Regression of post-transplant Kaposi sarcoma after discontinuing cyclosporin and giving mycophenolate mofetil instead

Magdi M. Hussein, Jacob M. Mooij and Haysam M. Roujouleh

Department of Nephrology and Dialysis, Al Hada Armed Forces Hospital, Taif, Saudi-Arabia

Sir,

There is an increased incidence of Kaposi sarcoma after transplantation with the highest number being reported in transplant patients from the area of Saudi-Arabia [1]. The disease has recently been linked to human herpes virus 8 infection [2]. The latency-associated nuclear antigen expressed in infected cells mainly during viral latency might, by its inhibition of the tumour suppression protein p53, contribute to the oncogenesis in Kaposi sarcoma [3]. Other risk factors include the use of cyclosporin and polyclonal antilymphocyte sera [4]. Besides its immunosuppressive action, a direct cancer promoting effect of cyclosporin by a cell-autonomous mechanism has been established [5]. Reduction of the immunosuppression, in particular cyclosporin, leads to regression or disappearance of the tumour in 17% patients with mucocutaneous involvement and 16% with visceral involvement [6]. However, in these cases there is a substantial risk of rejection of the transplanted organ due to the reduced immunosuppression.

So far, there are few, conflicting data concerning the response of the tumour to newer immunosuppressive strategies, such as mycophenolate mophetil (MMF). In one case Kaposi sarcoma regressed completely after discontinuation of cyclosporin, while the patient remained on MMF and prednisone therapy with stable renal function [7]. In a second case, Kaposi sarcoma developed during treatment with both cyclosporin and MMF, and later tacrolimus and MMF [8]. Eberhard et al. report an incidence of 0.8% of patients developing Kaposi sarcoma while on MMF treatment versus 0.1% in patients without MMF [9]. Schrama et al. describe a patient who developed Kaposi sarcoma 18 months after changing from cyclosporin to MMF [10].

Case.

We report here on a 52-year-old female patient, who developed Kaposi sarcoma after transplantation, and in whom the lesions disappeared after discontinuing cyclosporin and azathioprine and giving MMF instead, while the transplant function remained stable.

This patient, with end-stage renal disease of uncertain aetiology, received in our hospital a living related renal transplant in July 1997. She was positive for hepatitis B-surface antigen and for hepatitis C-antibodies, but hepatitis C-RNA was negative. HIV-test was also negative. Immunosuppression consisted of prednisone, cyclosporin and azathioprine. She did not receive polyclonal or monoclonal anti-lymphocyte antibodies. Her basal serum creatinine level after transplantation was around 260 µmol/l.

In May 1999, 22 months years after transplantation, she developed multiple dark blue lesions on the skin of arms and legs, which were histologically confirmed as Kaposi sarcoma. The chest X-ray was normal and there were no signs of internal organ involvement.

Cyclosporin and azathioprine were both discontinued completely, and instead of this, MMF was given in a dosage of 2 g per day. The steroids were continued in a dosage of 10 mg prednisone per day.

Within 2 months after discontinuing cyclosporin and azathioprine, the Kaposi lesions had almost disappeared and this remained so during a follow-up of 6 months. The transplant function remained stable with a serum creatinine around 270 µmol/l, with the patient remaining on MMF and prednisone.

Comment.

The case history confirms the importance of discontinuation of cyclosporin in the treatment of post-transplant Kaposi sarcoma. In addition, it suggests that MMF, while maintaining transplant function in the absence of cyclosporin, was apparently not interfering with the regression of the tumour.

References

  1. Qunibi WY, Barri Y, Alfurayh O, Almeshari K, Khan B, Taher S, Sheth K. Kaposi's sarcoma in renal transplant recipients: A report on 26 cases from a single institution. Transplant Proc1993; 25: 1402–1405[ISI][Medline]
  2. Sitas F, Carrara H, Beral V et al. Antibodies against Herpesvirus 8 in black South African patients with cancer. New Engl J Med1999; 340: 1863–1871[Abstract/Free Full Text]
  3. Friborg J, Kong W-P, Hottiger MO, Nabel GJ. P53 inhibition by the LANA protein of KSHV protects against cell death. Nature1999; 402: 889–894[ISI][Medline]
  4. Farge D, Lebbe C, Marjanovic Z et al. Human herpes virus-8 and other risk factors for Kaposi's sarcoma in kidney transplant recipients. Transplantation1999; 67: 1236–1242[ISI][Medline]
  5. Hojo M, Morimoto T, Maluccio M et al. Cyclosporine induces cancer progression by a cell-autonomous mechanism. Nature1999; 397: 530–534[ISI][Medline]
  6. Penn I. Sarcomas in organ allograft recipients. Transplantation1995; 60: 1485–1491[ISI][Medline]
  7. Vella JP, Mosher R, Sayegh MH. Kaposi's sarcoma after renal transplantation. New Engl J Med1997; 336: 1761[Free Full Text]
  8. Lee P-C, Wang Y-W, Su I-J, Lin Y-J, Lei H-Y. Immunosuppressive drugs and HHV-8 in a patient with a renal transplant and Kaposi's sarcoma. Lancet1998; 351: 1175–1176[ISI][Medline]
  9. Eberhard OK, Kliem V, Brunkhorst R. Five cases of Kaposi's sarcoma in kidney graft recipients-Possible influence of the immunosuppressive therapy. Transplantation1999; 67: 180–184[ISI][Medline]
  10. Schrama YC, De Haas ERM, Hené RJ. Concealed by veils. Nephrol Dial Transplant2000; 15: 259–261[Free Full Text]