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Long-Term Outcome of Double Lung Retransplantation After Heart and Lung Transplantation for Chronic Lung Allograft Dysfunction
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The Journal of Heart and Lung Transplantation, Vol 35, No 4S, April 2016
its onset (FVCCLAD/FVCBaseline < 0.8, n= 65) or BOS if FVC was preserved (FVCCLAD/FVCBaseline ≥ 0.8, n= 151). Changes in FVC ratio and FEV1 ratio (relative to posttransplant baseline) were described within R-CLAD and BOS at 6 month intervals after CLAD onset, up to 12 months. Changes were calculated comparing the last pulmonary function value on record during each 6 month interval to that of the prior interval. Results: Over 12 month follow-up, 57% of R-CLAD and 23% of BOS patients died. Patients with R-CLAD entered CLAD with a more severe impairment in FVC and FEV1, as compared with BOS (median CLAD onset FVC ratio 0.73, FEV1 ratio 0.62 in R-CLAD vs 0.91 and 0.76 for BOS). The trajectory of the median FVC ratio and median FEV1 ratio among alive and deceased patients over follow-up within each CLAD phenotype is described in Figure 1. In general, the greatest apparent losses in FVC and FEV1 occurred in patients dying in the first year of CLAD, while surviving patients experience an attenuated course of lung function loss over time. Conclusion: Physiological disease progression after CLAD is variable. A steep decline in lung function appears associated with worse one-year survival after CLAD. Further evaluation of patterns of lung function decline after CLAD and their association with patient survival may provide valuable prognostic information or define a useful surrogate for assessing treatment response in future CLAD treatment trials.
6( 05) Long-Term Outcome of Double Lung Retransplantation After Heart and Lung Transplantation for Chronic Lung Allograft Dysfunction L. Marien , O. Mercier, J. Le Pavec, J. Guihaire, S. Mussot, D. Fabre, L. Lamrani, P. Dartevelle, E. Fadel. Centre Chirurgicale Marie Lannelongue, Paris, France. Purpose: Chronic lung allograft dysfunction (CLAD) is a major factor limiting long-term survival after heart-lung transplantation (HLTx). Whether double lung retransplantation (DLRTx) could offer the same long-term results as after double lung transplantation (DLTx) is unknown? Hence, we compared outcomes of DLRTx after HLTx or DLTx. Methods: Between January 2006 and October 2015, we performed 25 DLRTx, including 11 after HLTx and 14 after DLTx. Charts were reviewed and data regarding transplantation and outcomes were collected. Coronary vasculopathy (CAV) occurrence in HLTx patients after DLRTx was compared to the HLTx cohort of the department. Results: These were 14 men and 11 women with a mean age of 39,4 years [range 17,6 to 62,7 years]. Time to retransplantation was similar between the two groups. The mean post-retransplant follow-up was 2,8 years [range 1,5 month to 9,47 years]. The overall in-hospital mortality rate was 8%. Two patients from the DLTx group died of a septic shock at day 9 and of primary graft dysfunction at day 10, respectively. The frequency of primary graft dysfunction (PGD) score 3 was similar between two groups with the overall H72 PGD rate of 4 patients/22 (18%). 1 and 5-year survivals were not statistically different between the groups (HLTx group: 70% and 55% vs. DLTx group: 80% and 30%; respectively; P= 0,4). 1 and 5-year CLAD Free survivals were not different between the two groups as well (HLTx group: 80% and 50% vs. DLTx group: 65% and 18%; respectively; P= 0,36). The time to CLAD was similar between groups (2,6± 2,8 years vs. 1,6± 1,4 years, P= 0,56). The
