Нейтропентия фебрилов отрицательно сказывается на результатах химиомобилизации у пациентов с множественной миеломой и повышает риск посттрансплантации инфекции у пациентов с лимфомой: реальные данные о мультицентрах в мире.

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1. INTRODUCTION

Hematological malignancies represent approximately 7% of all cancers worldwide, with lymphoid malignancies constituting more than one-half of these cases. 1 In 2020, Europe witnessed age-standardized incidence rates (per 100,000) of 16.4 for non-Hodgkin lymphoma, 6.8 for multiple myeloma (MM), and 2.7 for Hodgkin lymphoma. 2 , 3 MM is an incurable hematological malignancy that often relapses and is resistant to existing therapies. 4 Despite recent advancements in therapeutic strategies, achieving long-term remission and improving survival rates for these diseases remain formidable challenges. As such, high-dose chemotherapy coupled with autologous stem cell transplantation (ASCT) remains the cornerstone treatment for patients diagnosed with MM or lymphoma. 5 – 13

The safety and efficacy of ASCT, as well as the quantity of stem cells collected during apheresis, critically depend on the effectiveness of peripheral blood stem cell (PBSC) mobilization. 14 , 15 The CD34 + cell count is the predominant surrogate marker for hematopoietic stem/progenitor cells harvested from peripheral blood. Clinical evidence suggests that infusion of a minimum of 2 × 10 6 /kg CD34 + cells/kg is required to ensure reliable engraftment. 16

Various strategies have been used to mobilize CD34 + cells, including chemotherapy combined with granulocyte colony-stimulating factor (G-CSF), G-CSF monotherapy, and the plerixafor + G-CSF regimen. 17 – 20 Zhu et al 19 reported that G-CSF monotherapy was correlated with an increased incidence of mobilization failure. For patients with disease in partial response (PR) or suboptimal remission at the time of collection, chemotherapy + G-CSF is preferred to simultaneously reduce tumor burden and enhance stem cell yield, optimizing pre-ASCT disease status. 17 , 18

Febrile neutropenia (FN) frequently occurs as a complication of chemotherapy and G-CSF mobilization in individuals diagnosed with MM or lymphoma. 21 , 22 The mechanisms underlying FN are complex and involve immunosuppression and infection. However, the precise impact of FN on stem cell collection during chemotherapy + G-CSF mobilization is not well defined in the existing literature, underscoring the need for further research to better understand the incidence of FN during chemomobilization and its effects on CD34 + cell collection. 23 , 24

Post-transplant infection(s) is a major risk factor that influences transplant outcomes, with post-transplant FN and mucosal damage significantly contributing to pre-engraftment infection. 25 , 26 Nevertheless, the specific effect of FN during mobilization on the occurrence of pre-engraftment infections has not been adequately characterized. Identifying these associations is essential to optimize stem cell collection strategies and improve the management of post-transplant infections.

The objective of the present study was to evaluate the impact of FN on CD34 + stem cell collection and the risk for pre-engraftment infection(s), with the intent to identify the specific clinical conditions under which FN exerts its effects. Furthermore, this investigation explored the relationship between FN during mobilization and long-term survival of patients diagnosed with MM or lymphoma. A comprehensive assessment of the influence of FN during chemomobilization was conducted to optimize stem cell collection regimens and enhance strategies for managing post-transplant infections.

2. MATERIALS AND METHODS

2.1. Patients

This multicenter, real-world, retrospective investigation used data collected at the Tongji Hospital (Wuhan), Shanxi Bethune Hospital, and Shanxi Province Cancer Hospital (Shanxi, China) between October 1, 2010, and January 31, 2024. Data from 278 patients ≥18 years of age with confirmed MM or lymphoma ( Fig. 1 ) were collected. All patients underwent first-line chemotherapy, with or without radiation therapy, before undergoing stem cell mobilization and apheresis, followed by high-dose chemotherapy and ASCT within 12 months of mobilization initiation. The requirement for informed consent was waived due to the retrospective design of this study. Ethics approval was obtained from the Ethics Committees of the participating hospitals (TJ-IRB20230630 [Tongji Hospital], YXLL-2023-077 [Shanxi Bethune Hospital], and KY2024088 [Shanxi Province Cancer Hospital]). This study rigorously adhered to the ethical guidelines outlined in the Declaration of Helsinki.

