Vaccinating Lung Transplant Candidates

S366

The Journal of Heart and Lung Transplantation, Vol 36, No 4S, April 2017

Purpose: Valganciclovir (VGC) and other myelosuppressive drugs often cause leukopenia post-transplant. Dose reduction/early discontinuation of VGC therapy is associated with increased CMV infection. We sought to identify risk factors for leukopenia in CMV D+/R- cardiothoracic transplant recipients (CTR) on VGC therapy and associated outcomes. Methods: An analysis of all CMV D+/R- CTR from 11/11-8/15 was conducted; multiorgan transplant and death during transplant admission were excluded. Leukopenia was defined as WBC < 3000. Per center protocol all CMV D+/R- CTR received VGC for 6-12 months posttransplant. Results: Of the 66 CMV D+/R- CTR included, 31 (46.9%) experienced leukopenia during VGC prophylaxis. No differences in baseline demographics, other myelosuppressive drugs, or 1 year rejection rates were seen between the leukopenic and non-leukopenic groups (Table 1). While not statistically significant, a BMI < 25 and those receiving thymoglobulin induction had increased incidence of leukopenia. Nearly half (14/31, 45.2%) of leukopenic CTR were on higher VGC doses than recommended based on renal function at time of leukopenic event. Lower WBC early posttransplant were associated with increased risk of developing leukopenia, even though the median time to first leukopenic episode was 110 days. Rate of CMV viremia at 1 year was high, with viremia more prevalent in CTR who experienced leukopenia during VGC therapy. VGC was discontinued (n= 8, 25.8%) or dose reduced (n= 3, 8.7%) in 11 leukopenic CTR; 2/3 dose reductions were inappropriate based on renal function. 4/11 (36.4%) experienced CMV viremia within 60 days of VGC adjustment. Conclusion: Leukopenia is common among CMV D+/R- CTR during VGC prophylaxis. Early VGC discontinuation/dose reduction was associated with a significant risk for CMV viremia. Posttransplant decline in WBC may represent an early marker for leukopenic events, and a BMI < 25 and thymoglobulin induction may be risk factors for leukopenia during VGC prophylaxis.

Results: 145 heart transplants were performed during the study period; 22 (15.1%) required conversion to AZA, mostly due to GI intolerance. HTRs requiring AZA conversion were older but otherwise had similar baseline characteristics (Table 1). No differences in mortality, BPAR, and CMV viremia were seen between AZA and MPA cohorts. The AZA cohort had a higher rate of skin cancers (27.3 vs. 13.8%, p= 0.11), however the AZA group did have a longer post-transplant follow up. Maintenance immunosuppression was different as well, with AZA HTRs more likely to remain of corticosteroids as well as have mTORi added. Regarding hematologic toxicities, mean WBC and platelet count were similar between the AZA and MPA cohorts at 1 and 3 years with lower hemoglobin concentrations in the AZA cohort at 1 year (11.6 vs. 12.7 p= 0.006) but not 3 years (13.2 vs. 13.5 p= 0.69). Conclusion: In this limited cohort, AZA appears to be a safe alternative to MPA when toxicities necessitate conversion. Similar rejection rates were seen with no apparent increase in toxicities, although the increased numerical rate of skin cancers warrants judicious monitoring following AZA conversion.

1( 124) Vaccinating Lung Transplant Candidates M.G. Cortez , L. Potter.  Department of Pharmacy, The University of Chicago Medicine, Chicago, IL.

1( 123) Still Inferior? Risks of Azathioprine in Tacrolimus Based Regimens for Heart Transplant Recipients J.P. Casale , A.T. Logan, C.T. Doligalski.  Tampa General Hospital, Lutz, FL. Purpose: Mycophenolate (MPA) is the antimetabolite of choice in heart transplant recipients (HTRs), based largely on data from cyclosporine (CSA)based regimens. Toxicities of MPA are common and the risks associated with azathioprine (AZA) use in combination with tacrolimus is not well described. Methods: An analysis of all HTRs at a single center from 11/11-7/15 was conducted; re-transplant, multi-organ recipients and HTRs on CSA were excluded. Rates of cellular and antibody mediated rejection, CMV viremia, and skin cancers at 1 and 3 years were compared between AZA and MPA cohorts.

