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急性髓系白血病巩固治疗：时机至关重要。

AML consolidation therapy: timing matters.

作者信息

Reimann Adrian-Manuel, Schalk Enrico, Jost Felix, Mougiakakos Dimitrios, Weber Daniela, Döhner Hartmut, Récher Christian, Dumas Pierre-Yves, Ditzhaus Marc, Fischer Thomas, Sager Sebastian

机构信息

Department of Mathematics, Otto von Guericke University (OVGU), Magdeburg, Germany.

Clinics of Hematology and Oncology, Otto von Guericke University (OVGU), Magdeburg, Germany.

出版信息

J Cancer Res Clin Oncol. 2023 Nov;149(15):13811-13821. doi: 10.1007/s00432-023-05115-0. Epub 2023 Aug 3.

DOI:10.1007/s00432-023-05115-0
PMID:37535164
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10590325/
Abstract

PURPOSE

Infections due to severe neutropenia are the most common therapy-associated causes of mortality in patients with acute myeloid leukemia (AML). New strategies to lessen the severity and duration of neutropenia are needed.

METHODS

Cytarabine is commonly used for AML consolidation therapy; we compared high- and intermediate-dose cytarabine administration on days 1, 2, and 3 (AC-123) versus days 1, 3, and 5 (AC-135) in consolidation therapy of AML. Recently, clinical trials demonstrated that high-dose AC-123 resulted in a shortened white blood cell (WBC) recovery time compared with high-dose AC-135. Our main hypothesis is that this is also the case for different cytarabine dosage, granulocyte colony-stimulating factor (G-CSF) administration, and cycle lengths. We analyzed 334 treatment schedules on virtual cohorts of digital twins.

RESULTS

Comparison of 32,565 simulated consolidation cycles resulted in a reduction in the WBC recovery time for AC-123 in 99.6% of the considered cycles (median reduction 3.5 days) without an increase in the number of leukemic blasts (lower value in 94.2% of all cycles), compared to AC-135.

CONCLUSION

Our numerical study supports the use of AC-123 plus G-CSF as standard conventional AML consolidation therapy to reduce the risk for life-threatening infectious complications.

摘要

目的

严重中性粒细胞减少所致感染是急性髓系白血病（AML）患者最常见的与治疗相关的死亡原因。需要新的策略来减轻中性粒细胞减少的严重程度和持续时间。

方法

阿糖胞苷常用于AML巩固治疗；我们比较了在AML巩固治疗中，第1、2和3天给予高剂量和中等剂量阿糖胞苷（AC-123）与第1、3和5天给予阿糖胞苷（AC-135）的情况。最近，临床试验表明，与高剂量AC-135相比，高剂量AC-123可缩短白细胞（WBC）恢复时间。我们的主要假设是，对于不同的阿糖胞苷剂量、粒细胞集落刺激因子（G-CSF）给药和周期长度，情况也是如此。我们分析了数字双胞胎虚拟队列中的334个治疗方案。

结果

对32,565个模拟巩固周期进行比较，结果显示，与AC-135相比，在99.6%的考虑周期中，AC-123的WBC恢复时间缩短（中位数缩短3.5天），且白血病原始细胞数量未增加（在所有周期的94.2%中数值较低）。

结论

我们的数值研究支持使用AC-123加G-CSF作为标准的常规AML巩固治疗，以降低危及生命的感染并发症风险。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/33d5/11796911/79821c871be3/432_2023_5115_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/33d5/11796911/fc8a17662a57/432_2023_5115_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/33d5/11796911/536a96a31a24/432_2023_5115_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/33d5/11796911/adaf43e3385e/432_2023_5115_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/33d5/11796911/b15ba8af4c5d/432_2023_5115_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/33d5/11796911/79821c871be3/432_2023_5115_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/33d5/11796911/fc8a17662a57/432_2023_5115_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/33d5/11796911/536a96a31a24/432_2023_5115_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/33d5/11796911/adaf43e3385e/432_2023_5115_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/33d5/11796911/b15ba8af4c5d/432_2023_5115_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/33d5/11796911/79821c871be3/432_2023_5115_Fig5_HTML.jpg

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