- Email: [email protected]
Living-Donor Lobar Lung Transplantation with Undersized Lobar Grafts Can Provide Comparable Long-Term Pulmonary Function and Exercise Capacity to Cadaveric Lung Transplantation
S190
The Journal of Heart and Lung Transplantation, Vol 38, No 4S, April 2019
448 Initial Experience with Non-Perfused Organ Donors for Lung Transplantation Y. Watanabe,1 A. Healey,2 M. Scott,2 S. Lavery,2 K. Johnson,2 C. Mills,2 M. Galasso,1 M. Chen,1 J. Yeung,1 L. Donahoe,1 A. Pierre,1 M. de Perrot,1 K. Yasufuku,1 T.K. Waddell,1 S. Keshavjee,1 and M. Cypel.1 1Toronto Lung Transplant Program, Toronto General Hospital, Toronto, ON, Canada; and the 2Trillium Gift of Life Network, Toronto, ON, Canada. Purpose: Uncontrolled donation after death by circulatory criteria (uDCD) has the potential to alleviate some of the shortage of suitable lungs for transplantation. Non-Perfused Organ Donors (NPOD) differs from uDCD donors in that only lungs are obtained as no reperfusion is instituted after individuals suffer an unexpected sudden cardiac arrest. Family are approached rapidly by trained coordinators for consent to donate lungs. This study reviews our initial experience and challenges with NPOD donation. Methods: Data were collected from donors and recipients involved in NPOD lung transplants between February 2016 and October 2018. We describe NPOD donor volumes, ischemia time, utilization rates, length of intensive care unit (ICU) and hospital stay, and survival. Results: There were 101 referrals during this period. Of the 34 approached for donation, consent was obtained in 24 cases, and the lung transplant team evaluated 24 NPOD donors on site. Eleven donors were declined before retrieval because of medically unsuitable lungs, and 4 donors were declined after retrieval due to severe lung injury on site. Nine lungs underwent ex vivo lung perfusion in order to evaluate suitability for transplantation and eventually 3 were used for transplantation. Thus, the total utilization rate from consented donors was 12.5%. The mean warm ischemic time was 160 minutes (range: 106-175 minutes). The mean age of 3 recipients was 48 § 2.5 years. The 30-day mortality was 0%. One patient bridged to transplantation on extracorporeal membrane oxygenation (ECMO) was kept on ECMO for 5 days after transplant. Median ICU stay was 20 days (range: 5-78 days). Median hospital stay was 47 days (range: 18-100 days). Two out of 3 patients are alive at a median of 716 days (range: 100-936 days) with good performance status and lung function. One patient that was on ECMO prior to transplantation died of multisystem organ failure 100 days after transplantation. Conclusion: This study demonstrated the potential for NPOD lung donation. However, utilization rates are low. Therefore, improved strategies of lung preservation before retrieval are required to increase and select lungs that are utilizable for transplantation. 449 Time from Lung Transplant Donor Brain Death to Cross Clamp: An Analysis of the UNOS Registry O.K. Jawitz, V. Raman, Y. Barac, M. Mulvihill, C. Moore, A. Choi, M. Hartwig and J. Klapper. Department of Surgery, Duke University School of Medicine, Durham, NC. Purpose: It has been suggested that the length of time between donor brain death and cross clamp impacts post-transplant graft function and recipient survival in lung transplantation. Methods: The 2007-2018 United Network for Organ Sharing (UNOS) Registry was queried for all adult recipients undergoing isolated lung transplantation (single or bilateral) for the first time. Donation after circulatory death (DCD) donors or those with an unknown time from brain death until
cross clamp were excluded. Recipients were stratified by those who received an allograft from donors with times from brain death until cross clamp less than (SHORT) or greater than (LONG) the median. The primary outcome of interest was post-transplant survival, which was evaluated with Kaplan-Meier and Cox Proportional Hazards analyses. Results: 15,914 lung transplant recipients met inclusion criteria. Median time from donor brain death until cross clamp was 36 hours (IQR 17). Recipients of SHORT donors were more likely treated with IV antibiotics pre-transplant (12.3% vs 10.6%, p = 0.001) and spent a longer time on the waiting list (median 64 vs 58 days, p = 0.016). Both cohorts had similar lung allocation scores (median 40.8 vs 41.0, p = 0.292). Overall survival between the two cohorts was equivalent on Kaplan-Meier analysis (Figure 1, log-rank p = 0.776). On evaluation of other thresholds, time from donor brain death until cross clamp greater than the 75th percentile or less than the 25th percentile similarly did not impact recipient survival. After adjustment for donor and recipient characteristics, graft ischemic time, and year of transplant on Cox Proportional Hazards assessment, donor time from brain death until cross clamp was not associated with decreased survival (AHR 1.00, p = 0.981). Conclusion: Time from donor brain death until cross clamp is not associated with decreased post-transplant survival. Therefore, lung allografts from donors with a prolonged length of time from brain death until explant should not be viewed less favorably.
