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<p>Sex chromosome loss (SCL) occasionally occurs after sex-mismatched allogeneic hematopoietic stem cell transplantation (allo-HSCT), but its clinical significance remains unclear. This retrospective study analyzed 78 patients who developed SCL after sex-mismatched HSCT, comprising 27 cases with initial-onset SCL (detected within first month post-transplant) and 51 cases with late-onset SCL (median onset time: 6.1 months; range: 2-73.1 months). Based on the results of chimerism analysis, initial-onset SCL was found to predominantly reflect the physiological aging hematopoietic cells from older donors, rather than relapse-related clonal abnormalities. In contrast, late-onset SCL was significantly associated with worse overall survival (OS) (HR 8.190,95% CI 2.842-23.600), inferior event-free survival (EFS) (HR 4.691,95% CI 1.839–11.966), and higher relapse risk (HR 6.751,95% CI 1.912–23.841). Among late-onset SCL patients, the optimal initial SCL clone size threshold for predicting relapse was 6% (sensitivity of 88.6%, specificity of 75.0%). The multivariate analysis confirmed ≥6% initial SCL clone size as an independent risk factor for relapse (HR 3.546, 95%CI 1.540-8.161), EFS(HR 3.418, 95% CI 1.572-7.433) and OS (HR 11.665, 95% CI 3.926-34.663). In conclusion, late-onset SCL may be associated with poor clinical outcomes, with the ≥6% clonal threshold serving as a critical marker for identifying high-risk patients prone to treatment failure.</p>

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Is sex chromosome loss a predictive marker for outcome after sex-mismatched allogeneic hematopoietic stem cell transplantation?

  • 期刊论文

  • 发表日期：

    2026年3月20日

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  • Lu Gao,
  • Na Li,
  • Lin Feng,
  • Xiaohui Zhang,
  • Lanping Xu,
  • Yu Wang,
  • Yingjun Chang,
  • Xiaojun Huang,
  • Yueyun Lai

摘要

Sex chromosome loss (SCL) occasionally occurs after sex-mismatched allogeneic hematopoietic stem cell transplantation (allo-HSCT), but its clinical significance remains unclear. This retrospective study analyzed 78 patients who developed SCL after sex-mismatched HSCT, comprising 27 cases with initial-onset SCL (detected within first month post-transplant) and 51 cases with late-onset SCL (median onset time: 6.1 months; range: 2-73.1 months). Based on the results of chimerism analysis, initial-onset SCL was found to predominantly reflect the physiological aging hematopoietic cells from older donors, rather than relapse-related clonal abnormalities. In contrast, late-onset SCL was significantly associated with worse overall survival (OS) (HR 8.190,95% CI 2.842-23.600), inferior event-free survival (EFS) (HR 4.691,95% CI 1.839–11.966), and higher relapse risk (HR 6.751,95% CI 1.912–23.841). Among late-onset SCL patients, the optimal initial SCL clone size threshold for predicting relapse was 6% (sensitivity of 88.6%, specificity of 75.0%). The multivariate analysis confirmed ≥6% initial SCL clone size as an independent risk factor for relapse (HR 3.546, 95%CI 1.540-8.161), EFS(HR 3.418, 95% CI 1.572-7.433) and OS (HR 11.665, 95% CI 3.926-34.663). In conclusion, late-onset SCL may be associated with poor clinical outcomes, with the ≥6% clonal threshold serving as a critical marker for identifying high-risk patients prone to treatment failure.