ABSTRACT
Despite substantial improvements in early survival after lung transplantation, refractory acute rejection (RAR) and bronchiolitis obliterans syndrome (BOS) remain major contributors to transplant-related morbidity and mortality. We have utilized alemtuzumab, a humanized anti-CD52 antibody which results in potent lymphocyte depletion, in consecutive patients with RAR (n = 12) or BOS (n = 10). All patients failed conventional treatment with methylprednisolone and antithymocyte globulin and received strict infection prophylaxis. Alemtuzumab significantly improved histological rejection scores in RAR. Total rejection grade/biopsy was 1.98 +/- 0.25 preceding alemtuzumab versus 0.33 +/- 0.14 posttreatment, p-value <0.0001 (with a similar number of biopsies/patient per respective time interval). Freedom from BOS was observed in 65% of RAR patients 2 years after alemtuzumab treatment. Although there was no statistically significant change in forced expiratory volume in 1 second (FEV1) before and after alemtuzumab treatment in patients with BOS, a stabilization or improvement in BOS grade occurred in 70% of patients. Patient survival 2 years after alemtuzumab for BOS was 69%. Despite a dramatic decline in CD4 counts in alemtuzumab-treated patients, only one patient developed a lethal infection. Thus, we provide the first evidence that alemtuzumab is a potentially useful therapy in lung transplant recipients with RAR or BOS.
Subject(s)
Antibodies, Anti-Idiotypic/therapeutic use , Antibodies, Monoclonal/therapeutic use , Antibodies, Neoplasm/therapeutic use , Bronchiolitis Obliterans/drug therapy , Bronchiolitis Obliterans/etiology , Graft Rejection/drug therapy , Graft Rejection/etiology , Lung Transplantation/adverse effects , Adolescent , Adult , Aged , Alemtuzumab , Antibodies, Monoclonal, Humanized , Antigens, CD/immunology , Antigens, Neoplasm/immunology , Biopsy , Bronchiolitis Obliterans/pathology , CD4-Positive T-Lymphocytes/drug effects , CD4-Positive T-Lymphocytes/pathology , CD52 Antigen , Female , Forced Expiratory Volume/physiology , Glycoproteins/immunology , Graft Rejection/pathology , Humans , Kaplan-Meier Estimate , Lung/pathology , Lung/physiopathology , Lung/surgery , Male , Middle Aged , Survival Analysis , Treatment OutcomeABSTRACT
BACKGROUND: Controversy exists regarding the optimal use of bilateral lung transplant (BLT) in older recipients in diseases where either single or bilateral transplant is appropriate. International Society for Heart and Lung Transplant (ISHLT) guidelines suggest an upper age limit of 60 for BLT, despite limited data regarding outcomes with BLT in patients over 60. We hypothesize that BLT offers comparable, if not superior, clinical outcomes to SLT in all patients independent of recipient age. METHODS: In order to test our hypothesis, we conducted a case-control study to compare the effect of transplant operation on survival and the onset of bronchiolitis obliterans syndrome (BOS) in consecutive lung transplant recipients 61 years of age or older using Kaplan- Meier analysis and Cox proportional hazard models. RESULTS: We identified 107 consecutive lung transplant recipients 61 or older at the time of transplant. Patients received SLT (n=46) or BLT (n=61) based on donor organ availability. Comparable survival was achieved with BLT in older patients vs. SLT P=0.19). One-, two-, and five-year survival estimates in BLT were 82%, 75% and 68%, respectively, vs. in SLT 78%, 70% and 44%, respectively. A comparable onset of BOS was also observed in the patients who received BLT vs. SLT (P=0.23). CONCLUSION: Successful short- and medium-term outcomes are achieved with BLT in older recipients and are comparable to those achieved with SLT. Our results suggest that age over 60 should not exclude patients from consideration of BLT.
