Immunosuppressive treatment after solid organ transplantation and risk of post-transplant cutaneous squamous cell carcinoma.
BACKGROUND
The risk of cutaneous squamous cell carcinoma (CSCC) is found to be substantially increased after organ transplantation. The association with specific immunosuppressive regimens has been previously investigated, but results are not concordant. We aimed to clarify the relationship between separate immunosuppressive drugs, drug load, timing and risk of post-transplant CSCC.


METHODS
A population-based nested case-control study was performed in the Swedish organ transplantation cohort (n = 5931). All patients who developed CSCC during the follow-up (1970-97) were eligible as cases (n = 207). Controls (n = 189) were randomly selected from the cohort and individually matched to the cases on follow-up time, age at and calendar period of transplantation. Exposure information was collected through extensive and standardized review of medical records.


RESULTS
The median time to CSCC was 6.7 years. Post-transplant azathioprine (Aza) treatment considerably increased the risk of CSCC during all time periods analysed, and the risk augmented with increasing dose and duration. Patients who after the entire follow-up period had received a high accumulated dose of Aza had an 8.8-fold increased risk of CSCC in multivariate analysis (P < 0.0001), compared to patients never treated with Aza. Additionally, a high accumulated dose of corticosteroids during the same period conferred a 3.9-fold elevated risk of CSCC (P = 0.09), compared to the lowest accumulated dose of corticosteroids. Cyclosporine treatment was not associated with the risk of CSCC post-transplantation.


CONCLUSIONS
This study provides evidence that Aza treatment, but not cyclosporine treatment, is strongly associated with post-transplant CSCC risk. The results suggest that the risk of CSCC after organ transplantation is not only an effect of the immunosuppressive load per se.
Ingvar
Asa
A
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. asa.odenbro@ki.se
Smedby
Karin Ekström
KE
Lindelöf
Bernt
B
Fernberg
Pia
P
Bellocco
Rino
R
Tufveson
Gunnar
G
Höglund
Petter
P
Adami
Johanna
J
D000293:Adolescent; D000328:Adult; D000368:Aged; D001379:Azathioprine / Q000009:adverse effects / Q000627:therapeutic use; D002294:Carcinoma, Squamous Cell / Q000139:chemically induced / Q000453:epidemiology*; D016022:Case-Control Studies; D002648:Child; D015331:Cohort Studies; D016572:Cyclosporine / Q000009:adverse effects / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control*; D016027:Heart Transplantation / Q000276:immunology; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D016030:Kidney Transplantation / Q000276:immunology*; D016031:Liver Transplantation / Q000276:immunology; D016040:Lung Transplantation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D012878:Skin Neoplasms / Q000139:chemically induced / Q000453:epidemiology*; D013548:Sweden; D013997:Time Factors; D055815:Young Adult
D007166:Immunosuppressive Agents; D016572:Cyclosporine; D001379:Azathioprine