COMBINED BILATERAL LUNG TRANSPLANTATION AND BONE MARROW TRANSPLANTATION IN SELECT PATIENTS WITH END-STAGE LUNG DISEASE: A POTENTIAL FOR LONG-TERM ALLOGRAFT TOLERANCE INDUCTION

Abstract

SESSION TITLE: Tuesday Abstract Posters SESSION TYPE: Original Investigation Posters PRESENTED ON: 10/22/2019 01:00 PM - 02:00 PM PURPOSE: Lung transplantation is the only life-saving therapy for select patients with end-stage lung disease. However, certain end-stage lung patients are ineligible for conventional lung transplant with underlying diseases such as primary immunodeficiencies (PID) or those with bone marrow failure (e.g., telomere-mediated diseases), as these patients are poor candidates for life-long immunosuppression. METHODS: We have established a single institution clinical trial protocol and program for salvage transplant, using combined bilateral lung transplant followed by bone marrow transplant (Lung/BMTxp) from the cadaveric lung donor. This adult/pediatric protocol employs partial MHC-matching in addition to ABO/size compatibility, a non-myeloablative condition regimen, and procurement of vertebral bodies for stem cell isolation followed by CD3+/CD19+ lymphocyte depletion. RESULTS: To date, our institution has performed five combined, tandem Lung/BMTxp procedures in patients with either PID (n=4) or telomere-mediated disease (n=1) and end-stage lung disease. All patients were consented to an Institutional Review Board study protocol and protocol approved by the FDA. Of these 5 Lung/BMTxp recipients, 3 patients engrafted BM, one patient transiently engrafted but subsequently rejected BM, and another failed to engraft BM. Notably, the first patient, a 14 y/o F with an underlying form of Severe Combined Immunodeficiency (SCID; IL-7R deficiency) underwent successful BMTxp four months after Lung Txp and has maintained high lymphocyte donor chimerism (>99%) after donor lymphocyte infusion. She has been successfully weaned off all immunosuppression for over two years now and has had no allograft rejection or infections. Lung allograft tolerance has persisted despite a fall in myeloid chimerism to a stable 20% level that has been maintained long-term. The fourth patient, a 20 y/o M with interstitial lung disease and myelodysplastic syndrome with monosomy 7 underwent Lung Txp and successfully engrafted donor BM four months later. He has maintained >99% donor chimerism for 10 months now and is in the final stages of weaning off low dose tacrolimus and prednisone, with stable lung function and no evidence of rejection. Currently, two additional patients with PID and end-stage lung disease (a 30 y/o M with Chronic Granulomatous Disease and a 20 y/o M with SCID) are listed for Lung/BMTxp. CONCLUSIONS: Together, our early single center experience supports combined Lung/BMTxp as an effective salvage transplant strategy for select patients with end-stage lung disease who are not candidates for conventional lung transplant. The establishment of high-level donor lymphoid chimerism provides the potential to wean Lung/BMTxp recipients off all immunosuppression and induce long-term lung allograft tolerance. CLINICAL IMPLICATIONS: Our study describes a novel salvage combined transplant approach with the potential for long-term tolerance. DISCLOSURES: No relevant relationships by Jessie Barnum, source=Web Response No relevant relationships by XIAOHUA CHEN, source=Web Response no disclosure on file for Jonathan D'Cunha; No relevant relationships by Stefanie Hannan, source=Web Response No relevant relationships by Ritchie Koshy, source=Web Response no disclosure on file for Geoffrey Kurland; No relevant relationships by John McDyer, source=Web Response no disclosure on file for Shawna McIntyre; No relevant relationships by Matthew Morrell, source=Web Response No relevant relationships by Joseph Pilewski, source=Web Response No relevant relationships by Iulia Popescu, source=Web Response No relevant relationships by Pablo Sanchez, source=Web Response No relevant relationships by Heather Stanczak, source=Web Response no disclosure on file for Paul Szabolcs