Conversion to rapamycin immunosuppression for malignancy after kidney transplantation.
BACKGROUND
Malignancies are a well-known complication of immunosuppressive therapy among renal transplant recipients, representing an important cause of long-term morbidity and mortality. Rapamycin has been shown to limit the proliferation of a number of malignant cell lines in vivo and in vitro.


METHODS
Fifteen patients developed the following malignancies at a mean of 90.3 months (range = 10-252) after kidney transplantation: metastatic gastric cancer (n = 1), metastatic colon cancer (n = 1), bilateral nephrourothelioma (n = 1), skin cancer (n = 2), Kaposi's sarcoma (n = 2), posttransplant lymphoproliferative disorder (PTLD; n = 4), renal cell carcinoma T1 (n = 1), MALT lymphoma (n = 1), intramucous colon carcinoma (n = 1), liposarcoma of the spermatic cord (n = 1). After the diagnosis of malignancy, the patients were switched from calcineurin inhibitor-based immunosuppression to rapamycin (monotherapy, n = 3), or associated with steroids (n = 6) or with mycophenolate mofetil (n = 6).


RESULTS
Both patients with metastatic cancer underwent chemotherapy but succumbed after 6 and 13 months. Two patients with PTLD who underwent chemotherapy died after 12 and 36 months. At a mean follow-up of 32.7 months (range = 7-56), the remaining 11 patients are cancer-free. Two patients lost their grafts after 24 and 36 months after the switch due to chronic rejection. Renal graft function remained stable in all other patients from diagnosis throughout follow-up.


CONCLUSIONS
Our observations suggested that rapamycin-based immunosuppression offers the possibility for regression of nonmetastatic tumors. Nevertheless, it is difficult to assess whether tumor regression was due to rapamycin treatment or to the reduced immunosuppression.
Manuelli
M
M
Transplant Unit, Università Tor Vergata, Ospedale S Eugenio, Rome, Italy.
De Luca
L
L
Iaria
G
G
Tatangelo
P
P
Sforza
D
D
Perrone
L
L
Bellini
M I
MI
Angelico
R
R
Anselmo
A
A
Tisone
G
G
D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000276:immunology / Q000473:pathology; D005834:Genital Neoplasms, Male / Q000276:immunology / Q000473:pathology; D006801:Humans; D007165:Immunosuppression Therapy / Q000379:methods; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D016030:Kidney Transplantation / Q000009:adverse effects / Q000276:immunology*; D008080:Liposarcoma / Q000276:immunology / Q000473:pathology; D008297:Male; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000453:epidemiology / Q000276:immunology*; D020123:Sirolimus / Q000627:therapeutic use*; D012878:Skin Neoplasms / Q000276:immunology / Q000473:pathology; D013274:Stomach Neoplasms / Q000276:immunology / Q000473:pathology
D007166:Immunosuppressive Agents; D020123:Sirolimus