Registry of Hospital Das Clínicas of the University of São Paulo Medical School: First Official Solid Organ and Tissue Transplantation Report – 2008

OBJECTIVE: The aim of this study was to report a single center experience of organ and tissue transplantation INTRODUCTION: This is the first report of organ and tissue transplantation at the Hospital das Clínicas of the University of Sao Paulo Medical School. METHODS: We collected data from each type of organ transplantation from 2002 to 2007. The data collected were patient characteristics and actuarial survival Kaplan-Meier curves at 30 days, one year, and five years RESULTS: There were a total of 3,321 transplants at our institution and the 5-year survival curve ranged from 53% to 88%. CONCLUSION: This report shows that solid organ and tissue transplants are feasible within the institution and allow us to expect that the quality of transplantation will improve in the future.


INTRODUCTION
Transplantation has been an option for patients with end-stage organ disease and can provide a chance for survival. Our institution is one of the largest medical school hospitals in this country, with a relatively significant activity in complex procedures and transplants. [1][2][3][4][5] The aim of this registry was to report the experience of transplantation at our institution for the last five years. It represents a unique data repository in an effort to help patients with untreated disease with conventional therapy.

PATIENTS AND METHODS
Data were collected from each organ and tissue transplantation carried out from 2002 to 2007. The following parameters were studied: the number of transplants, age of recipient, indications for transplantation, maintenance immunosuppression protocols [calcineurin inhibitor (cyclosporine or tacrolimus), cytostatic drugs, and the use of steroids], major complications, causes of death, and the survival curve for each organ and tissue.
For statistical analysis, all data were reported as median, minimum, and maximum values. Survival rates were calculated using the Kaplan-Meier method. All analyses were performed with SPSS statistical software, version 10.0 (SPSS Inc., Chicago, IL, USA).

The registry of transplantation at the Hospital das
Clínicas of the University of Sao Paulo Medical School covers organ and tissue transplants from 2002 through 2007.
The total number of recipients who received transplants was 3,321 (Table 1). There were 1,288 and 2,033 transplants of solid organs and tissue, respectively ( Figure 1). The age of the recipients ranged from 0.6 to 90 years ( Table 2). The distribution of the solid organ transplants per year ranged from 187 to 265 transplants ( Figure 1).

Pediatric heart transplantation
Thirty-two pediatric patients aged from 0.9 years to 13.8 years (median: 6.0 years) were submitted to heart transplantation. The indications of heart transplantation were dilated cardiomyopathy in 25 patients (78%) and congenital heart disease in seven patients (22%).
The immunosuppression used for induction therapy was methylprednisolone and thymoglobulin in all patients. The maintenance immunosuppression was the administration of calcineurin inhibitor in all patients, azathioprine in 4 patients (13%), and mychophenolate in 21 patients (65%). The major complications were 68 episodes of rejection (2.1 episodes per patient) and 61 episodes of infection (1.9 episodes per patient). No cases of tumor, diabetes mellitus, graft vascular disease, or renal failure (dialysis) were observed. Thirteen patients (40%) developed systemic arterial hypertension. Two re-transplantations were carried out. Nine (28%) patients died. The causes of mortality were rejection in five patients (55%), infection in three (33%), and multiple organ failure in one (11%) (Figure 2). The Kaplan-Meier curve was 80% at 30 days, 70% at 1 year, and 70% at 5 years ( Figure 3).

Adult liver transplantation
Two hundred and four patients received 225 liver transplants (21 were re-transplants). The median age of recipients was 47 years (range, 14 to 70 years). The

Simultaneous pancreas-kidney transplantation
Thirty-seven patients received pancreas kidney transplants. The median age of recipients was 36 years (range, 25 years to 51 years). The indications were type I diabetes with renal chronic failure in 32 (86.5%) patients, type I diabetes following kidney transplantation in three (8.1%) patients, and type I diabetes in two (5.4%) patients. The immunosuppression for induction therapy was: IL2R (daclizumab), tacrolimus, mycophenolate and steroids in 16 patients (43%); and anti-thymocyte horse globulinthymoglobulin, tacrolimus, mycophenolate, and steroids in 21 (56.7%). The maintenance immunosuppression in all patients was tacrolimus, mycophenolate, and steroids. There were seven deaths. The causes of mortality were cardiovascular complications in four patients (57%), septic shock in two (29%), and tumor in one (14%) (Figure 2). The Kaplan-Meier overall recipient survival curve was 97.3% at 30 days, 84.9% at one year, and 74.2% at five years. The pancreatic graft survival curve was 97.3% at 30 days, 79.4% at one year, and 56.7% at five years; kidney graft survival was 97.3% at 30 days, 84.5% at one year, and 73.9% at five years ( Figure 3).

