Luo ZY, Fan LQ, Guo WL, Yang JP, Li ZY, Huang YX, Jiang H, Zhang XH. Effect of tandem autologous stem cell transplantation on survival in pediatric patients with high-risk solid tumors in South China. World J Stem Cells 2025; 17(2): 100621 [DOI: 10.4252/wjsc.v17.i2.100621]
Corresponding Author of This Article
Xiao-Hong Zhang, MD, Department of Pediatric Hematology Oncology, Guangdong Women and Children Hospital, No. 318 Renmin Road, Guangzhou 510000, Guangdong Province, China. 2018760286@gzhmu.edu.cn
Research Domain of This Article
Pediatrics
Article-Type of This Article
Retrospective Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Zi-Yan Luo, Li-Qun Fan, Wen-Ling Guo, Jian-Ping Yang, Zhuo-Yan Li, Yong-Xian Huang, Hua Jiang, Division of Hematology and Oncology, Department of Pediatrics, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou 510000, Guangdong Province, China
Xiao-Hong Zhang, Department of Pediatric Hematology Oncology, Guangdong Women and Children Hospital, Guangzhou 510000, Guangdong Province, China
Co-corresponding authors: Hua Jiang and Xiao-Hong Zhang.
Author contributions: Luo ZY and Fan LQ are co-first authors who contributed equally to this work. Luo ZY and Fan LQ both contributed to drafting the initial manuscript; Luo ZY, Fan LQ, Jiang H, and Zhang XH designed and performed the research study; Guo WL, Yang JP, Li ZY, and Huang YX provided help and advice on experiments and analyzed the data. All authors contributed to editorial changes in the manuscript and have read and approved the final manuscript. All authors have contributed significantly to the work and agreed to be accountable for all aspects of the work. Jiang H and Zhang XH as co-corresponding authors, contributed equally to the conceptualization, supervision, and final manuscript revisions, justifying their shared authorship. Jiang H was designed as the primary contact for all journal correspondence.
Supported by Guangzhou Municipal Science and Technology Bureau, Municipal School and College Joint Funding Project, No. 2024A03J1240.
Institutional review board statement: The study was reviewed and approved by the Institutional Review Board of Guangzhou Women and Children’s Medical Center, Guangzhou Medical University (Approval No. 2022-12008).
Informed consent statement: Informed consent was obtained from the legal guardians in this study.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: Data supporting the findings of this study are available from the corresponding author upon request.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Xiao-Hong Zhang, MD, Department of Pediatric Hematology Oncology, Guangdong Women and Children Hospital, No. 318 Renmin Road, Guangzhou 510000, Guangdong Province, China. 2018760286@gzhmu.edu.cn
Received: August 21, 2024 Revised: December 6, 2024 Accepted: February 12, 2025 Published online: February 26, 2025 Processing time: 186 Days and 20.2 Hours
Abstract
BACKGROUND
Despite advances in treatment, the prognosis for patients with high-risk pediatric solid tumors remains dismal. Tandem autologous stem cell transplantation (ASCT) offers promise for improving outcomes in these patients. This study aimed to examine the efficacy and prognostic factors of tandem ASCT in pediatric patients with high-risk solid tumors.
AIM
To determine the survival outcomes and prognostic factors in pediatric patients with high-risk solid tumors undergoing tandem ASCT.
METHODS
A total of 40 pediatric patients with high-risk solid tumors treated from March 2015 to August 2022 were included in this retrospective study. The diagnoses of the patients included neuroblastoma, germ cell tumors, atypical teratoid/rhabdoid tumor, medulloblastoma, and pineoblastoma. After induction chemotherapy, all patients received tandem ASCT and were allocated into two groups (group A and group B) based on high-dose chemotherapy regimens. Prognostic relevance was evaluated by examining patient characteristics, such as sex, age, lactate dehydrogenase levels, primary site, the number of metastatic sites, and bone marrow involvement.
