Immunity and Tolerance after Bilateral Orthotopic Lung Transplant (BOLT) in Tandem with a CD3+/CD19+ Depleted Vertebral Bone Marrow Transplant (BOLT+BMT) from 1 of 8 HLA-Matched Cadaveric Donors

P. Szabolcs,¹ X. Chen,¹ A. Donnenberg,² M. Hill,¹ J. Rowan,¹ S. Mcintyre,¹ G. Kurland,¹ J. Barnum,¹ J. McDyer.¹

¹BMT-CT, Children Hospital of Pittsburgh UPMC, Pittsburgh, PA
²IDM-HCC, University of Pittsburgh, Pittsburgh, PA.

Meeting: 2018 American Transplant Congress

Abstract number: 589

Keywords: Bone marrow transplantation, Lung transplantation, Mixed chimerism, Tolerance

Session Information

Session Name: Concurrent Session: Tolerance: Clinical Studies

Session Type: Concurrent Session

Date: Tuesday, June 5, 2018

Session Time: 4:30pm-6:00pm

Presentation Time: 5:18pm-5:30pm

Location: Room 210

Primary immunodeficiency patients may develop pulmonary complications and most are ineligible for either lung transplant or BMT due to futility. We report our first 2 subjects enrolled on NCT01852370 trial receiving tandem BOLT&BMT from the same deceased UNOS donor.

Case 1: 14 year old female with IL-7R SCID & recurrent pneumonia underwent BOLT from a 2/6 HLA antigen (1/8 allele level) matched donor. Marrow suspension prepared from T11-L4 VB was CD3+/CD19+ depleted(CliniMACS^®) then frozen along with ~20 fold fewer TNC & CD34+ cells from the iliac crest. At 3m post-BOLT, she started BMT conditioning. A month later, the marrow was thawed and infused (5E+06 CD34+ cells/kg and 8E+04 T cells/kg). She engrafted with 100% donor cells. Due to persistent T cell lymphopenia (mostly host), she received DLI ~10w later (5E+04 T cells/kg).

DLI resulted in dominant donor T and B cell chimerism (Fig1A, B) unlike other subsets (Fig1C,D). BAL values exhibited different kinetics (Fig1).

T/B cells, TCR/BCR repertoires, and TREC exceeded pre-BMT values by 3-6m (Fig2A,B). BK virus specific T cells cleared viremia (Fig2C).

Mild skin GVHD was cleared in 2w with <1mg/kg prednisone. Serial lung biopsies have been negative for rejection up to now (5m off IST). At 18m post-BMT (2m post-IST withdrawal), circulating donor T cells were unresponsive to host DC while responded to 3^rd party APC (Fig3). Tolerance towards host APC was Treg independent (Fig3).

Case 2: 38y/o female with CVID on ECMO underwent BOLT. She had 3 episodes of lung rejection before becoming eligible for BMT (1/8 match) 14 months later. She engrafted by day+12 with 95% whole blood chimerism but T cells of host origin that was treated with DLI.

Case 1 is the first in human to demonstrate durable engraftment, immune competence, and tolerance from deceased donor VB marrow matched only at a single class I MHC allele, providing proof of principle currently tested in adults.

CITATION INFORMATION: Szabolcs P., Chen X., Donnenberg A., Hill M., Rowan J., Mcintyre S., Kurland G., Barnum J., McDyer J. Immunity and Tolerance after Bilateral Orthotopic Lung Transplant (BOLT) in Tandem with a CD3+/CD19+ Depleted Vertebral Bone Marrow Transplant (BOLT+BMT) from 1 of 8 HLA-Matched Cadaveric Donors Am J Transplant. 2017;17 (suppl 3).

To cite this abstract in AMA style:

Szabolcs P, Chen X, Donnenberg A, Hill M, Rowan J, Mcintyre S, Kurland G, Barnum J, McDyer J. Immunity and Tolerance after Bilateral Orthotopic Lung Transplant (BOLT) in Tandem with a CD3+/CD19+ Depleted Vertebral Bone Marrow Transplant (BOLT+BMT) from 1 of 8 HLA-Matched Cadaveric Donors [abstract]. https://atcmeetingabstracts.com/abstract/immunity-and-tolerance-after-bilateral-orthotopic-lung-transplant-bolt-in-tandem-with-a-cd3-cd19-depleted-vertebral-bone-marrow-transplant-boltbmt-from-1-of-8-hla-matched-cadaveric-donors/. Accessed November 21, 2024.

« Back to 2018 American Transplant Congress