Xu et al. BMC Pediatrics(2024) 24:557
https://doi.org/10.1186/s12887-024-05030-4

BMC Pediatrics

RESEARCH

Open Access

Clinical analysis of immune reconstitution
after chemotherapy in children with acutelymphoblastic leukemia
Yuting Xu1, Ai Zhang1, Aiguo Liu1 and Qun Hu1*
Abstract
Objectives The aim of this retrospective study was to investigate the influence of chemotherapy on the immune
status of individual patients diagnosed with acute lymphoblastic leukemia (ALL) and to elucidate the clinicalcharacteristics of immune reconstitution in ALL patients following chemotherapy.
Methods Clinical data of children with ALL were gathered, including information on the number of lymphocyte
subsets prior to chemotherapy, at the end of therapy, six months, and one year after the end of the treatment.
Results A total of 146 children with ALL were included, and T cells, B cells, and NK cells all decreased to various
degrees prior to treatment. The abnormal CD3 + T cell numbers group experienced a considerably higher mortality(21.9% vs. 6.1%) and recurrence rate (31.3% vs. 11.4%) compared to the normal group (P < 0.05). T cells, B cells, andNK cells were all significantly compromised at the end of therapy compared to the beginning of chemotherapy, with
B cells being more severely compromised (P < 0.001). At the end of treatment, levels of B cells, CD4 + T cells, CD4/
CD8, IgG and IgM in low risk (LR) group were significantly higher than those in intermediate risk (IR) group (P < 0.01),
and levels of NK cells in LR group were evidently lower than those in IR group (P < 0.001). Six months after the end oftherapy, all the above indicators recovered (P < 0.001) except CD4/CD8 ratio (P = 0.451).
Conclusions The immune systems of the ALL patients were severely compromised upon therapy withdrawal,
particularly the B cells. At six months after the therapy ended, the B cells were basically restored to normal level, while
the T-cell compartment was not. The impaired numbers of CD3 + T cell may contribute to a weakened anti-tumor
response, potentially leading to a poorer prognosis.
Keywords Acute lymphoblastic leukemia, Chemotherapy, B cells, T cells, NK cells, Immune reconstitution*Correspondence:
Qun Huqunhu2013@163.com
1
Department of Pediatric Hematology and Oncology, Tongji Hospital,
Tongji Medical College, Huazhong University of Science and Technology,
Wuhan, China© The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0
International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you
give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified thelicensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images orother third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to thematerial. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation
or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://
creativecommons.org/licenses/by-nc-nd/4.0/.

Xu et al. BMC Pediatrics(2024) 24:557

Introduction
Acute lymphoblastic leukemia (ALL) is the predominantmalignancy in childhood, comprising approximately 28%
of childhood malignancies [1]. ALL encompasses B celllines (85%), T cell lines (10-15%) and mature B cell lines(< 5%). The global incidence of this disease exhibits slightvariation due to diagnostic and reporting methodologies, with a peak occurrence in children aged 2 to 5 years,
and a higher prevalence in males [2–5]. Currently, theprimary treatment modality for pediatric ALL is chemotherapy, typically administered within 2 to 3 years. Chemotherapy protocol primarily consists of an induction
phase (more than a month), followed by consolidation(two months) and re-induction (more than four months)
therapy, then maintenance phase (nearly 2 years; 6-mercaptopurine and methotrexate are the backbone of maintenance phase).
The initial maturation of B lymphocytes involves theorchestrated differentiation of B cells and the subsequent
expression of surface immunoglobulin (Ig). Following
this process, immature B cells exit the bone marrow andmigrate to secondary lymphoid tissues [6–8]. CD19 is akind of cluster differentiation antigen related to proliferation, differentiation, activation, and antibody productionof B cells. Various surface markers are expressed on B
cells at distinct developmental stages, with CD19 beinga key component of a multi-molecular surface complex
that plays a crucial role in antigen response and signaltransduction in T helper cells [9, 10]. It is noteworthy
that a significant majority of leukemia cells exhibit highexpression levels of CD19 [11]. CD20, a transmembraneprotein found in lipid rafts, is phosphorylated four times
and functions as a calcium channel to modulate B cell
activation and cell cycle progression [12, 13]. CD19 andCD20 are commonly used markers for counting B cells.
T cells primarily mature in the thymus and over 95% ofcirculating T cells express T cell surface receptors with α
and β chains [14]. CD3 molecules play a crucial role in
T cell signal transduction upon binding to T cell surface
receptors, with CD3 serving as the primary marker for
quantifying total T cells. CD4 + T cells and CD8 + T cells
are the two most common subsets of T lymphocytes, aswell as some other less common subsets. CD4 belongs to
the Ig superfamily and interacts with class II molecules ofthe major histocompatibility complex, while CD8 interacts with class I molecules of the major histocompatibility complex. Natural killer (NK) cells are innate immune
cells with distinctive functions, lacking antigen-specificreceptors but expressing a range of activation and inhibition receptors [15]. Among these receptors, activation
receptors play a crucial role in the cytotoxic activity of
NK cells [16, 17]. NK cells affect the host’s innate andadaptive immune responses by secreting cytokines andPage 2 of 10

