Outcomes following posttransplant viral-specific T-cell therapy in patients with sickle cell disease

Author:

Kinoshita Hannah1ORCID,Mandava Mamatha2,Jensen-Wachspress Mariah A.3,Lang Haili4,Joy Elisabeth3,Tanna Jay1,McCann Chase D3ORCID,O'Brien Samuel3,Burnett Sianna3,Shibli Abeer2,Hoq Fahmida5,Bhatia Monica6,Hanley Patrick J7,Dávila Saldaña Blachy J7ORCID,Mahadeo Kris M8,Bollard Catherine M.7,Keller Michael D.7,Abraham Allistair A.7ORCID

Affiliation:

1. Childrens National Medical Center, Washington, District of Columbia, United States

2. Children's National Hospital, Washington, District of Columbia, United States

3. Children's National Medical Center, Washington, District of Columbia, United States

4. Children's National Health System, Washington, District of Columbia, United States

5. CNH, Laytonsville, Maryland, United States

6. Columbia University, New York, New York, United States

7. George Washington University School of Medicine and Health Sciences, United States

8. MD Anderson Cancer Center, Houston, Texas, United States

Abstract

Hematopoietic stem cell transplantation (HSCT) is increasingly used as a curative approach for sickle cell disease (SCD). With the risk of graft-versus-host disease (GVHD), especially in the HLA-mismatched donors, intense immunosuppression is required leading to an increased risk of viral infection. Post-HSCT, adoptive transfer of virus-specific T cell (VSTs) therapies have not been well-studied in SCD patients. Here, we report the outcomes of patients with SCD at a single-center who received VSTs post-transplant to prevent or treat virus infections. Thirteen patients who received HSCT from HLA-matched (n=9) or mismatched (n=4) donors for SCD were treated with a total of 15 VST products for the treatment or prophylaxis of multiple viruses (cytomegalovirus, ebstein barr virus, adenovirus, BK virus, human herpes virus 6 +/- human parainfluenza virus 3). Of the patients evaluated, 46.2% (n=6)) received VSTs as treatment of virus infection. Eighty percent of patients with active viremia (n=4/5) achieved remission of at least 1 target virus. Seven additional patients (53.8%) received VSTs prophylactically and 6/7 (85.7%) remained virus-free post-infusion. No immediate infusion-related toxicities occurred, and severe de novo acute GVHD occurred in only 2 (15.4%) patients. Given the good safety profile, high-rate of clinical responses and sustained remissions when administered with standard anti-viral treatments, the routine use of VSTs post-HSCT as prophylaxis or treatment may improve the overall safety of transplant for patients with SCD.

Publisher

American Society of Hematology

Subject

Hematology

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