- Email: [email protected]
Is Systemic Lupus Erythematosus (SLE) Related Lung Disease a Contraindication to Lung Transplantation?
S256
The Journal of Heart and Lung Transplantation, Vol 34, No 4S, April 2015
6( 93) Update on the Outcomes of Lung Transplantation After Hematopoietic Stem Cell Transplantation: A Single-Center Experience S. Sugimoto , T. Oto, M. Okada, N. Iga, K. Miyoshi, M. Yamane, S. Miyoshi. General Thoracic Surgery, Okayama University Hospital, Okayama, Japan. Purpose: Because survival after hematopoietic stem cell transplantation (HSCT) has improved, the number of HSCT recipients who develop pulmonary complications has increased. Although lung transplantation (LT) is a well-established therapy for end-stage lung diseases, HSCT recipients have potential risks for LT, including nutritional compromise, relapse of underlying malignancy, recurrence of bronchiolitis obliterans syndrome, and increased susceptibility to infection due to hypogammaglobulinemia and prolonged immunosuppressive therapy. We previously reported the advantages of lower immunosuppression in living-donor lobar LT (LDLLT) involving the same donor as for HSCT; however, the outcomes of LT after HSCT have not been well described yet. Our study aimed to assess the long-term outcomes of LT after HSCT at our institution. Methods: We retrospectively investigated 20 patients who had undergone LT after HSCT at our institution between October 1998 and October 2014. Results: The male-to-female ratio was 2:3, and the median age at LT was 25.5 years (3-48 years). The median interval from HSCT to LT was 51.5 months (9-157 months). The median body-mass index at LT was 15.4 (10.5-22.8). Cadaveric LT (CLT) and LDLLT were performed for 6 and 14 patients, respectively. Four patients underwent LDLLT involving the same donor as for HSCT. The mean of acute rejection episodes was 0.9 per patient. Three of 20 patients developed chronic lung allograft dysfunction, and 1 patient underwent lung retransplantation. One patient died of relapse of hematological malignancy, and another patient died of posttransplantation lymphoproliferative disorder. While 2 patients died of infection, no patients had fatal infection after the initiation of periodic intravenous immunoglobulin for hypogammaglobulinemia after LT. The 1-year and 5-year survival rates of LT after HSCT were 89% and 64%, respectively. Conclusion: Although CLT and LDLLT from relatives who were not the HSCT donors have become more common, LT provides acceptable results for selected patients with end-stage pulmonary complications after HSCT. 6( 94) CLAD Is Different Down Under! M. Malouf ,1 M. Harkess,1 A. Middleton,1 S. Yerkovich,2 M. Benzmira,1 A. Havryk,1 M. Plit,1 P. Hopkins,2 D. Chambers,2 A.R. Glanville.1 1Lung Transplant Unit, St. Vincent’s Hospital, Sydney, Australia; 2Queensland Lung Transplant Service, The Prince Charles Hospital, Brisbane, Australia. Purpose: Recently, a restrictive phenotype of chronic lung allograft dysfunction (RCLAD) has been reported in ~30% of lung transplant (LTX) recipients with CLAD. RCLAD is reported to have a much worse prognosis than obstructive CLAD (bronchiolitis obliterans syndrome) (BOS). Our anecdotal experience and postmortem studies raised questions about the frequency of RCLAD. Methods: Retrospective analysis by 2 large Australian LTX units (Unit 1, 634 LTX) (Unit 2, 262 LTX) comprising 48 HLTX and 848 bilateral LTX 1986-2014. BOS was defined according to ISHLT criteria. RCLAD was defined as FVC< 80% of baseline (defined as mean of 2 FVC concurrent with 2 best FEV1s) with FEV1/FVC > 0.80 at time of CLAD diagnosis. 77/896 (8.5%) cases were excluded: death ≤ 90 days post transplant (n= 57) and other criteria (n= 20). Results: 441/819 (54%) patients had CLAD. 416/441(94.3%) had BOS and 25/441(5.7%) had RCLAD. There was no center effect of RCLAD frequency (p= 0.51, Fisher’s exact test), time to RCLAD (p= 0.58, log rank) or survival after CLAD diagnosis (p= 0.37, log rank). However in Unit 2, time to BOS was longer, (p= 0.004, log rank) and overall survival superior (p= 0.015, log rank). For the whole group, median (±SE) survival after onset of BOS vs RCLAD was 1275± 186 vs 308±162 days (p< 0.001, log rank) and time dependent Cox analysis confirmed CLAD, RCLAD and BOS were significant risk factors for survival (HR 2.19, 95%CI 1.60-3.04, p< 0.001) (HR 2.93, CI 1.50-5.73, p= 0.002) and (HR 1.93, CI 1.38-2.70, p< 0.001) respectively.