Purpose: In 2015, transplant pharmacists at the University of Chicago identified an opportunity to improve vaccination rates for transplant candidates. A pharmacist-led program was launched on 10/01/15 whereby the transplant pharmacist assesses patient records and outlines a vaccination plan for each patient as part of the pre-listing transplant pharmacy evaluation. This study evaluates the impact of this pharmacist-driven intervention on vaccination rates in our lung transplant candidates. Methods: Electronic medical records were retrospectively reviewed for waitlist dates, transplant dates, relevant serologic testing, and vaccines given for eight target vaccines: 13-valent pneumococcal conjugate; 23-valent pneumococcal polysaccharide; influenza; hepatitis A; hepatitis B; tetanus, diphtheria, and pertussis; varicella zoster; and herpes zoster. We present data for three cohorts: 1) pre-intervention including patients transplanted 1/01/14 - 6/30/15 (n= 37), 2) post-intervention/transplanted including patients transplanted 10/01/15 - 10/01/16 (n= 19), and 3) post-intervention/waitlist including patients on the waitlist as of 10/01/16 (n= 9). Each vaccine for each patient was categorized as not indicated, completed, in progress (e.g., for vaccines administered in sequence), or overdue for administration.

Abstracts S367 Results: Summarized in the table below, results from this study show a notable increase in vaccination rates for 6 of our 8 target vaccines as a result of this pharmacist-led intervention. Vaccination rates for varicella zoster and herpes zoster remained low due to the 4-week waiting period required between vaccination and eligibility for transplantation. Conclusion: This data demonstrates that a pharmacist-led assessment of vaccination can significantly improve vaccination rates among transplant candidates. We suggest that vaccine assessment become a routine part of a transplant pharmacist’s pre-listing evaluation.

Rate of Vaccination in Lung Transplant Candidates Pre-intervention Post-intervention Post-intervention (transplanted)(N= 37) (transplanted)(N= 19) (waitlisted)(N= 9) Vaccine Name 13-valent pneumococcal conjugate 23-valent pneumococcal polysaccharide Influenza Hepatitis A Hepatitis B

(Not indicated, completed, in progress, overdue) 0%, 32%, 22%, 46% 0%, 63%, 5%, 32% 0%, 67%, 11%, 22% 0%, 51%, 35%, 14% 0%, 53%, 26%, 21% 0%, 67%, 33%, 0% 24%, 54%, 0%, 22% 32%, 53%, 0%, 16% 0%, 89%, 0%, 11% 46%, 11%, 24%, 19% 32%, 16%, 42%, 11% 22%, 44%, 22%, 11% 11%, 24%, 38%, 27% 16%, 16%, 53%, 16% 0%, 56%, 33%, 11% 0%, 51%, 0%, 49% 0%, 79%, 0%, 21% 0%, 89%, 0%, 11%

Tetanus, diphtheria, and pertussis Varicella zoster

89%, 5%, 0%, 5%

Herpes zoster

14%, 8%, 0%, 78%

95%, 0%, 0%, 5%

67%, 0%, 0%, 33% 11%, 11%, 0%, 79% 33%, 0%, 0%, 67%

1( 125) Penicillium Species: Prevalence and Impact on Clinical Outcomes Following Lung Transplantation N. Hudec ,1 C. King,2 M. Fregoso,2 A. Brown,2 O.A. Shlobin,2 A.B. Cochrane.2  1Butler University, Indianapolis, IN; 2Inova Fairfax, Falls Church, VA. Purpose: Penicillium sp. (PEN) are one of the most common environmental fungi and are frequently isolated on post-transplant surveillance bronchoscopy (BAL). It is unclear if PEN colonization is associated with adverse outcomes post-transplant and if treatment with anti-fungal therapy is warranted. Azole activity against PEN has shown mixed sensitivity in in vitro analyses. Methods: Retrospective chart review. Results: We analyzed our 2012-2015 post-transplant cohort with reported PEN growth at some time after their lung transplant. We identified 56 patients, but excluded 3 with pre-transplant PEN colonization. Standard 12 month fungal prophylaxis (propx) was employed from 2012 to 2014 and changed to 6 month duration from 2014 to current. BAL-isolated PEN was almost uniformly treated with azoles in our post-transplant patients regardless of time after transplant. The majority of patients were male (60%), with IPF as the primary indication for lung transplant. 43 patients (81%) had PEN isolated on BAL while on azole therapy, while 10 (19%) developed it in the absence of azole antifungal propx. 9 patients (18%) grew PEN in the three months following the treatment for acute cellular rejection and 2 of these were not on azole antifungal at the time of PEN growth. 18 of the PEN cultures (36%) were obtained from BAL “for cause”, the remainder were in the context of routine surveillance. Nine patients (18%) had other concomitant fungal growth on BAL. Of the patients not on azole therapy at the time of PEN identification, 80% cleared without any treatment. Almost 33% of patients on azole propx at time of PEN identification did not receive any additional antifungal therapy and subsequently cleared PEN. About 15% of the cohort did not clear PEN despite at least 1.5 years of additional antifungal treatment. No deaths in this cohort were due to invasive fungal infections. There was no clear correlation between fungal clearance in patients treated or not treated with additional azole therapy.

