304: Alemtuzumab Induction Facilitates Steroid-Free Immunosuppression in Human Cardiac Transplantation: Two Year Outcomes

Abstract

Purpose: Lymphocytic bronchiolitis (LB) is the strongest risk factor for subsequent allograft loss due to obliterative bronchiolitis (OB), however it is poorly assessed by transbronchial biopsy (TBBx) because of sampling error, interpretation error, and the presence of non-alloreactive airway inflammation. We hypothesised that flow cytometric interrogation of small airway brushings -the 'B score' may be a better tool. Methods and Materials: 43 small airway brushings (2-3 cm from pleural surface, 2mm OD Olympus cytology brush) were obtained under radiologic guidance prior to TBBx from 28 patients (16 female, median age 41 (23-64), 14 CF, 7 COPD), and labelled with conjugated antibodies to epithelial cell antigen, CD3 and CD103 (an integrin which binds to the epithelial specific ligand e-cadherin) before undergoing flow cytometry. The B score was defined as the % of total nucleated cells which were CD3 ϩ CD103 ϩ . Results: No adverse events occurred. The mean B score was 0.71% (95% CI 0.47-0.96) and was higher in patients with A1 rejection (1.39% vs A0 0.53%, pϽ0.001), but was unrelated to B grade (B0 1.1%, B1 0.6%, B2 0.94%, Bx 0.78%, pϭNS) or A2 (nϭ2) rejection. Total CD3 ϩ cell counts were higher in B1/2 (2.16%) or Bx (2.18%) vs B0 biopsies (1.14%, pϭ0.01), however most cells were CD103 Ϫ suggesting that they were not alloreactive. Viral (Parainfluenza 2, CMV 1, Influenza B 1) or invasive fungal (Aspergillus 3, Acremonium 1) infection was associated with marked infiltration with CD3 ϩ CD103 Ϫ cells (no infection 0.46%, bacterial 0.39%, viral 2.08% (pϽ0.01), fungal 2.06% (pϽ0.01)). The B score was above the upper 95% CI in 9 (21%) cases (3 prior to or at the onset of refractory OB; 2 with unexplained (TBBx negative, infection negative) steroid responsive fall in FEV1; 2 stable OB; 1 Parainfluenza; 1 gastrooesophageal reflux). Conclusions: Flow cytometric interrogation of small airway brushings can accurately discriminate between infective and alloreactive LB. The B score is simple to obtain, low risk and may be a valuable addition to current lung allograft assessment.

Alemtuzumab Induction Versus Conventional Immunosuppression in Heart Transplant Recipients

“…Increases in freedom from rejection in the alemtuzumab group were maintained for up to 5 years (73% vs 56% with controls, P ¼ .0002). [13][14][15][16] Although we did not observe a reduction in grade !2 rejection, this discrepancy can be explained by the inclusion of AMR in our composite end point as prior studies did not either specify or report AMR episodes. [11][12][13] When ACR was analyzed independently, alemtuzumab was associated with lower rates of both grade !2 ACR and any grade of ACR despite lower immunosuppression therapy, a difference that is consistent with prior studies.…”

“…Although alemtuzumab induction is fairly common in kidney transplantation, only limited experience in OHT has been described, with follow-up outcomes reported at up to 5 years. [6][7][8][9][10][11][12][13][14][15][16] In these analyses, alemtuzumab reduced the rates of rejection and extended time to rejection but had no impact on survival. Additionally, in the largest study to date, renal function at 12 months was significantly worse among patients who received alemtuzumab, despite lower tacrolimus concentrations (49.8 + 17 vs 55.2 + 15 mL/min with standard immunosuppression, P ¼ .04).…”

Alemtuzumab for Cytolytic Induction of Immunosuppression in Heart Transplant Recipients

“…Investigators from the University of Pittsburgh additionally reported 2-, 3-, and 4-year outcomes from their retrospective review. [21][22][23] The same study and control patients reviewed at 1 year were included in the 2year review. 21 Overall survival remained no different between groups (alemtuzumab 86% vs control 90%, P = .30), and alemtuzumab patients continued to have greater freedom from significant rejection (2R or greater) (81% vs 50%, P < .001).…”

“…One retrospective cohort, 1 case series, 1 case-control series, and 1 open-label trial were identified and are detailed here. [17][18][19][20][21][22]…”

Immunosuppressive therapies after heart transplantation — The balance between under- and over-immunosuppression

“…Early results from a small retrospective study [41] and a small randomized trial [42] were promising, with similar survival, but fewer rejections, in HTs with alemtuzumab vs. HTs without alemtuzumab. These initial results were then confirmed in a larger case control series by Teuteberg et al [43][44][45][46][47]. Further studies on alemtuzumab are, however, needed before its routine use can be considered [48].…”