RESULTS
The median follow-up duration since the first ASCT was 24 months (range: 1-91 months), with 5-year overall survival (OS) and event-free survival (EFS) rates of 73% and 70%, respectively, for the entire cohort. The 3-year OS rates were 67% for group A and 87% for group B (P = 0.29), with corresponding 3-year EFS rates of 67% and 79% (P = 0.57). Among neuroblastoma patients, the 5-year OS and EFS were 69% and 63% (P = 0.23). Univariable analysis revealed a notable association of age ≥ 36 months and elevated lactate dehydrogenase level at diagnosis with poorer OS. Despite acute adverse effects, all patients demonstrated good tolerance to the treatment, with no occurrences of transplant-related mortality.
CONCLUSION
Tandem ASCT demonstrates promising survival outcomes for patients with high-risk solid tumors, particularly neuroblastoma, with manageable toxicity and no transplant-related mortality.
Core Tip: This study evaluates the efficacy of tandem autologous stem cell transplantation (ASCT) in improving survival outcomes for pediatric patients with high-risk solid tumors, including neuroblastoma. The results demonstrate that tandem ASCT provides encouraging 5-year overall survival and event-free survival rates, with manageable toxicity and no transplant-related mortality. Key prognostic factors, such as age and lactate dehydrogenase levels at diagnosis, were identified. This study highlights the potential of tandem ASCT as a feasible therapeutic option for high-risk pediatric solid tumors, paving the way for further optimizing treatment strategies.
Citation: Luo ZY, Fan LQ, Guo WL, Yang JP, Li ZY, Huang YX, Jiang H, Zhang XH. Effect of tandem autologous stem cell transplantation on survival in pediatric patients with high-risk solid tumors in South China. World J Stem Cells 2025; 17(2): 100621
The survival rates of pediatric tumors have been reported to be significantly improved, largely due to the adoption of targeted radiation therapy, aggressive surgical procedures, and intensive multiagent chemotherapy[1]. However, significant clinical and biological heterogeneity of solid tumors persists in survival outcomes, particularly neuroblastoma. Over the past few decades, the long-term prognosis for patients with high-risk solid tumors has generally remained poor[2]. Therefore, further exploration of novel therapeutic strategies is crucial for improving clinical outcomes. Autologous stem cell transplantation (ASCT) has been reported to enhance survival rates for high-risk tumors, including neuroblastoma, retinoblastoma, rhabdomyosarcoma, Wilms tumor, non-Hodgkin’s lymphoma, Hodgkin’s lymphoma, osteosarcoma, Ewing sarcoma, and brain tumors, compared to standard chemotherapy[3-8]. Therefore, to improve the prognosis for patients with high-risk solid tumors, investigation was conducted on the strategies involving high-dose chemotherapy (HDCT) followed by ASCT. In ASCT, the doses of chemotherapeutic agents can be escalated, even exceeding the limits of myeloablation, without increasing toxicity to patients; therefore, higher doses are administered in most ASCT regimens to maximize antitumor cytotoxicity[9]. Several pilot trials have demonstrated the feasibility and safety of ASCT, providing evidence for its role in improving survival outcomes in high-risk pediatric tumors[10-12].
Tandem ASCT, involving two sequential transplants, may offer superior survival outcomes compared to single ASCT. Tandem ASCT allows for two cycles of HDCT, potentially enhancing cytotoxic efficacy and reducing the likelihood of relapse. However, evidence supporting tandem ASCT remains limited, and its long-term efficacy and safety in pediatric solid tumors have yet to be fully established[12]. To address this gap, a retrospective analysis was performed on 40 pediatric patients with high-risk solid tumors receiving tandem ASCT. This study sought to examine the efficacy and safety of tandem ASCT while identifying prognostic factors associated with survival outcomes.
