Two Hundred Living Donor Kidney Transplantations Under Alemtuzumab Induction and Tacrolimus Monotherapy: 3-Year Follow-Up

Abstract

Alemtuzumab has been used in off-label studies of solid organ transplantation. We extend our report of the first 200 consecutive living donor solitary kidney transplantations under alemtuzumab pretreatment with tacrolimus monotherapy and subsequent spaced weaning to 3 years of follow-up. We focused especially on the causes of recipient death and graft loss, and the characteristics of rejection. The actuarial 1-, 2-and 3-year patient and graft survivals were 99.0% and 98.0%, 96.4% and 90.8% and 93.3% and 86.3%, respectively. The cumulative incidence of acute cellular rejection (ACR) at the following months was 2% ≤6, 9.0% ≤12, 16.5% ≤18, 19.5% ≤24, 23.5% ≤30, 24.0% ≤36 and 25% ≤42. The mean serum creatinine (mg/dL) and glomerular filtration rate (mL/min/1.73 m 2 ) at 1 and 3 years were 1.4 ± 0.6 and 58.7 ± 21.6 and 1.5 ± 0.7 and 54.9 ± 20.9, respectively. Fifty (25%) recipients had a total of 89 episodes of ACR. About 88.7% of ACR episodes were Banff 1, and of those, 82% were steroid-sensitive. Nine (4.5%) recipients had antibodymediated rejection (AMR). About 76.5% were weaned but only 46% are currently on spaced dose (qod or less) tacrolimus monotherapy, and 94.4% remained steroidfree from the time of transplantation. Infectious complications were uncommon. This experience suggests the 3-year efficacy of this approach.

Adverse Outcomes of Tacrolimus Withdrawal in Immune–Quiescent Kidney Transplant Recipients

“…Some of these previous trials targeted patients who are apparently low risk as defined by relatively limited conventional clinical criteria, including living donor source, human leukocyte antigen (HLA) matching (particularly at class II loci), and lack of HLA sensitization. 11,[14][15][16] Although these previously performed studies confirmed high rates of AR after CNI withdrawal, despite the selection criteria, the studies also suggested that a subset of these clinically low-risk transplant recipients can be safely withdrawn from CNI without negative consequences to the patient or graft. If it were possible to prospectively identify the subset of individuals capable of tolerating CNI withdrawal using objective and reproducible histologic and immunologic criteria, it would permit targeting CNI withdrawal to only those most likely to benefit from the intervention.…”

“…4,5 The adverse effects of CNIs, including drug-induced renal parenchymal fibrosis, allograft dysfunction, and cardiovascular morbidity among others, have raised concerns that CNIs may contribute to poor long-term outcomes and have resulted in a desire to develop immunosuppression protocols that avoid, withdraw, or minimize their use. [6][7][8] Published studies of CNI withdrawal in unselected cohorts of kidney transplant recipients taking standard three-drug immunosuppression indicate that elimination of CNI increases the risk of AR, 6,7,[9][10][11][12][13][14][15][16] which can potentially precipitate a fibrogenic process that contributes to graft failure. Some of these previous trials targeted patients who are apparently low risk as defined by relatively limited conventional clinical criteria, including living donor source, human leukocyte antigen (HLA) matching (particularly at class II loci), and lack of HLA sensitization.…”

Prophylaxis of invasive mycoses in solid organ transplantation

“…However, the use of OKT3 has declined substantially in the current immunosuppressive era, whereas the use of newer antilymphocyte agents, including alemtuzumab, a monoclonal antibody directed against CD52 expressed on B-and T-lymphocytes, is on the rise [14]. It appears that patients who receive these lymphocyte-depleting agents for the treatment of allograft rejection are signifi cantly more likely to develop an opportunistic infection compared with patients who receive them for induction therapy [15,16]. In our lung transplantation program, mold-active antifungal prophylaxis is used when alemtuzumab is administered to treat steroid-refractory rejection (BD Alexander, MD, MHS, personal communication, September 2009).…”

Modern Immunosuppressive Therapy in Kidney Transplantation

“…As an induction agent, it produces a profound depletion of lymphocytes and is associated with more frequent and severe adverse effects, such as neutropenia, thrombocytopenia, thyroid disease, autoimmune hemolytic anemia and other autoimmune diseases [16][17][18]. It is hoped that alemtuzumab induction could permit patients to be maintained on unconventional strategy with less intensive immunosuppression, such as tacrolimus monotherapy [19], steroid-free [20], steroid and calcineurin inhibitor (CNI) free regimen [21].…”