Polyethylene glycol-conjugated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) primary prophylaxis significantly reduces the duration of neutropenia in non-Hodgkin’s lymphoma patients treated with chemotherapy: a randomised trial (NCT05834751)

Introduction

Neutropenia is a prevalent and severe side effect of tumor chemotherapy that significantly raises the chances of bacterial and fungal infections in patients, posing a significant threat to their lives (1). Additionally, neutropenia can result in reduced chemotherapy doses, delayed chemotherapy intervals, and decreased treatment effectiveness, all of which can interfere with the overall treatment process (2,3).

Filgrastim stimulates the proliferation of white blood cells (WBCs) or neutrophils in the human body, and is currently the preferred drug for preventing and treating chemotherapy-induced myelosuppressive leukopenia (4). However, it has a short half-life and often requires multiple doses in a treatment cycle (5,6). Additionally, some patients still experience neutropenia and develop infections or require hospitalization after the use of recombinant human granulocyte colony-stimulating factor (rhG-CSF).

Mecapegfilgrastim (code name: HHPG-19K), a long-acting rhG-CSF, was developed by covalently bonding a 19-kDa polyethylene glycol (PEG) to the N terminus of filgrastim (7). A range of phase Ia, Ib, II, and III studies have shown that mecapegfilgrastim can be used for the primary prophylaxis of neutropenia after chemotherapy for malignant tumors, including lymphoma, and is as effective and safe as daily filgrastim in patients with specific malignant tumor such as non-small cell lung cancer and breast cancer (8-12).

However, currently, clinical research supporting the use of mecapegfilgrastim in lymphoma patients undergoing chemotherapy is limited (13). This study compared the efficacy and safety of mecapegfilgrastim in reducing neutropenia in lymphoma patients undergoing chemotherapy with the efficacy and safety of filgrastim. Notably, as the treatment time increases, the interfering factors that may affect the hematopoietic function of patients gradually increase. Thus, to better evaluate the preventive effects of mecapegfilgrastim, we focused on changes in blood cell counts after the first chemotherapy cycle, and included the efficacy of subsequent cycles as a secondary indicator for reference. We present this article in accordance with the CONSORT reporting checklist (available at https://tcr.amegroups.com/article/view/10.21037/tcr-2025-1-2613/rc).

Methods

Ethical statement

The study was approved by the Ethics Committee of The First Hospital of Jilin University (No. 23K046-001). Informed consent was obtained from all patients. This study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments.

Patients

A total of 154 lymphoma patients admitted to the Hematology Department of The First Hospital of Jilin University from September 2020 to September 2022 were selected as the research subjects. All the patients were newly diagnosed with non-Hodgkin’s lymphoma (NHL) with indications for systematic immune-chemotherapy. The patients met the indications for granulocyte colony-stimulating factor (G-CSF) therapy and had no contraindications to its use.

Inclusion and exclusion criteria

Patients were included in the study if they met the following inclusion criteria: (I) were aged between 18 and 80 years; (II) were of either sex; (III) had been newly diagnosed with malignant lymphoma as confirmed by histopathology, cytology, and immunomolecular biology, requiring multi-cycle chemotherapy; (IV) were eligible for: (i) a high-risk chemotherapy regimen as defined in major guidelines [i.e., had a febrile neutropenia (FN) risk >20% without rhG-CSF support, including ICE (ifosfamide, carboplatin, etoposide), RICE (rituximab, ifosfamide, carboplatin, etoposide), HyperCVAD (hyper-cyclophosphamide, vincristine, adriamycin, dexamethasone), and DHAP (dexamethasone, high-dose cytarabine, cisplatin)]; (ii) a moderate-risk chemotherapy regimen [i.e., had 10%< FN risk <20% without rhG-CSF support, including R-CHOP/CHOP-like regimens, EPOCH (etoposide, prednisone, oncovin, cyclophosphamide, hydroxydaunorubicin), and R-GemOx (rituximab, gemcitabine, methotrexate, oxaliplatin)]; (iii) a modified chemotherapy regimen based on one of the above two regimens (e.g., a regimen using liposomal doxorubicin instead of conventional doxorubicin); (iv) had an estimated survival time >8 months; (v) had normal bone marrow hematopoietic function [i.e., an absolute neutrophil count (ANC) ≥1.5×10⁹/L, a platelet count ≥80×10⁹/L, hemoglobin ≥75 g/L, and a WBC count ≥3.0×10⁹/L); (vi) had no significant abnormalities on electrocardiography and no significant cardiac dysfunction; (vii) agreed to use effective contraception during the study period and for 6 months after ceasing treatment (reproductive-age female patients had to test negative for pregnancy before treatment); and (viii) voluntarily agreed to participate in this clinical trial and signed the informed consent form.

