PRELIMINARY EVALUATION OF THE ASSOCIATION BETWEEN EARLY TACROLIMUS CONCENTRATIONS AND ACUTE GVHD RISK IN HAPLOIDENTICAL STEM CELL TRANSPLANTATION: FINE-GRAY AND LANDMARK ANALYSES
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Abstract
Background: Haploidentical hematopoietic stem cell transplantation using post-transplant cyclophosphamide (haplo-PTCY) has improved outcomes for patients without fully matched donors. However, acute graft-versus-host disease (GVHD) remains a significant complication despite reduced incidence via PTCY. Tacrolimus (TAC) plays a crucial role in GVHD prophylaxis, yet optimal levels and their early post-transplant impact on GVHD remain unclear. Objectives: To evaluate the association between TAC levels in weeks 1-4 and the risk of acute GVHD grades II-IV and III-IV after haplo-PTCY. Methods: Retrospective study of 59 patients undergoing haplo-PTCY at Blood Transfusion and Hematology Hospital (2019-2024). TAC levels (ng/mL) were analyzed alongside GVHD. Mann-Whitney tests assessed differences in medians, Fine-Gray proportional hazards models estimated hazard ratios (HR) accounting for competing risks, and landmark analyses at days 7 and 14 evaluated cumulative incidence. Data were analyzed using EZR and SPSS software, with significance at p<0.05. Results: The GVHD III-IV group had lower median TAC levels in week 1 (1.75 [95% CI 1.10-2.50] vs. 6.3 [95% CI 0.90-25.50], p=0.012). Landmark analysis showed higher cumulative incidence of GVHD III-IV in the low TAC group (<6 ng/mL) at day 7 – week 1 (14.3%, p=0.008) and day 14 – week 1-2 (12.5%, p=0.036). Univariate Fine-Gray analysis revealed an HR of 0.39 (95% CI 0.20-0.77, p=0.006) for week 1 TAC levels, indicating a reduced risk per 1 ng/mL increase. Conclusion: Week 1-2 TAC levels are significantly associated with grade III-IV acute GVHD after haplo-PTCY, and it is recommended to maintain ≥ 6 ng/mL early. Larger prospective studies are needed to confirm findings, given the small sample and limited events.
Keywords
Tacrolimus, acute GVHD, haplo-PTCY, Fine-Gray model, landmark analysis, competing risks.
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References
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