Conclusion: The poor prognostic significance of RCLAD is confirmed albeit with a slightly longer median survival than previously reported. However our large two unit study finds RCLAD is a rare phenomenon compared to recent reports (p< 0.001, Fisher’s exact test). The striking difference in frequency is currently unexplained. 6( 95) Is Systemic Lupus Erythematosus (SLE) Related Lung Disease a Contraindication to Lung Transplantation? E.L. Bush ,1 H. Faust,2 J. Lee,2 J.P. Singer,1 S. Hays,2 L. Leard,2 M.E. Kleinhenz,2 G. Dincheva,1 M. Brzezinski,3 G. Wieselthaler,1 C.W. Hoopes,4 J.A. Golden,2 J. Kukreja.1 1Division of Cardiothoracic Surgery, Univ California, San Fran, San Francisco, CA; 2Division of Pulmonary and Critical Care, Univ California, San Fran, San Francisco, CA; 3Department of Anesthesia, Univ California, San Fran, San Francisco, CA; 4Division of Cardiothoracic Surgery, University of Kentucky, Lexington, KY. Purpose: Given the systemic involvement of SLE many thoracic transplant programs consider this diagnosis to be a contraindication to lung transplantation. Complicating the decision to consider lung transplantation for this rare indication, the biomedical literature assessing lung transplantation for SLE is limited to case reports. Herein, we report the largest cohort of patients with SLE-related end stage lung disease undergoing lung transplantation at a single-institution. Methods: We performed a retrospective chart review of all patients undergoing lung or heart and lung transplantation at our institution between 1994 and 2014 with a rheumatologist confirmed diagnosis of SLE. Recipient demographics and preoperative, perioperative and postoperative clinical characteristics were collected. Survival was estimated using a Kaplan-Meier analysis. Results: We identified 6 patients, all female. Four patients had fibrotic lung disease while 2 had isolated pulmonary hypertension. None had evidence of active extra-pulmonary SLE manifestations at the time of transplant. Leading up to transplant 4 (67%) were receiving SLE-directed immunosuppression. Bilateral lung transplantation was performed in 5 (83%)patients and one underwent combined heart-lung transplantation because of severe secondary pulmonary hypertension with right heart failure. Median age was 44 (range: 19-66), median postoperative hospital stay was 29 days (range: 24-86). There was 1 early death at 41 days. In the remaining 5 patients, there were only two episodes of A2 or greater rejection: one patient had A2 rejection at 16 months another had A3 rejection at 33 months. Only 1 patient has developed chronic lung allograft dysfunction manifest as BOS 3. None of the patients developed systemic complications of SLE post transplant. Overall, our cohort has an estimated 3-year survival of 83% with a median follow-up of 4 years. Conclusion: Lung transplantation is rarely performed for SLE or other autoimmune diseases out of concern for extra-pulmonary progression of disease following transplant. To our knowledge, our case series represents the largest cohort of SLE patients undergoing lung transplantation at a single-institution. Our results suggest that in carefully selected patients, successful outcomes can be achieved with transplantation for isolated thoracic organ failure secondary to SLE. 6( 96) Lung Transplant (LT) for Non-Scleroderma Connective Tissue Lung Disease (NS-CTLD): Wasting a Precious Commodity? J. Kukreja ,1 E.L. Bush,1 C.W. Hoopes,2 G. Dincheva,1 M. Brzezinski,3 J. Lee,4 M. Kleinhenz,4 L. Leard,4 S. Hays,4 J. Golden,4 J. Singer.4 1Cardiothoracic Surgery, Univ of California, San Francisco, CA; 2Cardiothoracic Surgery, Univ of Kentucky, Lexington, KY; 3Anesthesia, San Fracisco Veterans Administration Hospital, San Francisco, CA; 4Medicine, Univ of California, San Francisco, CA. Purpose: LT for systemic autoimmune diseases is controversial due to concern that recurrent pulmonary and extra-pulmonary organ involvement will result in poorer outcomes. We previously showed comparable 1- and 3-year survival and freedom from bronchiolitis obliterans syndrome (fBOS) for persons undergoing LT for scleroderma associated interstitial lung disease (Scl-ILD) and idiopathic pulmonary fibrosis (IPF). We hypothesized that, like Scl-ILD, persons undergoing LT for NS-CTLD (lupus, mixed connective tissue disease [MCTD], sjogren’s disorder, dermatomyositis [DM] and polymyositis [PM]) would have similar outcomes as LT for IPF.