chemokines, and then kill infected or cancerous cells
through a variety of mechanisms.
The ongoing advancements in contemporary risk-oriented therapy and the introduction of novel treatments
have led to a notable increase in the 5-year survival rateof children diagnosed with ALL, rising from 50–85-90%[2, 18, 19]. This study aims to examine the immune status of pediatric ALL patients prior to commencing chemotherapy and the subsequent recovery of immune cells
at various intervals post-treatment. The objective is tofurnish empirical evidence supporting immune reconstitution in children with ALL after chemotherapy and todevelop pertinent rehabilitation strategies.

Materials and methods
This research involved a cohort of 146 children diagnosed with ALL who underwent immune function
testing at Tongji Hospital, affiliated to Tongji Medical
College, Huazhong University of Science and Technology, between January 2015 and May 2019, with follow-up
conducted until November 2021. All children were diagnosed based on the guidelines outlined by the National
Comprehensive Cancer Network Pediatric Acute Lymphoblastic Leukemia [20]. Patients were stratified into
three risk groups (low risk, intermediate risk, and highrisk) based on clinical, biological, and therapeutic
responses. Please refer to supplementary Table 1 for specific hierarchical details. The enrolled children began toreceive treatment with Chinese Children’s Cancer Group
ALL-2015 (CCCG-ALL-2015) protocol after diagnosis, which mainly included the following parts: window
phase, PVDL induction, consolidation therapy, interim
maintenance, reinduction and maintenance therapy (seesupplementary Table 2 and supplementary file). The trial
was registered with the Chinese Clinical Trial Registry(ChiCTR-IPR-14005706) on June 4th, 2014. Approval
for this study was obtained from the Ethics Committeeof Tongji Hospital, affiliated with Tongji Medical College, Huazhong University of Science and Technology,
and informed consent was obtained from the guardiansor the individuals themselves (reference no. 2020-S207).
The study assessed NK cells and the T-cell compartment, including CD3 + T cells, CD4 + T cells, CD8 + T
cells, and CD4/CD8 ratio, as well as the B cells andimmunoglobulin levels, in children diagnosed with ALL
at four time points: before treatment (E1), at the end oftreatment (E2), 6 months post-treatment (E3), and 12
months post-treatment (E4).
Flow cytometry was used to analyze the absolute values
and percentages of peripheral blood lymphocyte subsets,
including T cells, B cells, and NK cells. The BD FACSCalibur flow analyzer was utilized in conjunction with corresponding fluorescent monoclonal antibodies (CD3FITC,
CD16CD56PE, CD4PE-Cy7, CD8APC-Cy7, CD19APC)

Xu et al. BMC Pediatrics(2024) 24:557

Page 3 of 10

Table 1 Demographic and clinical characteristics of children
with ALL before treatment
Characteristic
Gender, n(%)
Male
FemaleAge/year, M(Min-Max)
Height/cm, M(IQR)
Weight/kg, M(IQR)
BMI/kg/m2, M(IQR)
Risk, n(%)
LR
IR/HR
Immunotyping, n(%)
B-ALL
T-ALL

The data were analyzed by SPSS 26.0 software. Data
following a normal distribution were presented asmean ± standard deviation, while non-normal distribution data were presented as median (M) and interquartile
range (IQR), and categorical data were expressed as percentages. The Mann-Whitney U test was used to analyze
quantitative data for two independent samples, the Wilcoxon signed rank test for paired samples, and the chisquared test for categorical data. P < 0.05 was considered
statistically significant.

