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.
Transplant Unit, Università Tor Vergata, Ospedale S Eugenio, Rome, Italy.
M
M
Manuelli
L
L
De Luca
G
G
Iaria
P
P
Tatangelo
D
D
Sforza
L
L
Perrone
M I
MI
Bellini
R
R
Angelico
A
A
Anselmo
G
G
Tisone
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