Search

Pediatric lung transplantation poses unique challenges, from donor shortage to surgical access, intraoperative cardiopulmonary support and postoperative management. Moreover, experience with pediatric lung transplantation is scarce, especially in patients younger than 12 years old. In this study, we present our 15-year experience with lung transplantation in pediatric patients younger than 12 years old. Records of pediatric (≤18 years old) patients transplanted at our institution between 01/2005 and 10/2020 were retrospectively reviewed. Outcomes were compared between pediatric patients <12 years old vs. pediatric patients ≥12 years old. Median (IQR) follow-up was 49 (20-87) months. During the study period, among the 1,741 lung-transplanted patients, 125 (7%) patients were pediatric, being 43 (34%) patients <12 years old (median age, 8 years, 14 patients being ≤5 years old), and 82 (66%) patients ≥12 years old (median age, 15 years). Patients <12 years old were more often transplanted for primary pulmonary hypertension (40% vs. 12%, p<0.001). Intraoperatively, patients <12 years old required more often a clamshell approach (42% vs. 18%, p=0.005) and ECMO support (49% vs. 30%, p=0.043) than patients ≥12 years old. Need for cardiopulmonary bypass did not differ between groups (28% vs. 16%, p=0.11, respectively). Postoperative complications such as primary graft dysfunction (PGD) grade 3 at 72 hours (10% vs. 10%, p=1.00), rethoracotomy for bleeding (14% vs. 10%, p=0.78), need for hemodialysis (7% vs. 13%, p=0.28), tracheostomy (26% vs. 16%, p=0.19) and in-hospital mortality (5% vs 8%, p=0.42) did not differ between patients <12 vs. ≥12 years old, respectively. Mechanical ventilation time was longer in patients <12 years old (median time, 53 vs. 15 hours, p=0.006). At 5- and 10-year follow-up, graft survival (%) (81 vs. 67, 81 vs. 61, p=0.31) and freedom from chronic lung allograft dysfunction (CLAD, %) (83 vs. 62, 62 vs. 60, p=0.30) did not differ between patients <12 vs. ≥12 years old, respectively. Lung transplantation in patients <12 years old is feasible with a postoperative course comparable to patients ≥12 years old, and yields a satisfactory long-term survival and freedom from CLAD. [ABSTRACT FROM AUTHOR]

Purpose Experience with treatment of early donor specific anti-HLA antibodies (eDSA) after lung transplantation in children is very limited. At our institution, since 2013, we have treated patients with eDSA with successive infusions (first infusion: 2gr/kg, then 0.5gr/kg every 4 weeks for a maximum of 6 months) of IgA and IgM-enriched human intravenous immunoglobulins (Pentaglobin, IgGAM), combined in some cases with a single dose of anti-CD20 antibody (Rituximab) and plasmapheresis (PE) or immunoabsorption. Aim of this study was to present the 5-year results of the IgGAM-based therapy in pediatric lung recipients. Methods Records of pediatric (<18 years old) patients transplanted at our institution between 01/2013 and 10/2018 were reviewed. Outcomes of patients with eDSA and treated with IgGAM (IgGAM group) and without eDSA (control group) were compared with the product-limit method of Kaplan-Meier and the log-rank test. Median (IQR) follow-up amounted to 27 (9, 47) months. Results During the study period, among the 60 lung-transplanted pediatric patients (median age 13 years), 26 (43%) formed the IgGAM group and 33 (55%) the control group. One (2%) patient was treated only with PE and Rituximab and not considered in the study. Among the 26 IgGAM patients, 14 (54%) showed only eDSA (possible subclinical antibody-mediated rejection, AMR). The remaining 12 (46%) patients showed graft dysfunction concomitant with eDSA (possible clinical AMR). Median time to eDSA detection was 23 (14, 64) days after transplantation. As of October 2018, treatment was completed in 23 (88%) patients. Under IgGAM treatment eDSA cleared in 22 (96%) patients. At follow-up, 5 (20%) IgGAM vs. 5 (15%) control patients developed hypogammaglobulinemia requiring substitution (p=0.73). No IgGAM vs. 3 (10%) control patients developed post-transplant lymphoproliferative disease (p=0.25). At 5 years, graft survival (%) was 76 vs. 84 (p=0.78); freedom (%) from chronic lung allograft rejection (CLAD) was 88 vs. 75 (p=0.54), and from infection requiring hospitalization 53 vs. 23 (p= 0.021), in IgGAM vs. control patients, respectively. Conclusion After lung transplantation, an IgGAM-based treatment for eDSA yielded high eDSA clearance while decreasing the risk of severe infections. IgGAM patients showed 5-year CLAD-free survival at least as good as control patients without eDSA. [ABSTRACT FROM AUTHOR]

