title: Transplantation of high panel-reactive antibody left ventricular assist device patients without crossmatch using on-bypass pheresis and alemtuzumab.
abstract: BACKGROUND
  Highly sensitized (HS) left ventricular assist device (LVAD) patients with high panel-reactive antibody (PRA) levels present a challenge. Alemtuzumab, a potent depleting agent for T and B lymphocytes (months to years), and plasmapheresis, offer an opportunity for heart transplantation to these patients who might die of VAD complications on the transplant waiting list. This study compared rates of acute rejection and survival of a HS LVAD cohort with a contemporaneous control group after heart transplant.
  
  
  METHODS
  Clinical courses of 31 consecutive patients who underwent transplantation between January 2006 and January 2011 were reviewed. Eight patients with a T or B PRA of 70 or more (HS+) received non-crossmatched, ABO-compatible hearts using intraoperative plasmapheresis and alemtuzumab induction. Controls (HS-) received basiliximab induction. Acute rejection was defined as International Society for Heart and Lung Transplantation grades 2R or higher, or antibody-mediated rejection.
  
  
  RESULTS
  The difference in survival between HS+ and HS- groups at 1 year (100% vs 94%) or at a mean follow-up of 2.3 and 2.4 years (75% vs 70%) was not significant. Retrospective lymphocytotoxic crossmatches were positive in 7 of 8 HS+ patients (6 T+ and B+, 1 B+) vs none in the HS- group (p < 0.001). There was a trend toward increased risk of cellular rejection per 100 patient-days beyond 1 year in the HS+ group (p = 0.07). Risk of humoral rejection was significantly increased in the HS+ group (38% vs 4%; p = 0.04).
  
  
  CONCLUSIONS
  Heart transplantation with plasmapheresis and alemtuzumab in HS LVAD patients, most with a positive crossmatch, does not compromise midterm survival. The expected higher rates of rejection, especially beyond the first postoperative year, demand adjustments in surveillance strategies and immunosuppressive management.
authors.affiliation: Department of Surgery, University of Texas Medical Branch, Galveston, TX, USA. slick@utmb.edu
authors.forename: Scott D
authors.initials: SD
authors.lastname: Lick
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Beckles
authors.forename: Giovanni
authors.initials: G
authors.lastname: Piovesana
authors.forename: Smita
authors.initials: S
authors.lastname: Vaidya
authors.forename: Alexander
authors.initials: A
authors.lastname: Indrikovs
authors.forename: N Alexander
authors.initials: NA
authors.lastname: Barbagelata
authors.forename: Vincent
authors.initials: V
authors.lastname: Valentine
mesh_terms: D000328:Adult; D000074323:Alemtuzumab; D000906:Antibodies / Q000276:immunology*; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000627:therapeutic use*; D000912:Antibodies, Neoplasm / Q000008:administration & dosage / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D002315:Cardiopulmonary Bypass; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000453:epidemiology / Q000276:immunology / Q000517:prevention & control*; D006085:Graft Survival / Q000276:immunology; D016027:Heart Transplantation / Q000276:immunology* / Q000379:methods; D006353:Heart-Assist Devices; D006650:Histocompatibility Testing; D006801:Humans; D015994:Incidence; D007430:Intraoperative Care; D008297:Male; D008875:Middle Aged; D010956:Plasmapheresis / Q000379:methods*; D012189:Retrospective Studies; D012307:Risk Factors; D015996:Survival Rate / Q000639:trends; D013781:Texas / Q000453:epidemiology; D055815:Young Adult
chemical_list: D000906:Antibodies; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D000970:Antineoplastic Agents; D000074323:Alemtuzumab