Patients were excluded from the study if they met any of the following exclusion criteria: (I) had lymphoma with central nervous system involvement; (II) had undergone hematopoietic stem cell transplantation or organ transplantation; (III) were currently participating in other drug clinical trials; (IV) had uncontrolled infections, and a body temperature ≥38 ℃; (V) had liver function test results showing total bilirubin, alanine aminotransferase, and aspartate aminotransferase levels >2.5 times the upper limit of normal (ULN) or >5 times the ULN if caused by liver metastasis, or renal function test results showing serum creatinine >2 times the ULN; (VI) had severe chronic diseases affecting essential organs such as the heart, kidney, or liver; (VII) had severe uncontrolled diabetes; (VIII) were pregnant or lactating females; (IX) had allergic diseases or an allergic constitution; (X) had a suspected or confirmed history of drug abuse, substance abuse, or alcoholism; (XI) had severe mental or neurological disorders affecting their understanding of informed consent, and/or expression or observation of adverse events (AEs); (XII) were human immunodeficiency virus-positive; and/or (XIII) were considered unsuitable for inclusion by the researchers.

Study design

This study was a prospective, randomized, open-label, single-center clinical study. The randomization tables used to allocate the patients at a 1:1 ratio to the polyethylene glycol-conjugated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) group or G-CSF group were created using SAS software. The random allocation sequence was generated by using the software and was concealed from the personnel responsible for participant enrollment and intervention assignment until the moment of allocation. The patients in the PEG-rhG-CSF group received a single subcutaneous injection of 6 mg of PEG-rhG-CSF per chemotherapy cycle. The dose was administered approximately 48 hours after chemotherapy (i.e., on the third day after chemotherapy), excluding prednisone. The preferred injection site was the lower edge of the deltoid muscle on either arm. The patients in the G-CSF group first received 5 µg/kg/day of G-CSF approximately 48 hours after chemotherapy (i.e., on the third day after chemotherapy), and subsequently received the same dose once daily until there were two recorded ANC values ≥2.0×10⁹/L, or one recorded ANC value ≥5.0×10⁹/L, whichever occurred first, for a maximum of 14 days.

In the first chemotherapy cycle for all patients, the duration of neutropenia, the incidence of FN, the incidence of additional hospitalization during chemotherapy breaks, and the corresponding economic indicators were observed. If a patient had an ANC <0.5×10⁹/L and developed neutropenic fever, G-CSF was subcutaneously injected at a dose of 5 µg/kg daily, and blood tests were performed daily until the peripheral blood routine showed an ANC ≥2.0×10⁹/L.

Endpoints

The primary efficacy endpoint was the duration of grade 3 or higher neutropenia (≥ G3 neutropenia), defined as the time from the first measurement of an ANC below 1.0×10⁹/L to recovery to a level of 1.0×10⁹/L or higher during the first cycle after drug administration. The unit of measurement was days.

The secondary efficacy endpoints were: (I) the incidence of ≥ G3 neutropenia, which was defined as an ANC below 1.0×10⁹/L in each cycle after drug administration; and (II) the incidence of FN in each cycle after drug administration, and the costs related to FN. FN was defined as an ANC below 0.5×10⁹/L or an ANC below 1.0×10⁹/L that was expected to decrease to below 1.0×10⁹/L within 48 hours, together with a single oral temperature of ≥38.3 ℃ or ≥38.0 ℃ sustained for more than 1 hour, or an axillary temperature of >38.5 ℃ sustained for more than 1 hour.

