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510 Cryoprobe Versus Forceps Biopsy for Post-Lung Transplant Surveillance
S178
The Journal of Heart and Lung Transplantation, Vol 31, No 4S, April 2012
509 Prospective Surveillance and Treatment of De Novo Donor Specific Antibodies after Lung Transplantation Ameliorates 1-Year Risk of BOS H.W. Ainge Allen,1 A.P. Havryk,1 M.A. Malouf,1 M. Plit,1 C. Benden,1 N. Watson,2 A.R. Glanville.1 1Department of Cardiopulmonary Transplant, St Vincent’s Hospital, Sydney, NSW, Australia; 2NSW Transplantation and Immunogenetics Laboratory, Australian Red Cross Blood Service, Sydney, NSW, Australia. Purpose: Development of circulating de novo donor specific antibodies (DSA) has been reported as a risk factor for bronchiolitis obliterans syndrome (BOS) after lung transplantation (LTX). We assessed the utility of a prospective surveillance and management strategy to detect and treat de novo DSA and the impact on BOS development. Methods and Materials: Single centre retrospective review of 83 consecutive LTX recipients transplanted January 2009-March 2011. Circulating DSA were determined by LUMINEX (LabScreen single antigen assay) at date of transplant, serially thereafter and when antibody mediated rejection (AMR) was suspected based on histopathological criteria (capillary injury ⫹/⫺ C4d staining) with or without graft dysfunction. DSA with mean fluorescent intensity (MFI) ⬎1000 were treated with IVIG, therapeutic plasma exchange and rituximab. Primary efficacy was defined by freedom from BOS grade 1. De novo DSA were analysed as a time dependent covariate using a Cox proportional hazards model. Results: Sera on 68/83 LTX recipients were analyzed by LUMINEX post transplant. Circulating DSA (MFI⬎1000) were detected in 39/68 (57%) during the study period, MFI (mean⫾SD,peak) ⫽ 3324⫾4859, 24580. Class I DSA were detected in 27/39, MFI ⫽1,351⫾2673,12499 and Class II DSA in 30/39, MFI⫽ 2299⫾4600, 24580. C4D staining of transbronchial biopsies was positive in 5/14. At mean 1 year follow up, de novo DSA were not a risk factor for BOS (HR 0.98,CI 0.64-11.16,p⫽0.18). Conclusions: A prospective surveillance and management strategy to detect and treat significant de novo DSA ameliorates the 1-year risk of BOS. Optimum frequency of surveillance and durability of effect is yet to be determined. 510 Cryoprobe Versus Forceps Biopsy for Post-Lung Transplant Surveillance L. Yarmus, J. Akulian, C. Gilbert, J. Orens, C. Merlo, D. Feller-Kopman. Pulmonary and Critical Care Medicine, The Johns Hopkins University, Baltimore, MD. Purpose: Obtaining sufficient tissue during post-lung transplant (LT)surveillance is important as the diagnosis of acute cellular rejection, lymphocytic bronchiolitis and infection directly impact therapy. Transbronchial biopsies (TBBx) using standard biopsy forceps suffer from crush artifact and small size. Recent studies have shown superior sample size and architectural preservation when comparing cyroprobe biopsies (CB) to standard forceps TBBx. There have been no studies assessing the use of CB in the LT population. We present the results from the first 4 patients enrolled in an IRB approved study comparing CB to forceps TBBx in patients undergoing surveillance biopsies after LT. Methods and Materials: Patient undergoing routine surveillance bronchoscopy post-LT are sequentially enrolled. All patients underwent 10 forceps biopsies followed by 5 biopies using a cryoprobe (Erbe, Germany) positioned under fluoroscopic guidance. A temperature of -89.5°C was applied for 3-5 seconds and the cryoprobe sample attached to the probe were removed. The procedure was performed under general anesthesia using rigid bronchoscopy with a bronchial blocker in place. Results: 4 patients, (53 ⫾ 12 years, 3 females). Specimen areas were 9.7mm2 (range 0.15-25mm2) for forceps and 31.3mm2(range 16-60mm2) for cryoprobe. 0/4 patients showed pathology on forceps biopsy, and 1/4 patients showed mild acute cellular rejection (A1Bx) on cryoprobe biopsy and no evidence of rejection on standard TBBX. No pneumothorax or clinically significant bleeding was noted. Conclusions: The use of cryoprobes is potentially an exciting alternative technique to increase diagnostic yield in TBBx during post-LT surveillance bronchoscopy.