The Journal of Heart and Lung Transplantation, Vol 34, No 4S, April 2015
6( 93) Update on the Outcomes of Lung Transplantation After Hematopoietic Stem Cell Transplantation: A Single-Center Experience S. Sugimoto , T. Oto, M. Okada, N. Iga, K. Miyoshi, M. Yamane, S. Miyoshi. General Thoracic Surgery, Okayama University Hospital, Okayama, Japan. Purpose: Because survival after hematopoietic stem cell transplantation (HSCT) has improved, the number of HSCT recipients who develop pulmonary complications has increased. Although lung transplantation (LT) is a well-established therapy for end-stage lung diseases, HSCT recipients have potential risks for LT, including nutritional compromise, relapse of underlying malignancy, recurrence of bronchiolitis obliterans syndrome, and increased susceptibility to infection due to hypogammaglobulinemia and prolonged immunosuppressive therapy. We previously reported the advantages of lower immunosuppression in living-donor lobar LT (LDLLT) involving the same donor as for HSCT; however, the outcomes of LT after HSCT have not been well described yet. Our study aimed to assess the long-term outcomes of LT after HSCT at our institution. Methods: We retrospectively investigated 20 patients who had undergone LT after HSCT at our institution between October 1998 and October 2014. Results: The male-to-female ratio was 2:3, and the median age at LT was 25.5 years (3-48 years). The median interval from HSCT to LT was 51.5 months (9-157 months). The median body-mass index at LT was 15.4 (10.5-22.8). Cadaveric LT (CLT) and LDLLT were performed for 6 and 14 patients, respectively. Four patients underwent LDLLT involving the same donor as for HSCT. The mean of acute rejection episodes was 0.9 per patient. Three of 20 patients developed chronic lung allograft dysfunction, and 1 patient underwent lung retransplantation. One patient died of relapse of hematological malignancy, and another patient died of posttransplantation lymphoproliferative disorder. While 2 patients died of infection, no patients had fatal infection after the initiation of periodic intravenous immunoglobulin for hypogammaglobulinemia after LT. The 1-year and 5-year survival rates of LT after HSCT were 89% and 64%, respectively. Conclusion: Although CLT and LDLLT from relatives who were not the HSCT donors have become more common, LT provides acceptable results for selected patients with end-stage pulmonary complications after HSCT. 6( 94) CLAD Is Different Down Under! M. Malouf ,1 M. Harkess,1 A. Middleton,1 S. Yerkovich,2 M. Benzmira,1 A. Havryk,1 M. Plit,1 P. Hopkins,2 D. Chambers,2 A.R. Glanville.1 1Lung Transplant Unit, St. Vincent’s Hospital, Sydney, Australia; 2Queensland Lung Transplant Service, The Prince Charles Hospital, Brisbane, Australia. Purpose: Recently, a restrictive phenotype of chronic lung allograft dysfunction (RCLAD) has been reported in ~30% of lung transplant (LTX) recipients with CLAD. RCLAD is reported to have a much worse prognosis than obstructive CLAD (bronchiolitis obliterans syndrome) (BOS). Our anecdotal experience and postmortem studies raised questions about the frequency of RCLAD. Methods: Retrospective analysis by 2 large Australian LTX units (Unit 1, 634 LTX) (Unit 2, 262 LTX) comprising 48 HLTX and 848 bilateral LTX 1986-2014. BOS was defined according to ISHLT criteria. RCLAD was defined as FVC< 80% of baseline (defined as mean of 2 FVC concurrent with 2 best FEV1s) with FEV1/FVC > 0.80 at time of CLAD diagnosis. 77/896 (8.5%) cases were excluded: death ≤ 90 days post transplant (n= 57) and other criteria (n= 20). Results: 441/819 (54%) patients had CLAD. 416/441(94.3%) had BOS and 25/441(5.7%) had RCLAD. There was no center effect of RCLAD frequency (p= 0.51, Fisher’s exact test), time to RCLAD (p= 0.58, log rank) or survival after CLAD diagnosis (p= 0.37, log rank). However in Unit 2, time to BOS was longer, (p= 0.004, log rank) and overall survival superior (p= 0.015, log rank). For the whole group, median (±SE) survival after onset of BOS vs RCLAD was 1275± 186 vs 308±162 days (p< 0.001, log rank) and time dependent Cox analysis confirmed CLAD, RCLAD and BOS were significant risk factors for survival (HR 2.19, 95%CI 1.60-3.04, p< 0.001) (HR 2.93, CI 1.50-5.73, p= 0.002) and (HR 1.93, CI 1.38-2.70, p< 0.001) respectively.