The AEs were evaluated using the Common Terminology Criteria for Adverse Events (CTCAE), version 4.035.0.

Statistical analysis

SPSS 25.0 was used to conduct the statistical analysis. All the statistical tests were two-tailed, and a P value ≤0.05 was considered statistically significant. The confidence interval (CI) was set at 95% for all results. Covariance analysis models were used to compare the continuous variables between the groups, and adjusted means and 95% CIs were calculated. Chi-squared tests were used to compare the categorical variables between groups, and Bonferroni correction was applied to calculate the adjusted P values and CIs for pairwise comparisons. The comparison of efficacy outcomes between the two groups was based on the per protocol set population, using observed values. Descriptive statistics were used for all data, including demographic data, baseline characteristics, efficacy assessment outcomes, and safety data.

No missing data were encountered for the primary and secondary efficacy endpoints in this analysis. For the primary efficacy outcome, the ≥ G3 neutropenia duration in the first chemotherapy cycle was compared between the PEG-rhG-CSF group and the G-CSF group. A non-inferiority margin of 1 day was assumed, and the difference in efficacy between the two groups was calculated by covariance analysis. The 95% CI was calculated, and if the upper limit of the CI was less than or equal to 1, non-inferiority was established. In the case of non-inferiority, the difference between the upper limit of the 95% CI and 0 was further compared to determine whether the efficacy of PEG-rhG-CSF was superior.

Under the condition of a non-inferiority margin of 1, with a typical standard deviation of 2.6, a one-sided significance level of 2.5%, and a power of 90%, the sample size required for evaluating the non-inferiority of the primary efficacy outcome was calculated, resulting in a total of 146 patients (73 per group).

In addition, the neutrophil counts were analyzed by analysis of variance during the entire sampling period of the first chemotherapy cycle, and the corrected mean values and 95% CIs were calculated.

Results

Baseline characteristics of patients

Of the 154 enrolled patients, 78 were male and 76 were female. The patients were aged 18–77 years. Based on the type of medication, the patients were divided into the PEG-rhG-CSF group (n=77) and the G-CSF group (n=77) (Figure 1). There were no significant differences between the two patient groups in terms of their clinical characteristics (Table 1).

Figure 1 Study flow chart. FAS, full-analysis set; G-CSF, granulocyte colony-stimulating factor; PEG-rhG-CSF, polyethylene glycol-conjugated recombinant human granulocyte colony-stimulating factor; PPS, per protocol set; SAS, safety analysis set.

Duration of ≥ G3 neutropenia in the first cycle

During the first chemotherapy cycle, the corrected mean duration of ≥ G3 neutropenia was 1.56±2.23 days in the PEG-rhG-CSF group and 2.34±2.82 days in the G-CSF group, with a difference of 0.78 days. The 95% CI for the difference was –1.59 to 0.03, indicating non-inferiority (Figure 2). Although non-inferiority was achieved in the overall study population, the subgroup of patients with B-cell NHL showed superior results in terms of the mean duration of ≥ G3 neutropenia.

Figure 2 Mean duration of grade ≥3 neutropenia in cycle 1. Data are presented as mean ± SD. CI, confidence interval; G-CSF, granulocyte colony-stimulating factor; PEG-rhG-CSF, polyethylene glycol-conjugated recombinant human granulocyte colony-stimulating factor; SD, standard deviation.

In cycle 1, the corrected mean ANCs of the PEG-rhG-CSF group first peaked on day 5, and continued to increase since day 6 throughout cycle, this pattern was not observed in the G-CSF group. The difference in the mean ANC between the groups on this peak day (day 5) was statistically significant, with a value of 5.73 (95% CI: 2.61–8.85; P=0.005) (Figure 3).

