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Low absolute neutrophil count during induction therapy is an adverse prognostic factor in childhood acute lymphoblastic leukaemia

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Abstract

Variation in normal blood cells during chemotherapy has not been recognised as a risk factor guiding chemotherapy in childhood acute lymphoblastic leukaemia (ALL). This study aims to explore whether variations in normal haematopoiesis determine prognosis as well as to improve risk-stratified treatment in childhood ALL. A retrospective study of 279 cases of ALL treated with the CCCG-ALL-2015 regimen in the Division of Pediatric Blood Diseases Center, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, from May 2015 to January 2017 was performed to analyse the prognostic impact of blood cell levels on day 19 of induction therapy by Kaplan-Meier method. Patients with childhood ALL with absolute neutrophil count (ANC) ≤ 90 cells/μl, absolute monocyte count (AMC) ≤ 10 cells/μl or absolute lymphocyte count (ALC) ≤ 1000 cells/μl on day 19 of induction therapy had a lower event-free survival (EFS) rate than those with higher values (all P < 0.05). Multivariate analysis confirmed that ANC ≤ 90 cells/μl and ALC ≤ 1000 cells/μl were independent adverse prognostic factors (HR = 1.981 and 2.162, respectively, both P < 0.05). Among patients with minimal residual disease (MRD) < 1% on day 19 of induction therapy, those with ANC ≤ 90 cells/μl had lower EFS than those with ANC > 90 cells/μl (70.8 ± 6.1% vs 86.4 ± 3.1%, P = 0.001). In the subgroup with the BCR/ABL1 fusion gene, patients with ANC ≤ 90 cells/μl on day 19 of induction therapy also had lower EFS than those with ANC > 90 cells/μl (34.4 ± 25.2% vs 25.0 ± 21.7%, P = 0.041). ANC and ALC during induction therapy are independent prognostic factors for childhood ALL. ANC contributes to guiding the prognosis of patients with low-level MRD or the BCR/ABL1 fusion gene.

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Data availability

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

Abbreviations

ALC:

absolute lymphocyte count

ALL:

acute lymphoblastic leukaemia

AMC:

absolute monocyte count

ANC:

absolute neutrophil count

ALC-19:

ALC on the 19th day of induction therapy

AMC-19:

AMC on the 19th day of induction therapy

ANC-19:

ANC on the 19th day of induction therapy

CCCG-ALL-2015:

Chinese Children’s Cancer Group study ALL-2015

EFS :

event-free survival

HSC:

haematopoietic stem cell

HSCT:

haematopoietic stem cell transplantation

MLL-R:

MLL rearrangement

MRD:

minimal residual disease

MRD-19:

MRD on the 19th day of induction therapy

TKI:

tyrosine kinase inhibitors

WBC:

white blood cell

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Acknowledgements

We owe thanks to the patients in our study and their family members. We acknowledge the staffs of all centres for their assistance in this study.

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Authors and Affiliations

  1. State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tian**, 300020, China

    **aoyan Chen, Chao Liu, Aoli Zhang, WenQi Wu, Lipeng Liu, Yang Lan, Meihui Yi, Luyang Zhang, Min Ruan, Lixian Chang, Li Zhang, Yao Zou, Yumei Chen, Wenyu Yang, Ye Guo, **aojuan Chen, Yingchi Zhang & **aofan Zhu

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  1. **aoyan Chen
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  2. Chao Liu
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  6. Yang Lan
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  17. Yingchi Zhang
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  18. **aofan Zhu
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Contributions

Conception and design: Yingchi Zhang, **aofan Zhu; development of methodology: Min Ruan, Lixian Chang, Li Zhang, Yao Zou, Yumei Chen, Wenyu Yang, Ye Guo, **aojuan Chen; acquisition of data: **aoyan Chen, Chao Liu, Aoli Zhang, WenQi Wu, Lipeng Liu, Yang Lan, Meihui Yi and Luyang Zhang; writing, review and/or revision of the manuscript: **aoyan Chen, Yingchi Zhang and **aofan Zhu. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Yingchi Zhang or **aofan Zhu.

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The authors declare that they have no conflict of interest.

Ethics approval

This study was performed in line with the principles of the Declaration of Helsinki. Approval was obtained from the Ethics Committee and Institutional Review Board of Chinese Academy of Medical Sciences and Peking Union Medical College (approval number: IIT2015010-EC-1).

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Chen, X., Liu, C., Zhang, A. et al. Low absolute neutrophil count during induction therapy is an adverse prognostic factor in childhood acute lymphoblastic leukaemia. Ann Hematol 100, 2269–2277 (2021). https://doi.org/10.1007/s00277-021-04412-3

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  • DOI: https://doi.org/10.1007/s00277-021-04412-3

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