Introduction: The importance of polyomavirus BK as cause of nephropathy in renal ... We report a rare case of BK polyoma virus encephalitis in a lung transplant.
Abstracts S31 6( 3) Carfilzomib for Refractory Antibody Mediated Rejection and Allosensitization in Heart Transplantation L. Sacha ,1 J.J. Teuteberg,2 A. Zeevi,3 C. Bermudez,2 R. Kormos,2 C. Ensor,1 J. McDyer,4 M.A. Shullo.1 1Pharmacy and Therapeutics, University of Pittsburgh, Pittsburgh, PA; 2Heart and Vascular Institute, UPMC, Pittsburgh, PA; 3Histopathopathy, University of Pittsburgh, Pittsburgh, PA; 4Medicine, University of Pittsburgh, Pittsburgh, PA. Introduction: Both persistent and de novo donor specific antibodies(DSA) after heart transplant correlate with significantly worse mortality compared to that of patients without DSAs. Recently there is increasing interest in proteasome inhibitors for therapy, given their targeted effect on plasma cells. Carfilzomib is a proteasome inhibitor which, in contrast to bortezomib, irreversibly inhibits activity of the 20S proteasome and results in less neuropathic side effects. This is a case series of two allosensitized patients who received carfilzomib (CFZ); one heart transplant(HTX) candidate and one HTX recipient. Case Report: Patient A is a 54 y/o female with a HVAD as a bridge to HTX, highly sensitized with cPRA of 100% based on IgG HLA-antibodies(Ab) and a 96% cPRA based on C1q testing. IVIG and plasmapheresis(PP) were ineffective; therefore she was treated with one round of CFZ therapy consisting of 6 treatments of PP, CFZ 20 mg/m2 and IVIG. After the first round of therapy, cPRA and anti-HLA Ab strength were mildly reduced and the C1q positive Ab were eradicated. This response was not sustained and not sufficient for HTX listing. A second round of CFZ therapy, successfully reduced her cPRA to 51% by eliminating C1q positive class I HLA-Ab and considering only class II strong HLA-Ab. Ten days later she was successfully transplanted across C1q negative weak class I and II DSA. Patient B is 58 y/o male, 4 years post HTX with a first episode of antibody mediated rejection (AMR) with strong Class II C1q positive DQ8 DSA. He was symptomatic with an EF of 25% and failed to have a sustained respond to steroids, PP, IVIG, and rituximab. After one round of CFZ therapy as defined above, no C1q positive DSA were detected and remains asymptomatic with an EF of 50-55% 5 months later. Summary: For allosensitized HTX candidates or those with AMR, a regimen of, PP, CFZ, and IVIG results in a rapid decline in Ab, as well as a decrease in their ability to activate complement. Further study is warranted on the use of CFZ for these indications.
6( 4) Belatacept as Primary Immunosuppression in a Lung Transplant Recipient P. Ong ,1 L. Mudambi,1 A. Fuentes,2 K. Dawson,2 N. Sinha,3 B. Mankidy,3 S. Scheinin,1 T. Kaleekal,3 S. Jyothula.3 1Pulmonary and Critical Care Medicine, Baylor College of Medicine, Houston, TX; 2Department of Pharmacy, Houston Methodist Hospital, Houston, TX; 3JC Walter Jr Transplant Center, Houston Methodist Hospital, Houston, TX. Introduction: Belatacept is a recently-introduced, selective costimulation blocker approved for immunosuppression in renal transplant recipients. This
agent has a potential benefit over standard calcineurin (CNI) based immunosuppression in that it avoids CNI nephrotoxicity. To our knowledge, available literature regarding the use of belatacept in lung transplantation is currently limited to one case study. Case Report: We report on a 64 year old female who underwent bilateral lung transplantation 2 years prior secondary to Idiopathic Pulmonary Fibrosis. Current immunosuppression consisted of tacrolimus, sirolimus and prednisone. The patient presented to the acute care setting with decreased appetite, tiredness, shortness of breath and minimal epistaxis. Empiric antibiotics were initiated and a bronchoscopy showed alveolar hemorrhage. Of note, the patient also presented with acute kidney injury, thrombocytopenia, and confusion/lethargy. A peripheral smear showed the presence of schiztocytes, and a diagnosis of Thrombocytopenic Thrombotic Purpura / Hemolytic Uremic Syndrome (TTP/HUS) was made. She received 5 sessions of therapeutic plasma exchange. At that time, her TTP/HUS was thought to be secondary to tacrolimus - which was discontinued. Sirolimus was also stopped due to the uncertain nature of her alveolar hemorrhage. After extensive deliberation, this patient was started on belatacept every 2 weeks and ciprofloxacin for meningococcal prophylaxis. She could not be placed on cell cycle inhibitors due to leucopenia and existing bone marrow suppression. The patient’s platelet count, mental status and renal function eventually improved with plasma exchange, and she was discharged to a rehabilitation facility. A surveillance bronchoscopy performed 4 weeks after initiating belatacept was negative for acute rejection. Furthermore, donor specific antibodies remained negative at this time. Summary: In summary, we present the case of a lung transplant patient unable to tolerate CNI or mTOR based immunosuppression who is successfully maintained on the costimulatory antagonist belatacept at present. Belatacept may be considered in lung transplant recipients as an immunosuppressive agent of last resort for those unable to tolerate more conventional therapies, and further studies are needed to fully elucidate its utility in this population. 