incidence of CAV remained steady between groups and when comparing with the global HLTx cohort. 3 patients in both groups had a positive virtual crossmatch and had plasmapheresis. 4 patients (36%) from the HLTx group and 9 patients (81%) from the DLTx group developed donor specific antibodies with a mean time of 75 months and 6 months, respectively (p= 0.245). Conclusion: DLRTx after HLTx demonstrated satisfactory long-term survival with low post-operative mortality and low complication rate. Survival benefit was similar to DLRTx after DLTx with no higher risk of coronary disease. Hence, DLRTx seems to be a good option for the patients with endstage CLAD after HLTx. 6( 06) Role of CD4+CD25highCD127- Treg Cells in Long Term Outcome of Lung Recipients D. Piloni ,1 M. Morosini,2 S. Magni,2 A. Balderacchi,2 L. Scudeller,3 E. Cova,2 T. Oggionni,2 G. Stella,2 C. Tinelli,3 F. Antonacci,2 F. Meloni.1 1Department of Internal Medicine, University of Pavia, Pavia, Italy; 2Cardiothoracic and Vascular Dept., Pneumology Unit, IRCCS Policlinico San Matteo Foundation, Pavia, Italy; 3Clinical Epidemiology and Biometric Unit, Scientific Direction, IRCCS Policlinico San Matteo Foundation, Pavia, Italy. Purpose: The role of CD4+CD25highCD127- Treg cells in solid-organ transplant (Tx) acceptance has been extensively studied in experimental models and analyzed also in the clinics. In previous studies on kidney and liver recipients, higher peripheral Treg cell counts early after Tx, have been correlated with graft survival, while decreased counts were associated to acute and chronic rejection. As for lung transplantation and the occurrence of Chronic Lung Allograft Dysfunction (CLAD), evidences are limited and somehow contradictory. The present study aims to analyze long term kinetic of CD4+CD25highCD127dim regulatory T cells in the peripheral blood of a cohort of lung recipients and test its association to several clinical and pharmacological variables (type of maintenance IS, azithromycin, extracorporeal photo-apheresis, infections, neoplasia, kidney failure, chronic lung allograft dysfunction ). Methods: From jan 2009 to dec 2014, 137 lung transplant recipients were submitted to an immunological follow up (I-FU) (median:105.9 months (3.3-310.5). I-FU consisted of a complete peripheral immuno-phenotype (Flow Cytometry), inclusive of CD4+CD25highCD127-T cell determination and FOXP3 expression (globally 1943 determinations were analyzed). Linear OR regression models for repeated measures were used to test the association between Treg and relevant variables, adjusting for time from Tx. Also, ordered logistic models for panel data were used to test the association between CLAD grades and Treg in the previous three months. Results: Among those variables significantly associated at peripheral Treg cell counts at univariate analysis: azathioprine therapy (OR 4.65, 95%CI 0.43-8.85, p= 0.03) , ECP (OR -6.03, 95%CI -8.25--3.80, p< 0.001), RAS (OR -6.6, 95%CI -11.59--1.60, p< 0.001), BOS (OR -8.15, 95%CI -11.80-4.47, p= 0.03); only BOS retained its significance at multivariate model. Treg cell counts were progressively decreased according to severity of CLAD dysfunction (OR -1.13, 95%CI -1.9- -0.28, p= 0.009). Furthermore, patients with higher mean peripheral CD4+CD25highCD127- Treg counts had a significantly lower risk (OR 0.97, 95%CI 0.95-0.99, p= 0.032) of presenting CLAD or progressing in the graft dysfunction in the following trimester. Conclusion: Our present data confirm animal observations on the protective role of CD4+CD25highCD127- Treg cell subset with respect to CLAD. 6( 07) Impact of Persistent Versus Transient Donor Specific HLAAntibodies on Graft Outcome Following Lung Transplantation D. Sroussi , C. Gauvain, E. Lhuillier, C. Dupin, G. Dauriat, G. Jebrak, P. Mordant, G. Thabut, H. Mal, C. Suberbielle, O. Brugière. Hôpital Bichat, Paris, France. Purpose: Chronic Lung Allograft Dysfunction (CLAD) is the main complication after lung transplantation (LTx) and remains the most common cause of graft failure and death. The objective was to determine whether the persistence of donor-specific HLA antibodies (DSA) during follow-up is associated with the development of CLAD and/or graft survival.