MATERIALS AND METHODS
Patients
This study included 40 pediatric patients with high-risk solid tumors undergoing tandem ASCT at the Guangzhou Women and Children’s Medical Center between March 2015 and August 2022. Patient characteristics are summarized in Table 1. Initial diagnosis and staging were conducted for each patient based on bilateral bone marrow (BM) aspiration, computed tomography scans, and magnetic resonance imaging scans to assess distant metastasis and tumor extent. All patients were classified as stage 3 or stage 4 according to histological examination. Surgery was performed to lessen tumor burden whenever feasible, followed by conventional chemotherapy. Upon receiving 6-15 cycles of induction chemotherapy, patients achieved very good partial remission (VGPR) or complete remission (CR) before proceeding to ASCT. Only patients undergoing tandem ASCT were included in this study.
Following induction therapy, patients underwent tandem ASCT as a consolidation therapy. The HDCT regimens adopted in this study are listed in Supplementary Table 1. All patients received etoposide/carboplatin/cyclophosphamide as the first HDCT regimen, with doses tailored to individual cases. For the second HDCT, the allocation of patients into two groups was determined by the timing and conditioning regimen. Patients in group A (n = 21) receiving transplantation before December 2019 were treated with an irinotecan/temozolomide/etoposide/carboplatin/cyclophosphamide regimen developed based on our center’s experience. From January 2020, patients in group B (n = 19) who underwent transplantation were administered a busulfan/melphalan regimen following European Society for Blood and Marrow Transplantation guidelines. This regimen has demonstrated improved outcomes in solid tumors, including neuroblastoma, as reported in previous studies[13,14].
Additionally, the interval between the first and second ASCT was at least 12 weeks to reduce cumulative toxicity and facilitate patient recovery. Between the two ASCT procedures, radiotherapy was administered to optimize tumor control while minimizing cumulative toxicity, following expert recommendations from the 2021 International Neuroblastoma Risk Group and the 2024 National Comprehensive Cancer Network guidelines[15]. Radiotherapy targeting the primary tumor site or metastatic sites was delivered to all patients according to their respective manifestations. Radiation doses ranging from 20 to 25 Gy were prescribed in accordance with standard clinical practice and international guidelines. A schematic illustration summarizing the study design was shown in Figure 1.
Figure 1 Schematic illustration of the study design.
ASCT: Autologous stem cell transplantation; HDCT: High-dose chemotherapy; OS: Overall survival; EFS: Event-free survival; LDH: Lactate dehydrogenase.
Peripheral blood stem cell collection
Peripheral blood stem cell (PBSC) collection was carried out based on hematopoietic recovery regardless of complete marrow clearance, in alignment with established guidelines[16]. Blood counts were monitored 3-5 times weekly to track hematopoietic recovery following chemotherapy. After recovery, granulocyte colony-stimulating factor was given to patients daily at a dose of 5-10 μg/kg and maintained until the completion of leukapheresis. PBSC collection was initiated on the fifth day of granulocyte colony-stimulating factor treatment, targeting a minimum yield of 2 × 106 CD34+ cells/kg and 6 × 108 mononuclear leucocyte cells/kg per ASCT. These cells were intended for BM rescue during tandem ASCT. The collected PBSCs were cryopreserved in a liquid nitrogen tank for subsequent use.
Hematological recovery
Neutrophil recovery was defined as the first of three consecutive days with an absolute neutrophil count exceeding 0.5 × 109/L. The definition of platelet recovery was the first transfusion-free day within the past seven days when the platelet count exceeded 20 × 109/L.
Statistical analysis
All statistical analyses were conducted using SPSS software (version 26.0). The Student t-test was used to evaluate the differences between the groups. Survival outcomes, including overall survival (OS) and event-free survival (EFS), were estimated using the Kaplan-Meier method, and survival rates were compared via the log-rank test. Univariable analysis was conducted using the χ2 test to identify prognostic factors for disease progression. P < 0.05 was considered statistically significant.