6( 5) Successful Use of Cidofovir and Leflunomide in Lung Transplant Recipient with BK Polyomavirus Encephalitis P. Ong ,1 A. Fuentes,2 K. Dawson,2 N. Sinha,3 B. Mankidy,3 M. Loebe,3 T. Kaleekal,3 S. Jyothula.3 1Pulmonary and Critical Care Medicine, Baylor College of Medicine, Houston, TX; 2Department of Pharmacy, Houston Methodist Hospital, Houston, TX; 3JC Walter Jr Transplant Center, Houston Methodist Hospital, Houston, TX. Introduction: The importance of polyomavirus BK as cause of nephropathy in renal allograft recipients is well documented, and it is also a known cause of urothelial disease causing hematuria after bone marrow transplantation. We report a rare case of BK polyoma virus encephalitis in a lung transplant patient, and its successful treatment with cidofovir, leflunomide and reduced immunosuppression. Case Report: We present the case of a 58-year-old African American female with a history of bilateral lung transplantation 3 years ago for COPD. The patient was recently diagnosed with Bronchiolitis Obliterans Syndrome and treated with rabbit antithymocyte globulin (rATG). Maintenance immunosuppression included tacrolimus, sirolimus and low dose prednisone. Approximately 1 month after receiving rATG, the patient was admitted for acute renal failure and hyperkalemia requiring dialysis. During this hospitalization, her mental status deteriorated, with a waxing and waning course, and delirium was initially suspected. MRI of the brain showed moderate signal change in the peri-ventricular white matter and on the pons. A lumbar puncture was performed showing elevated protein, normal glucose, and an elevated opening pressure. Further viral studies revealed a BK Virus PCR of 750 copies/ul. Her plasma BK virus PCR was negative. Given her mental status, MRI results, and CSF PCR findings, the patient was initiated on Cidofovir 2mg/kg IV every 2 weeks and Leflunomide 40 mg daily. This regimen was extrapolated from protocols in patients who developed renal allograft BK virus nephropathy. After a prolonged ICU stay, the patient transitioned to acute care and acute rehabilitation where her weakness and mental status improved. After one month of treatment with cidofovir, leflunamide and reduced immunosuppression, she has improved with physical therapy and is no longer bedridden. A repeat lumbar puncture after 4 weeks of treatment showed clearance of the virus from the CSF. Summary: In summary, BK virus encephalitis may be a potential cause of altered mental status and leathery in severely immunosuppressed lung transplant recipients. Treatment with Cidofovir and Leflunomide, along with reduced immunosuppression, can be considered in this setting.
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The Journal of Heart and Lung Transplantation, Vol 32, No 4S, April 2014
6( 6) Ultrasound-accelerated, Catheter-directed Thrombolysis in the Treatment of LVAD Thrombosis R.T. Cole , E.C. Clermont, D. Gupta, M. Jokhadar, M. Millard, K. McTeague, V. Babaliaros. Cardiology, Emory University, Atlanta, GA. Introduction: The advances in the field of mechanical circulatory support in the last 10 years have been substantial, but the risk of catastrophic complications remains, including LVAD thrombosis. Herein we present a case of LVAD thrombosis treated with a novel therapy (Ultrasound-accelerated catheter-directed thrombolysis, or UACDT). Case Report: A 43 year-old woman with dilated cardiomyopathy underwent placement of a HeartWare LVAD as a bridge-to-transplant. She re-presented on POD 180 with evidence of acute LVAD thrombosis, including new symptomatic CHF, elevated LDH (6000 U/L), and pump power spikes. Echo revealed a poorly unloaded left ventricle. The patient was started on heparin and tirofiban infusions with some improvement. However, on day 5 pump power rose abruptly to a peak of 45W, and the pump speed spontaneously dropped from 2700 to 2400 RPM. At this time the decision was made to use ultrasound-accelerated, catheter-directed thrombolytics (UACDT) as salvage therapy. In the cath lab, an EkoSonic catheter was placed directly into the apical inflow cannula, and UACDT was used for 67 hours at a rate of alteplase 1 mg/hour. This led to complete normalization of pump power (4 watts) and flow (6.0 lpm) and marked clinical improvement. Summary: Our patient presented with an acute LVAD thrombosis and failed conservative treatment with heparin/tirofiban infusions. Thus, a more aggressive treatment was chosen (UACDT). To our knowledge, this is the first case of LVAD thrombosis managed with UACDT.