Combined lung and liver transplantation is an uncommon procedure and poses several management challenges. At our institution, since 2005, we have been performing liver transplantation before lung transplantation (liver first strategy), because this strategy might improve the liver coagulopathy thus reducing the risk of bleeding, and spare the successively transplanted lung allograft from the liver reperfusion fluid. Aim of this study was to present our 15-year experience with the liver first strategy for combined lung-liver transplantation. Records of lung-transplanted patients between 01/2005 and 10/2021 at our institution were retrospectively reviewed. Outcomes were compared between patients undergoing combined lung-liver vs. patients undergoing lung-only transplantation. Median (IQR) follow-up was 53 (22-93) months. During the study period, among the 1822 lung-transplanted patients, 17 (0.9%) patients required combined lung-liver transplantation (male sex, n=15; median age, 30 years; lung transplant indication: cystic fibrosis, n=15; lung fibrosis, n=1; porto-pulmonary hypertension, n=1), the remaining 1805 (99.1%) patients undergoing lung-only transplantation. While median lung cold ischemic time (min.) was longer (first lung, 610 vs. 401, p<0.01; second lung, 692 vs. 510, p<0.01) and the intraoperative need for packed red blood cells greater (10 vs. 2 units, p<0.01) in the combined group, only one patient in this group showed primary graft dysfunction (PGD) grade 3 at 72 hours after transplantation (5.9% vs. 5.4%, p=0.61). Prevalence of rethoracotomy for bleeding (18% vs. 10%, p=0.41), temporary dialysis (24% vs. 11%, p=0.12), anti-HLA donor-specific antibodies (DSA, 12% vs. 19%, p=0.35), and in-hospital mortality (12% vs. 7%, p=0.32) did not differ in the lung-liver vs. lung-only transplantation group. Median and hospital stay time (33 vs. 23 days, p<0.01) was longer in the lung-liver group. At-5 years, lung graft survival (62% vs. 66%) and freedom from chronic lung allograft dysfunction (62% vs. 63%) did not differ between the lung-liver vs. lung-only groups (p=0.74 and p=0.71, respectively). Notwithstanding the longer ischemic times and the complexity of the procedure, the liverfirst strategy for combined lung-liver transplantation did not impair lung graft survival and function. [ABSTRACT FROM AUTHOR]

