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Published on: January 2, 2017
Conversion to sirolimus in posttransplant renal neoplasms
V Lopez1, C Gutierrez, M Cabello
1Nephrology Department, Carlos Haya Hospital, Malaga, Spain. verolopezjim@yahoo.es
Background:
Calcineurin inhibitors (CNIs) have been associated with the development of posttransplant malignancies, especially lymphoma and solid organ tumors. Sirolimus (SRL) has been shown to inhibit the growth of tumor cell lines in vitro and in vivo and has proven effective in clinical practice for the treatment of Kaposi's sarcoma. Organ transplant patients treated with CNIs who develop a tumor may thus benefit from conversion to SRL.
Patients And Methods:
From December 2001 to May 2006, 25 patients who developed a tumor were converted from a CNI-based immunosuppressive regimen to SRL. We analyzed the evolution of the tumor, renal function, and the adverse effects resulting from the change of immunosuppression.
Results:
The mean follow-up was 19 months. Creatinine clearance (Cockcroft-Gault) increased from 59.5 +/- 21.7 to 66.0 +/- 24.2 mL/min at 12 months (P = .4) and serum cholesterol from 176.7 +/- 46.8 to 216.4 +/- 40.3 mg/dL (P = .01). Proteinuria rose from 0.3 +/- 0.1 to 1.3 +/- 0.9 g/24 hours (P = .004). Adverse events included anemia, thrombocytopenia, and oral ulcers in 20% of cases, cutaneous eruption and gastrointestinal alterations in 12%, and edema in 24%. Four (16%) patients had improved blood pressure readings. Six (24%) patients died and one experienced an acute rejection episode after conversion to SRL. Nineteen (76%) patients displayed a favorable evolution with no evidence of tumor progression.
Conclusions:
Conversion to SRL stabilized tumor progression in 76% of long-term renal transplant patients who developed a neoplasm over a mean follow-up of 19 months. Moreover, renal function improved. The most important adverse effects were increased cholesterol and proteinuria.
Insights
Switching organ transplant patients from calcineurin inhibitors (CNIs) to sirolimus (SRL) stabilized tumor progression in 76% of cases. Renal function improved, but cholesterol and proteinuria increased.
Area of Science:
- Nephrology
- Oncology
- Immunology
Background:
- Calcineurin inhibitors (CNIs) are linked to posttransplant malignancies like lymphoma and solid organ tumors.
- Sirolimus (SRL) demonstrates anti-tumor properties in vitro and in vivo, and is effective for Kaposi's sarcoma.
- Conversion to SRL may benefit transplant patients with tumors who are on CNIs.
Purpose of the Study:
- To evaluate the impact of converting from CNI-based immunosuppression to SRL in organ transplant patients who developed tumors.
- To analyze tumor evolution, renal function, and adverse effects following SRL conversion.
Main Methods:
- 25 patients with tumors were switched from CNIs to SRL between December 2001 and May 2006.
- Tumor progression, renal function (creatinine clearance, proteinuria), and adverse events were monitored.
- Mean follow-up was 19 months.
Main Results:
- Tumor progression stabilized in 76% of patients.
- Creatinine clearance showed a non-significant increase; proteinuria significantly increased (P=.004).
- Adverse events included anemia, thrombocytopenia, oral ulcers, skin rash, GI issues, and edema. Improved blood pressure was noted in 16%.
Conclusions:
- Conversion to SRL stabilized tumor progression in most renal transplant patients with neoplasms.
- Renal function generally improved, despite increased cholesterol and proteinuria.
- SRL conversion is a viable strategy for managing post-transplant malignancies.
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