academic attending phycisian Hannover Medical School Hannover, Germany
Introduction/Rationale: Leukemia is treated successfully with allogeneic hematopoietic stem cell transplantation (HSCT). Innate and adaptive imunity contribute to viral and relapse control in patients post-allogeneic HSCT. We reasoned that the coopertion of CMV/mHag-T cells could prevent or delay CMV-reactivation (CMV-R) and relapse post-allo-HSCT. Immune responses against minor histocompatibility antigen mutations (mHag), can eliminate residual normal and malignant hematopoietic cells persisting after HSCT.
Methods: Highly sensitive real-time quantitative PCR, is routinely analysed in our laboratory for all eligable patients to determine possible host-chimerism post-HSCT. Peripheral blood (PB) from 74 patients was collected and analyzed between day 0 and 300 post-HSCT using tetramer staining, cytotoxic assays and flowcytometry in all patients eligible. Clinical and demographic data of all patients were correlated with the presence/abscence of CMV- or mHag-CTLs.
Results: The relationship CMV-CTL and mHag-CTL (HA-1, HA-2, HA-8 and H-Y), host chimerism and cumulative relapse incidence (CIR) was analysed in 74 patients undergoing allogeneic HLA-matched HSCT. We verified a strong association between mHag-CTL presence and low host chimerism (88%, 36/41 patients), with significantly higher mHag-CTL levels at days 150 (p < 0.05) and 300 (p < 0.01) in patients in remission. Loss/low of mHag-CTLs between days 50 and 150 correlated with early relapse in 8/9 patients. CMV-CTL presence (≥ 1 CMV-CTL/µl peripheral blood) was associated with significantly higher mHag-CTL expansion (p < 0.01).
Conclusion: Our resulats demonstrate the essential role of sustained mHag-CTLs during early post-transplant phases for maintaining leukemia remission and highlight the supportive role of CMV-CTLs in immune recovery. Monitoring these NK-/T-cell populations provides valuable insights into relapse risk and offers a foundation for guiding and refining immunotherapeutic interventions aiming at reducing relapse-related mortality.