6( 7) Teen Pocket PATH: A Randomized Pilot of a Mobile Health Application To Improve Adherence Among Adolescent Solid Organ Transplant Recipients D.A. Shellmer ,1 A. DeVito Dabbs,2 M. Dew,3 G. Mazariegos.1 1Hillman Center for Pediatric Transplantation, University of Pittsburgh/Children’s Hospital of Pittsburgh, Pittsburgh, PA; 2Nursing, University of Pittsburgh, Pittsburgh, PA; 3Epidemiology, Psychiatry, University of Pittsburgh, Pittsburgh, PA. Purpose: In this study we sought to examine the impact of a mobile health application (Teen Pocket PATH® [TPP]) specifically developed for use with solid organ adolescent transplant patients and their primary caregivers on self-monitoring and adherence. Methods: Starting in 2012 we recruited adolescent solid organ transplant patients who were 0-2 years post-transplantation and their primary caregivers for participation. Participants were randomly assigned to either the active TPP mobile health application intervention or standard care for a period of 3 months. Participants completed measures assessing self-reported
adherence, barriers to adherence, and health related quality of life at baseline and at the end of the study. Laboratory values for the primary immunosuppressant prescribed, rejection episodes, and number and length of hospital stays were obtained from the medical record. We also collected electronic data detailing medication adherence patterns for participants in the TPP arm of the study and paper logs for those in standard care. Results: To date a total of 24 participants (12 in the TPP arm and 12 in the control arm) and their primary caregivers have been recruited into the study. Of these 17 participants and their caregivers have completed the 3-month randomized control trial. The participant sample (aged 11-18 years) was 54.2% female, 95.8% White, and 29% cardiothoracic transplant recipients. The caregiver sample (aged 33-57 years) was primarily female (69.6% were mothers), White (95.8%), currently married (78.3%), and employed fulltime (43.5%). Preliminary results suggest that all TPP participants engaged in daily monitoring of their medications through the use of the TPP mobile health application, while the majority of participants in the standard care group reported not keeping paper and pencil logs. The TPP participant group reported fewer late adminitrations of their primary immunosuppressant medication than the standard care group at the end of the study period. Conclusion: The TPP mobile health application shows promise in assisting adolescents and their primary caregivers monitor medication adherence compared to traditional paper and pencil logs. In addition, reminder features of the TPP intervention appear to enhance participants’ abilities to take medications on time. 6( 8) Longer Versus a Shorter Duration Exercise Rehabilitation Program Following Lung Transplant: A Randomised Controlled Trial L.M. Fuller ,1 B. Button,1 B. Tarrant,1 R. Steward,1 G. Snell,2 A. Holland.3 1Physiotherapy, The Alfred Hospital, Melbourne, Australia; 2Lung Transplant AIRMED, The Alfred Hospital, Melbourne, Australia; 3Physiotherapy La Trobe University, The Alfred Hospital, Melbourne, Australia. Purpose: Exercise rehabilitation is a key element of the recovery process following adult lung transplantation. Worldwide, exercise rehabilitation programs vary in type, duration and format. This study aimed to investigate the effects of a longer versus shorter duration rehabilitation program after lung transplantation. Methods: Post lung transplantation patients aged 18 years or older who had undergone either single(SLTX) or bilateral lung (BSLTX) transplantation were randomised to either a shorter rehabilitation program (7 weeks) or a longer program (14weeks). Exercise sessions were thrice weekly and consisted of cardiovascular training on bike ergometer and treadmill and upper and lower limb strength training.Outcome measures were taken at baseline,7 weeks,14 weeks & 6 months by assessors who were blinded to group allocation. Functional exercise capacity was measured by 6 minute walk test (6MWT).Strength of quadriceps and hamstrings was measured on an isokinetic dynamometer (KinCom) and recorded as the average peak torque (APT) of six repetitions for both muscle groups. Quality of life (QOL) was assessed with SF36. Results: 66 participants (33 females) with a mean age of 51(SD 13),had BSLTX(86%) & primary diagnosis of COPD in 41%. The 6MWD increased in both groups with no significant difference between groups at any time point (mean 6 month 6MWD short 590(SD85) m vs long 568(SD127) m, p= 0.50). Similarly, at six months there was no difference between groups in quadriceps APT (105 (6)Nm vs mean103(6)Nm p= 0.62 ), hamstring APT(50(2.7) Nm vs 48(2.8)Nm, p= 0.31 ) or mental or physical health domains of QOL. Conclusion: Shorter duration (7weeks) of rehabilitation achieves comparable outcomes to 14 weeks of rehabilitation for functional exercise capacity, LL limb strength and QOL at six months after lung transplantation. 6( 9) Perceived Control: A Target for Improving Psychosocial Outcomes Early After Heart Transplant L. Doering ,1 K. Hickey,2 B. Chen,1 F. Idemundia,1 E. Carter,3 D. Pickham,3 C. Castillo,2 D. Mancini,4 M. Deng,5 J. Kobashigawa,6 B. Drew.3 1School of Nursing, UCLA, Los Angeles, CA; 2School of Nursing, Columbia University, New York, NY; 3School of Nursing, UCSF, San Francisco, CA; 4Columbia University Medical Center, New York, NY; 5UCLA Ronald Reagan Medical Center, Los Angeles, CA; 6Cedars-Sinai Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA.
