Are patients with inflammatory eye disease treated with systemic immunosuppressive therapy at increased risk of malignancy?

Yates, William B; McCluskey, Peter J; Wakefield, Denis

doi:10.1186/1869-5760-3-48

Journal of Ophthalmic Inflammation and Infection

Table 1 Studies which demonstrated an increased incidence of malignancy associated with systemic immunosuppressive therapy in transplant recipients

From: Are patients with inflammatory eye disease treated with systemic immunosuppressive therapy at increased risk of malignancy?

Immunosuppressive therapy	Study	Risk of malignancy	References
Azathioprine	1	162 patients with renal allografts treated with AZA (100 to 150 mg/day) found 22 NMSC developed at 3-year follow-up	[12]
	2	A comparison of AZA-based therapy (n = 3,139) and CSA-based therapy (n = 412) in transplant recipients found 1,255 skin malignancies developed in the AZA group (40%) compared to 90 in the CSA-based group (22%)	[13]
	3	12 malignancies, most commonly NMSC, developed in a group of transplant recipients of n = 287 during 12-month follow-up	[14]
	4	19 NMSC developed in 7 out of 51 kidney recipients (14%) treated with AZA + prednisone for between 4 and 45 months of treatment; dosing of AZA was kept at approximately 3 mg/kg/day for the duration after transplantation; 16 SCC, 1 BCC and 3 keratoacanthomas; conclusions suggested that tumours were increased in incidence and also prone to early reoccurrence	[15]
Mycophenolate mofetil	1	503 patients with renal allografts were randomised into 3 groups, 2 with varied MMF dosages (2 g, n = 173; 3 g, n = 164) and a group with AZA therapy (n = 166); 12 malignancies (lymphoma/LPD and non-skin carcinoma) were found in the group treated with 3 g MMF compared to 8 treated with 2 g MMF at 3-year follow-up	[12]
Cyclosporine	1	142 malignancies developed in 141 organ transplant recipients treated with cyclosporine, 41% lymphomas compared to 12% observed in the AZA, prednisone or prednisolone group at 20-year follow-up	[16]
Cyclosporine	2	84 malignancies observed in 1,113 patients treated with combination CSA therapy (group 1) found a 1.99% cumulative risk of cancer 2 years post-transplant versus only 0.31% in the control (patients without CSA exposure or group 2); 43% of tumours observed (n = 38) were NMSC in group 1 compared to 27% in group not exposed to CSA, despite shorter time of exposure	[17]
	3	295 renal allograft recipients treated with AZA + prednisone (115) or AZA + prednisone + CSA (180) found 51 patients (19%) had at least 1 NMSC; it was found that the incidence of NMSC in AZA + prednisone was 29 per 1,000 person-years compared to 48 per 1,000 years in the group with additional CSA therapy	[18–21]

Follow-up of 3,823 patients treated with AZA, CYP or chlorambucil for >3 months found a 60-fold increase in NHL and 25-fold increase in SCC during the 5-year follow-up compared to the general UK and Australia population. SCC and BCC incidence in solid transplant recipients given systemic immunosuppressive therapy was demonstrated to be a four- to sevenfold increase in low sunshine exposure areas and a 20-fold increase in areas of high sun exposure compared to the general population. NHL incidence in transplant patients treated with immunosuppressive drugs show a 28- to 49-fold increase compared to age-matched controls.

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