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<p>Central nervous system (CNS) relapse remains a clinically significant yet underexplored pattern of recurrence in adult patients with acute lymphoblastic leukemia (ALL) after allogeneic hematopoietic cell transplantation (allo-HCT). We retrospectively analyzed 748 adult ALL patients who underwent allo-HCT between 2009 and 2022 following a modified hyper-CVAD regimen with six planned doses of intrathecal (IT) chemoprophylaxis. Most patients received total body irradiation (TBI)-based conditioning. CNS relapse occurred in 38 (5.1%) patients at a median of 10.6 months post-HCT. Notably, 84.2% of CNS relapses occurred in Philadelphia chromosome (Ph)-positive ALL. Thus, Ph-positive ALL compared to Ph-negative ALL (9.7% vs. 1.4%, <i>p</i> &lt; 0.001) and hyperleukocytosis at diagnosis (8.1% vs. 2.5%, <i>p</i> &lt; 0.001) were associated with CNS relapse. Notably, negative pre-transplant measurable residual disease (MRD) in Ph-positive ALL and prophylactic IT and TBI-based conditioning were associated with reduced CNS relapse risk in Ph-negative ALL. Five-year overall survival of CNS relapse and the other relapse was 30.4% and 7.6%, respectively, and isolated CNS relapse showed the most favorable outcomes. Our findings suggest that Ph-positive ALL with poor molecular response and high initial tumor burden may represent a biologically distinct high-risk subgroup for CNS relapse, warranting novel CNS-directed preventive strategies to improve post-HCT outcomes.</p>

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Relapse patterns focusing on central nervous system involvement after allogeneic hematopoietic cell transplantation in adult patients with acute lymphoblastic leukemia

  • 期刊论文

  • 发表日期：

    2026年3月14日

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  • Jong Hyuk Lee,
  • Jaehyun Ahn,
  • Daehun Kwag,
  • Gi June Min,
  • Sung-Soo Park,
  • Silvia Park,
  • Sung-Eun Lee,
  • Byung-Sik Cho,
  • Ki-Seong Eom,
  • Yoo-Jin Kim,
  • Hee-Je Kim,
  • Chang-Ki Min,
  • Seok-Goo Cho,
  • Jae-Ho Yoon

摘要

Central nervous system (CNS) relapse remains a clinically significant yet underexplored pattern of recurrence in adult patients with acute lymphoblastic leukemia (ALL) after allogeneic hematopoietic cell transplantation (allo-HCT). We retrospectively analyzed 748 adult ALL patients who underwent allo-HCT between 2009 and 2022 following a modified hyper-CVAD regimen with six planned doses of intrathecal (IT) chemoprophylaxis. Most patients received total body irradiation (TBI)-based conditioning. CNS relapse occurred in 38 (5.1%) patients at a median of 10.6 months post-HCT. Notably, 84.2% of CNS relapses occurred in Philadelphia chromosome (Ph)-positive ALL. Thus, Ph-positive ALL compared to Ph-negative ALL (9.7% vs. 1.4%, p < 0.001) and hyperleukocytosis at diagnosis (8.1% vs. 2.5%, p < 0.001) were associated with CNS relapse. Notably, negative pre-transplant measurable residual disease (MRD) in Ph-positive ALL and prophylactic IT and TBI-based conditioning were associated with reduced CNS relapse risk in Ph-negative ALL. Five-year overall survival of CNS relapse and the other relapse was 30.4% and 7.6%, respectively, and isolated CNS relapse showed the most favorable outcomes. Our findings suggest that Ph-positive ALL with poor molecular response and high initial tumor burden may represent a biologically distinct high-risk subgroup for CNS relapse, warranting novel CNS-directed preventive strategies to improve post-HCT outcomes.