2.2. Chemomobilization and apheresis of hematopoietic stem cells

In patients diagnosed with MM, stem cell mobilization is primarily performed using 1 of 2 chemotherapy-based regimens: cyclophosphamide (CTX) or etoposide. For patients with lymphoma, the mobilization regimen primarily included dexamethasone, high-dose cytarabine (Ara-C), and cisplatin (DHAP), CTX, or etoposide. The CTX regimen involved a single dose of CTX (3 g/m 2 intravenously [IV]) administered over a 2-day period. The etoposide regimen for patients with MM involved an infusion of etoposide 375 mg/m 2 on both days 1 and 2. The etoposide regimen for patients with lymphoma involved a single IV dose of etoposide 1.6 g/m 2 on day 1. The DHAP regimen consisted of dexamethasone 40 mg daily from days 1 to 4, cisplatin 100 mg/m 2 on day 1, and Ara-C 2 g/m 2 administered twice on day 2.

Subcutaneous G-CSF (10 µg/kg/d) was initiated on day +5 after completion of chemotherapy or earlier if the peripheral white blood cell count fell to ≤1.0 × 10 9 /L or the absolute neutrophil count (ANC) dropped to ≤0.5 × 10 9 /L, whichever occurred first, and continued daily until the final day of apheresis. 27 When the CD34 + cell count reached 20 cells/μL or white blood cell count reached ≥5 × 10 9 /L, apheresis procedures were initiated to isolate PBSCs. The collection process typically continued for 1 to 3 days, with the aim of obtaining CD34 + cells at a minimum dose of 2 × 10 6 /kg. Mobilization outcomes were categorized according to CD34 + cell count, as follows: optimal, ≥5 × 10 6 /kg; successful, ≥2 × 10 6 /kg; and failed, <2 × 10 6 /kg. Collection days were defined as the number of days on which leukapheresis was performed.

2.3. Preconditioning regimen for transplantation

For patients diagnosed with MM, the melphalan conditioning regimen was administered before autologous stem cell infusion on day 0, consisting of melphalan 100 mg/(m 2 ·day) on days −3 to −2. In patients with impaired renal function, the dose was reduced to 70 mg/(m 2 ·day). 28

For patients with lymphoma, the conditioning regimens mainly consisted of BCNU, etoposide, Ara-C, and melphalan (BEAM), and thiotepa, busulfan, and cyclophosphamide (TBC). The BEAM regimen comprised carmustine 300 mg/(m 2 ·d) on day −6, etoposide 200 mg/(m 2 ·d) from days −5 to −2, Ara-C 400 mg/(m 2 ·d) from days −5 to −2, and melphalan 140 mg/(m 2 ·d) on day −1. The TBC regimen involved thiotepa 250 mg/(m 2 ·d) from days −9 to −7, busulfan 3.2 mg/(kg·d) from days −6 to −4, and CTX 60 mg/(kg·d) from days −3 to −2. Dosage adjustments were made based on the patient’s overall health status and tolerance.

2.4. Standardized definitions

FN is characterized by a sustained core temperature ≥100.4°F (38.0°C) over a 1-hour period or a single core temperature measurement exceeding 101°F (38.3°C), coupled with an ANC <500 cells/μL, or an anticipated decline in ANC to <500 cells/μL within the following 48 hours. 29 Pathogen types, concurrent infection(s), and diagnostic methods associated with FN are listed in Supplementary Table 1, https://links.lww.com/BS/A169 .

The efficacy assessment of MM followed the International Myeloma Working Group consensus criteria for response evaluation and minimal residual disease assessment. 30 Lymphoma efficacy assessment was based on the Lugano classification. 31 The follow-up period commenced at the time of stem cell transplantation.

In this study, post-transplant infection was defined as any infection occurring after hematopoietic stem cell transplantation but before neutrophil engraftment. Therefore, pre-engraftment infection specifically refers to infection(s) that manifest between the time of transplantation and the achievement of neutrophil engraftment. This definition encompasses clinically documented infections identified through physical examination or imaging alterations that are deemed by the attending clinician to be indicative of an infection site, despite the absence of corroborating microbiological data.

2.5. Statistical analysis

Descriptive statistical analyses were used to encapsulate patient profiles, with variable data assessed for normality. Continuous variables are expressed as median (range), while categorical variables are expressed as percentage. The chi-squared test was used to compare the composition ratios between groups.