Number91(62.3)
55(37.7)
4.7(1.3–14.3)
108.0(96.0-120.2)
18.0(15.0–23.0)
15.8(14.9–16.9)
73(50)
73(50)

Results
Analysis of immune cells before chemotherapy

A total of 146 children diagnosed with ALL were includedin the study, with the clinical features detailed in Table 1.
Prior to treatment, there was no statistically significant
variance in immune cells observed among children basedon gender (T-cell compartment, B cells, NK cells, and all
immunoglobulin subclasses). However, children classified as LR exhibited significantly lower levels of CD8 + T
cells (P = 0.020) and NK cells (P < 0.001) compared tothose classified as IR/HR. Additionally, children diagnosed with B-ALL demonstrated evidently higher levels of CD3 + T cells (P = 0.020), CD4 + T cells (P = 0.004),
CD4/CD8 ratio (P = 0.034), and B cells compared to thosediagnosed with T-ALL (P = 0.019, Table 2).
Out of the 146 cases ALL examined, 14 cases diedand the mortality was 9.5%, 3 cases died from treatment-related complications (severe infection leading toseptic shock) and 11 cases died from disease progression (9 cases died after relapse and 2 cases died during

130(89)16(11)and hemolysin from BD for the analysis. Fasting peripheral venous blood samples of 2 ~ 3mL were collected withheparin anticoagulation and stored at room temperature
for analysis within 24 h. A total of 50mL of anticoagulant
and 10mL of fluorescence-labeled antibodies were added
to a specialized test tube, mixed thoroughly, and allowed
to incubate at room temperature for 15 min. Subsequently, 450mL of hemolysin was added, followed by a
5-minute incubation away from light, and the computer
system was used for analysis. The level of immunoglobulin was assessed using Beckman immune scattering turbidimetry, with serum samples of 3 ~ 5mL collected foranalysis.

Table 2 Analysis of immune cells of children with different risk and immunophenotype before chemotherapy

CD3 + T cells
NK cells
CD4 + T cells
CD8 + T cells
CD4/CD8
B cells
IgA
IgG
IgM

Risk
LR
(n = 73)1477(1040–2550)
166(78–265)
811(545–1221)
621(410–844)
1.36(1.06–1.68)
422(203–716)
0.78(0.47–1.07)
8.70(7.55–10.65)
0.91(0.71–1.12)

I/HR(n = 73)2137(998–3223)
283(113–660)
920(530–1696)
820(418–1543)
1.14(0.84–1.71)
631(204–1108)
0.70(0.54–1.21)
9.00(7.30-10.45)
0.84(0.60–1.19)

P
0.065
0.001
0.308
0.020
0.054
0.095
0.731
0.891
0.661

Immunophenotype
B-ALL(n = 130)1907(1131–2765)
197(86–394)890(581–1534)
733(431–1107)
1.27(1.02–1.70)
525(236–1013)
0.73(0.51–1.08)
9.10(7.37–10.60)
0.91(0.70–1.13)

T-ALL(n = 16)1025(429–2369)
280(89-1129)453(252–970)
455(147–973)
0.96(0.79–1.32)
161(65–695)
0.79(0.52–1.22)
8.35(7.35–9.72)
0.73(0.50–1.57)

P
0.020
0.312
0.004
0.069
0.034
0.019
0.584
0.259
0.267

The bold fonts describes the difference in the number of immune cells in patients with different risk levels (low risk, intermediate risk, high risk) and different
immunophenotypes before chemotherapy

Xu et al. BMC Pediatrics(2024) 24:557

treatment). A total of 23 patients experienced relapses(15.7%), in which 14 cases exhibited bone marrow recurrence, 6 cases had central nervous system recurrence,and 3 cases had mixed recurrence (involving both bonemarrow and central nervous system). Statistical analysis revealed that the mortality rate (P = 0.02) and recurrence rate (P = 0.006) were significantly higher in children
with abnormal CD3 + T cell numbers (outside the normal
range) prior to chemotherapy compared to those in thenormal group (Fig. 1).
Analysis of immune cells at the end of chemotherapy

Fifteen patients withdrew from the study for various
reasons (such as voluntary abandonment or transfer toanother hospital), while the remaining participants successfully completed the treatment regimen. The median
duration of treatment was 2.5 years. Following chemotherapy, bone marrow assessment indicated complete
remission, and blood routine parameters returned tobaseline levels. The study has shown that the immune
cells in children with ALL decreased distinctly after chemotherapy, particularly the levels of CD4/CD8 (69/131,
52.7%), NK cells (82/131, 62.6%), B cells (112/131, 85.5%),
and IgM (98/131, 74.8%).