RESULTS
Patient characteristics
A total of 40 patients (29 boys and 11 girls) who underwent tandem ASCT following HDCT were enrolled in this study. Patient characteristics are outlined in Table 1. The median age at diagnosis was 45 months (range: 17-108 months), with 21 patients (52.5%) aged ≥ 36 months and 19 patients (47.5%) aged < 36 months. The most common diagnosis was neuroblastoma (87.5%), followed by the germ cell tumor (5.0%), atypical teratoid/rhabdoid tumor (2.5%), medulloblastoma (2.5%), and pineoblastoma (2.5%). The abdomen was the most frequent primary site (75%), whereas the mediastinum was the second most common (15.0%). Multi-organ (≥ 3) metastasis was present in 70% of patients, and 57.5% had BM involvement at diagnosis. The median lactate dehydrogenase (LDH) level was 675 (range: 227-4003) U/L. All patients received 6-15 cycles of induction chemotherapy (median: 9 cycles) prior to the first ASCT, achieving CR/VGPR.
Hematological recovery
All patients achieved completed hematopoietic engraftment. During the first ASCT, the median time to neutrophil recovery (absolute neutrophil count > 0.5 × 109/L) was 8 days in group A and 10 days in group B, while the time to platelet recovery was 4 days in group A and 9 days in group B. In the second ASCT, neutrophil group B recovery demonstrated faster neutrophil recovery (7 days vs 9 days) but required more time for platelet recovery (10 days vs 4 days) (Supplementary Figure 1). Differences in engraftment times were attributed to variations in conditioning regimens. Importantly, no obvious increase in toxicity was found in patients receiving extended chemotherapy cycles (10+), possibly due to effective supportive care and individualized dose strategies.
Patient survival
Among the 40 patients, 30 remained alive after a median follow-up of 24 months (range: 1-91 months). As displayed in Figure 1, the 5-year OS and EFS rates were 73% and 70%, respectively (Figure 2A and B). The 3-year OS rates were 67% for group A and 87% for group B (Figure 2C, P = 0.29). Similarly, the 3-year EFS rates for patients in groups A and B were 67% and 79% (Figure 2D, P = 0.57), respectively. In this cohort, group B demonstrated improved survival trends; however, the differences were not statistically significant.
Figure 2 Results of Kaplan-Meier analysis of patient overall survival and event-free survival.
A and B: Probabilities of overall survival (A) and event-free survival (B) for patients following the first autologous stem cell transplantation; C and D: Overall survival (C) and event-free survival (D) of patients in different groups after the first autologous stem cell transplantation. OS: Overall survival; EFS: Event-free survival.
Outcomes based on histologic type
The 40 patients were classified into five tumor groups according to histologic diagnosis: The neuroblastoma (n = 35), germ cell tumor (n = 2), atypical teratoid/rhabdoid tumor (n = 1), medulloblastoma (n = 1), and pineoblastoma (n = 1) groups. Survival rates for patients with neuroblastoma and those with other tumors are presented in Figure 2. At the time of follow-up, the 5-year OS rate for patients with neuroblastoma stood at 69%, with all patients with other tumor types still alive (Figure 3A). However, the difference in OS between neuroblastoma and other tumors did not reach statistical significance (P = 0.23).
Figure 3 Results of overall survival and event-free survival analysis for patients with neuroblastoma and other tumors.
A and B: Probabilities of overall survival (A) and event-free survival (B) in patients with neuroblastoma and other tumors; C and D: Overall survival (C) and event-free survival (D) of patients with neuroblastoma in different groups. OS: Overall survival; EFS: Event-free survival.
The 5-year EFS rate was 63% among the subgroup of 35 patients with high-risk neuroblastoma who underwent tandem ASCT (Figure 3B). When comparing conditioning regimens, trends favoring group B were observed among 18 patients in group A and 17 in group B; additionally, the 3-year OS rate was 61% for group A and 87% for group B, with corresponding 3-year EFS rates of 61% and 79% (Figure 3C and D). These differences failed to reach statistical significance (P = 0.44).