Statistical analyses were performed using Prism version 9.0 (GraphPad Inc., San Diego, California); differences with p < 0.050 were considered to be statistically significant. Variables that achieved statistical significance in univariate analyses, Kaplan–Meier survival analysis for time-to-event outcomes, and logistic regression for binary outcomes, were further evaluated using multivariate models to assess their independent prognostic or predictive utility. Specifically, significant variables from the Kaplan–Meier analysis were entered into a multivariate Cox proportional hazards regression model, with results expressed as hazard ratio (HR) with corresponding 95% confidence interval (CI), while those from univariate logistic regression were included in a multivariate binary logistic regression model, with results reported as odds ratio (OR) and corresponding 95% CI. In both cases, likelihood ratio tests were used to evaluate the null hypothesis that the HR was equal to 1.

3. RESULTS

3.1. Patient characteristics

Data from 278 patients were divided into 2 groups: MM (n = 148) and lymphoma (n = 130) (Table 1 ). The causative agents of FN were identified using a combination of blood culture, nucleic acid testing, metagenomic next-generation sequencing, and clinical diagnosis (Supplementary Table 1, https://links.lww.com/BS/A169 ). The identified pathogens include bacteria, fungi, and viruses. However, the causative agent remains undetermined in most FN cases. Concurrent infections have been observed in various anatomical sites, including the respiratory tract, bloodstream, gastrointestinal tract, perianal area, skin, and urinary tract.

Based on the occurrence of FN during stem cell mobilization, the MM group was divided into the FN (n = 32 [21.6%]) and non-FN groups. Among patients with MM, 29 were ≥60 years of age, including 5 (15.6%) in the FN group. The study group comprised 59 females. In total, 112 patients with MM underwent first-line therapy before stem cell mobilization. Prior radiotherapy was documented in 3 (2.6%) patients in the non-FN group, and 86 had previously received lenalidomide. Of the 140 patients with MM who achieved remission before stem cell mobilization, 28 (87.5%) belonged to the FN group. The median time from chemotherapy to FN onset was 7 days (range, 0–14 days). All patients in the FN group received antimicrobial agents, primarily carbapenems, beta-lactam/beta-lactamase inhibitor combinations, or cephalosporins.

Fifty-three of 130 patients in the lymphoma group were diagnosed with diffuse large B-cell lymphoma (Supplementary Table 2, https://links.lww.com/BS/A169 ). Similar to patients with MM, those with lymphoma were stratified into FN and non-FN groups, with 47 (36.2%) developing FN (Table 1 ). Eight patients were ≥60 years of age, including 4 (8.5%) in the FN group. The study cohort comprised 62 females. Seventy patients underwent first-line therapy before stem cell mobilization. A history of radiotherapy was reported in 17 patients and 14 previously received lenalidomide. Remission before stem cell mobilization was achieved in 117 patients. The median time from chemotherapy to the onset of FN was 8 days (range, 0–17 days). All patients in the FN group received antimicrobial agents, primarily carbapenems, beta-lactam/beta-lactamase inhibitor combinations, or cephalosporins.

The incidence of FN during stem cell mobilization varied significantly over time in both the lymphoma ( p = 0.014) and MM ( p < .001) groups (Supplementary Figure 1, https://links.lww.com/BS/A170 ). Specifically, the lowest rates were observed in the 2020–2024 cohort (29.3% in lymphoma and 11.7% in MM) compared with earlier periods. This trend likely reflects the improvements in supportive care and prophylactic strategies over time.

CD34 + cell yield remained stable across the 3 time periods in patients with MM ( p = 0.369), whereas those with lymphoma exhibited a significant increase in yield over time ( p < .001), with the highest median yield in 2020–2024 (6.40 × 10 6 /kg [range, 0.56–35.40 × 10 6 /kg]). In contrast, post-transplant infection rates did not differ significantly according to the apheresis period in either disease group (lymphoma, p > 0.999; myeloma, p = 0.075).

3.2. Impact of FN on long-term survival in patients with MM

The estimated 5-year overall survival (OS) rates for patients with MM and lymphoma were 79.2% (95% CI, 69.6%–86.1%) and 75.1% (95% CI, 62.2%–84.2%), respectively ( Fig. 2 A and B ). Among those with MM, the median follow-up duration was 34.9 months (range, 4.7–146.8 months). Of the 148 patients, 28 (18.9%) survived beyond 5 years. In the lymphoma group, the median follow-up duration was 30.6 months (range, 0.2–164.3 months). Of the 130 patients, 18 (13.8%) survived beyond 5 years.

Analysis revealed that FN during chemomobilization was associated with poor long-term survival in patients with MM ( p = 0.002) ( Fig. 2 C ). The multivariate Cox regression analysis initially included all baseline variables; however, previous radiotherapy was excluded due to multicollinearity (variance inflation factor [VIF] >10). The final model identified FN during stem cell mobilization ( p = 0.002) and age <60 years ( p = 0.037) as independent predictors of long-term survival in patients with MM (Supplementary Table 3, https://links.lww.com/BS/A169 ).

