Alemtuzumab in the Treatment of Refractory Acute Rejection and Bronchiolitis Obliterans Syndrome After Human Lung Transplantation

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.

International practical guidelines on diagnosis, prevention and treatment of bronchiolitis obliterans syndrome

“…Усиленная иммуносупрессия с тотальным облучени ем лимфоцитов [173,174] [175,176] могут оказать положительное влияние на снижение легочной функции, обуслов ленное СОБ, но у данных методов, помимо высокой стоимости, имеются значительные побочные эф фекты, поэтому нужны дополнительные клиничес кие исследования для уточнения их эффективности при СОБ. В одноцентровых исследованиях показа но, что в профилактике и лечении СОБ также могут играть роль другие иммуносупрессивные препараты, такие как сиролимус [177], алемтузумаб [178,179] или антитимоцитарный глобулин [180], но для уточ нения места этих препаратов и альтернативных методов долговременной поддерживающей имму носупрессии (например, ингибитора рецепторов mTOR эверолимуса) в профилактике и лечении СОБ нужны дополнительные исследования. Наконец, не обходимы многоцентровые исследования для уста новления оптимальных режимов иммуносупрес сивной терапии, при помощи которой было бы возможно адекватно предотвратить острую и хрони ческую дисфункцию трансплантата без чрезмерного риска инфекции или других нежелательных побоч ных эффектов.…”

Chronic lung allograft dysfunction phenotypes and treatment

“…Another drug with potential to slow down disease progression is alemtuzumab (Campath-1H), an antagonist of CD52 which is expressed on B-cells, lymphocytes, dendritic cells and monocytes. This drug was found to improve interstitial changes and lung function in four patients who likely had rCLAD (73), while it was also described in successful treatment of persistent acute rejection (74). Another approach of treating rCLAD might be trying to decrease or erase HLA antibodies by using plasmapheresis, intravenous immunoglobulins and rituximab, which has shown to be partly successful in at least reducing the antibody titre (75).…”

Monitoring of Nonsteroidal Immunosuppressive Drugs in Patients With Lung Disease and Lung Transplant Recipients

“…Additionally, the CBC count should be monitored intermittently to detect signifi cant bone e37S leukemia. [199][200][201] Alemtuzumab has also been used to treat autoimmune cytopenias, non-Hodgkin's lymphoma, and T-cell prolymphocytic leukemia. [199][200][201] Alemtuzumab is used as induction therapy prior to solid organ transplant, including lung transplant.…”

“…[199][200][201] Alemtuzumab has also been used to treat autoimmune cytopenias, non-Hodgkin's lymphoma, and T-cell prolymphocytic leukemia. [199][200][201] Alemtuzumab is used as induction therapy prior to solid organ transplant, including lung transplant. [199][200][201] Some experience has been reported for its use in treatment of acute solid organ rejection.…”

“…[199][200][201] Alemtuzumab is used as induction therapy prior to solid organ transplant, including lung transplant. [199][200][201] Some experience has been reported for its use in treatment of acute solid organ rejection. [199][200][201] A summary of common clinically signifi cant side effects of alemtuzumab is presented in Table 14 .…”