Campath-1H Induction Plus Rapamycin Monotherapy for Renal Transplantation: Results of a Pilot Study

Abstract

Campath-1H, an anti-CD52 monoclonal antibody, was used as induction therapy (40 mg i.v. total dose) in 29 primary human renal transplants, and the patients were maintained on rapamycin monotherapy (levels 8-15 ng/mL) post-transplant. Campath-1H profoundly depletes lymphocytes long-term and more transiently depletes B cells and monocytes. All patients are alive and well at 3-29 months of follow up. One graft was lost because of rejection. There have been no systemic infections and no malignancies. Eight of 29 patients have experienced rejection, which was successfully treated in seven of eight patients. Five of these patients had pathological evidence of a humoral component of their rejection. Seven of the 29 patients were converted to standard triple therapy on account of rejection. Rapamycin was generally well tolerated in that there were no significant wound-healing problems; two lymphoceles required surgical drainage; and most patients were treated with a lipid-lowering agent. Flow crossmatch testing post-transplant revealed evidence of alloantibody in two patients tested with previous combined cellular and humoral rejection. Biopsies have shown no chronic allograft nephropathy to date. In view of the relatively high incidence of early humoral rejection, we plan to modify the immunosuppressive regimen in subsequent pilot studies. This clinical trial provides insight into the use of Campath-1H induction in combination with rapamycin maintenance monotherapy.

Homeostatic proliferation is a barrier to transplantation tolerance

“…Those data and the present study have important implications in clinical settings. Lymphodepletion is increasingly used as part of newer strategies in solid organ transplantation 5,6 . The occurrence of homeostatic proliferation during lymphoid reconstitution, an event that may be especially relevant in the setting of age-related thymic involution 28 or protocols that employ thymic irradiation, may present a barrier to the establishment of transplantation tolerance, and may also be relevant to selftolerance and autoimmunity.…”

“…Studies demonstrating the importance of alloreactive T-cell deletion during tolerance induction have promoted use of peritransplant T-cell-depleting therapies in clinical trials [3][4][5][6] . But potentially complicating wide-scale, nonspecific T-cell depletion is the finding that extensive T-cell proliferation can occur under conditions of lymphopenia.…”

Terapia de indução com alentuzumabe em receptores de transplante renal

“…27 Prospective studies have also compared the use of induction therapies with thymoglobulin or alemtuzumab in renal transplant recipients receiving TAC, TAC and MMF, or SRL. 20,21,28 Acute rejection incidences were 18%, 23%, and 28%, respectively. Despite the high proportion of organs from extended-criteria donors and acute rejection incidence, patients receiving alemtuzumab achieved renal function on average 8.9 mL/min higher than that observed in patients receiving thymoglobulin (61.6 vs. 52.7 mL/ min).…”

“…10 Thymoglobulin (Thymoglobuline ® ) is a immunosuppressive agent composed of polyclonal antibodies directed against a When combined with sirolimus (SRL), the incidence of acute rejection episodes was 27.6%, and some of those episodes had a humoral component, requiring specific treatment. 20 The use of alemtuzumab and maintenance of immunosuppression with calcineurin inhibitors and mycophenolate mofetil (MMF), with no corticosteroid, has resulted in reducing the incidence of acute rejection to 9.1%. 21 This was probably due to the fact that memory T cells, more resistant to depletion and to the action of corticosteroids and SRL, are sensitive to calcineurin inhibitors, particularly tacrolimus (TAC).…”

The response of intestinal stem cells and epithelium after alemtuzumab administration

“…The use of alemtuzumab has changed the spectrum of infections in transplant patients, and it does not render patients more susceptible to viral or bacterial infections compared to conventional triple immunosuppression. 13 Infections still remain a significant cause of morbidity. 14,15 Recently, our results revealed the alteration of tight junctions and the disruption of intestinal barrier function in intestinal transplantation with the use of alemtuzumab.…”