Figure 3 Variations in the ANCs during cycle 1. *, the intergroup difference in corrected mean ANCs on day 5, PEG-rhG-CSF vs. G-CSF, P=0.005, 5.73 (95% CI: 2.61, 8.85). ANCs, absolute neutrophil counts; CI, confidence interval; G-CSF, granulocyte colony-stimulating factor; PEG-rhG-CSF, polyethylene glycol-conjugated recombinant human granulocyte colony-stimulating factor.

Incidence of ≥ G3 neutropenia

In cycle 1, the incidence rates of ≥ G3 neutropenia in the PEG-rhG-CSF and G-CSF groups were 44.16% and 53.25%, respectively (P=0.26), and no statistically significant difference between the two groups was observed. However, in cycles 2–4, the patients in the PEG-rhG-CSF group had a lower incidence of ≥ G3 neutropenia. The incidence rates of ≥ G3 neutropenia during chemotherapy cycles 2–4 were 22.08% and 38.96% in the PEG-rhG-CSF group and the rhG-CSF group, respectively, and the difference between the two groups was statistically significant (P=0.02) (Figure 4).

Figure 4 Incidence of grade ≥3 neutropenia in the PEG-rhG-CSF and G-CSF groups. G-CSF, granulocyte colony-stimulating factor; PEG-rhG-CSF, polyethylene glycol-conjugated recombinant human granulocyte colony-stimulating factor.

Incidence of FN in each cycle

No significant difference was observed in the incidence of FN between the PEG-rhG-CSF group and the G-CSF group. During the first treatment cycle, FN occurred in 5 patients (6.49%) in the PEG-rhG-CSF group and in 4 patients (5.19%) in the G-CSF group (P>0.99). During cycles 2–4, 2 patients in each group developed FN. The most common sites of infection were the upper respiratory tract and lungs. After systemic anti-infection treatment, the symptoms of patients improved, and their body temperature returned to normal. There were no deaths due to FN in either group.

Subgroup analysis

The risk of neutropenia is directly related to the selected chemotherapy regimen. In this study, all the included patients received moderate- or high-risk chemotherapy regimens. To determine whether stratification factors confounded the efficacy evaluation, we conducted an exploratory subgroup analysis based on the primary efficacy outcome in the first chemotherapy cycle, which had the most negligible effect on previous treatment (Table 2).

In relation to the patients who received the R-CHOP/CHOP regimen, the duration of ≥ G3 neutropenia in the first chemotherapy cycle was 1.05±1.56 days for the PEG-rhG-CSF group and 2.46±2.67 days for the G-CSF group. The use of PEG-rhG-CSF significantly reduced the duration of neutropenia, with a difference of 1.41 days and a 95% CI of –2.44 to –0.38 (P=0.008; Figure 5). However, no such significant difference in the duration of ≥ G3 neutropenia was observed in the patients who received the R-CDOP/CDOP (rituximab, cyclophosphamide, doxorubicin liposomal, oncovin, prednisone/cyclophosphamide, doxorubicin liposomal, oncovin, prednisone) regimen or other chemotherapy regimens.

Figure 5 Mean duration of grade ≥3 neutropenia in cycle 1 (R-CHOP/CHOP). Data are presented as mean ± SD. CHOP, cyclophosphamide, hydroxydaunorubicin, oncovin, prednisone; CI, confidence interval; G-CSF, granulocyte colony-stimulating factor; PEG-rhG-CSF, polyethylene glycol-conjugated recombinant human granulocyte colony-stimulating factor; R-CHOP, rituximab, cyclophosphamide, hydroxydaunorubicin, oncovin, prednisone; SD, standard deviation.

For the patients with B-cell lymphoma, the duration of ≥ G3 neutropenia in the first chemotherapy cycle was significantly shorter in the PEG-rhG-CSF group than the G-CSF group, with durations of 1.34±2.15 and 2.31±2.88 days, respectively, and a difference of 0.97 days (95% CI: –1.88 to –0.07, P=0.04) (Figure 6). There was no statistically significant difference in the ≥ G3 neutropenia duration in the first chemotherapy cycle for patients with T-cell lymphoma.

