PURPOSE: Lung transplant candidates with panel reactive antibodies (PRA) titer of 10% or more are considered highly sensitized and prospective cross matching is required to avoid hyperacute rejection or sub optimal organ function post transplant. Few lung transplant centers in the United States accept highly sensitized patients for lung transplantation. We evaluated a novel protocol utilizing a three-step approach to reduce the PRA to achieve a negative crossmatch and transplantation.
METHODS: Adult patients evaluated for lung transplant with Class I PRA greater than 10% by flow cytometry were eligible. Patients with a known allergy or hypersensitivity to study drugs were excluded. Baylor IRB approved the study. After informed consent was obtained, patients were initiated on therapy and moved from one step to the next after 4 weeks if there was inadequate PRA reduction. Step 1: Mycophenolate mofetil. Step 2: Alemtuzumab (Campath 1H). Step 3: Plasmapheresis and IVIG. A sample size of 6 was based on the past number of highly sensitized patients seen at our center in order for the study to be completed within 18 to 24 months. Data was collected prospectively. Primary endpoint was a negative prospective cross match leading to allograft transplantation. Secondary endpoints included survival,acute rejection and FEV1 one-year post transplant.
RESULTS: From 2/2/04 to 2/2/06 we prospectively enrolled and followed up 6 subjects (n=6). All subjects were females. Median Age was 55. Diagnosis included Pulmonary hypertension (n=1), Interstitial Lung Disease (ILD)(n=2), Emphysema (n=3). PRA trend is shown in Fig 1.Primary endpoint was reached in 4/6 patients(66%). 1/6 after step 1, 1/5 after step 2 and 2/4 after step 3.Secondary end points are shown in Table 1.Post transplant survival at 1 year was 2/4(50%).
CONCLUSION: Significant PRA reduction was achieved and 66% of the subjects could be transplanted with this approach. However one-year mortality was significantly higher than non-sensitized cohorts.
CLINICAL IMPLICATIONS: In this high risk population who are often denied lung transplantation our multimodal approach may allow patients to obtain a life saving procedure.
DISCLOSURE: Babith Mankidy, Product/procedure/technique that is considered research and is NOT yet approved for any purpose, Mycophenolate mofetil (CellCept) is an inhibitor of purine synthesis of human lymphocytes and proliferation of human lymphocytes. It is commonly used for prophylaxis or treatment of organ rejection co.