For patients with lymphoma, univariate analysis did not identify any factors that were significantly associated with long-term survival. All baseline variables were entered into the multivariate model, and previous lenalidomide use (VIF >10) was excluded for multicollinearity. The final multivariate Cox model did not identify any factors significantly associated with long-term survival in patients with lymphoma (Supplementary Table 4, https://links.lww.com/BS/A169 ). The estimated 5-year OS rates in the FN and non-FN subgroups was 61.0% and 84.4%, respectively.

3.3. Impact of FN during chemomobilization on CD34 + cell mobilization, apheresis, and transplantation outcomes

In the MM group, 123 patients received the CTX regimen, and 25 received etoposide for stem cell mobilization (Table 2 ). There was a statistically significant association between mobilization regimen and the occurrence of FN ( p = 0.017). Among those who experienced FN, 29 (90.6%) required >5 days of G-CSF administration before apheresis to achieve a target CD34 + cell count of 2 × 10 6 /kg ( p < .001), and 15 (46.9%) underwent apheresis for >2 days ( p = 0.007).

The median CD34 + cell yield was significantly lower in the FN group, at 3.75 (range 0.55–23.04) × 10 6 /kg ( p < .001). Optimal mobilization was achieved in only 10 (31.3%) patients in the FN group ( p < .001).

The median interval from apheresis to transplantation was 1.39 months (0.33–5.83 months) in the FN group ( p = 0.068). After transplantation, neutrophil engraftment occurred at a median of 12 days (6–24 days) ( p = 0.006) and platelet engraftment occurred at 13 days (7–23 days) ( p = 0.028) in this group. Post-transplant infection was documented in 23 (71.9%) patients with previous FN ( p > 0.999).

In the lymphoma group, 39 patients received the DHAP regimen, 8 the CTX regimen, and 23 received the etoposide regimen for stem cell mobilization (Supplementary Table 5, https://links.lww.com/BS/A169 ). There was no statistically significant association between mobilization regimen and the occurrence of FN ( p = 0.715) (Table 3 ). Among patients with FN, 37 (78.7%) required >5 days of G-CSF administration before apheresis to reach the target CD34 + cell count of 2 × 10 6 /kg ( p = 0.530) and 15 (31.9%) underwent apheresis for >2 days ( p = 0.001).

The median CD34 + cell yield in the FN group was 5.60 (0.57–30.00) × 10 6 /kg ( p = 0.850). Optimal mobilization was achieved in 25 (53.2%) patients with FN ( p > 0.999). The median time from apheresis to transplantation was 1.17 months (0.27–6.40 months) ( p = 0.242). Neutrophil engraftment occurred at a median of 11 days (8–22 days) ( p = 0.328) and platelet engraftment occurred at 13 days (9–24 days) ( p = 0.017).

Notably, post-transplant infections occurred in 43 (91.5%) patients in the FN group ( p = 0.034), suggesting an elevated risk for infection in this population.

3.4. FN as an independent risk factor influencing optimal mobilization in patients with MM

In patients with MM, univariate analysis indicated that >5 days of G-CSF administration before stem cell apheresis ( p = 0.004), >2 days of apheresis ( p = 0.013), and FN during mobilization ( p < .001) were risk factors for reduced optimal mobilization ( Fig. 3 A ). Multivariate analysis further identified FN during mobilization as the sole independent factor influencing optimal mobilization (OR, 3.06 [95% CI, 1.22–8.03]; p = 0.019) ( Fig. 3 B ). For patients with lymphoma, univariate analysis identified 2 factors significantly associated with optimal stem cell mobilization: apheresis duration <2 days ( p = 0.009); and apheresis performed between 2020 and 2024 ( p = 0.002). Multivariate analysis further confirmed that apheresis during 2020–2024 remained an independent predictor of successful mobilization (OR, 0.33 [95% CI, 0.11–0.92]; p = 0.037) (Supplementary Table 6, https://links.lww.com/BS/A169 ).