450 Living-Donor Lobar Lung Transplantation with Undersized Lobar Grafts Can Provide Comparable Long-Term Pulmonary Function and Exercise Capacity to Cadaveric Lung Transplantation D. Nakajima, T.F. Chen-Yoshikawa, T. Menju, T. Sato, M. Sonobe, Y. Yamada, Y. Yutaka, A. Ohsumi, M. Hamaji and H. Date. Thoracic Surgery, Kyoto University, Kyoto, Japan. Purpose: There has been concern of graft size mismatch due to the use of small lobar grafts for living-donor lobar lung transplantation (LDLLT). The purpose of this study is to compare the post-transplant pulmonary function and exercise capacity between LDLLT and conventional cadaveric lung transplant (CLT) patients. Methods: We performed 103 bilateral lung transplants, including 65 LDLLT and 38 CLT, between June 2008 and May 2017. The size matching criteria was as follows: in LDLLT, the calculated forced vital capacity (FVC) of the grafts was > 45% of the recipient predicted FVC; in CLT, the donor predicted vital capacity (VC) was between 70 and 130% of the recipient predicted VC. Pulmonary function and 6-minute walking distance were tested at 1, 3, 6, 12 months, and every year after transplantation. Results: The LDLLT patients received significantly smaller grafts than the CLT patients: the mean graft FVC was 65% of the recipient predicted FVC in the LDLLT, whereas the mean donor predicted VC was 98% of the recipient predicted VC in the CLT (P < 0.01). The LDLLT group demonstrated a similar %FVC to the CLT group after transplantation, although significant difference was found at 3 years between the groups (P = 0.03;
Abstracts Figure). Both groups demonstrated excellent 6-minute walking distance, sustained around 500 m throughout the study period (Figure). There was no significant difference in the incidence of chronic lung allograft dysfunction (CLAD) per donor between the groups (16% in LDLLT vs. 16% in CLT). The 1, 3, and 5-year survival rates did not differ between the groups (93, 82, and 75% in LDLLT vs. 89, 78, and 78% in CLT). Conclusion: LDLLT patients, who received significantly undersized lobar grafts, demonstrated great long-term pulmonary function, exercise tolerance, and survival rates, comparable to the CLT patients.