Kidney transplantation
A total of 715 patients aged from 3 to 78 years (median, 41.3 years) were submitted to kidney transplantation. The indications for pediatric and adult kidney transplantation are given in Tables 4 and 5, respectively. The most common indication was chronic glomerulonephritis in 140 patients (21%).
Pediatric kidney transplantation: 50 children received kidney transplants. The median age was 13 years (range, 3 to 17 years). The immunosuppression used for induction therapy in children was basiliximab in 14 patients (28%), daclizumab in 28 (56%), and antithymocyte globulin in six (12%). The maintenance immunosuppression was tacrolimus, mychophenolate, and steroids in 45 patients (90%); and cyclosporine, mycophenolate, and steroids in five (10%). Four patients died. The causes of death for the four were acute edema, sudden death, infection, and an unknown cause ( Figure 2). The Kaplan-Meier graft survival curve was 95.9% at 30 days, 88.7% at one year, and 76.7% at five years. The patient survival curve was 100% at 30 days, 97.7% at one year, and 78.1% at five years ( Figure 3).

Pediatric bone marrow transplantation
Thirty-four patients received autologous bone marrow transplants. The median age of recipients was 6.6 years. The indications were the following: neuroblastoma in 25 patients, Ewing sarcoma in three, non-Hodgkin lymphoma in three, meduloblastoma in two, and Wilms' tumor in one. The immunosuppression for induction therapy was carboplatin (CBDCA), etoposide (ETO), and melphalan (MELFA) in 29 patients; bleomycin, etoposide, cytarabine, and melphalan (BEAM) in two; CBDCA/ETO in three; and cisplatin (CDDP), cyclophosphamide (CTX), and vincristine (VCR) in two. The number of deaths was seven. The causes of mortality were tumor in six patients (86%) and septic shock in one (Figure 2). The Kaplan-Meier survival curve was at 96.8% at 30 days, 93.1% at one year, and 67% at five years ( Figure 3).
Five children with acute myeloid leukemia (AML) and 18 children with acute lymphocytic leukemia (ALL) underwent to allogeneic bone marrow transplantation.  Table 6.

Bone transplantation
A total of 1167 patients received bone, ligament, or tendon transplants. The median age of recipients was 48 years (range, 2 to 90 years). The indications for transplantation were either odontologic (813 patients, 69.7%) or orthopedic (354 patients, 30.3%). Odontological indications of bone transplantation were mandibular and maxilar bone loss caused by tumors, trauma, and periodontal disease. Orthopedic indications were divided into the following groups: hip surgery (177, 50%), knee surgery (128, 36%), tumor surgery (35, 10%), and shoulder surgery (14, 4%). The main indication for hip surgery was revision hip arthoplasty with femoral or acetabular bone loss. Bone and ligament transplantation in knee surgery was used in revision knee arthoplasty, reconstruction of anterior cruciate ligament injury, (patellar graft, semitendinosus and gracilis graft), and severe trauma. The indications for the tumor group were benign lesions (unicameral and aneurismal bone cysts, non-osteogenic fibromas), and malignant tumors (Ewing sarcoma and osteosarcoma). Indications for shoulder surgery were repair of rotator cuff injuries and acromioclavicular dislocations using ligaments and rotator cuff grafts. Immunosuppression was not used for induction or maintenance therapy, since bone, ligament, and tendon transplantation, unlike transplantation of other solid organs, do not cause death in the event of graft failure. The main complications of bone transplantation were infection and immunogenic reaction against the graft. Of 35 patients in the tumor group, two (5.7%) developed infection, two (5.7%) had immunogenic reactions, three (8.6%) had allograft fractures that required revision and autologous bone grafts, and one (2.9%) had recurrence of the tumor in the leg that had received the transplantation, and the leg was therefore amputated.

Skin transplantation
Eighty-one patients aged 0.3 years to 78 years (median, 34 years) received skin transplants. The main use of this transplantation was for temporary skin coverage until an autogenous graft could be implanted. The indications for skin transplantation were large burns with few skin donor areas in 38 patients (46.9%), wound bed preparation in 28 (34.5%), hemodynamic instability in seven (8.6%), pyoderma gangrenosum in four (4.9%), aplasia cutis in two (2.4%), and giant congenital nevi in two (2.4%). After 3-5 days, the allogeneic skin was removed and the wound bed was evaluated. If there was sufficient granulation tissue then an autogenous graft was made; if the granulation tissue was not good, a new transplantation was performed. In this way, 22 patients received a re-transplantation for wound bed preparation. The mortality rate of the patients was 16.4%: 13 patients died, five in the group of hemodynamic instability and eight in the group of large burns with few donor skin sites.

COMMENTS AND DISCUSSION
The total number of solid organ transplant procedures (38.7%) of all transplants remained unchanged during the period (range, 2002 to 2007). The number of tissue transplants increased during the last two years, especially bone transplants.
Immunosuppression: The most common combinations of therapies included calcineurin inhibitor and mycophenolate. A smaller percent of patients were taking a calcineurin inhibitor combined with azathioprine.
Outcomes: Overall survival at 30 days, one year, and five years shows that the results of our institution 6-21 are compatible with previously reported data. [22][23][24][25][26] Infection and rejection were the main causes of death in the majority of the organ transplants in our report. This indicates that these two complications remain a challenge for physicians who take care of organ transplant patients.
We will continue to update our experience in an attempt to describe what is presently occurring in organ transplantation in our institution.

CONCLUSION
This is the initial registry report from our institution. It will help us define baseline data that will form the basis of comparison for our future reports. This report shows that solid organ and tissue transplantations are feasible within the institution and they allow us to expect that the quality of results will improve in the future.

APPENDIx
The members of the Solid Organ and Tissue