Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
[Preprint]. 2024 Jan 8:rs.3.rs-3832106.
doi: 10.21203/rs.3.rs-3832106/v1.

Pretransplant Desensitization of Donor-Specific Anti-HLA Antibodies with Plasmapheresis and Immunoglobulin Produces Equivalent Outcomes to Patients with No Donor Specific Antibodies in Haploidentical Hematopoietic Cell Transplant

Hunter Cochran  1 , Michael Slade  2 , Feng Gao  3 , Sonia Godbole  1 , Aaron Pruitt  1 , Elisa De Togni  2 , Chang Liu  1 , Brenda Grossman  4 , Ramzi Abboud  3
Affiliations

Pretransplant Desensitization of Donor-Specific Anti-HLA Antibodies with Plasmapheresis and Immunoglobulin Produces Equivalent Outcomes to Patients with No Donor Specific Antibodies in Haploidentical Hematopoietic Cell Transplant

Hunter Cochran et al. Res Sq. .

Update in

Abstract

In patients requiring haploidentical hematopoietic cell transplant (haplo-HCT), the presence of donor specific anti-HLA antibodies (DSAs) is associated with high rates of primary graft failure and poor overall survival (OS). There is limited data regarding the effect of desensitization. Adult patients undergoing haplo-HCT at Washington University School of Medicine from 2009-2021 were identified. Patients were divided into three cohorts: no DSA, untreated DSA or treated DSA. DSA testing was performed. Desensitization therapy using plasmapheresis and IVIg (immunoglobulin) was performed. We retrospectively identified 304 patients for study inclusion. 14 of 30 patients with DSAs underwent desensitization. By day +2, 57% of patients cleared all DSAs. OS was expectedly worse in patients with untreated DSAs. There were similar results between treated DSA and patients without DSA (OS median: control: 352 days vs. treated: 1331 days vs. untreated: 137 days, p = 0.02). RFS was also significantly different between the groups however with similar RFS in treated DSA and control groups (RFS median: control: 248 vs. treated: 322 v. untreated: 119, p = 0.03). Desensitization before haplo-HCT produces similar outcomes to patients without DSAs. While the optimal desensitization protocol has not been established, all patients received a backbone of plasmapheresis and immunoglobulin.

PubMed Disclaimer

Conflict of interest statement

Declarations Conflict of Interest: The authors declare that they have no conflicts relating to this manuscript. Additional Declarations: The authors have declared there is NO conflict of interest to disclose.

Figures

Figure 1
Figure 1
The timeline of our desensitization protocol backbone. Additional sessions added per provider discretion prior to day −13. PE plasmapheresis. IVIG Intravenous immunoglobulin. Tacro Tacrolimus. MMF Mycophenolate Mofetil. SC Infusion Stem Cell infusion. PTCy Post-Transplant Cyclophosphamide. Conditioning Chemo is dependent on provider choice and patient condition.
Figure 2
Figure 2
MFI (Mean Fluorescence Intensity) value of the highest DSA (Donor specific antibody) at three time points including pre-desensitization, post-desensitization pre-transplant (Day −1), and post additional desensitization PE/IVIG post-transplant (Day +2). Each line represents 1 of 14 patients with DSAs who went through the desensitization protocol. Average MFI of all patients at these time points are illustrated via dashed line.
Figure 3
Figure 3
Overall Survival comparison of patients with no DSA, untreated patients with DSAs, and desensitized patients with DSAs. DSA Donor Specific Antibody.
Figure 4
Figure 4
Relapse Free Survival comparison of patients with no DSAs, untreated patients with DSAs, and desensitized patients with DSAs. DSA Donor Specific Antibody. RFS Relapse Free Survival.
Figure 5
Figure 5
Left. Cumulative incidence of neutrophil engraftment and Right. Cumulative incidence of platelet engraftment between the three groups of patients: patients with no DSA, untreated patients with DSAs, and desensitized patients with DSAs.
See this image and copyright information in PMC

References

    1. Takami A. Hematopoietic stem cell transplantation for acute myeloid leukemia. Int J Hematol. 2018. May;107(5):513–8. - PubMed
    1. Switzer GE, Bruce JG, Myaskovsky L, DiMartini A, Shellmer D, Confer DL, et al. Race and ethnicity in decisions about unrelated hematopoietic stem cell donation. Blood. 2013. Feb 21;121(8):1469–76. - PMC - PubMed
    1. Morin-Zorman S, Loiseau P, Taupin JL, Caillat-Zucman S. Donor-Specific Anti-HLA Antibodies in Allogeneic Hematopoietic Stem Cell Transplantation. Front Immunol [Internet]. 2016. [cited 2023 Jan 8];7. Available from: 10.3389/fimmu.2016.00307 - DOI - PMC - PubMed
    1. Ciurea SO, de Lima M, Cano P, Korbling M, Giralt S, Shpall EJ, et al. High risk of graft failure in patients with anti-HLA antibodies undergoing haploidentical stem-cell transplantation. Transplantation. 2009. Oct 27;88(8):1019–24. - PMC - PubMed
    1. Zou J, Romee R, Slade M, Phelan D, Keller J, Mohanakumar T, et al. Untreated Donor Specific Antibodies against HLA are Associated with Poor Outcomes in Peripheral Blood Haploidentical Hematopoietic Cell Transplantation. Bone Marrow Transplant. 2017. Jun;52(6):898–901. - PMC - PubMed

Publication types