Conclusion: PEN growth appears to be common after lung transplantation whether or not patients are on azole antifungal therapy. In fact, it may persist despite azole antifungal therapy. Further studies to assess the clinical significance of PEN would be helpful to define its pathogenicity and thus the optimal treatment strategy, and if treatment is required. 1( 126) Pain Pathway in Lung Transplantation Is Associated with Excellent Peri-Operative Outcomes: A Case Series D.B. Berkheim ,1 T.A. Nicholas,2 M.J. Moulton,1 H.M. Strah,3 A. Siddique.1  1Surgery Division of Cardiothoracic Surgery, University of Nebraska Medical Center, Omaha, NE; 2Anesthesiology, University of Nebraska Medical Center, Omaha, NE; 3Internal Medicine Division of Pulmonary, Critical Care, Sleep & Allergy, University of Nebraska Medical Center, Omaha, NE. Purpose: A comprehensive pain management pathway has not been previously described in lung transplantation. We describe a standardized perioperative pain pathway that is safe and associated with excellent clinical outcomes in a small series of patients. Further study will assess peri-operative functionality as well as chronic pain and need for opioid medications. Methods: Six patients have received lung transplants at our institution, all were managed under this pathway. The pain service met patients pre-operatively and managed them. Patients received pregabalin and acetaminophen pre-operatively and continued throughout their stay. Intraoperative pain control was at the discretion of the anesthesia team. In the first 24 to 48 hrs a hydromorphone PCA was initiated. POD 1-2, a thoracic epidural (0.1% bupivacaine) was placed. POD 3-4, the patient was transitioned from PCA to PO oxycodone. Data from the patient’s chart was gathered retrospectively and summarized below. Results: Indications included cystic fibrosis, IPF, COPD and lymphangioleiomyomatosis. Three patients had clamshell incisions, 1 patient had a right posterolateral thoracotomy, and 2 patients had bilateral anterolateral thoracotomy without division of the sternum. Mean time to postoperative epidural placement was 22.9 hrs. Mean NRS pain scores (0 to 10) at 24 hrs. was 4.5. All other mean pain scores were less than 3.8 during hospitalization. Mean time to extubation was 28.2 hrs. Mean ICU length of stay was 3.1 days. Mean hospital length of stay was 21.3 days. Mean days of epidural use was 7.2 days. There have been no mortalities. There were no epidural complications. At follow up two patients are still requiring opioid medication for pain issues unrelated to the index surgery. Average post-op six-minute walk distance at initial outpatient rehab visits was 1244 ft. Four patients have finished rehab and had an average final six-minute walk distance of 1425 ft. Conclusion: A comprehensive pain management pathway has not been previously described in lung transplantation. We describe a standardized perioperative pain pathway that is safe and associated with excellent clinical outcomes in a small series of patients. Further study will assess peri-operative functionality as well as chronic pain and need for opioid medications. 1( 127) Intra-Patient Variability of Tacrolimus Levels and Lung Allograft Outcomes: A Single Centre Experience L. Diannelidou-Stamelou ,1 L. Spurr,1 N. Leaver,1 J. Smith,1 A. Simon,1 M. Carby,1 A. Reed,1 L. Wei,2 H. Lyster.1  1Royal Brompton & Harefield NHS Foundation Trust, London, United Kingdom; 2Department of Practice and Policy, University College London, London, United Kingdom. Purpose: Intra-patient variability (IPV) of tacrolimus (TAC) levels has been reported as a risk factor for poor long-term outcomes in patients after renal transplantation. Post-lung transplantation, immunosuppression is TAC, aiming for a target range of 8-13ng/ml for the first three months then reduced to 5-10ng/ml thereafter; together with mycophenolate mofetil and corticosteroids. The aim of this study was to investigate whether high IPV of TAC levels within the first year after lung transplantation was associated with poor outcomes. Methods: Retrospective analysis of transplants from October 2010-14 identified lung transplant recipients who received TAC. We excluded patients who died or had TAC discontinued within 1-year. Coefficient of variance (COV) was defined as SD/mean of TAC levels taken at monthly intervals. High variability (HV) was defined as a COV greater than the median. Outcomes were