3.5. FN and susceptibility to post-transplant infection in patients with lymphoma

Among the patients with lymphoma, univariate analysis revealed that FN during chemomobilization was significantly associated with an increased risk for post-transplant infection (OR, 0.29 [95% CI, 0.10–0.86]; p = 0.034) ( Fig. 4 A ). To rigorously assess the independent contribution of FN during chemomobilization, as many relevant baseline covariates as possible were included in multivariate analysis. The multivariate analysis confirmed that FN during chemomobilization remained a significant independent predictor of post-transplant infection (OR, 0.18 [95% CI, 0.04–0.60]; p = 0.009) ( Fig. 4 B ). In patients with MM, univariate analysis failed to demonstrate a notable correlation between FN during chemomobilization and post-transplant infection (Supplementary Table 7, https://links.lww.com/BS/A169 ).

4. DISCUSSION

The use of G-CSF, with or without plerixafor, as a standalone mobilization strategy for patients with MM or lymphoma has been widely adopted in many transplant centers. Such patients are generally in good clinical condition before apheresis and typically do not require chemotherapy to reduce the residual tumor burden before stem cell collection. However, a subset of patients still require chemotherapy-based mobilization to eliminate potentially malignant cells. In these cases, FN may arise during the mobilization or collection period, posing additional clinical challenges.

FN is a frequent and significant complication of stem cell mobilization and ASCT. This multicenter retrospective study investigated the impact of FN on patients diagnosed with MM or lymphoma during chemomobilization, focusing on stem cell mobilization efficacy and the incidence of pre-engraftment infections. The reported incidence of FN during chemomobilization varies considerably across studies. Khouri et al 23 reported an FN incidence of 24%. Topcuoglu and Ozcan 24 observed higher rates of lymphoma (46.7%) and MM (66.7%) among patients treated between 2001 and 2007. Similarly, Laszlo et al 32 reported an FN incidence rate of 23.3% in patients with MM.

In our multicenter retrospective study, the overall incidence of FN during chemomobilization was 28.4%. We found a higher FN rate in patients with lymphoma (36.2%) than in those with MM (21.6%). Importantly, temporal trends suggest ongoing improvements in clinical management and, during the most recent period (2020–2024), the incidence of FN has declined to 29.3% in patients with lymphoma and 11.7% in those with MM, reflecting potential advances in supportive care and prophylactic strategies. The incidence of FN differs between patients with lymphoma and MM. 33 – 35 Compared with MM, lymphoma originates directly from and destroys lymphocytes themselves, potentially exerting a more profound and systemic impact on the entire immune system. Furthermore, patients with lymphoma often receive more intensive and cumulative doses of chemotherapy, which likely contribute to their heightened susceptibility to FN during stem cell mobilization.

While Topcuoglu and Ozcan 24 suggested that FN occurrence does not influence the total CD34 + cell yield, Khouri et al 23 reported differences between the FN and non-FN groups. Our research demonstrated a substantially diminished CD34 + cell yield and a lower rate of optimal mobilization in patients with FN and MM than in the non-FN MM group, indicating that FN may be a primary factor contributing to suboptimal mobilization.

Guidelines recommend limiting stem cell collection to no more than 4 days, with reconsideration of the mobilization strategy if the target is not reached by day 4. 36 Khouri et al 23 reported that FN patients required ≥4 days of collection more often than non-FN patients (48% vs 37%). Our findings indicated that patients with FN and MM required extended G-CSF stimulation periods (exceeding 5 days) and exhibited lower rates of optimal mobilization. Prolonged use of G-CSF for >5 days extended stem cell collection beyond 2 days and FN during chemomobilization were associated with suboptimal mobilization outcomes. Previous studies have associated lenalidomide treatment with decreased CD34 + cell yield, although verification remained inconclusive in this study, possibly due to an insufficient dose or duration of lenalidomide therapy in real-world scenarios. 37 – 40

Neutropenic infection remains a major complication in patients undergoing ASCT, with the duration of neutropenia being a significant risk factor. 41 The existing literature indicates that early post-transplant infections are primarily linked to severe neutropenia, previous fungal infections, and the use of central venous catheters. 41 – 45 Consistent with these findings, our study reported a pre-engraftment infection rate of 72.3% and 81.5% in patients with MM and lymphoma, respectively. This phenomenon could be attributed to the inherently compromised immune function in patients with lymphoma, coupled with the more intensive and cumulative doses of chemotherapy they typically receive, which together contribute to a higher pre-engraftment infection rate than that in patients with MM. Notably, patients who experienced FN during mobilization demonstrated a significantly higher incidence of pre-engraftment infections, particularly among those with lymphoma. These results suggest that FN during the mobilization phase may be associated with an increased risk of infection before neutrophil and platelet engraftment. The development of FN during mobilization may indicate that latent or colonizing pathogens are more likely to cause clinical manifestations in patients after chemotherapy-induced immunosuppression.