451 Predicted Total Lung Capacity Ratio between Donors and Recipients Does Not Predict Outcomes in Non-Volume Reduced Lung Transplantation R. Poyanmehr,1 W. Sommer,1 F. Ius,1 J. Salman,1 T. Siemeni,1 M. Avsar,1 C. K€ uhn,1 M. Greer,2 J. Gottlieb,2 T. Welte,2 A. Haverich,1 1 I. Tudorache, and G. Warnecke.1 1Departement of Cardiothoracic Surgery, Medizinische Hochschule Hannover, Hannover, Germany; and the 2 Departement of Pneumology, Medizinische Hochschule Hannover, Hannover, Germany. Purpose: A predicted total lung capacity (pTLC) ratio of 1.3 between donor and recipient has been described before as beneficial regarding survival after lung transplantation. Here, we wished to analyze data from our center regarding the effect of pTLC ratio on short- and long-term outcome following non-volume reduced lung transplantation. Methods: Between 01/2005 and 08/2018 a total of 1506 lung transplantations were performed at our center. Predicted TLC-ratio was calculated retrospectively and short- as well as long-term outcome parameters were recorded. 156 transplantations with volume reduction procedures or lobar transplantations were excluded from the analysis. Results: Median pTLC-ratio of all 1350 transplantations was 1.02 (IQR 0.961.08); (female 1.06, IQR 1.0-1.14, n=625; male 0.99, n= 725, IQR 0.91-1.05). Median follow-up time of the cohort was 41.3 months. The analysis revealed no significant correlation between pTLC ratio and mechanical ventilation time (p=0.09), postoperative ICU stay (p=0.19) or total hospital stay (p=0.26). Recipients showing PGD grade 2 or 3 (ISHLT 2005 criteria) at any time after transplantation had a median pTLC ratio of 1.02, this not being statistically different to recipients without signs of PGD at any time point (median pTLC ratio 1.02) (p=0.21). When dividing transplants into subgroups according to the respective donor/recipient pTLC-ratio (0.9-1.0; 1.0-1.1; 1.1-1.2; 1.2-1.3; 1.31.4) no survival difference between the different pTLC groups was detectable (p=0.24). Upon subanalysis of recipient’s underlying diseases, no significant correlations between pTLC ratio and %predicted FEV1 at any time after transplantation were seen in COPD, IPF or IPAH patients. The cohort of cystic fibrosis patients showed a significant negative correlation between higher pTLC ratios and %predicted FEV1 at time of discharge from the initial hospital stay following transplantation (p=0.01), however, this was not detectable anymore in spirometry 1 year after transplantation (p=0.21). Conclusion: Focusing only on those transplants performed without surgical donor lung size reductions, specific donor/recipient pTLC ratios did not impact short- and long-term outcomes in this single-center analysis. This suggests a wider range of pTLC-ratios may be safely used for allocation in lung transplantation. 452 Human (Mesenchymal Stem Cells) SC Loaded Single Lung Allograft A. Grant, R.R. Gonzalez, N. Sinha, B. Forsberg, A. Klima, A. Patel, C. Piechazeck, R. Vianna, M. Mirsaeidi, M. Loebe and A. Ghodsizad Surgery, Miami Transplant Institute University of Miami, Miami, FL.
S191 Purpose: Single lung transplantation is an acceptable therapeutic option. Here we use our single lung porcine allograft as a vehicle for stem cell transfer. We present our protocol for perfusion of porcine lungs with human stem cells using our ex-vivo machine. Methods: Adult pigs underwent unilateral left pneumonectomy. The explanted lungs were removed from surgical field and connected to ex-vivo circuit. Porcine lungs were perfused with human albumin after explanation. Lungs were ventilated during perfusion. Total ex vivo perfusion <3 hours. 2 methods of BMC administration were compared: In group 1 CD133+ cells were only passed through the needle. In group2, MSCs were perfused into the pulmonary artery using the ex vivo machine Results: 1. Human male somatic CD133+ Cells were passed through a Microlance needle (BD Gr.20, ; 0,8 £ 40 mm, 26 Gauge)without injection into the lung. 750,000 human CD133+ cells (mobilized peripheral blood), purity (92.4-99.4%), frozen sample were used and different verification runs pump/syringe (n=10, flow rate up to 4mL/min, 30sec), viability was not unchanged (Table 1). 2. 100,000,000 human BMCs were perfused using the ex-vivo machine. The viability of the cells before and after lung perfusion did not show any significant in regard to viability rate, FACS and histological characteristics. Conclusion: Both methods showed safe application route for pulmonary stem cell transfer. The viability of CD105+/45- cells is not as affected during ex vivo perfusion as rest of the cells. The Ex-Vivo mediated transfer is more practical for lung treatment. More histologic and cell culture studies are needed to confirm the feasibility.