Although use of extended-criteria donor organs (ECD) has increased in lung transplantation, their impact on outcomes remains unclear. The Eurotransplant (ET) lung donor score (ELDS) was designed to classify lung donor quality, taking into account donor history, tobacco exposure, age, arterial blood gases, chest x-ray and bronchoscopic findings. This retrospective single-center study evaluates the impact of ECD on graft function and survival. Records of lung allograft recipients transplanted at our institution between 01/2010 and 10/2020 were reviewed. Individual ELDS were calculated from the corresponding ET donor reports. Outcomes were compared between recipients of ideal donors (ELDS 6, Group 1), of intermediate-risk donors (ELDS 7-8, Group 2), and of extended-criteria donors (ELDS 9-15, Group 3). Median (IQR) follow-up was 46 (20-77) months. In total, 238/1,283 (19%) patients received Group 1 donor organs, 651 (51%) patients Group 2 donor organs, and 394 (30%) patients Group 3 donor organs. Group 2 and 3 recipients were older than group 1 recipients (median age, 52 and 54 vs. 43 years, p<0.001). The need for intraoperative ECMO support (26% vs. 28% vs. 26%, p=0.64), occurrence of grade 3 primary graft dysfunction at 72 hours after transplantation (4% vs. 5% vs. 7%, p=0.31), duration of mechanical ventilation (median 13 vs. 14 vs. 14 hours, p=0.18), and in-hospital mortality (5% vs. 5% vs. 4%, p=0.58) did not differ between groups 1, 2 and 3 recipients, respectively. At 1-year follow-up, no difference in median forced expiratory volume in one second (% predicted) existed between Groups 1, 2 and 3 (89 vs. 86 vs. 85, p=0.29), respectively. At 5 and 8 years, graft survival (%) did not differ significantly between Groups 1, 2 and 3 (5-year: 73 vs. 69 vs. 70; 8-year: 67 vs. 60 vs. 60, p=0.28), respectively. ECD (Group 3) recipients did however exhibit significantly lower 5- and 8-year freedom from chronic lung allograft dysfunction (CLAD, %) compared to group 1 recipients (5-year: 61 vs. 70; 8-year: 55 vs. 64, p=0.039), respectively. In the Cox´s analysis, increasing ELDS values were associated with CLAD (HR=1.068; 95%CI 1.000-1-140, p=0.051). ECD lungs constituted one third of our donor pool. Their use did not negatively impact the recipient survival, but CLAD-free survival was worse in ECD recipients. [ABSTRACT FROM AUTHOR]

The development of early detectable anti-HLA donor specific antibodies after lung transplantation (eDSA) has been associated with antibody-mediated rejection (AMR) and poor graft survival. At our institution, eDSA patients were treated with successive infusions (first infusion: 2g/kg, then 0.5g/kg once every 4 weeks for a maximum of 6 months) of IgA- and IgM-enriched human intravenous immunoglobulins (IgGAM), usually combined with a single dose of anti-CD20 antibody (Rituximab) since 2013. In some cases, plasmapheresis (PE) or immunoabsorption were added before the first IgGAM dose. Aims of this study were to present the 6-year results of the IgGAM-based therapy. Records of patients transplanted at our institution between 02/2013 and 09/2019 were reviewed. Outcomes were compared between patients with eDSA and treated with IgGAM and patients without eDSA (control group). Median follow-up was 35 (16-56) months. During the study period, among the 816 transplanted patients, 186 (23%) patients formed the IgGAM group and 609 (75%) the control group. The remaining 21 (2%) patients (12 patients with eDSA but not treated, and 9 patients treated only with PE and Rituximab) were excluded. eDSA developed at a median of 14 days after transplantation. Thirty-four (18%) IgGAM patients showed graft dysfunction at the same time with eDSA detection (possible clinical AMR). Immunoabsorption/PE were performed in 71 (38%) patients and Rituximab was given to 132 (71%) patients. Treatment was completed in 167 (90%) patients (still on treatment, n=8; in-hospital deaths, n=4; treatment interrupted earlier as per protocol, n=7). In these 167 patients, IgGAM treatment cleared eDSA in 150 (90%) patients, 23 (15%) patients showing eDSA recurrence at a median 9months after treatment end. Clearance was worse in patients with preformed eDSA (p<0.001). In IgGAM vs control patients and at 6-year follow-up, respectively, graft survival (%) was 72 vs. 75 (p=0.58) and freedom from CLAD (%) 72 vs. 65 (p=0.36). Graft and CLAD-free survival did not differ between IgGAM patients with and without graft dysfunction (p=0.66 and p=0.37). After lung transplantation, a treatment based on IgGAM yielded high eDSA clearance. Patients with eDSA and IgGAM treatment have good 6-year graft survival similar to control patients. [ABSTRACT FROM AUTHOR]