511 Prospective Surveillance and Treatment of Pre-Existing Donor Specific Antibodies Ameliorates 1-Year Risk of BOS after Lung Transplantation H.W. Ainge Allen,1 A.P. Havryk,1 M.A. Malouf,1 M. Plit,1 C. Benden,1 N. Watson,2 A.R. Glanville.1 1Department of Cardiopulmonary Transplant, St Vincent’s Hospital, Sydney, NSW, Australia; 2NSW Transplantation and Immunogenetics Laboratory, Australian Red Cross Blood Service, Sydney, NSW, Australia. Purpose: The finding of circulating pre-existing donor specific antibodies (DSA) at the time of transplant has been reported as a risk factor for bronchiolitis obliterans syndrome (BOS) after lung transplantation (LTX). We assessed the utility of a prospective surveillance and management strategy to detect and treat pre-existing DSA and the impact on BOS development. Methods and Materials: Single centre retrospective review of 83 consecutive LTX January 2009-March 2011. Circulating DSA were determined by LUMINEX (LabScreen single antigen assay) at date of transplant. DSA with mean fluorescent intensity (MFI) ⬎1000 were treated with IVIG, therapeutic plasma exchange and rituximab. Primary efficacy was defined by freedom from BOS grade 1. Pre-existing DSA were analysed in a multivariable Cox proportional hazards model incorporating severity of lymphocytic bronchiolitis as a time dependent variable. Results: Sera on 64/83 LTX recipients were analyzed by LUMINEX pre transplant. Circulating DSA (MFI⬎1000) were detected in 11/64 (17%), MFI (mean⫾SD,peak) was 1583⫾5299, 24,789. Class I DSA were detected in 8 patients, and Class II DSA in 4. At a mean 1-year follow up, pre-existing DSA were not a risk for BOS or death by univariate or multivariate analysis. Conclusions: A prospective surveillance and management strategy to detect and treat pre-existing DSA ameliorates the risk of BOS development within the first year post LTX. Durability of effect is yet to be determined. 512 Lessons from the Lung: 186 Autopsies after Lung Transplantation M. Malouf, A. Havryk, M. Plit, C. Benden, S. Rainer, A. Glanville. The Lung Transplant Unit, St Vincent’s Hospital, Darlinghurst, NSW, Australia. Purpose: Lung transplant (LTX) recipients have the highest mortality rate of all solid organ transplant recipients largely due to the development of chronic graft dysfunction from obliterative bronchiolitis (OB) manifest clinically as the bronchiolitis obliterans syndrome (BOS). We assessed the utility of autopsy examination to detect contributing factors to cause of death (COD) after LTX. Methods and Materials: Single centre retrospective review of 186 autopsies from a total 740 LTX 1986-2011. Autopsy rate was 186/390 (48%), comprising 54/126 (43%) single LTX (SLT), 98/209 (47%) bilateral LTX (BLT) and 34/55 (62%) heart LTX (HLT). Results: 40 autopsies (SLT,n⫽13, BLT,n⫽21, HLT, n⫽6) performed ⱕ 90 days post LTX showed: diffuse alveolar damage (DAD)(19) antibody mediated rejection (1), severe rejection (2), mild rejection (2); bronchial dehiscence (13), tracheal dehiscence (1), bronchopneumonia (15), invasive fungal infection (IFI) with Aspergillus (5), mucormycosis (1), candida (1)
The Journal of Heart and Lung Transplantation, Vol 31, No 4S, April 2012