Figure 6 Mean duration of grade ≥3 neutropenia in cycle 1 (B-cell NHL). Data are presented as mean ± SD. CI, confidence interval; G-CSF, granulocyte colony-stimulating factor; NHL, non-Hodgkin’s lymphoma; PEG-rhG-CSF, polyethylene glycol-conjugated recombinant human granulocyte colony-stimulating factor; SD, standard deviation.

Safety analysis

Throughout the treatment process, 72 (93.51%) and 74 (96.10%) patients in the PEG-rhG-CSF group and G-CSF group, respectively, reported AEs. There were no unexpected AEs or cases of trial withdrawal due to intolerable AEs. Most AEs were considered directly related to the chemotherapy drugs, with neutrophilia, muscle/bone pain, and fatigue being the most common AEs caused by the study drug. Notably, in the NHL patients receiving systemic chemotherapy, the occurrence of neutrophilia was higher in the PEG-rhG-CSF group than the G-CSF group, and the difference was statistically significant. However, the two groups showed no differences in myalgia and fatigue throughout the treatment cycle (Table 3). One serious adverse event (SAE) was reported during the trial, which was considered unrelated to the study drug.

Cost-effectiveness and convenience analysis

In addition, we compared related costs incurred during the entire treatment process. In the G-CSF group, the median times of injection was 4, despite the significantly higher unit cost of PEG-rhG-CSF compared to G-CSF, the PEG-rhG-CSF group demonstrated no statistically significant difference in total first-cycle hospitalization costs relative to the G-CSF group. This translated to nonsignificant differences in total hospitalization costs during the initial treatment phase: ¥25,448.17±15,267.95 for PEG-rhG-CSF versus ¥23,770.40±12,166.45 for conventional G-CSF (P=0.45).

Regarding treatment schedule adherence, longitudinal analysis across four chemotherapy cycles showed comparable treatment delay patterns in early phases. The mean delay duration between PEG-rhG-CSF and G-CSF groups remained statistically indistinguishable during the whole 4 cycles (3.87±5.44 vs. 5.77±6.63 days, P=0.054). However, cycle-stratified analysis uncovered differential temporal effects. While no significant intergroup variations emerged between cycles 1–2 (P=0.22) and 2–3 (P=0.16), a clinically meaningful divergence manifested during the 3rd–4th cycle interval. The PEG-rhG-CSF group exhibited significantly shorter treatment delays (0.95±2.26 days) compared to the G-CSF group (2.17±4.39 days, P=0.03).

Efficacy analysis

An efficacy analysis was conducted of the patients who received at least 4 cycles of treatment and underwent mid-term evaluation by positron emission tomography-computed tomography (PET-CT). The complete response (CR) rate in the PEG-rhG-CSF group reached 73.58%, while in the G-CSF group, the CR rate reached 63.64%; however, the difference between the two groups was not statistically significant.

Discussion

Neutropenia is a common and severe complication of cancer chemotherapy. Chemotherapy drugs kill cancer cells and have a cytotoxic effect on normal cells in the human body, including neutrophils, which exert anti-infection effects, often leading to neutropenia. Neutropenia increases the risk of bacterial and fungal infections in patients, resulting in FN, which can be life threatening in chemotherapy (14,15).

A previous multicenter phase II clinical study with 160 pediatric patients suffering from NHL or malignant solid tumors showed the efficacy and safety of PEG-rhG-CSF (16). Further comparisons showed that the efficacy of PEG-rhG-CSF in the primary prevention of neutropenia was superior to its efficacy in the secondary prevention of neutropenia, and reduced the costs to some extent. Moreover, in both primary and secondary prevention, the use of PEG-rhG-CSF protected patients against neutropenia (17,18). In this study, the efficacy of PEG-rhG-CSF was compared to that of G-CSF. The primary efficacy endpoint was the duration of ≥ G3 neutropenia after the first dose. The non-inferiority threshold was initially set at one day, which meant that if the maximum duration of neutropenia after using PEG-rhG-CSF exceeded that of G-CSF by no more than one day, PEG-rhG-CSF would be considered as effective as G-CSF. The calculated difference in duration was 0.78 days, and the upper limit of the 95% CI for the difference was 0.03, which showed the non-inferiority of PEG-rhG-CSF compared to G-CSF. Additionally, from the first monitoring after administration, the ANC of the PEG-rhG-CSF group remained higher than that of the G-CSF group. An earlier upward trend was observed on the line chart. This suggests that PEG-rhG-CSF may provide additional benefits to patients.

