Proteasome Inhibitor Carfilzomib-Based Therapy for Antibody-Mediated Rejection of the Pulmonary Allograft: Use and Short-Term Findings.

We present this observational study of lung transplant recipients (LTR) treated with carfilzomib (CFZ)-based therapy for antibody-mediated rejection (AMR) of the lung. Patients were considered responders to CFZ if complement-1q (C1q)-fixing ability of their immunodominant (ID) donor-specific anti-human leukocyte antibody (DSA) was suppressed after treatment. Treatment consisted of CFZ plus plasma exchange and immunoglobulins. Fourteen LTRs underwent CFZ for 20 ID DSA AMR. Ten (71.4%) of LTRs responded to CFZ. DSA IgG mean fluorescence intensity (MFI) fell from 7664 (IQR 3230-11 874) to 1878 (653-7791) after therapy (p = 0.001) and to 1400 (850-8287) 2 weeks later (p = 0.001). DSA C1q MFI fell from 3596 (IQR 714-14 405) to <30 after therapy (p = 0.01) and <30 2 weeks later (p = 0.02). Forced expiratory volume in 1s ( FEV1 ) fell from mean 2.11 L pre-AMR to 1.92 L at AMR (p = 0.04). FEV1 was unchanged after CFZ (1.91 L) and subsequently rose to a maximum of 2.13 L (p = 0.01). Mean forced expiratory flow during mid forced vital capacity (25-75) (FEF25-75 ) fell from mean 2.5 L pre-AMR to 1.95 L at AMR (p = 0.01). FEF25-75 rose after CFZ to 2.54 L and reached a maximum of 2.91 L (p = 0.01). Responders had less chronic lung allograft dysfunction or progression versus nonresponders (25% vs. 83%, p = 0.04). No deaths occurred within 120 days and 7 patients died post CFZ therapy of allograft failure. Larger prospective interventional studies are needed to further describe the benefit of CFZ-based therapy for pulmonary AMR.

Clinical outcomes of solid organ transplant recipients with ehrlichiosis.

Because of our experience with severe Ehrlichia infections in lung transplant recipients, we reviewed all cases of ehrlichiosis in solid organ transplant recipients at Barnes-Jewish Hospital in St. Louis, Missouri. Between 1996 and 2007, 25 cases of ehrlichiosis were identified. We retrospectively collected demographic, clinical, laboratory, and outcomes data, and we compared the 5 cases in lung transplant recipients with 20 cases in other solid organ transplant recipients (heart, 2; kidney, 13; liver, 5). The presenting symptoms in the majority of both groups consisted of fever and headache. Clinical outcomes were worse in the lung transplant group and included a greater need for intensive care unit treatment (80% vs. 20%, P=0.02), longer length of hospital stay (21 vs. 5 days, P=0.02), and propensity to develop acute lung injury or acute respiratory distress syndrome (60% vs. 10%, P=0.04). No mortalities occurred in either group of patients. In an endemic area, ehrlichiosis is not unusual in solid organ transplant recipients, and lung transplant recipients tend to have a more severe illness.