509 Prospective Surveillance and Treatment of De Novo Donor Specific Antibodies after Lung Transplantation Ameliorates 1-Year Risk of BOS H.W. Ainge Allen,1 A.P. Havryk,1 M.A. Malouf,1 M. Plit,1 C. Benden,1 N. Watson,2 A.R. Glanville.1 1Department of Cardiopulmonary Transplant, St Vincent’s Hospital, Sydney, NSW, Australia; 2NSW Transplantation and Immunogenetics Laboratory, Australian Red Cross Blood Service, Sydney, NSW, Australia. Purpose: Development of circulating de novo donor specific antibodies (DSA) has been reported as a risk factor for bronchiolitis obliterans syndrome (BOS) after lung transplantation (LTX). We assessed the utility of a prospective surveillance and management strategy to detect and treat de novo DSA and the impact on BOS development. Methods and Materials: Single centre retrospective review of 83 consecutive LTX recipients transplanted January 2009-March 2011. Circulating DSA were determined by LUMINEX (LabScreen single antigen assay) at date of transplant, serially thereafter and when antibody mediated rejection (AMR) was suspected based on histopathological criteria (capillary injury ⫹/⫺ C4d staining) with or without graft dysfunction. DSA with mean fluorescent intensity (MFI) ⬎1000 were treated with IVIG, therapeutic plasma exchange and rituximab. Primary efficacy was defined by freedom from BOS grade 1. De novo DSA were analysed as a time dependent covariate using a Cox proportional hazards model. Results: Sera on 68/83 LTX recipients were analyzed by LUMINEX post transplant. Circulating DSA (MFI⬎1000) were detected in 39/68 (57%) during the study period, MFI (mean⫾SD,peak) ⫽ 3324⫾4859, 24580. Class I DSA were detected in 27/39, MFI ⫽1,351⫾2673,12499 and Class II DSA in 30/39, MFI⫽ 2299⫾4600, 24580. C4D staining of transbronchial biopsies was positive in 5/14. At mean 1 year follow up, de novo DSA were not a risk factor for BOS (HR 0.98,CI 0.64-11.16,p⫽0.18). Conclusions: A prospective surveillance and management strategy to detect and treat significant de novo DSA ameliorates the 1-year risk of BOS. Optimum frequency of surveillance and durability of effect is yet to be determined. 510 Cryoprobe Versus Forceps Biopsy for Post-Lung Transplant Surveillance L. Yarmus, J. Akulian, C. Gilbert, J. Orens, C. Merlo, D. Feller-Kopman. Pulmonary and Critical Care Medicine, The Johns Hopkins University, Baltimore, MD. Purpose: Obtaining sufficient tissue during post-lung transplant (LT)surveillance is important as the diagnosis of acute cellular rejection, lymphocytic bronchiolitis and infection directly impact therapy. Transbronchial biopsies (TBBx) using standard biopsy forceps suffer from crush artifact and small size. Recent studies have shown superior sample size and architectural preservation when comparing cyroprobe biopsies (CB) to standard forceps TBBx. There have been no studies assessing the use of CB in the LT population. We present the results from the first 4 patients enrolled in an IRB approved study comparing CB to forceps TBBx in patients undergoing surveillance biopsies after LT. Methods and Materials: Patient undergoing routine surveillance bronchoscopy post-LT are sequentially enrolled. All patients underwent 10 forceps biopsies followed by 5 biopies using a cryoprobe (Erbe, Germany) positioned under fluoroscopic guidance. A temperature of -89.5°C was applied for 3-5 seconds and the cryoprobe sample attached to the probe were removed. The procedure was performed under general anesthesia using rigid bronchoscopy with a bronchial blocker in place. Results: 4 patients, (53 ⫾ 12 years, 3 females). Specimen areas were 9.7mm2 (range 0.15-25mm2) for forceps and 31.3mm2(range 16-60mm2) for cryoprobe. 0/4 patients showed pathology on forceps biopsy, and 1/4 patients showed mild acute cellular rejection (A1Bx) on cryoprobe biopsy and no evidence of rejection on standard TBBX. No pneumothorax or clinically significant bleeding was noted. Conclusions: The use of cryoprobes is potentially an exciting alternative technique to increase diagnostic yield in TBBx during post-LT surveillance bronchoscopy.