An exploratory analysis of the secondary efficacy endpoints was also carried out. Although there was no statistically significant difference in the incidence rate of ≥ G3 neutropenia during the first chemotherapy cycle, as the treatment progressed to cycles 2–4, the incidence rate of ≥ G3 neutropenia in the PEG-rhG-CSF group was found to be significantly lower than that in the control group. Thus, the efficacy advantage of PEG-rhG-CSF became evident gradually, and the protection was more pronounced with the regular application of PEG-rhG-CSF in each chemotherapy cycle as the treatment duration increased. Similarly, a phase III clinical study of breast cancer patients showed the effectiveness of the continuous application of PEG-rhG-CSF or G-CSF for prevention over multiple cycles (9). Based on the above results, PEG-rhG-CSF rapidly stimulates hematopoiesis of granulocytes in the bone marrow after administration, while G-CSF does not exert the same effects. Further, for long-term treatment, PEG-rhG-CSF also has better hematopoietic protective effects, which are only observed when the bone marrow is repeatedly damaged by chemotherapy-induced toxicity.

Health economic evaluations further corroborated the therapeutic superiority of PEG-rhG-CSF. In systemic treatment regimens for malignancies, maintaining chemotherapy schedule adherence with full-dose intensity remains a paramount clinical objective. This study demonstrated significantly reduced treatment delays during the third and fourth cycle intervals with PEG-rhG-CSF (vs. G-CSF), providing compelling evidence for its prophylactic efficacy. Notably, while no statistically significant difference in total treatment costs was observed between groups, PEG-rhG-CSF’s single-dose administration per cycle substantially reduces hospitalization duration (compared to multi-dose G-CSF regimens). This streamlined protocol enhances clinical workflow efficiency and improves patient quality of life through minimized healthcare facility exposure.

To identify those most likely to benefit from this advantage, we conducted a subgroup analysis of different chemotherapy regimens. In the patient sample of this study, a considerable proportion of patients received the R-CHOP/CHOP-like chemotherapy regimen. To increase the comparability of the results, the patients were categorized into the R-CHOP/CHOP group, R-CDOP/CDOP group, and other chemotherapy regimen group based on their actual treatment regimens. Significant differences in the main efficacy indicators were observed in the R-CHOP/CHOP subgroup, with a shorter duration of ≥ G3 neutropenia observed after prophylaxis with PEG-rhG-CSF. Currently, liposomal doxorubicin appears to have lower cardiac toxicity than doxorubicin, and the risk of infection-related complications is relatively low (19). Therefore, when using chemotherapy regimens with stronger side effects, PEG-rhG-CSF may be preferred as the primary prophylactic measure. Our findings suggest that PEG-rhG-CSF has a better preventive effect on ≥ G3 neutropenia than G-CSF in NHL patients receiving R-CHOP/CHOP chemotherapy.

NHL is a highly heterogeneous disease, with different subtypes exhibiting differences in progression rates, treatment methods, and prognoses. The metabolic signaling pathways of tumor cells and their immune microenvironment also differ, and their effects on drug responses are still unclear (17,20). Therefore, we compared the efficacy of PEG-rhG-CSF in patients with B-cell and T-cell lymphomas as subgroups. PEG-rhG-CSF was more efficacious in patients with B-cell lymphomas. During the first cycle, the duration of ≥ G3 neutropenia was significantly shortened. The mechanism underlying this remains unclear, but it may be related to the faster progression rate of T-cell lymphomas, which places an additional burden on the overall body function of patients, including the hematopoietic function, reducing the effect of the bone marrow stimulating prevention treatment; however, this requires further research and exploration.

