Positive Flow Cytometry Crossmatches and Donor-Specific Hla Antibodies May Not Be Contraindications to Heart Transplantation

Abstract

Flow cytometry and Luminex-based single HLA antigen assays are sensitive methods to determine the presence of HLA antibodies (Ab), donor specifically directed HLA Abs (DSA) and pre-Tx crossmatch (FCXM) outcomes for potential heart Tx (HTX) recipients (recips). We evaluated the effect of sensitization from pre-Tx blood transfusions (BT) received before HTx on HLA Ab (PRA), DSA, FCXM results and clinical outcomes. Between January 2004 and May 2009, 182 adult patients underwent HTx (171 -1º and 11 -Re-Txs). We reviewed their UNOS status, pre-Tx BT, pregnancies, Flow PRA, pre-Tx recip/donor FCXMs, HLA Abs, specificity and specificity titers, induction therapy (OKT3 or ATG), and patient and graft survivals of the 171 -1 recips. Of the 171 first HTx recips 167 (98%) received BTs before HTx. Pre-Tx PRAs were 0% in 108 (63%); 1-10% in 21 (12%), 11-25% in 15 (9%) and >25% in 27 (16%) patients. There were no differences in pre-Tx BT exposures. One year survivals were 90%, 86%, 100% and 96% respectively for each BT group. All patients were pre-Tx AHG-XM negative. Nine of the 171 patients were pre-Tx FCXM positive (3 with 0% PRA; 1 with 11-25% PRA and 5 with >25% PRA). All 9 were DSA positive, however, only 3 of these 9 recips expired within the first 12 months post-Tx. These three recips were not immunologically different from the remaining 6 DSA positive, FCXM positive recips in regard to PRA, DSA or DSA titer. Therefore, these data suggest that heart Tx recips, with positive pre-Tx FCXMs and DSAs may be successfully transplanted. Some recips with positive FCXMs and DSAs may result in patient/graft loss. We do not yet know how to identify the immune factors relevant to good or bad patient outcomes. Disclosure: All authors have declared no conflicts of interest.Introduction: Although the ISHLT scoring system is the basis of therapeutic decisions for heart transplant acute rejection (AR) it does not always reflect the severity of functional alterations during AR. Myocardial wall motion and deformation analysis, easy to perform by Tissue Doppler (TD) and 2D strain imaging, reveal myocardial dysfunction undetectable or underestimated by simple echocardiography. We compared the lesions detectable in endomyocardial biopsies (EMBs) with functional data provided by TD and 2D strain imaging. Methods: Between 1/2006 -6/2009 all patients underwent left ventricular (LV) wall motion and myocardial deformation analysis by TD and 2D-strain imaging, before EMB. Alterations of TD and 2D-strain parameters were tested for relationships to the morphologic grade of acute rejection. Results: Of 136 cellular ARs detected in the EMBs of 95 patients, 104 (76.5%) were mild (1 R), 28 (20.6%) moderate (2 R) and 4 (2.9%) severe (3 R). Of all patients with 1 R rejection, 26 (25.0%) were slightly symptomatic (fatigue etc.) but only 2 showed LV dysfunction detectable by simple echocardiography. Nevertheless, all 26 symptomatic plus 9 asymptomatic mild ARs (1 R) were accompanied by reduction with ≥ 15% of peak systolic wall motion velocity and strain rate...

Immunosuppression in the sensitized heart transplant recipient

“…Approximately two-third of patients with donor-specific antibodies (DSAs) detected with FCXM or SPA had an AMR-free course following deceased donor renal transplant [12]. A much smaller cohort of nine heart transplant patients who were CDC-negative and FCXM-positive was noted to have a comparable outcome -three of nine died within 1 year [13], suggesting that the findings in the renal transplant population may apply to heart transplant patients. A retrospective review of 565 adult cardiac transplant recipients found that patients with a negative CDC crossmatch but with DSA by Luminex had poor 1-year survival (42%) and that the ability to fix C4d, but not antibody titer or subclass, was strongly associated with poor allograft survival.…”