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Purpose <p>Aggressive natural killer cell leukemia (ANKL) is a rare malignancy with poor prognosis and unclear treatment strategies. Given the poor prognosis and lack of a standardized treatment for ANKL, this study aimed to evaluate the clinical outcomes of L-asparaginase (L-ASNase)-based chemotherapy and hematopoietic stem cell transplantation (HCT).</p> Methods <p>This retrospective study analyzed 51 patients with ANKL (2000–2023) to assess the clinical outcomes and efficacy of L-ASNase-based chemotherapy.</p> Results <p>Among the study patients, 18 (36.7%) had poor performance status (ECOG-PS ≥ 3) and 7 (13.7%) died before initiating chemotherapy. Of the 44 treated patients, 30 (58.9%) received L-ASNase-based regimens, showing higher response rates (46.7% vs. 21.4%) and a slightly longer median duration of response (4.5 vs 4.2&#xa0;months) than non-L-ASNase regimens. Complete administration of L-ASNase in the first cycle improved response rates (<i>p</i> = 0.019), but poor performance led to premature discontinuation (<i>p</i> = 0.011). Among the responders, those who subsequently underwent HCT demonstrated prolonged survival compared to those who did not. Median progression-free survival and overall survival were 0.8 and 1.6 months, respectively.</p> Conclusion <p>HCT was associated with improved survival, particularly among patients who responded to initial therapy. However, given the high frequency of poor performance status at diagnosis, a stepwise approach, including early supportive care, careful chemotherapy administration, and timely HCT, is crucial for optimizing ANKL outcomes.</p>

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Aggressive natural killer cell leukemia therapy in the L-asparaginase era: why are we failing?

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年10月23日

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  • Sang Eun Yoon,
  • Junhun Cho,
  • Hyun-Young Kim,
  • Seok Jin Kim,
  • Won Seog Kim

摘要

Purpose

Aggressive natural killer cell leukemia (ANKL) is a rare malignancy with poor prognosis and unclear treatment strategies. Given the poor prognosis and lack of a standardized treatment for ANKL, this study aimed to evaluate the clinical outcomes of L-asparaginase (L-ASNase)-based chemotherapy and hematopoietic stem cell transplantation (HCT).

Methods

This retrospective study analyzed 51 patients with ANKL (2000–2023) to assess the clinical outcomes and efficacy of L-ASNase-based chemotherapy.

Results

Among the study patients, 18 (36.7%) had poor performance status (ECOG-PS ≥ 3) and 7 (13.7%) died before initiating chemotherapy. Of the 44 treated patients, 30 (58.9%) received L-ASNase-based regimens, showing higher response rates (46.7% vs. 21.4%) and a slightly longer median duration of response (4.5 vs 4.2 months) than non-L-ASNase regimens. Complete administration of L-ASNase in the first cycle improved response rates (p = 0.019), but poor performance led to premature discontinuation (p = 0.011). Among the responders, those who subsequently underwent HCT demonstrated prolonged survival compared to those who did not. Median progression-free survival and overall survival were 0.8 and 1.6 months, respectively.

Conclusion

HCT was associated with improved survival, particularly among patients who responded to initial therapy. However, given the high frequency of poor performance status at diagnosis, a stepwise approach, including early supportive care, careful chemotherapy administration, and timely HCT, is crucial for optimizing ANKL outcomes.