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The study has revealed that levels of CD4 + T cells(P = 0.003) and CD4/CD8 (P < 0.001) were obviously
higher in children with LR group compared to the IRgroup at the end of chemotherapy, whereas NK cells weresignificantly lower in LR group (P < 0.001). Furthermore,
B cells (P = 0.002), IgG (P = 0.008), and IgM (P = 0.007) levels were significantly higher in LR group compared to IRgroup. Evaluation of bone marrow remission status was
conducted on day 46 after initiation of chemotherapy,
and incomplete remission at this time point indicatedpoor prognosis. The study demonstrated that on day 46,
the levels of IgA (P = 0.012) and IgG (P = 0.032) in patients
without complete remission were notably lower compared to those in patients who achieved complete remission (Table 3).
In addition, NK cells, T-cell compartment (CD3 + T
cells, CD4 + T cells, CD8 + T cells, and CD4/CD8 ratio),
B cells, IgA, IgG, and IgM experienced a significant
decrease following the completion of chemotherapy,
with B cells showing the most pronounced reduction(P < 0.001, Figs. 2 and 3).
Within 6 months after completion of treatment, 17
cases had repeated infections, with respiratory tract
infections being the most common, and no serious infections occurred. The study discovered that there was no
statistically significant difference in the incidence of
infection in patients with decreased B cells, CD3 + T cells,
NK cells, IgM, IgG and CD4/CD8 compared to normal
patients (P > 0.05, see supplementary Table 3).
Analysis of immune cells reconstruction after treatment

The study proved that the T-cell compartment substantially returned to baseline levels six months after theend of chemotherapy, with the exception of a persistent decrease in CD4/CD8 levels in 57.8% (26/45) ofcases. Subsequent analysis of immune cells recovery in
38 children at the six-month mark post-chemotherapy(E3) indicated significant improvement in all indexes(P < 0.001, Table 4) except for CD4/CD8, which did notshow significant recovery (P = 0.451) compared to the endof chemotherapy (E2).
A cohort of 30 pediatric patients diagnosed with ALL
were monitored for a period of 12 months post-treatment. Among these patients, 14 cases (46.7%) exhibited a decrease in CD4/CD8 levels, while other immune
parameters returned to baseline values. Our findings suggest that CD4/CD8 ratios were aberrant both pre- andpost-chemotherapy. Subsequent analysis of 18 patients
disclosed a further decline in CD4/CD8 ratios following
chemotherapy, although these values displayed a trend
towards normalization with prolonged follow-up duration (Fig. 4).
Fig. 1 Effect of abnormal CD3 + T cell numbers (outside the reference
range) on prognosis

Xu et al. BMC Pediatrics(2024) 24:557

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Table 3 Immune cells of ALL children with different risk and D46 remission status after chemotherapy

CD3 + T cells
NK cells
CD4 + T cells
CD8 + T cells
CD4/CD8
B cells
IgA
IgG
IgM

Risk
LR
(n = 73)1017(656–1375)
32(17–90)482(293–651)
393(287–629)
1.07(0.86–1.47)
17(9–55)
0.46(0.29–0.66)
6.70(5.20–8.50)
0.28(0.20–0.45)IR(n = 58)921(650–1259)
107(42–183)373(253–488)424(279–605)
0.77(0.63–1.08)
8(2–70)
0.50(0.33–0.78)
5.40(3.75–7.60)
0.21(0.11–0.36)

P
0.477<0.0010.003
0.609<0.001
0.002
0.411
0.008
0.007

D46 remission statusYesNo(n = 119)(n = 12)963
931(648–1366)(685–1178)
49
108(23–130)(37–190)
422
431(264–586)(262–480)
399
446(281–630)(316–563)
0.99
0.90(0.73–1.36)(0.64–1.28)
12
6(6–63)(5–22)
0.47
0.29(0.33–0.75)(0.13–0.52)
6.10
4.80
(4.90-8.00)(3.45–6.65)
0.27
0.19
(0.16–0.43)(0.10–0.31)

P
0.892
0.126
0.555
0.981
0.490
0.156
0.012
0.032
0.088

The bold fonts describes the difference in the number of immune cells in patients with different risk levels (low risk and intermediate risk) and in remission status at
the 46th day after chemotherapy

