From the Research
Donor lymphocyte infusion (DLI) is a recommended therapeutic option for patients with thalassemia who have relapsed after stem cell transplantation (SCT), with the most recent and highest quality study suggesting its efficacy in achieving full donor chimerism and improving survival outcomes 1.
Key Considerations
- The recommended approach involves administering escalating doses of donor lymphocytes, typically starting with 1 × 10^5 CD3+ cells/kg and gradually increasing to 1 × 10^6 and then 1 × 10^7 CD3+ cells/kg if needed, with intervals of 4-8 weeks between infusions.
- Before initiating DLI, immunosuppression should be tapered off completely when possible.
- The timing of DLI is crucial, with better outcomes observed when administered for mixed chimerism rather than waiting for complete relapse.
- Patients should be closely monitored for graft-versus-host disease (GVHD), which is the main complication of DLI but also indicates the desired graft-versus-thalassemia effect.
Rationale
- DLI works by introducing donor T-cells that recognize recipient hematopoietic cells as foreign, eliminating residual recipient cells and promoting full donor chimerism.
- This approach is particularly valuable because it can potentially restore complete donor chimerism without the need for a second full transplant procedure, though its success rate varies depending on the degree of mixed chimerism at the time of intervention.
- A recent study demonstrated the safety and efficacy of a DLI that was depleted of CD45RA+ naive T cells, with no dose-limiting grade III/IV acute GvHD or adverse events attributable to the DLI observed at any dose level 1.
Clinical Implications
- DLI should be considered as a therapeutic option for patients with thalassemia who have relapsed after SCT, particularly those with mixed chimerism.
- The decision to proceed with DLI should be made on a case-by-case basis, taking into account the individual patient's risk factors and disease status.
- Further research is needed to fully understand the efficacy and safety of DLI in this patient population, as well as to optimize dosing and administration strategies.