The Journal of Heart and Lung Transplantation, Vol 38, No 4S, April 2019
448 Initial Experience with Non-Perfused Organ Donors for Lung Transplantation Y. Watanabe,1 A. Healey,2 M. Scott,2 S. Lavery,2 K. Johnson,2 C. Mills,2 M. Galasso,1 M. Chen,1 J. Yeung,1 L. Donahoe,1 A. Pierre,1 M. de Perrot,1 K. Yasufuku,1 T.K. Waddell,1 S. Keshavjee,1 and M. Cypel.1 1Toronto Lung Transplant Program, Toronto General Hospital, Toronto, ON, Canada; and the 2Trillium Gift of Life Network, Toronto, ON, Canada. Purpose: Uncontrolled donation after death by circulatory criteria (uDCD) has the potential to alleviate some of the shortage of suitable lungs for transplantation. Non-Perfused Organ Donors (NPOD) differs from uDCD donors in that only lungs are obtained as no reperfusion is instituted after individuals suffer an unexpected sudden cardiac arrest. Family are approached rapidly by trained coordinators for consent to donate lungs. This study reviews our initial experience and challenges with NPOD donation. Methods: Data were collected from donors and recipients involved in NPOD lung transplants between February 2016 and October 2018. We describe NPOD donor volumes, ischemia time, utilization rates, length of intensive care unit (ICU) and hospital stay, and survival. Results: There were 101 referrals during this period. Of the 34 approached for donation, consent was obtained in 24 cases, and the lung transplant team evaluated 24 NPOD donors on site. Eleven donors were declined before retrieval because of medically unsuitable lungs, and 4 donors were declined after retrieval due to severe lung injury on site. Nine lungs underwent ex vivo lung perfusion in order to evaluate suitability for transplantation and eventually 3 were used for transplantation. Thus, the total utilization rate from consented donors was 12.5%. The mean warm ischemic time was 160 minutes (range: 106-175 minutes). The mean age of 3 recipients was 48 § 2.5 years. The 30-day mortality was 0%. One patient bridged to transplantation on extracorporeal membrane oxygenation (ECMO) was kept on ECMO for 5 days after transplant. Median ICU stay was 20 days (range: 5-78 days). Median hospital stay was 47 days (range: 18-100 days). Two out of 3 patients are alive at a median of 716 days (range: 100-936 days) with good performance status and lung function. One patient that was on ECMO prior to transplantation died of multisystem organ failure 100 days after transplantation. Conclusion: This study demonstrated the potential for NPOD lung donation. However, utilization rates are low. Therefore, improved strategies of lung preservation before retrieval are required to increase and select lungs that are utilizable for transplantation. 449 Time from Lung Transplant Donor Brain Death to Cross Clamp: An Analysis of the UNOS Registry O.K. Jawitz, V. Raman, Y. Barac, M. Mulvihill, C. Moore, A. Choi, M. Hartwig and J. Klapper. Department of Surgery, Duke University School of Medicine, Durham, NC. Purpose: It has been suggested that the length of time between donor brain death and cross clamp impacts post-transplant graft function and recipient survival in lung transplantation. Methods: The 2007-2018 United Network for Organ Sharing (UNOS) Registry was queried for all adult recipients undergoing isolated lung transplantation (single or bilateral) for the first time. Donation after circulatory death (DCD) donors or those with an unknown time from brain death until
cross clamp were excluded. Recipients were stratified by those who received an allograft from donors with times from brain death until cross clamp less than (SHORT) or greater than (LONG) the median. The primary outcome of interest was post-transplant survival, which was evaluated with Kaplan-Meier and Cox Proportional Hazards analyses. Results: 15,914 lung transplant recipients met inclusion criteria. Median time from donor brain death until cross clamp was 36 hours (IQR 17). Recipients of SHORT donors were more likely treated with IV antibiotics pre-transplant (12.3% vs 10.6%, p = 0.001) and spent a longer time on the waiting list (median 64 vs 58 days, p = 0.016). Both cohorts had similar lung allocation scores (median 40.8 vs 41.0, p = 0.292). Overall survival between the two cohorts was equivalent on Kaplan-Meier analysis (Figure 1, log-rank p = 0.776). On evaluation of other thresholds, time from donor brain death until cross clamp greater than the 75th percentile or less than the 25th percentile similarly did not impact recipient survival. After adjustment for donor and recipient characteristics, graft ischemic time, and year of transplant on Cox Proportional Hazards assessment, donor time from brain death until cross clamp was not associated with decreased survival (AHR 1.00, p = 0.981). Conclusion: Time from donor brain death until cross clamp is not associated with decreased post-transplant survival. Therefore, lung allografts from donors with a prolonged length of time from brain death until explant should not be viewed less favorably.