Univariable analyses
Univariable analyses were conducted to identify prognostic factors linked to 3-year OS and EFS in patients with high-risk neuroblastoma (Table 2). The OS was significantly worse for patients aged ≥ 36 months at diagnosis than for those aged < 36 months (55.4% vs 100%, P = 0.03). Similarly, their 3-year EFS was notably lower (51.3% vs 100%, P = 0.03). These findings identified age ≥ 36 months as a critical adverse prognostic factor. Elevated LDH level (≥ 1000 U/L) at diagnosis was markedly associated with poorer OS compared to lower LDH levels (30% vs 82%, P = 0.04). Besides, elevated LDH demonstrated a trend toward poorer 3-year EFS (30.0% vs 77.4%); however, this difference did not reach statistical significance (P = 0.08).
Table 2 Univariable analysis of 35 pediatric patients with high-risk neuroblastoma, n (%).
Additionally, no significant survival differences were identified with respect to sex (P = 0.54) or MYCN amplification. The MYCN-amplified patients exhibited 100% OS (P = 0.10) and EFS (P = 0.12), but their sample size was limited. Survival outcomes were not significantly affected by neuron-specific enolase (NSE) levels (P > 0.05). Overall, these findings highlighted age and LDH levels as key prognostic factors, while sex, MYCN status, and NSE levels were not remarkably associated with survival.
Toxicity of tandem ASCT and adverse events
The toxicities associated with tandem ASCT were summarized in Table 3. Fever, vomiting, and diarrhea were the most common adverse events observed in all patients, followed by hypomagnesemia, hypokalemia, mucositis, elevated liver enzymes, myocarditis, and renal insufficiency. Infections were highly prevalent during the neutropenic period, affecting 92.5% of patients. Among them, respiratory tract infections accounted for the majority, followed by gastrointestinal infections. Detected pathogens included Escherichia coli, Klebsiella pneumoniae, and Candida albicans. Only three patients developed sepsis (systemic inflammatory response syndrome with bacteremia), all of whom responded successfully to antibiotic therapy. In group B, veno-occlusive disease (VOD) occurred in 15.8% of patients; however, this difference between the groups did not achieve statistical significance (P = 0.24). Notably, no transplant-related mortality was observed during tandem ASCT, even in patients who received up to 15 cycles of induction chemotherapy. This underscored the effectiveness of supportive care measures.
Table 3 Toxicity in patients with solid tumors who underwent tandem autologous stem cell transplantation, n (%).
Parameter
First ASCT
Second ASCT
Group A (n = 21)
Group B (n = 19)
Group A (n = 21)
Group B (n = 19)
Hematologic toxicity
Fever (BT ≥ 38.0 °C)
17 (81.1)
18 (94.7)
17 (80.1)
16 (84.2)
Septicemia
2 (9.5)
1 (5.3)
0 (0)
0 (0)
Non-hematologic toxicity
Mucositis
1 (4.8)
3 (15.8)
2 (9.5)
5 (26.3)
Vomiting
14 (66.7)
16 (84.2)
12 (57.1)
11 (57.9)
Diarrhea
10 (47.6)
13 (68.4)
10 (47.6)
11 (57.9)
Elevated liver enzymes
4 (19.0)
4 (21.1)
1 (4.7)
4 (21.1)
Renal insufficiency
0 (0)
1 (5.3)
0 (0)
1 (5.3)
Hypokalemia
5 (23.8)
10 (52.6)
2 (9.5)
4 (21.1)
Hypomagnesemia
8 (38.0)
6 (31.6)
7 (33.3)
2 (10.5)
Hepatic VOD
0 (0)
0 (0)
0 (0)
3 (15.8)
Myocarditis
2 (9.5)
1 (5.3)
0 (0)
0 (0)
Treatment-related mortality
0
0
DISCUSSION
Despite recent progress in therapy, managing high-risk pediatric solid tumors remains challenging, with poor long-term survival rates[17,18]. Tandem ASCT has emerged as a promising strategy for improving outcomes in this population[19]. Numerous studies, including ours, have demonstrated the potential of tandem ASCT to enhance survival in high-risk pediatric patients, particularly those with neuroblastoma. For instance, Adra et al[20] highlighted the superior outcomes of tandem ASCT compared to salvage chemotherapy in adults with high-risk testicular granular cell tumor, supporting its role as a standard treatment option for this high-risk group. Therefore, this study retrospectively analyzed the efficacy of tandem ASCT in pediatric patients with high-risk solid tumors.