511 Prospective Surveillance and Treatment of Pre-Existing Donor Specific Antibodies Ameliorates 1-Year Risk of BOS after Lung Transplantation H.W. Ainge Allen,1 A.P. Havryk,1 M.A. Malouf,1 M. Plit,1 C. Benden,1 N. Watson,2 A.R. Glanville.1 1Department of Cardiopulmonary Transplant, St Vincent’s Hospital, Sydney, NSW, Australia; 2NSW Transplantation and Immunogenetics Laboratory, Australian Red Cross Blood Service, Sydney, NSW, Australia. Purpose: The finding of circulating pre-existing donor specific antibodies (DSA) at the time of transplant has been reported as a risk factor for bronchiolitis obliterans syndrome (BOS) after lung transplantation (LTX). We assessed the utility of a prospective surveillance and management strategy to detect and treat pre-existing DSA and the impact on BOS development. Methods and Materials: Single centre retrospective review of 83 consecutive LTX January 2009-March 2011. Circulating DSA were determined by LUMINEX (LabScreen single antigen assay) at date of transplant. DSA with mean fluorescent intensity (MFI) ⬎1000 were treated with IVIG, therapeutic plasma exchange and rituximab. Primary efficacy was defined by freedom from BOS grade 1. Pre-existing DSA were analysed in a multivariable Cox proportional hazards model incorporating severity of lymphocytic bronchiolitis as a time dependent variable. Results: Sera on 64/83 LTX recipients were analyzed by LUMINEX pre transplant. Circulating DSA (MFI⬎1000) were detected in 11/64 (17%), MFI (mean⫾SD,peak) was 1583⫾5299, 24,789. Class I DSA were detected in 8 patients, and Class II DSA in 4. At a mean 1-year follow up, pre-existing DSA were not a risk for BOS or death by univariate or multivariate analysis. Conclusions: A prospective surveillance and management strategy to detect and treat pre-existing DSA ameliorates the risk of BOS development within the first year post LTX. Durability of effect is yet to be determined. 512 Lessons from the Lung: 186 Autopsies after Lung Transplantation M. Malouf, A. Havryk, M. Plit, C. Benden, S. Rainer, A. Glanville. The Lung Transplant Unit, St Vincent’s Hospital, Darlinghurst, NSW, Australia. Purpose: Lung transplant (LTX) recipients have the highest mortality rate of all solid organ transplant recipients largely due to the development of chronic graft dysfunction from obliterative bronchiolitis (OB) manifest clinically as the bronchiolitis obliterans syndrome (BOS). We assessed the utility of autopsy examination to detect contributing factors to cause of death (COD) after LTX. Methods and Materials: Single centre retrospective review of 186 autopsies from a total 740 LTX 1986-2011. Autopsy rate was 186/390 (48%), comprising 54/126 (43%) single LTX (SLT), 98/209 (47%) bilateral LTX (BLT) and 34/55 (62%) heart LTX (HLT). Results: 40 autopsies (SLT,n⫽13, BLT,n⫽21, HLT, n⫽6) performed ⱕ 90 days post LTX showed: diffuse alveolar damage (DAD)(19) antibody mediated rejection (1), severe rejection (2), mild rejection (2); bronchial dehiscence (13), tracheal dehiscence (1), bronchopneumonia (15), invasive fungal infection (IFI) with Aspergillus (5), mucormycosis (1), candida (1)