Conclusion: The poor prognostic significance of RCLAD is confirmed albeit with a slightly longer median survival than previously reported. However our large two unit study finds RCLAD is a rare phenomenon compared to recent reports (p< 0.001, Fisher’s exact test). The striking difference in frequency is currently unexplained. 6( 95) Is Systemic Lupus Erythematosus (SLE) Related Lung Disease a Contraindication to Lung Transplantation? E.L. Bush ,1 H. Faust,2 J. Lee,2 J.P. Singer,1 S. Hays,2 L. Leard,2 M.E. Kleinhenz,2 G. Dincheva,1 M. Brzezinski,3 G. Wieselthaler,1 C.W. Hoopes,4 J.A. Golden,2 J. Kukreja.1 1Division of Cardiothoracic Surgery, Univ California, San Fran, San Francisco, CA; 2Division of Pulmonary and Critical Care, Univ California, San Fran, San Francisco, CA; 3Department of Anesthesia, Univ California, San Fran, San Francisco, CA; 4Division of Cardiothoracic Surgery, University of Kentucky, Lexington, KY. Purpose: Given the systemic involvement of SLE many thoracic transplant programs consider this diagnosis to be a contraindication to lung transplantation. Complicating the decision to consider lung transplantation for this rare indication, the biomedical literature assessing lung transplantation for SLE is limited to case reports. Herein, we report the largest cohort of patients with SLE-related end stage lung disease undergoing lung transplantation at a single-institution. Methods: We performed a retrospective chart review of all patients undergoing lung or heart and lung transplantation at our institution between 1994 and 2014 with a rheumatologist confirmed diagnosis of SLE. Recipient demographics and preoperative, perioperative and postoperative clinical characteristics were collected. Survival was estimated using a Kaplan-Meier analysis. Results: We identified 6 patients, all female. Four patients had fibrotic lung disease while 2 had isolated pulmonary hypertension. None had evidence of active extra-pulmonary SLE manifestations at the time of transplant. Leading up to transplant 4 (67%) were receiving SLE-directed immunosuppression. Bilateral lung transplantation was performed in 5 (83%)patients and one underwent combined heart-lung transplantation because of severe secondary pulmonary hypertension with right heart failure. Median age was 44 (range: 19-66), median postoperative hospital stay was 29 days (range: 24-86). There was 1 early death at 41 days. In the remaining 5 patients, there were only two episodes of A2 or greater rejection: one patient had A2 rejection at 16 months another had A3 rejection at 33 months. Only 1 patient has developed chronic lung allograft dysfunction manifest as BOS 3. None of the patients developed systemic complications of SLE post transplant. Overall, our cohort has an estimated 3-year survival of 83% with a median follow-up of 4 years. Conclusion: Lung transplantation is rarely performed for SLE or other autoimmune diseases out of concern for extra-pulmonary progression of disease following transplant. To our knowledge, our case series represents the largest cohort of SLE patients undergoing lung transplantation at a single-institution. Our results suggest that in carefully selected patients, successful outcomes can be achieved with transplantation for isolated thoracic organ failure secondary to SLE. 6( 96) Lung Transplant (LT) for Non-Scleroderma Connective Tissue Lung Disease (NS-CTLD): Wasting a Precious Commodity? J. Kukreja ,1 E.L. Bush,1 C.W. Hoopes,2 G. Dincheva,1 M. Brzezinski,3 J. Lee,4 M. Kleinhenz,4 L. Leard,4 S. Hays,4 J. Golden,4 J. Singer.4 1Cardiothoracic Surgery, Univ of California, San Francisco, CA; 2Cardiothoracic Surgery, Univ of Kentucky, Lexington, KY; 3Anesthesia, San Fracisco Veterans Administration Hospital, San Francisco, CA; 4Medicine, Univ of California, San Francisco, CA. Purpose: LT for systemic autoimmune diseases is controversial due to concern that recurrent pulmonary and extra-pulmonary organ involvement will result in poorer outcomes. We previously showed comparable 1- and 3-year survival and freedom from bronchiolitis obliterans syndrome (fBOS) for persons undergoing LT for scleroderma associated interstitial lung disease (Scl-ILD) and idiopathic pulmonary fibrosis (IPF). We hypothesized that, like Scl-ILD, persons undergoing LT for NS-CTLD (lupus, mixed connective tissue disease [MCTD], sjogren’s disorder, dermatomyositis [DM] and polymyositis [PM]) would have similar outcomes as LT for IPF.