450 Living-Donor Lobar Lung Transplantation with Undersized Lobar Grafts Can Provide Comparable Long-Term Pulmonary Function and Exercise Capacity to Cadaveric Lung Transplantation D. Nakajima, T.F. Chen-Yoshikawa, T. Menju, T. Sato, M. Sonobe, Y. Yamada, Y. Yutaka, A. Ohsumi, M. Hamaji and H. Date. Thoracic Surgery, Kyoto University, Kyoto, Japan. Purpose: There has been concern of graft size mismatch due to the use of small lobar grafts for living-donor lobar lung transplantation (LDLLT). The purpose of this study is to compare the post-transplant pulmonary function and exercise capacity between LDLLT and conventional cadaveric lung transplant (CLT) patients. Methods: We performed 103 bilateral lung transplants, including 65 LDLLT and 38 CLT, between June 2008 and May 2017. The size matching criteria was as follows: in LDLLT, the calculated forced vital capacity (FVC) of the grafts was > 45% of the recipient predicted FVC; in CLT, the donor predicted vital capacity (VC) was between 70 and 130% of the recipient predicted VC. Pulmonary function and 6-minute walking distance were tested at 1, 3, 6, 12 months, and every year after transplantation. Results: The LDLLT patients received significantly smaller grafts than the CLT patients: the mean graft FVC was 65% of the recipient predicted FVC in the LDLLT, whereas the mean donor predicted VC was 98% of the recipient predicted VC in the CLT (P < 0.01). The LDLLT group demonstrated a similar %FVC to the CLT group after transplantation, although significant difference was found at 3 years between the groups (P = 0.03;
Abstracts Figure). Both groups demonstrated excellent 6-minute walking distance, sustained around 500 m throughout the study period (Figure). There was no significant difference in the incidence of chronic lung allograft dysfunction (CLAD) per donor between the groups (16% in LDLLT vs. 16% in CLT). The 1, 3, and 5-year survival rates did not differ between the groups (93, 82, and 75% in LDLLT vs. 89, 78, and 78% in CLT). Conclusion: LDLLT patients, who received significantly undersized lobar grafts, demonstrated great long-term pulmonary function, exercise tolerance, and survival rates, comparable to the CLT patients.