Discussion
ALL is the predominant hematological malignancy inpediatric patients, typically managed through a diverse
array of chemotherapeutic agents. Prolonged administration of these medications may compromise the immune
system, leading to a sustained state of immunosuppression post-treatment [21, 22]. This impediment hinders
the immune system’s ability to effectively combat infections and malignancies. Therefore, it is imperative toinvestigate alterations in immune cells in pediatric ALL
patients pre- and post-chemotherapy, as well as to determine the optimal timeframe for immune cells recovery
following treatment.
A total of 146 patients with ALL were included in thisstudy, most of them were male, similar to previous studies[23]. In a British study (UKALL2003) [24], males received
chemotherapy for longer, whereas in this study, males
received the same chemotherapy regimen as females.
This study found evidence of immune cells dysregulationin 146 children with ALL prior to chemotherapy, characterized by decreased levels of CD3 + T cells, CD4 + T
cells, CD8 + T cells, and CD4/CD8 ratios. Specifically, theproportion of CD4/CD8 was significantly lower in 41 out
of 146 cases (28.1%), consistent with findings from previous research [25–27]. The decline in CD4/CD8 ratios
suggests compromised T-cell compartment, diminishedability to eradicate leukemic cells, and reduced antitumor efficacy. The levels of CD3 + T cells, CD4 + T cells,
CD8 + T cells, CD4/CD8 ratio, and B cells were found tobe significantly higher in children with B-ALL comparedto those with T-ALL (P < 0.05). Conversely, the levels of

CD8 + T cells and NK cells were lower in children in LR
group compared to those in IR group (P < 0.05), suggesting varying degrees of abnormal immune cell numbers
based on risk stratification. It could also be connected
to recurrent cytogenetic abnormalities associated withfavorable prognosis in LR group, but no pertinent
research has been conducted to bolster this theory. Prior
to chemotherapy, the mortality and recurrence rates werehigher in the group with abnormal CD3 + T cell numbers (outside the reference range) compared to the normal group (P < 0.05). An abnormal number of CD3 + T
cells may contribute to a weakened anti-tumor response,
potentially leading to a poorer prognosis. It is proposedthat the number of CD3 + T cells may serve as a valuable
indicator for predicting prognosis.
A significant decrease in CD4/CD8 (69/131, 52.7%)
and NK cells (82/131, 62.6%) was observed following
chemotherapy, suggesting that these cells may be particularly vulnerable to the effects of chemotherapy. Furthermore, a notable reduction in B cells (112/131, 85.5%)
was also noted, indicating a substantial impairment of B
cells post-chemotherapy. These findings are consistent
with previous research [26, 28, 29], highlighting the significant impact of chemotherapy on the B cells throughout the treatment process. The study found that LRgroup had lower intensity of chemotherapy compared tothose with IR group, leading to higher levels of B cells,
CD4 + T cells, CD4/CD8, IgG, and IgM at the end oftreatment, and it is consistent with previous research [30,31]. Prior to chemotherapy initiation, LR group exhibited lower levels of NK cells compared to those with IR

Xu et al. BMC Pediatrics(2024) 24:557

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Fig. 2 Effect of chemotherapy on T-cell compartment and NK cells in 98 patients. NotesP value: ns, P ≥ 0.05; *, P < 0.05; **, P < 0.01; ***, P < 0.001

Xu et al. BMC Pediatrics(2024) 24:557

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Fig. 3 Effect of chemotherapy on B cells and all immunoglobulin subclasses in 98 patients. Notes P value: ns, P ≥ 0.05; *, P < 0.05; **, P < 0.01; ***, P < 0.001

Xu et al. BMC Pediatrics(2024) 24:557

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Table 4 Analysis of immune cells reconstitution during E2 and E3 in 38 children with ALL

CD3 + T cells
NK cells
CD4 + T cells
CD8 + T cells
CD4/CD8
B cells
IgA
IgG
IgM
T + B + NK cells

E2(n = 38)972(658–1352)
40(19–119)425(288–598)
392(291–631)
1.00(0.74–1.40)
12(6–38)
0.41(0.27–0.61)
5.55(4.40–6.77)
0.24(0.13–0.31)
1083(767–1504)

Fig. 4 Changes of CD4/CD8 in 18 patients in three different periods (E2,
E3, E4)group, and this discrepancy persisted at the end of chemotherapy (P < 0.05). The difference in the number of NK
cells between the two groups before treatment may be
the main factor leading to this result. It is necessary to

E3(n = 38)1571(997–2111)
150(102–251)728(402–959)
616(459–906)
0.98(0.76–1.31)
527(245–718)
0.73(0.53–1.22)
7.25(6.17–8.92)
0.59(0.36–0.72)
2332(1411–3014)

