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A history of preexisting malignancy has been considered a contraindication to cardiac transplantation. The reasons for this prejudice include concerns about potentially deficient intrinsic immunomodulation and fear of cancer recurrence (or development of second cancers) because of therapeutic immunosuppression. In the past four years at the Northern Indiana Heart Institute seven patients with preexisting malignancies underwent cardiac transplantation. Their two-year survival rate was 100%, which is comparable to a rate of 81% in non-malignancy patients. After an average 31 months of follow-up (range = 6-56 months), only one patient has had a recurrent tumor (basal cell carcinoma). Statistical comparison of immunosuppression dosages, incidences of rejection, and incidences of infections between patients with preexisting malignancy and those without preexisting malignancy was performed. We found that the only significant difference was an increased number of infections in preexisting malignancy patients. Additionally, we found no difference in the incidence of posttransplant coronary artery disease in the preexisting malignancy group when compared with those patients without preexisting malignancies. This study demonstrates that patients who have been successfully treated for malignancies have no greater incidence of rejection than those patients without preexisting malignancy. Furthermore, preexisting malignancy patients require no significant modulation of immunosuppression. Although preexisting malignancy patients have a higher incidence of infections than patients without preexisting malignancy, their two-year survival is not worse than the patients without preexisting malignancy.

Fetal rat pancreases frozen to and stored at -196 C were used for transplantation into streptozotocin-induced diabetic syngeneic adult recipients. Transplantation was carried out either directly after thawing from -196 C, or after a 21-day growth period in a syngeneic, normoglycemic adult carrier. All transplants were placed under the kidney capsule. A single, frozen fetal rudiment was sufficient to restore blood glucose, urine volume, and urine glucose to normal, provided it had first been grown for 21 days in a normal carrier. It vitro perfusion studies showed that fetal pancreases stored at -196 C were equivalent to fresh rudiments in their responses to a glucose stimulus.

Improved viability and function of insulin-producing beta (B) cells of frozen-stored human fetal pancreatic tissue was obtained by a two-step method utilizing high concentrations of dimethyl sulfoxide (DMSO). Human fetal pancreata (14-23-week gestation) obtained from pathologic abortions were teased and cultured overnight. Prior to freezing the tissues were immersed in 0.9% saline containing 0.5 M DMSO for 30 min (room temperature) and then placed in 2.1 M DMSO on ice for 5 min. The tissues were frozen by the method previously developed in our laboratory and stored at -196 degrees C. The frozen-stored tissues were subsequently thawed at 24 degrees C and cultured overnight before viability testing. Viability and function of the B cells were assessed by several specific assay methods; glucose plus theophylline-induced insulin release during static incubation and perifusion, 3H-leucine incorporation into insulin, and insulin content of the tissue grown in athymic mice for 7 days. The response to glucose plus theophylline stimulation, measured on the frozen-thawed tissue one day after thawing, was 80% of the level measured in control tissue maintained in organ culture. Frozen-thawed tissues maintained in organ culture for 1 week responded comparably in the in vitro assay systems. The insulin content of frozen-thawed pancreatic tissue removed from athymic mice 1 week after transplantation was approximately 60% of the amount measured in the control grafts. These results demonstrate the utility of our procedure in the maintenance of the viability and function of frozen-stored human B cells both in culture and after transplantation.

Human fetal pancreases were dissected into 1- to 2- mm3 fragments and frozen to -196 C using a modification of procedures previously used successfully for cryopreservation of the rat fetal pancreas. Freeze-recovered pancreatic pieces were able to incorporate radioactive amino acids into proteins. When placed into organ culture, nonfrozen control and freeze-recovered pancreas tissue secreted radioimmoassayable insulin in response to glucose plus theophylline, but not to glucose alone. Freeze-killed pancreatic pieces were totally inactive functionally. With respect to those parameters tested, freeze-recovered pancreas tissues were equivalent to nonfrozen tissue.