451 Predicted Total Lung Capacity Ratio between Donors and Recipients Does Not Predict Outcomes in Non-Volume Reduced Lung Transplantation R. Poyanmehr,1 W. Sommer,1 F. Ius,1 J. Salman,1 T. Siemeni,1 M. Avsar,1 C. K€ uhn,1 M. Greer,2 J. Gottlieb,2 T. Welte,2 A. Haverich,1 1 I. Tudorache, and G. Warnecke.1 1Departement of Cardiothoracic Surgery, Medizinische Hochschule Hannover, Hannover, Germany; and the 2 Departement of Pneumology, Medizinische Hochschule Hannover, Hannover, Germany. Purpose: A predicted total lung capacity (pTLC) ratio of 1.3 between donor and recipient has been described before as beneficial regarding survival after lung transplantation. Here, we wished to analyze data from our center regarding the effect of pTLC ratio on short- and long-term outcome following non-volume reduced lung transplantation. Methods: Between 01/2005 and 08/2018 a total of 1506 lung transplantations were performed at our center. Predicted TLC-ratio was calculated retrospectively and short- as well as long-term outcome parameters were recorded. 156 transplantations with volume reduction procedures or lobar transplantations were excluded from the analysis. Results: Median pTLC-ratio of all 1350 transplantations was 1.02 (IQR 0.961.08); (female 1.06, IQR 1.0-1.14, n=625; male 0.99, n= 725, IQR 0.91-1.05). Median follow-up time of the cohort was 41.3 months. The analysis revealed no significant correlation between pTLC ratio and mechanical ventilation time (p=0.09), postoperative ICU stay (p=0.19) or total hospital stay (p=0.26). Recipients showing PGD grade 2 or 3 (ISHLT 2005 criteria) at any time after transplantation had a median pTLC ratio of 1.02, this not being statistically different to recipients without signs of PGD at any time point (median pTLC ratio 1.02) (p=0.21). When dividing transplants into subgroups according to the respective donor/recipient pTLC-ratio (0.9-1.0; 1.0-1.1; 1.1-1.2; 1.2-1.3; 1.31.4) no survival difference between the different pTLC groups was detectable (p=0.24). Upon subanalysis of recipient’s underlying diseases, no significant correlations between pTLC ratio and %predicted FEV1 at any time after transplantation were seen in COPD, IPF or IPAH patients. The cohort of cystic fibrosis patients showed a significant negative correlation between higher pTLC ratios and %predicted FEV1 at time of discharge from the initial hospital stay following transplantation (p=0.01), however, this was not detectable anymore in spirometry 1 year after transplantation (p=0.21). Conclusion: Focusing only on those transplants performed without surgical donor lung size reductions, specific donor/recipient pTLC ratios did not impact short- and long-term outcomes in this single-center analysis. This suggests a wider range of pTLC-ratios may be safely used for allocation in lung transplantation. 452 Human (Mesenchymal Stem Cells) SC Loaded Single Lung Allograft A. Grant, R.R. Gonzalez, N. Sinha, B. Forsberg, A. Klima, A. Patel, C. Piechazeck, R. Vianna, M. Mirsaeidi, M. Loebe and A. Ghodsizad Surgery, Miami Transplant Institute University of Miami, Miami, FL.
S191 Purpose: Single lung transplantation is an acceptable therapeutic option. Here we use our single lung porcine allograft as a vehicle for stem cell transfer. We present our protocol for perfusion of porcine lungs with human stem cells using our ex-vivo machine. Methods: Adult pigs underwent unilateral left pneumonectomy. The explanted lungs were removed from surgical field and connected to ex-vivo circuit. Porcine lungs were perfused with human albumin after explanation. Lungs were ventilated during perfusion. Total ex vivo perfusion <3 hours. 2 methods of BMC administration were compared: In group 1 CD133+ cells were only passed through the needle. In group2, MSCs were perfused into the pulmonary artery using the ex vivo machine Results: 1. Human male somatic CD133+ Cells were passed through a Microlance needle (BD Gr.20, ; 0,8 £ 40 mm, 26 Gauge)without injection into the lung. 750,000 human CD133+ cells (mobilized peripheral blood), purity (92.4-99.4%), frozen sample were used and different verification runs pump/syringe (n=10, flow rate up to 4mL/min, 30sec), viability was not unchanged (Table 1). 2. 100,000,000 human BMCs were perfused using the ex-vivo machine. The viability of the cells before and after lung perfusion did not show any significant in regard to viability rate, FACS and histological characteristics. Conclusion: Both methods showed safe application route for pulmonary stem cell transfer. The viability of CD105+/45- cells is not as affected during ex vivo perfusion as rest of the cells. The Ex-Vivo mediated transfer is more practical for lung treatment. More histologic and cell culture studies are needed to confirm the feasibility.