At least one ASCT is currently regarded as the standard of care for high-risk neuroblastoma, as confirmed by multiple studies and international guidelines[3,21]. The superiority of tandem ASCT over single ASCT remains a topic of debate. According to a large international randomized controlled trial, tandem ASCT improves EFS and OS in high-risk solid tumors as opposed to single ASCT[3]. Survival rates for tandem ASCT have been illustrated to range from 52% to 57%, whereas those for single ASCT are 48.4%[3,20,22]. This study reported 5-year OS and EFS rates of 73% and 70% for patients with high-risk solid tumors treated with tandem ASCT, demonstrating outcomes comparable to or slightly exceeding those reported in the literature. These results highlight the potential benefits of tandem ASCT in this population.
PBSC collection has emerged as another point of variability in ASCT protocols. Seif et al[12] reported that PBSCs collected led to a 3-year EFS of 44.8%, regardless of interim BM assessment. Our cohort, in contrast, demonstrated a markedly higher 5-year EFS of 70%, possibly due to our protocol of collecting PBSCs only when no residual tumor was detected in the BM. Additionally, all patients achieved CR/VGPR after induction chemotherapy, with response rates exceeding the 40%-70% typically reported in the literature[3,23]. These factors likely contributed to the superior outcomes observed in this study.
Univariable analysis revealed that age and LDH levels were identified as significant prognostic factors for survival, consistent with previous studies[24,25]. Patients aged ≥ 36 months at diagnosis exhibited remarkably worse OS and EFS relative to younger patients, highlighting the critical role of age in neuroblastoma risk stratification[26]. Similarly, elevated LDH levels at diagnosis (≥ 1000 U/L) were significantly associated with poorer OS, aligning with its role as a biomarker for aggressive disease. Interestingly, while OS was affected by LDH levels, these levels were not closely related to EFS. Such a result suggested a complex interplay between metabolic activity and treatment resistance. Other commonly reported prognostic factors, including sex, MYCN amplification, and NSE levels, showed no obvious correlation in our cohort, potentially attributed to the small sample size or variations in tumor biology[27-30]. Consequently, larger studies are warranted to verify these findings. Therefore, we hypothesized that more aggressive tumor biology and greater metastatic burden at diagnosis might be reflected by the poorer outcomes observed in children with elevated LDH levels, in line with prior studies[25]. Elevated LDH levels are indicative of rapid cell turnover, tissue damage, and hypoxic environments, which may contribute to resistance to intensive therapy and higher relapse rates. This finding underscores the importance of incorporating LDH levels into risk stratification and treatment planning.
Additionally, this study emphasized the need to consider the similarities between high-risk solid tumors and hematologic malignancies in the context of ASCT. Studies on hematologic cancers have consistently demonstrated the critical role of pre-transplant disease control in improving outcomes[31-33]. For instance, aggressive disease at transplant, characterized by high LDH or residual disease, has been linked to poor post-transplant survival in both settings. These similarities among malignancies could offer valuable insights into risk stratification and conditioning regimens, thereby enhancing the efficacy and safety of ASCT protocols across diverse tumor types.
