Successful transplantation of B. cepacia complex infected cystic fibrosis patients; transplanting B. cenocepacia (genomovar III) infected patients

The Journal of Heart and Lung Transplantation Volume 23, Number 2S

91 SURVIVAL FOLLOWING LUNG TRANSPLANTATION (LT) OF CYSTIC FIBROSIS (CF) PATIENTS INFECTED WITH BURKHOLDERIA CEPACIA COMPLEX (BCC) B.D. Alexander,1 E.A. Wills,1 L.B. Reller,1 E.S. Yow,2 S.M. Palmer,3 R.D. Davis,4 C.W. Woods,1 J.J. LiPuma,5 1Division of Infectious Diseases and International Health, Department of Medicine, Duke University Medical Center, Durham, NC; 2Duke Clinical Research Institute, Duke University Medical Center, Durham, NC; 3 Division of Pulmonary and Critical Care Medicine, Department of Medicine, Duke University Medical Center, Durham, NC; 4 Division of Cardiovascular and Thoracic Surgery, Department of Surgery, Duke University Medical Center, Durham, NC; 5 Department of Pediatrics and Communicable Diseases, University of Michigan Medical School, Ann Arbor, MI Purpose: Some centers consider Bcc infection in CF patients prior to LT a contraindication to transplantation. Recent studies suggest that within the Bcc, B. cenocepacia (formerly genomovar III) is associated with particularly increased rates of mortality compared to other species. We investigated the impact of Bcc infection on mortality following LT to determine if B. cenocepacia is associated with a higher post-LT mortality. Methods: Isolates from Bcc-infected CF patients were recovered from frozen stocks and species designation within the Bcc was determined by 16S rDNA and recA gene analyses. Associations between mortality and infection were assessed using survival analysis. Results: Seventy-five consecutive CF patients underwent LT from 9/92 to 8/02. Fifty-six patients had no Bcc isolated within 1 year prior to LT (Group 1). Nineteen patients had Bcc pre-LT (Group 2); 9 had B. cenocepacia, 9 had other Bcc species, and from 1 no stored isolate was available (not included in the species specific analysis). Bccinfected patients had significantly worse survival. Overall survival in Group 1 was 96%, 93%, 78% and 69% at 1 month, 1 year, 3years, and 5 years, respectively, as compared to 84%, 63%, 55% and 22% in Group 2 (p-value ⫽ 0.0078, Log-Rank Test). For patients infected with B. cenocepacia, survival at 1 month,1 year, and 3 years was 78%, 33%, and 33% respectively, significantly worse than survival as noted above for Group 1 or those infected with other Bcc species, 89%, 89%, and 74% (1 month, 1 year, and 3 years, respectively) (p-value ⫽ 0.0010). Conclusions: Infection with Bcc is associated with decreased survival following LT. Mortality is significantly worse for those infected with B. cenocepacia as compared to other Bcc species. Although the number of patients with B. cenocepacia is relatively small, our results support careful screening of all CF patients for Bcc, and possible exclusion of those infected with B. cenocepacia. 92 HIGH DOSE RATE BRACHYTHERAPY FOR IN-STENT RESTENOSIS OF LUNG TRANSPLANT BRONCHI S.M. Studer,1 B.A. Johnson,1 K.R. McCurry,2 E. Cano,1 A.T. Iacono,1 1 Division of Pulmonary & Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA; 2Division of Cardiothoracic Surgery, University of Pittsburgh Rationale: Bronchial stenosis after lung transplantation results in obstructive airways disease and increased risk of pulmonary infection. Stenting of bronchial stenosis results in improved airway patency and a reduced infection rate in the year following stent placement. Recurrence of bronchial stenosis after stent placement that fails attempts at debridement and dilatation is a particularly challenging complication. We report our experience with brachytherapy for treatment of 5 cases of recurrent bronchial stenosis after stent placement in lung transplant recipients (LTRs).

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Methods: Five LTRs with recurrent bronchial stenosis after stent placement were treated unsuccessfully with mechanical debridement and laser therapy to eliminate in-stent granulation tissue. Each was subsequently treated once with high dose rate intraluminal brachytherapy (IR-192). The calculated dose of 700 cGy in 4 LTRs and 500 cGy in 1 LTR was delivered to the targeted area of in-stent restenosis. Results: Each patient had an initial complete response after brachytherapy. Follow-up bronchoscopies at 2 weeks, 3 months and 6 months after therapy revealed airway patency in all the treated areas. One patient with 2 stents underwent successful brachytherapy treatment of only one in-stent stenosis while the untreated stent required three subsequent dilatation procedures to date. Three of the 5 patients realized and maintained a mean of 56% improvement in their FEV1 compared to pre-treatment values. One patient had no significant change in his spirometry at 3 months after his procedure and one patient’s overall spirometry decreased secondary to obliterative bronchiolitis but maintained large (brachytherapy-treated) airway patency. There were no treatment-related complications observed. Conclusion: Recurrence of bronchial stenosis following stent placement that fails treatment with debridement and dilatation may benefit from HDR brachytherapy for control of granulation tissue. In our series a dose rate of 500 –700 cGy administered as a single treatment resulted in sustained airway patency and no significant adverse events.