The Journal of Heart and Lung Transplantation, Vol 35, No 4S, April 2016
its onset (FVCCLAD/FVCBaseline < 0.8, n= 65) or BOS if FVC was preserved (FVCCLAD/FVCBaseline ≥ 0.8, n= 151). Changes in FVC ratio and FEV1 ratio (relative to posttransplant baseline) were described within R-CLAD and BOS at 6 month intervals after CLAD onset, up to 12 months. Changes were calculated comparing the last pulmonary function value on record during each 6 month interval to that of the prior interval. Results: Over 12 month follow-up, 57% of R-CLAD and 23% of BOS patients died. Patients with R-CLAD entered CLAD with a more severe impairment in FVC and FEV1, as compared with BOS (median CLAD onset FVC ratio 0.73, FEV1 ratio 0.62 in R-CLAD vs 0.91 and 0.76 for BOS). The trajectory of the median FVC ratio and median FEV1 ratio among alive and deceased patients over follow-up within each CLAD phenotype is described in Figure 1. In general, the greatest apparent losses in FVC and FEV1 occurred in patients dying in the first year of CLAD, while surviving patients experience an attenuated course of lung function loss over time. Conclusion: Physiological disease progression after CLAD is variable. A steep decline in lung function appears associated with worse one-year survival after CLAD. Further evaluation of patterns of lung function decline after CLAD and their association with patient survival may provide valuable prognostic information or define a useful surrogate for assessing treatment response in future CLAD treatment trials.
6( 05) Long-Term Outcome of Double Lung Retransplantation After Heart and Lung Transplantation for Chronic Lung Allograft Dysfunction L. Marien , O. Mercier, J. Le Pavec, J. Guihaire, S. Mussot, D. Fabre, L. Lamrani, P. Dartevelle, E. Fadel. Centre Chirurgicale Marie Lannelongue, Paris, France. Purpose: Chronic lung allograft dysfunction (CLAD) is a major factor limiting long-term survival after heart-lung transplantation (HLTx). Whether double lung retransplantation (DLRTx) could offer the same long-term results as after double lung transplantation (DLTx) is unknown? Hence, we compared outcomes of DLRTx after HLTx or DLTx. Methods: Between January 2006 and October 2015, we performed 25 DLRTx, including 11 after HLTx and 14 after DLTx. Charts were reviewed and data regarding transplantation and outcomes were collected. Coronary vasculopathy (CAV) occurrence in HLTx patients after DLRTx was compared to the HLTx cohort of the department. Results: These were 14 men and 11 women with a mean age of 39,4 years [range 17,6 to 62,7 years]. Time to retransplantation was similar between the two groups. The mean post-retransplant follow-up was 2,8 years [range 1,5 month to 9,47 years]. The overall in-hospital mortality rate was 8%. Two patients from the DLTx group died of a septic shock at day 9 and of primary graft dysfunction at day 10, respectively. The frequency of primary graft dysfunction (PGD) score 3 was similar between two groups with the overall H72 PGD rate of 4 patients/22 (18%). 1 and 5-year survivals were not statistically different between the groups (HLTx group: 70% and 55% vs. DLTx group: 80% and 30%; respectively; P= 0,4). 1 and 5-year CLAD Free survivals were not different between the two groups as well (HLTx group: 80% and 50% vs. DLTx group: 65% and 18%; respectively; P= 0,36). The time to CLAD was similar between groups (2,6± 2,8 years vs. 1,6± 1,4 years, P= 0,56). The