In terms of safety, the incidence of neutrophilia was significantly higher in the PEG-rhG-CSF group than the G-CSF group, which may be attributed to the efficacy advantage of PEG-rhG-CSF. The ANC count of most of the neutropenia patients was below 12×10⁹/L, and it recovered to normal within 2 days. In both the PEG-rhG-CSF and G-CSF groups, 6 and 9 patients experienced muscle pain, respectively, which was significantly relieved after rest or the administration of non-steroidal anti-inflammatory drugs. One SAE, which was considered to be thrombocytopenia caused by targeted drugs unrelated to the study drug, was reported in the PEG-rhG-CSF group. No unexpected AEs or cases of trial withdrawal due to intolerable AEs were observed in either group, demonstrating that PEG-rhG-CSF and G-CSF have comparable safety and tolerability.

We conducted an efficacy analysis of the patients who had received at least 4 cycles of treatment and underwent mid-term evaluation by PET-CT. Due to the multiple factors influencing efficacy, the data presented in this article should be considered preliminary. The CR rate of the PEG-rhG-CSF group reached 73.58%, while in the G-CSF group, it reached 63.64%.

This study had a number of limitations. At the design stage, we intended to investigate the use of antibiotics during the chemotherapy interval, and collect the corresponding cost data. However, due to the differences in medical costs and local strategies for infection control in different residential areas, the comparability of the data collected during the chemotherapy interval after patients’ discharge was low, making it impossible to conduct any further statistical analysis of the economic health indicators. In addition, the chemotherapy regimens used in NHL patients are diverse and may be adjusted based on each patient’s physical condition. The patients included in this study predominantly received R-CHOP/CHOP-like chemotherapy regimens; thus, further research with larger samples and more diverse chemotherapy regimens needs to be conducted. Furthermore, the findings regarding the influence of tumor cell origin on neutropenia and prophylactic efficacy are subject to the following limitations. First, to better reflect the intrinsic characteristics of the tumors, this study primarily discusses the prophylactic outcomes following the first treatment cycle; however, the influence of chemotherapy regimens remains a significant confounding factor. Second, due to the limited sample size, further stratification of patients by tumor cell origin and chemotherapy regimen resulted in subgroups that were too small for meaningful between-group comparisons. Moreover, this study lacked data on patient gene expression profiles, some regulatory factors within the immune microenvironment are not yet fully elucidated in current research, making it difficult to identify more suitable statistical metrics for analysis and interpretation.

Conclusions

In conclusion, this study showed that PEG-rhG-CSF has good efficacy and safety in the primary prevention of neutropenia in NHL patients undergoing chemotherapy. Its efficacy was not inferior to, and in specific circumstances was even superior, to that of the traditional G-CSF prophylactic strategy. Moreover, it has the advantage of being administered once per treatment cycle, which helps to alleviate patient suffering, shorten hospitalization periods, increase patient compliance, and ensure the timely execution of chemotherapy regimens. It provides a new reliable alternative for preventing neutropenia in NHL patients undergoing chemotherapy.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the CONSORT reporting checklist. Available at https://tcr.amegroups.com/article/view/10.21037/tcr-2025-1-2613/rc

Trial Protocol: Available at https://tcr.amegroups.com/article/view/10.21037/tcr-2025-1-2613/tp

Data Sharing Statement: Available at https://tcr.amegroups.com/article/view/10.21037/tcr-2025-1-2613/dss

Peer Review File: Available at https://tcr.amegroups.com/article/view/10.21037/tcr-2025-1-2613/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tcr.amegroups.com/article/view/10.21037/tcr-2025-1-2613/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was approved by the Ethics Committee of The First Hospital of Jilin University (No. 23K046-001). Informed consent was obtained from all patients. This study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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(English Language Editor: L. Huleatt)