P<0.001<0.001<0.001<0.0010.451<0.001<0.001<0.001<0.001<0.001further expand the sample size to provide a stronger conclusion in the future.
This study observed a significant decrease in NK cells,
T-cell compartment, B cells and all immunoglobulin subclasses following chemotherapy (P < 0.001), suggesting asubstantial impact of chemotherapy on the immune cellsof children. Notably, B cells were found to be the most
severely affected, aligning with findings from previous
studies [26, 30]. Six months after the end of chemotherapy, all indexes, with the exception of CD4/CD8, exhibited significant recovery compared to post-treatment
levels (P < 0.001), in which B cells basically returned tonormal. Conversely, the CD4/CD8 ratio did not demonstrate significant recovery, aligning with findings
from previous studies [32–34]. Although the number of
immune cells decreased sharply after treatment in children with ALL, there was no significant difference in theincidence of infection between patients with abnormal
immune cells and normal patients after treatment. Thismay be because the study was retrospective in nature,
meaning that some patients lost relevant data because
they received treatment in different hospitals. Leukemia
patients may be more susceptible to infections after treatment ends than the general population. A study involving 2,204 patients discovered that leukemia survivors
experienced higher infection rates (RR = 1.77, 95%CI:
1.69–1.71) and noticeably higher infection-related deaths(HR = 149.3, 95%CI: 20.4-1091.9) one year after treatment
concluded compared to controls [35].
Through examining the immune cells of pediatric patients diagnosed with ALL both before and after
chemotherapy treatment, the study established that

Xu et al. BMC Pediatrics(2024) 24:557

chemotherapeutic agents exert a notable impact on the
immune response of afflicted individuals. Specifically,
high-intensity chemotherapy regimens have been foundto induce substantial impairment in overall immune
indexes, with B cells exhibiting the most pronounced
deterioration. However, it was observed that the numberof humoral immune indexes (B cells and all immunoglobulin subclasses) recovered at a faster rate comparedto the T-cell compartment following the end of chemotherapy. The examination of immune cells throughout
and following leukemia treatment can offer valuable
insights for clinical practice. In cases where immune
reconstruction is compromised and prolonged immunodeficiency is present, interventions to enhance immunity
may be necessary to mitigate the risk of severe infections.
The degree of immune dysfunction in children with ALL
may serve as a prognostic indicator, aiding in clinical risk
stratification.

Conclusions
Acute lymphoblastic leukemia is a prevalent hematological malignancy in pediatric patients, with chemotherapy serving as the primary therapeutic modality. While
chemotherapeutic agents effectively induce tumor cell
apoptosis, they also elicit collateral damage to healthy
immune cells, leading to significant impairment of thehost immune barrier and prolonged immunodeficiency.
After the completion of chemotherapy, the B cells experienced the most severe impairment, but recovered rapidly and ultimately returned to baseline levels within 6months post-treatment. In contrast, the CD4/CD8 levels
did not return to normal after 12 months of treatment,
consequently impacting the T lymphocyte levels. Prior
to treatment, patients with abnormal CD3 + T cells were
found to have elevated risks of mortality and recurrencecompared to those with normal levels, indicating thepotential utility of this index in prognostic assessments.
AbbreviationsALL	Acute lymphoblastic leukemia
LR	Low risk
IR	Intermediate riskHR	High risk
Ig	Immunoglobulin
NK	Natural killer
M	Median
IQR	Interquartile range
MRD	Minimal residual disease
BMI	Body mass index

Supplementary Information

The online version contains supplementary material available at https://doi.
org/10.1186/s12887-024-05030-4.
Supplementary Material 1: (supplementary file)
Supplementary Material 2: (supplementary tables)

Page 9 of 10

Acknowledgements
We gratefully thank all the staff of the Department of Pediatric Hematology
and Oncology, Tongji Hospital of Tongji Medical College, Huazhong Universityof Science and Technology, for their help in performing this study.
Author contributions
QH designed the study. YX performed the data collection and statisticalanalysis. AZ and AL supervised the project. YX wrote the original draft. QH was
responsible for the revision of the manuscript. All authors read and approved
the manuscript.
Funding
This work was partially supported by the CCCG-ALL-2015 study (research
project no. WHTJ-2015043).
Data availability
All primary data are included in this article and additional data that support
the findings of this study are available from the corresponding author upon
reasonable request.

Declarations
Ethics approval and consent to participate
The study was approved by the ethics committee of Tongji Medical College,
Huazhong University of Science and Technology (reference no. 2020-S207),
China, in accordance with the declaration of Helsinki. The patients/participants
provided their written informed consent to participate in this study.
Consent for publication
Not applicable.
Competing interests
The authors declare no competing interests.
Received: 19 March 2024 / Accepted: 23 August 2024

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