Malignant Melanoma in Organ Allograft Recipients1,2

Abstract

Three groups of tumors were studied. The first group was melanomas inadvertently transmitted from donors. Brain metastases from melanoma were often misdiagnosed in the donors as primary brain tumors or cerebral hemorrhage. Eleven donors provided organs to 20 recipients of whom 3 never manifested evidence of melanoma, 1 showed local spread of tumor beyond the allograft, and 16 had metastases. Of the last group 11 died from melanoma, but 4 patients had complete remissions following transplant nephrectomy and discontinuation of immunosuppressive therapy. The second group was Melanomas treated pretransplantation. Thirty patients had cutaneous melanomas and one an ocular melanoma. Six patients (19%) had recurrences posttransplantation. Three were treated < 2 years pretransplantation, 2 between 2-5 years pretransplantation, and one 120 months pretransplantation. The third group was De novo melanomas. Cutaneous melanomas occurred in 164 patients, melanomas of unknown origin in 8, and ocular melanomas in 5. Melanomas constituted 5.2% of posttransplant skin cancers compared with 2.7% in the general population. Unusual features of cutaneous melanomas were that 6 (4%) occurred in children, and 9 (5%) occurred in bone marrow recipients who were treated for leukemia. Forty-four patients (27%) who had cutaneous melanomas also had other skin cancers. Forty-seven of 68 patients (69%) had thick skin lesions (Clark's level III or greater or > 0.76 mm by Breslow's technique). Lymph node metastases occurred in 32 patients (20%) with cutaneous melanomas. Fifty patients (30%) with cutaneous melanomas died of their malignancies, as did 5 with melanomas of unknown origin, and 1 with ocular melanoma. The risks of melanoma may be reduced by stringent selection of donors; by waiting at least 5 years between treatment of melanoma and undertaking transplantation; and, perhaps, by reducing sunlight exposure and by early excision of suspicious dysplastic lesions.

Inhibition of Polymorphonuclear Leukocyte–Mediated Graft Damage Synergizes With Short-Term Costimulatory Blockade to Prevent Cardiac Allograft Rejection

“…Long-term use of current immunosuppression has multiple deleterious side effects, including direct nephrotoxicity leading to renal failure, increased susceptibility for infections, and increased frequency of cutaneous and hematological malignancies. 5,6 These clinical problems have prompted efforts to develop novel strategies for achieving long-term allograft function and survival without life-long immunosuppression.…”

The critical role of type‐1 innate and acquired immunity in tumor immunotherapy

“…Although it is much more difficult to address cancer immunosurveillance in humans, three lines of evidence suggest that cancer immunosurveillance indeed occurs in humans: (i) immunosuppressed transplant recipients display higher incidences of non-viral tumors, such as melanomas, colon, lung, pancreas, bladder, kidney, and endocrine system cancers, than agematched immunocompetent control populations, 12) (ii) the presence of lymphocytes within the tumor can be a positive prognostic indicator of patient survival, 13) and (iii) cancer patients are able to develop spontaneous innate and acquired immune responses to the tumors that they bear 14,15) (also reviewed elsewhere 16,17) ). The analysis of immune responses of cancer patients against the tumor that they bear has led to the identification of a large array of immunogenic tumor antigens recognized by CD8…”

Melanoma in Immunosuppressed Patients

“…However, several studies have reported no deaths due to melanoma in cases of malignant melanoma in situ or thin superficial spreading melanoma in the organ transplant recipients. 29,34,44,52 In a recent European multicenter retrospective study of 100 melanomas (91 occurred 25 ); others have not found a significant difference. 6 Other factors found to correlate with increased risk of melanoma included use of T lymphocyte-depleting antibodies and excessive UV radiation exposure.…”

“…6,25,47 De novo melanomas tend to develop 3 years posttransplant or later, 40 with reports ranging from 14 to 236 months. 29 The mean time for melanoma development in the OTR population is 61 months posttransplant, 44 with some studies documenting a range of 40 to 132 months. 29,34,52 In the general population, key prognostic factors that determine the stage of disease include Breslow thickness, Clark level, ulceration, lymph node involvement, number of mitoses, and distant metastasis.…”