93 SUCCESSFUL TRANSPLANTATION OF B. cepacia COMPLEX INFECTED CYSTIC FIBROSIS PATIENTS; TRANSPLANTING B. cenocepacia (GENOMOVAR III) INFECTED PATIENTS A. De Soyza,1 A. McDowell,2 J.R.W. Govan,3 K.F. Gould,4 P.A. Corris,1 1Transplantation and Immunobiology, University of Newcastle, Newcastle, Tyne and Wear, United Kingdom; 2 Biomolecular Sciences Group, School of Pharmacy, Queen’s University, Belfast, Northern Ireland, United Kingdom; 3Medical Microbiology, University of Edinburgh, Edinburgh, Lothian, United Kingdom; 4Medical Microbiology, Freeman Hospital, Newcastle, Tyne and Wear, United Kingdom Introduction: Previously, we reported that Cystic Fibrosis patients with pre-transplant B. cenocepacia (genomovar III) infections had poor post-transplant outcomes compared to those with other B. cepacia complex pre-transplant infections. Methods: We determined the prevalence and clonality of Burkholderia cepacia complex genomovars isolated from patients referred for transplant assessment between 1989 to the present and, where appropriate, related strain type to transplant outcome. Results: Isolates from 29 patients were identified as B. cepacia complex organisms by molecular analysis. Thirteen patients (45%) were infected with the highly transmissible ET-12 strain of B. cenocepacia recA lineage III-A, while all remaining patients were infected with genetically unique B. cenocepacia, B. multivorans and B. vietnamiensis strains. All previously reported post-transplant deaths were associated with ET-12 infection. We have altered our peri-transplant management of the B. cenocepacia infected patient and successfully transplanted 2 ET-12 infected patients and a further patient with a non-ET12 B. cenocepacia infection. We now omit induction T-cell ablation, reduce target trough cyclosporin levels, washout the pleural cavities with the disinfectant taurolidine, and commence a 48 hour multi-antibiotic regimen (dependent on recent sensitivities). Their antibiotic regimens were aztreonam, clindamycin, gentamicin and systemic taurolidine (250ml 2% taurolidine qds) and in the second patient clindamycin, chloramphenicol and temocillin with nebulised taurolidine administration. The patient with a unique

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The Journal of Heart and Lung Transplantation February 2004

B. cenocepacia strain did well with aztreonam. All 3 patients are alive at up to 18 months post transplant Conclusions: The ET-12 strain is the predominant cause of B. cenocepacia infections in CF patients referred to our pulmonary transplant centre, and is associated with poor transplant outcomes using standard treatment regimens.

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Since 1985, 151 heart-lung transplants have been performed at Harefield Hospital for congenital heart disease. Twenty (15%) of these patients had complex pulmonary atresia (PA) with a ventricular septal defect and major arterio-pulmonary collateral arteries and constitute the subject of this abstract. The ages of the patients were between 1.1 and 43 (mean 18.3) years. There were 13 males and 7 females. In 6 patients there had been no previous operation, 7 patients had undergone 1 lateral thoracotomy, 4 patients 2 lateral thoracotomies and 3 patients 3 or more lateral thoracotomies. Sixteen patients (80%) died without leaving hospital after their transplant (0 –130 days). Two of the younger patients died of rejection, 1 of which was hyperacute, and 1 child died of graft failure. The remaining 13 patients died as a consequence of bleeding and massive transfusion, which led to multi-organ failure. There was 1 survivor from the group of patients who had had no previous operations and 3 from the group that had had 1 previous thoracotomy. Factors contributing to bleeding included extensive native mediastinal arterial and venous collaterals, adhesions from previous operations and hyperactive sternal bone marrow secondary to polycythaemia. There were 2 late deaths, both from obliterative bronchiolitis, 2.4 and 7.5 years after transplantation (Tx). Two patients (10%) are alive and well 12.5 and 17.5 years after Tx. Fourteen of the 16 early deaths occurred prior to 1992, when our policy for acceptance for Tx of complex PA was reviewed. Since that date 4 patients referred for Tx underwent a palliative procedure with 1 death, 7 further patients underwent stage correction with 1 death (14%). Five patients were either removed from or died on the waiting list, 2 patients were transplanted and both died. One adult patient remains on the waiting list and no new patient has been added to it since 1998. It is concluded that heart-lung Tx in this group of patients has very poor results. These results have led to a policy in our unit of only accepting such patients under very exceptional circumstances.

