofmann J., Weisshaar D., Kiprov D. Long-Term Success of Treatment for Cardiac Transplant AMR May Depend Upon Suppressing Class II Donor Specific Antibodies Am J Transplant. 2017;17 (suppl 3).
To cite this abstract in AMA style:
Hofmann J, Weisshaar D, Kiprov D. Long-Term Success of Treatment for Cardiac Transplant AMR May Depend Upon Suppressing Class II Donor Specific Antibodies [abstract]. https://atcmeetingabstracts.com/abstract/long-term-success-of-treatment-for-cardiac-transplant-amr-may-depend-upon-suppressing-class-ii-donor-specific-antibodies/. Accessed November 21, 2024.« Back to 2018 American Transplant Congress