CD45RA-depleted DLI for the Prevention of Viral Infections in High-risk Patients After Haploidentical Transplantation

CD45RA-depleted DLI for the Prevention of Viral Infections in High-risk Patients After Transplantation: a Prospective, Multicenter, Single-arm, Pragmatic Clinical Study

The goal of this clinical trial is to learn whether giving patients a special type of donor immune cells (called CD45RA Depleted DLI) can help prevent viral infections after a stem cell transplant. It will also learn about the safety of this treatment. The main questions it aims to answer are:

Does this treatment lower the chance of getting serious viral infections after transplant? What medical problems do patients have when receiving this treatment?

Following allogeneic hematopoietic stem cell transplantation (allo-HSCT), delayed immune reconstitution and long-term use of immunosuppressants leave patients in a prolonged immunocompromised state, predisposing them to various infections, which represent a leading cause of transplant-related mortality. Conventional antiviral agents such as ganciclovir and valganciclovir are associated with hematologic toxicities, including neutropenia and anemia, potentially complicating post-transplant management. Meanwhile, newer antivirals such as cidofovir have not yet been approved in China, limiting patient access. Antiviral cell therapies, represented by virus-specific T cells (VSTs), are expensive and require prolonged culture periods. Therefore, there is an urgent need to identify effective strategies to prevent viral infections after HSCT, especially in high-risk patients.

Previous studies suggest that adoptive donor lymphocyte infusion (DLI) can facilitate immune reconstitution; however, the CD45RA-positive naïve T cells contained in conventional DLI are a major cause of graft-versus-host disease (GvHD). By depleting naïve T cells from donor lymphocytes ex vivo while retaining donor memory T cells (Tm), it is possible to promote post-transplant immune reconstitution without increasing the risk of GvHD. This study plans to conduct a prospective, multicenter, single-arm pragmatic clinical trial. Using the CliniMACS® cell selection system, we will selectively deplete CD45RA-positive T cells ex vivo and infuse the CD45RA-depleted donor lymphocytes (i.e., CD45RA Depleted DLI) to prevent viral infections in high-risk patients after transplantation. The efficacy, safety, and impact on post-transplant immune reconstitution of this regimen will be evaluated.

Primary objective: To evaluate the efficacy and safety of CD45RA Depleted DLI in preventing viral infections in high-risk patients after transplantation.

Secondary objective: To evaluate the impact of CD45RA Depleted DLI on immune reconstitution after transplantation.

Inclusion Criteria:

Participants must meet all of the following criteria:

• Patients undergoing allogeneic hematopoietic stem cell transplantation (any conditioning regimen or graft source is allowed).
• Presence of at least one high-risk factor for post-transplant viral infection (any of the following):
• Age ≥50 years or ≤14 years
• Non-sibling matched transplantation
• In vivo or ex vivo T-cell depletion
• Myeloablative conditioning
• Conditioning containing radiotherapy
• Second transplantation
• CMV IgG or EBV IgG donor/recipient mismatch (donor positive, recipient negative)
• History of grade II or higher acute graft-versus-host disease (aGVHD) after transplantation and use of high-dose corticosteroids (prednisone equivalent ≥1 mg/kg/day)
• Availability of a suitable lymphocyte donor (see "Donor Selection Criteria").
• Adequate organ function meeting the following laboratory criteria:
• Liver function: ALT and AST ≤10× upper limit of normal (ULN); total bilirubin ≤5× ULN
• Renal function: BUN and creatinine ≤1.25× ULN
• No cardiac dysfunction on electrocardiogram or echocardiogram
• Pulmonary function: oxygen saturation >90% without supplemental oxygen
• The patient or legal guardian has the desire and request to receive treatment, signs the informed consent form before treatment, and is willing to comply with the treatment plan, follow-up schedule, and laboratory tests.

Exclusion Criteria:

Patients meeting any of the following criteria will be excluded from this study:

• Active grade II-IV acute graft-versus-host disease (aGVHD)
• Active aGVHD requiring prednisone or equivalent corticosteroid >0.5 mg/kg/day
• Active viral infection
• Uncontrolled or relapsed malignancy
• Other serious acute or chronic physical or psychiatric conditions, or laboratory abnormalities, that may compromise patient safety or compliance, or affect informed consent, study participation, follow-up, or interpretation of results.