Multivariate analysis identified FN as an independent factor that adversely affected optimal mobilization in patients with MM. Non-FN patients exhibited a 3.06 times higher likelihood of achieving optimal mobilization than those with FN. Early identification and intervention of the FN may improve optimal mobilization rates in patients with MM. A limitation of this study in identifying specific pathogens in patients with FN merits further research to explore the impact of different pathogens on stem cell mobilization and post-transplant infection rates.

The estimated 5-year OS rates for MM and lymphoma in our study were consistent with those reported by other centers. 9 , 12 , 46 , 47 In our multivariate Cox model, FN levels during stem cell mobilization and age <60 years were identified as independent predictors of long-term survival in patients with MM. Notably, our comprehensive literature review failed to identify previous studies that specifically investigated the association between FN during mobilization and long-term survival outcomes. This observation raises the intriguing hypothesis that FN may serve as a subtle indicator of either suboptimal stem cell quality or compromised host conditions. Patients with FN may have an underlying disease that is inherently aggressive or biologically complex. These intrinsic disease characteristics could not only predispose patients to the development of FN but also reflect a poorer overall prognosis. Although this suboptimal quality does not appear to directly compromise the immediate success of the transplantation process, it can manifest as a long-term prognostic factor.

The present study had some limitations, the first of which was baseline imbalances that may have influenced the outcomes. For example, patients with FN and MM included a significantly lower proportion of females, and more patients with lymphoma in the FN group did not undergo treatment with lenalidomide. However, univariate logistic regression analysis revealed that female sex was not a significant risk factor for suboptimal mobilization or post-transplant infection in patients with MM. Although lenalidomide, a potent immunomodulatory agent, is effective against indolent B-cell lymphomas, its role in other lymphoma subtypes remains unclear due to the genetic heterogeneity and complex classification of the disease.

In conclusion, FN during chemomobilization emerged as an independent risk factor for impaired stem cell mobilization in patients with MM, and was associated with a higher risk for pre-engraftment infection(s) in patients with lymphoma. Future prospective, multicenter, large-scale studies are warranted to validate and expand these findings and to develop more standardized and effective mobilization regimens.

ACKNOWLEDGMENTS

This work was supported by grants from the National High Technology Research and Development Program of China (Grant 2021YFA1101500 to Professor Yicheng Zhang and Professor Jia Wei), the Key Research and Development Program of Hubei Province (Grant 2022BCA017 to Professor Yicheng Zhang and Professor Jia Wei), and the Fundamental Research Program of Shanxi Province (Grant 202303021211224 to Dr. Weiwei Tian).

ETHICAL APPROVAL

Ethics approval was obtained from the Ethics Committees (TJ-IRB20230630 for Tongji Hospital, YXLL-2023-077 for Shanxi Bethune Hospital, and KY2024088 for Shanxi Province Cancer Hospital). The research adhered rigorously to the ethical guidelines outlined in the Declaration of Helsinki.

AUTHOR CONTRIBUTIONS

All authors have reviewed and endorsed the article. H.Q. and X.W. analyzed the data and prepared the figures and tables. H.Q., X.W., and L.Y. authored the manuscript. J.P., J.Z., S.H., J.Z., J.G., Y.F., F.M., Y.C., and L.H. collected the data and instructed the analysis of clinical data. J.W., L.M., and L.S. instructed and revised the study design. W.T., Y.Z., and J.W. designed the study and reviewed, revised, and contributed to the manuscript, figures, and tables.

Supplementary Material

Footnotes

Conflict of interest: The authors declare that they have no conflict of interest.

H.Q., X.W., and L.Y. contributed equally to this study.

The additional data collected in this study are available from the corresponding authors on reasonable request.

This work was supported by grants from the National High Technology Research and Development Program of China (Grant 2021YFA1101500 to Professor Yicheng Zhang and Professor Jia Wei), the Key Research and Development Program of Hubei Province (Grant 2022BCA017 to Professor Yicheng Zhang and Professor Jia Wei), and the Fundamental Research Program of Shanxi Province (Grant 202303021211224 to Dr. Weiwei Tian).

Due to the retrospective design, informed consent was waived by the Ethics Committee. The study involved only clinical data analysis with minimal risk, ensured patient confidentiality, and could not be effectively conducted without the waiver. Participants will be informed during follow-up. The waiver supports the evaluation of hospital-acquired infections in autologous stem cell transplant patients and guides future infection management strategies.

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