Resolution of renal allograft-associated post-transplant lymphoproliferative disorder with the introduction of sirolimus

1Division of Nephrology and 3Department of Laboratory Medicine and Pathobiology, St. Michael's Hospital and 2Department of Pathology, University Health Network University of Toronto, Ontario, Canada Lymphoid neoplasia has remained a serious complication following solid organ transplantation. Recent data suggest an 11.8-fold higher risk of lymphoma compared with the general population over a 10 year period [1]. Although the risk is greatest within the first year post-transplant, the incidence remains high throughout the entire post-transplant period. Risk factors include unrestrained proliferation of Epstein–Barr virus (EBV) and the overall immunosuppression burden [2,3]. Post-transplant lymphoproliferative disorder (PTLD) may also occur within the allograft and may be mistaken for acute rejection. The mTOR inhibitor sirolimus is currently under investigation as an anti-tumour agent, and its use as an immunosuppressive agent in solid organ transplants has been associated with a lower risk of post-transplant malignancies, including PTLD [4,5]. A 32-year-old patient with end-stage renal disease secondary to vesicoureteric reflux received a one haplotype-matched kidney from his sister. He had been on thrice weekly haemodialysis for 2.5 years. Both donor and recipient were cytomegalovirus IgG negative, but EBV IgG positive. At the time of transplant, a donor kidney biopsy was performed as per standard practice at our institution. The biopsy revealed normal renal histology. The recipient had a panel-reactive antibody of 0% and was a one-haplotype match with his donor. At the time of transplant, he was enrolled into a prospective three-arm clinical trial comparing steroid avoidance, rapid steroid tapering and standard steroid dosing. He had been randomized to an immunosuppressive regimen of basilixmab 20 mg on day 0 and day 4 post-transplant, solumedrol 1 mg/kg pre-transplant and 1 mg/kg bid for 48 h post-transplant, followed by a rapid oral prednisone taper with discontinuation of prednisone by day 7, EC-MPS 720 mg bid and cyclosporin microemulsion, dosed to keep 2 h post-dose (C2) levels between 1200 and 1600 ng/ml. There were no immediate or early surgical complications and the allograft functioned well with an immediate decline in serum creatinine. However, by day 5 post-transplant, the creatinine had stabilized at 200–240 µmol/l with a C2 cyclosporin level of 1430 ng/ml. At that time, the white blood cell count was 6.2 × 109/l and the lymphocytes were normal at 2.2 × 109/l. The patient remained asymptomatic and afebrile. Renal ultrasound and Dopplers were normal, and there was no response to reduction in cyclosporin dose. A renal biopsy was performed on day 7 post-transplant (Figure 1). There was no tubulitis, vasculitis or glomerulitis. Despite intensive screening of all biopsy sections, no evidence for either cellular- or antibody-mediated rejection could be found. However, there was a dense intense infiltrate of mononuclear cells occupying approximately one-quarter of the renal cortex. The cells were monotonous and medium size, fairly atypical with a moderate degree of mitotic activity. Although some T cells were present, the predominant cells were B lymphocytes (CD20+) demonstrating both κ and λ light chain positivity, but negative for EBV virus by in situ hybridization.

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