In lung transplantation, intraoperative extracorporeal membrane oxygenation (ECMO) allows transplanting high-risk patients, such as those with idiopathic pulmonary arterial hypertension (iPAH). However, early postoperative course is more complicated in patients with than without ECMO, with higher prevalence of severe primary graft dysfunction (PGD), a risk factor for chronic lung allograft dysfunction (CLAD). Aim of this retrospective study was to test the hypothesis if the worse early postoperative course in ECMO patients translates in a worse long-term graft function too. Our institutional lung database was searched for patients who were transplanted with intraoperative ECMO between January 2010 and September 2019. Perioperative and follow-up results were compared between patients transplanted with ECMO and without ECMO. Follow-up amounted to a median of 41 (19-71) months. During the study period, among the 1,189 lung-transplanted patients, 316 (27%) patients required ECMO and the remaining 848 (71%) patients did not. Twenty-four (2%) patients requiring intraoperative cardiopulmonary bypass (CPB) support were excluded. ECMO patients showed a higher pre-transplant surgical risk profile (iPAH, 23% vs 0%, p<0.001; lung fibrosis, 42% vs 28%, p<0.001; ECMO as bridge to transplantation, 25% vs 0, p<0.001; median LAS score 42.2 vs 34.8, p<0.001) and a more complicated early postoperative course (PGD grade 3 at 72 hours, 15% vs. 1%, p<0.001; in-hospital mortality, 11% vs 2%, p<0.001) than patients without ECMO. While graft survival was worse in patients with than in patients without ECMO, freedom from CLAD, biopsy-confirmed rejection and pulsed-steroid therapy did not differ between groups (figure 1). The worse graft survival in ECMO patients was driven by a higher in-hospital mortality, but graft function at follow-up did not differ in discharged patients transplanted with and without ECMO. [ABSTRACT FROM AUTHOR]

Purpose The development of anti-HLA donor specific antibodies early after lung transplantation (eDSA) is associated with antibody-mediated rejection (AMR) and poor graft survival. At our institution, since 2013, we have treated patients with eDSA with successive infusions (first infusion: 2gr/kg, then 0.5gr/kg every 4 weeks for a maximum of 6 months) of IgA and IgM-enriched human intravenous immunoglobulins G (Pentaglobin®, IgGAM), combined in some cases with a single dose of anti-CD20 antibody (Rituximab) and plasmapheresis (PE) or immunoabsorption. Aims of this study were to present the 5-year results of the IgGAM-based therapy and its impact on graft survival. Methods Records of patients transplanted at our institution between 03/2013 and 10/2018 were reviewed. Outcomes of patients with eDSA and treated with IgGAM (IgGAM group) and without eDSA(control group) were compared using the product-limit method of Kaplan-Meier and the log-rank test. Median (IQR) follow-up amounted to 29 (14, 48) months. Results During the study period, among the 705 transplanted patients, 158 (22%) patients formed the IgGAM group and 530 (75%) the control group. Among the remaining 17 (3%) patients, 10 patients developed eDSA but were not treated and 7 were treated only with PE and Rituximab, and thus were not considered in the study. Among the 158 IgGAM patients, 132 (84%) showed only eDSA (possible subclinical AMR) and were pre-emptively treated. The remaining 26 (16%) patients showed graft dysfunction concomitant with eDSA (possible clinical AMR). Median time to eDSA detection was 14 (11, 20) days after transplantation. As of October 2018, treatment was completed in 138 (87%) patients. IgGAM treatment cleared eDSA in 126 (91%) patients (median time 3 months), 15 (12%) patients showing eDSA recurrence at a median of 9 months after treatment end. During treatment time, freedom from biopsy-confirmed rejection (%) was 72 vs. 65 in IgGAM vs. control patients. At 5 years, graft survival (%) was 71 vs. 75 (p=0.74) and freedom from CLAD 84 vs. 70 (p=0.28) in IgGAM vs. control patients, respectively. Conclusion After lung transplantation, a IgGAM-based treatment for eDSA yielded high eDSA clearance. IgGAM patients showed improved 5-year CLAD-free survival in comparison to control patients. Graft survival was similar between groups. [ABSTRACT FROM AUTHOR]