incidence of CAV remained steady between groups and when comparing with the global HLTx cohort. 3 patients in both groups had a positive virtual crossmatch and had plasmapheresis. 4 patients (36%) from the HLTx group and 9 patients (81%) from the DLTx group developed donor specific antibodies with a mean time of 75 months and 6 months, respectively (p= 0.245). Conclusion: DLRTx after HLTx demonstrated satisfactory long-term survival with low post-operative mortality and low complication rate. Survival benefit was similar to DLRTx after DLTx with no higher risk of coronary disease. Hence, DLRTx seems to be a good option for the patients with endstage CLAD after HLTx. 6( 06) Role of CD4+CD25highCD127- Treg Cells in Long Term Outcome of Lung Recipients D. Piloni ,1 M. Morosini,2 S. Magni,2 A. Balderacchi,2 L. Scudeller,3 E. Cova,2 T. Oggionni,2 G. Stella,2 C. Tinelli,3 F. Antonacci,2 F. Meloni.1 1Department of Internal Medicine, University of Pavia, Pavia, Italy; 2Cardiothoracic and Vascular Dept., Pneumology Unit, IRCCS Policlinico San Matteo Foundation, Pavia, Italy; 3Clinical Epidemiology and Biometric Unit, Scientific Direction, IRCCS Policlinico San Matteo Foundation, Pavia, Italy. Purpose: The role of CD4+CD25highCD127- Treg cells in solid-organ transplant (Tx) acceptance has been extensively studied in experimental models and analyzed also in the clinics. In previous studies on kidney and liver recipients, higher peripheral Treg cell counts early after Tx, have been correlated with graft survival, while decreased counts were associated to acute and chronic rejection. As for lung transplantation and the occurrence of Chronic Lung Allograft Dysfunction (CLAD), evidences are limited and somehow contradictory. The present study aims to analyze long term kinetic of CD4+CD25highCD127dim regulatory T cells in the peripheral blood of a cohort of lung recipients and test its association to several clinical and pharmacological variables (type of maintenance IS, azithromycin, extracorporeal photo-apheresis, infections, neoplasia, kidney failure, chronic lung allograft dysfunction ). Methods: From jan 2009 to dec 2014, 137 lung transplant recipients were submitted to an immunological follow up (I-FU) (median:105.9 months (3.3-310.5). I-FU consisted of a complete peripheral immuno-phenotype (Flow Cytometry), inclusive of CD4+CD25highCD127-T cell determination and FOXP3 expression (globally 1943 determinations were analyzed). Linear OR regression models for repeated measures were used to test the association between Treg and relevant variables, adjusting for time from Tx. Also, ordered logistic models for panel data were used to test the association between CLAD grades and Treg in the previous three months. Results: Among those variables significantly associated at peripheral Treg cell counts at univariate analysis: azathioprine therapy (OR 4.65, 95%CI 0.43-8.85, p= 0.03) , ECP (OR -6.03, 95%CI -8.25--3.80, p< 0.001), RAS (OR -6.6, 95%CI -11.59--1.60, p< 0.001), BOS (OR -8.15, 95%CI -11.80-4.47, p= 0.03); only BOS retained its significance at multivariate model. Treg cell counts were progressively decreased according to severity of CLAD dysfunction (OR -1.13, 95%CI -1.9- -0.28, p= 0.009). Furthermore, patients with higher mean peripheral CD4+CD25highCD127- Treg counts had a significantly lower risk (OR 0.97, 95%CI 0.95-0.99, p= 0.032) of presenting CLAD or progressing in the graft dysfunction in the following trimester. Conclusion: Our present data confirm animal observations on the protective role of CD4+CD25highCD127- Treg cell subset with respect to CLAD. 6( 07) Impact of Persistent Versus Transient Donor Specific HLAAntibodies on Graft Outcome Following Lung Transplantation D. Sroussi , C. Gauvain, E. Lhuillier, C. Dupin, G. Dauriat, G. Jebrak, P. Mordant, G. Thabut, H. Mal, C. Suberbielle, O. Brugière. Hôpital Bichat, Paris, France. Purpose: Chronic Lung Allograft Dysfunction (CLAD) is the main complication after lung transplantation (LTx) and remains the most common cause of graft failure and death. The objective was to determine whether the persistence of donor-specific HLA antibodies (DSA) during follow-up is associated with the development of CLAD and/or graft survival.