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2383 Rebound and Overshoot of Donor Specific Antibodies to HLA Following Plasma Exchanges during Hematopoietic Progenitor Cell Transplantation: A Case Report

Program: Oral and Poster Abstracts
Session: 721. Clinical Allogeneic Transplantation: Conditioning Regimens, Engraftment, and Acute Transplant Toxicities: Poster II
Hematology Disease Topics & Pathways:
Biological, apheresis, Therapies, Technology and Procedures, immunotherapy, transplantation
Sunday, December 6, 2020, 7:00 AM-3:30 PM

Sajjad Hassan1*, Kamille West, MD2*, William Ward2*, Jennifer A Kanakry3,4* and Willy A. Flegel, MD2,5

1Department of Transfusion Medicine, National Institutes of Health, Rockville, MD
2Department of Transfusion Medicine, National Institutes of Health, Bethesda, MD
3Experimental Transplantation and Immunology Branch, National Cancer Institute, Bethesda, MD
4Experimental Transplantation and Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD
5Department of Transfusion Medicine, NIH Clinical Center, National Institutes of Health, Bethesda, MD

Background/Case Studies: Donor specific antibodies (DSA) to HLA have been associated with graft loss in hematopoietic progenitor cells (HPC) transplantation. There are limited data that therapeutic plasma exchange (TPE) and immunotherapy results in desensitization with successful engraftment. We report an attempt of desensitization during transplantation and observed a rebound and overshooting of DSA.

Study Design/Methods: A 27 year old female with treatment refractory cutaneous T cell lymphoma was scheduled for HPC transplantation from her HLA-haploidentical half-sister. The donor carried the HLA DRB1*13:03 antigen, to which the patient had DSA.

Results/Findings: Pre-transplant DSA mean fluorescence intensity (MFI) was 2000, with confirmation on independent samples, as well as no prozone effect and linear correlation on dilution. Given no alternative donor options at the time, a desensitization approach of immunosuppression with tacrolimus and mycophenolate mofetil (MMF) days -21 through day -3, as well as TPE and immunoglobulin infusion on days -6, -4, and -1 ensued. Unexpectedly, DSA increased to a MFI of 9000 on day -7 and greater than 19,000 on day -1. Despite 2 additional post-transplantation TPE/IVIG procedures as well as graft-versus-host disease prophylaxis with high-dose, post-transplantation cyclophosphamide, sirolimus, and MMF, DSA remained elevated. Flow cytometric cross match was negative pre-transplant and turned positive after transplantation. Primary graft failure occurred and was attributed to antibody mediated rejection. A second transplantation from a 7/8 HLA-matched unrelated donor, not carrying HLA DRB1*13:03 antigen, resulted in successful engraftment.

Conclusions: Rarely, unexpected and rapid changes in DSA can occur despite use of current desensitization approaches. This is problematic when it occurs after conditioning has already started, as it is unlikely to be overcome by additional TPE or other interventions. Overshoot of DSA in HPC transplantation has rarely been reported before. The cause, such as underlying disease, immunotherapy, chemotherapy or TPE, remains unknown. Further studies are needed to explore, if TPE has a role in rebound with overshoot of DSA.

Disclosures: No relevant conflicts of interest to declare.

See more of: 721. Clinical Allogeneic Transplantation: Conditioning Regimens, Engraftment, and Acute Transplant Toxicities: Poster II
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