Furthermore, the safety of ASCT in pediatric patients with high-risk solid tumors has been extensively demonstrated in previous studies[3,23]. As reported in a study, transplant-related mortality rates range from 2% to 15.9% in children undergoing ASCT for solid tumors[34]. However, this study revealed no transplant-related mortality, highlighting the feasibility and safety of tandem ASCT in this population. More importantly, acute toxicities during transplantation were common but manageable, including mucositis, gastrointestinal toxicity, infections, and electrolyte disturbances. Severe adverse effects, such as elevated liver enzymes, renal insufficiency, VOD, and myocarditis, were also observed. Ladenstein et al[23] reported a 9% incidence of VOD in neuroblastoma patients undergoing melphalan, aligning with the 7.5% observed in this study. Interestingly, while the incidence of VOD was higher in the busulfan/melphalan regimen, it was not associated with increased transplant-related mortality, further demonstrating the safety of this regimen.
Despite the controversy surrounding HDCT regimen selection, emerging evidence suggests potential advantages of certain regimens. Ladenstein et al[23] proposed busulfan and melphalan as a standard HDCT regimen for neuroblastoma due to their efficacy in improving EFS and reducing severe adverse events. In this study, the busulfan/melphalan regimen was preferred over the irinotecan/temozolomide regimen, particularly for hematologic recovery and lower toxicity profiles. However, carboplatin, etoposide, and melphalan have been suggested by prior research as effective regimens for transplantation[35]. Variability in reported outcomes underscores the necessity for future randomized studies to identify the optimal conditioning regimen for high-risk solid tumors. Collectively, the toxicity profile observed in this study highlighted the manageable nature of tandem ASCT, even in patients undergoing intensive induction therapy. Although the potential advantages of busulfan/melphalan regimens are observed in this study, the lack of consensus regarding the optimal HDCT regimen warrants further investigation. Future multicenter, prospective studies are critical for establishing evidence-based guidelines for conditioning regimens and toxicity management in pediatric ASCT.
Although the findings are promising, there are several limitations in this study. First, the generalizability of the results is restricted by the retrospective design and small sample size. Given the single-center nature of this study, the potential selection and reporting biases cannot be excluded. Additionally, no formal power calculation was performed, and the study may be underpowered to detect subtle differences in efficacy, safety, and prognostic factors. Future studies should incorporate predefined power analyses to ensure robust statistical comparisons. Moreover, definitive conclusions regarding the superiority of tandem ASCT over alternative approaches are precluded by the absence of a randomized control group. Furthermore, the results may have been confounded by treatment heterogeneity, including differences in conditioning regimens and maintenance therapies. Although the survival outcomes in this cohort were remarkable, the short follow-up period limits the understanding of long-term toxicities and late effects associated with tandem ASCT. Future multicenter, prospective trials with predefined statistical power, standardized treatment protocols, and extended follow-up are needed to validate these findings and develop evidence-based guidelines. These trials should include standardized conditioning regimens, toxicity management protocols, and risk stratification methods to optimize the efficacy and safety of ASCT for high-risk pediatric solid tumors.
CONCLUSION
In summary, this study highlights the effectiveness of tandem ASCT in treating high-risk solid tumors, providing favorable survival outcomes with manageable toxicity. However, limitations, such as the small sample size, single-center design, and short follow-up, warrant caution in interpreting the results. Future multicenter studies with larger cohorts and extended follow-up are needed to confirm these findings and optimize treatment protocols.
Footnotes
Provenance and peer review: Unsolicited article; Externally peer reviewed.
Peer-review model: Single blind
Specialty type: Cell and tissue engineering
Country of origin: China
Peer-review report’s classification
Scientific Quality: Grade B, Grade B, Grade C, Grade C
Novelty: Grade B, Grade B, Grade C
Creativity or Innovation: Grade B, Grade B, Grade B
Scientific Significance: Grade B, Grade B, Grade C
P-Reviewer: Goebel WS; Guo WC; Li SC S-Editor: Wang JJ L-Editor: A P-Editor: Li X
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