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<p>Post-transplant tyrosine kinase inhibitors (TKIs) show promise in preventing relapse after allogeneic hematopoietic cell transplantation (allo-HCT) for Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL). However, their real-world use and efficacy remain unclear. A comprehensive study across seven centers included Ph+ALL patients who underwent allo-HCT between 2002 and 2022. Post-transplant TKIs were administered in 28% of patients (49 of 173 transplanted in complete remission): 7% as prophylaxis during complete molecular remission (CMR), and 21% in response to measurable residual disease (MRD) positivity. Median first post-transplant TKI duration was 13.7 months for the prophylactic group and 4.0 months for the MRD-triggered group. Prophylactic TKIs appear particularly beneficial for patients not in CMR at allo-HCT, showing a trend towards higher 5-year relapse-free survival (RFS) compared to those not receiving prophylactic TKIs (100% vs. 73%; <i>P</i> = 0.11). Significant RFS differences were observed between the prophylactic, non-TKI, and MRD-triggered groups. However, patients with white blood cell counts &lt;15000/µl at diagnosis and no additional chromosomal abnormalities—an MRD-triggered high efficacy cluster—demonstrated comparable 5-year RFS regardless of TKI strategy (100% vs. 85% vs. 80%; <i>P</i> = 0.87). This cluster highlights the potential effectiveness of MRD-triggered TKI administration in select low-risk patients, suggesting tailored TKI strategies based on risk factors.</p>

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Post-transplant TKIs for Ph+ ALL: practices to date and clinical significance

  • 期刊论文

  • 发表日期：

    2025年1月17日

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  • Satoshi Nishiwaki,
  • Seitaro Terakura,
  • Takanobu Morishita,
  • Tatsunori Goto,
  • Yuichiro Inagaki,
  • Kotaro Miyao,
  • Nobuaki Fukushima,
  • Daiki Hirano,
  • Naoyuki Tange,
  • Shingo Kurahashi,
  • Yachiyo Kuwatsuka,
  • Masanobu Kasai,
  • Hiroatsu Iida,
  • Kazutaka Ozeki,
  • Masashi Sawa,
  • Tetsuya Nishida,
  • Hitoshi Kiyoi

摘要

Post-transplant tyrosine kinase inhibitors (TKIs) show promise in preventing relapse after allogeneic hematopoietic cell transplantation (allo-HCT) for Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL). However, their real-world use and efficacy remain unclear. A comprehensive study across seven centers included Ph+ALL patients who underwent allo-HCT between 2002 and 2022. Post-transplant TKIs were administered in 28% of patients (49 of 173 transplanted in complete remission): 7% as prophylaxis during complete molecular remission (CMR), and 21% in response to measurable residual disease (MRD) positivity. Median first post-transplant TKI duration was 13.7 months for the prophylactic group and 4.0 months for the MRD-triggered group. Prophylactic TKIs appear particularly beneficial for patients not in CMR at allo-HCT, showing a trend towards higher 5-year relapse-free survival (RFS) compared to those not receiving prophylactic TKIs (100% vs. 73%; P = 0.11). Significant RFS differences were observed between the prophylactic, non-TKI, and MRD-triggered groups. However, patients with white blood cell counts <15000/µl at diagnosis and no additional chromosomal abnormalities—an MRD-triggered high efficacy cluster—demonstrated comparable 5-year RFS regardless of TKI strategy (100% vs. 85% vs. 80%; P = 0.87). This cluster highlights the potential effectiveness of MRD-triggered TKI administration in select low-risk patients, suggesting tailored TKI strategies based on risk factors.