LUNG TRANSPLANT WITH CONCOMITANT CARDIAC SURGERY: RESULTS AND LONG-TERM SURVIVAL K. Parekh,1 N. Moazami,1 B.F. Meyers,1 T.J. Guthrie,1 E.P. Trulock,2 J.D. Cooper,1 G.A. Patterson,1 1Division of Cardiothoracic Surgery, Washington University School of Medicine, St. Louis, MO; 2Division of Pulmonary Medicine, Washington University School of Medicine, St. Louis, MO Introduction: Patients requiring simultaneous cardiac surgery and lung transplantation are clinically challenging. Our aim was to study the operative results and long-term survival of patients who underwent concomitant cardiac surgery and lung transplantation at our institution. Methods: A retrospective chart review of patients was performed. Survival was analyzed by Kaplan-Meier method. Results: From 1988 –2003, 35 (15 single; 20 bilateral) of 700 lung transplant recipients underwent concomitant cardiac surgery. The cardiac procedures included patent foramen ovale closure (n ⫽ 18), atrial septal defect repair (n ⫽ 9), ventricular septal defect repair (n ⫽ 2), coronary bypass (n ⫽ 3), and other (n ⫽ 3). Ischemic time, use of ECMO, length of hospital stay and mortality were not significantly different in this group of patients compared to those who had lung transplantation alone (table1). Ventilator time and ICU stay was longer in the cardiac surgery group. Survival was not different between the two groups (figure1). Conclusions: Cardiac surgery and lung transplantation can be performed with acceptable morbidity and mortality compared to isolated transplantation. The survival in these patients is similar to other lung transplant recipients.

HEART-LUNG TRANSPLANTATION FOR COMPLEX PULMONARY ATRESIA: A SINGLE CENTRE EXPERIENCE R. Radley-Smith,1 N.R. Banner,1 A. Khaghani,1 J. Wray,1 M. Yacoub,1 1Transplant Directorate, Royal Brompton and Harefield NHS Trust, Harefield, Middlesex, United Kingdom

Comparison of selected outcomes following lung transplant Variable

Age at transplant (years) Ischemic time (minutes) ECMO required Ventilator (days) ICU (days) Length of Stay (days) Hospital mortality

Concomitant Cardiac Surgery (n ⴝ 35)

Lung Transplant Only (n ⴝ 665)

p value

39 ⫾ 12 301 ⫾ 72 3 (9%) 5 (IQR: 2–10) 6 (IQR: 4–11) 18 (IQR: 13–32) 4 (11%)

48 ⫾ 12 285 ⫾ 66 16 (2%) 2 (IQR: 1–4) 3 (IQR: 2–5) 17 (IQR: 12–24) 49 (7%)

⬍0.001 0.177 0.073 ⬍0.001 ⬍0.001 0.217 0.328

96 FREQUENT SURVEILLANCE BIOPSIES DO NOT IMPROVE SURVIVAL FOLLOWING HEART TRANSPLANT C.K. Wallace,1 M. Koerner,2,3 V. Thohan,2,3 G. Torre-Amione,2,3 1 Baylor College of Medicine, Houston, TX; 2Department of Medicine, Cardiology Section, Baylor College of Medicine, Houston, TX; 3The Methodist DeBakey Heart Center, The Methodist Hospital, Houston, TX Background: Routine surveillance biopsies are used in the post-heart transplant setting to detect and treat sub-clinical acute rejection. No outcome data exists to establish that this identification and treatment improves transplant survival. Preliminary data suggested that frequent biopsies were unnecessary; based on these data we modified our biopsy regimen in 1999. We then sought to determine whether decreasing the frequency of post-transplant surveillance biopsies affected the survival of our heart transplant patients. Methods: Between 1990 and 1998, 253 heart transplants were performed at our center. Post-transplant biopsies were performed q wk for 4 wks, q 2 wks until 3 months, q month through month 6, at months 8, 10, 12 and then annually for life. Beginning in 1999, all routine biopsies after month 6 were eliminated and patients were biopsied only when clinically indicated. 135 patients have been followed under this schedule. Kaplan-Meier survival curve analyses were performed to compare the survival of the early group with the survival of the later group. Survival was also compared to overall