Analysis of the incidence, characteristics, and risk factors of complications during induction chemotherapy in children with high-risk neuroblastoma

• Published in: European journal of pediatrics Vol. 183; no. 1; pp. 185 - 202
• Main Authors: Du, Jiaxi, Yuan, Xiaojun
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.01.2024; Springer Nature B.V
• Subjects: Bacterial infections; Bone marrow; Bone Marrow Neoplasms - drug therapy; Chemotherapy; Child; Children; Hemorrhage; Humans; Incidence; Induction Chemotherapy - adverse effects; Infant; Infections; Medical prognosis; Medicine; Medicine & Public Health; Metastases; Metastasis; Myelosuppression; Neuroblastoma; Neuroblastoma - drug therapy; Neuroblastoma - pathology; Patients; Pediatrics; Phosphopyruvate hydratase; Prognosis; Quality of Life; Retrospective Studies; Risk Factors; Side effects; High-risk neuroblastoma; Infection; Induction chemotherapy; Hemorrhagic
• ISSN: 1432-1076; 0340-6199; 1432-1076
• DOI: 10.1007/s00431-023-05273-w

Patients with high-risk neuroblastoma (HR-NB) exhibit suboptimal 5-year survival rates, leading to a widespread international preference for high-intensity chemotherapeutic regimens in these children. We analyzed the incidence and risk factors for complications during induction chemotherapy in children with HR-NB and tried to assist clinicians in predicting such complications and optimizing therapeutic strategy. The clinical data of children with HR-NB admitted to our hospital from January 2007 to December 2019 were retrospectively analyzed. The incidence, characteristics, and risk factors of complications (infection, hemorrhage, and chemotherapy-related adverse reactions (CRAR)) requiring hospitalization during induction chemotherapy in these children were explored. (1) A total of 108 patients with HR-NB were included in the final analysis. The overall infection rate was 92.6% (100/108), with the highest incidence of 71.3% observed during the first cycle. FN, bacterial infection, as well as fungal infection were common infectious complications in children with HR-NB during induction chemotherapy. (2) The overall hemorrhage rate was 24.1% (26/108), with the highest incidence of 14.8% also observed in the first cycle. Among the children with hemorrhage, there were 72% with bone marrow involved, while 65.0% of them had a high vanillylmandelic acid (VMA) value. And children with hemorrhage also exhibited neuron-specific enolase (NSE) ≥ 200 µg/L in 88.5% of cases and lactic dehydrogenase (LDH) ≥ 1000U/L in 73.1% of cases. (3) The incidence of CRAR rate was 100%, and 99.1% (107/108) patients experienced myelosuppression. The incidence of myelosuppression peaked in the third cycle, reaching up to 85.2%. Most children suffered severe myelosuppression existed with bone marrow metastases (76.3%), abnormal VMA (67.5%), and LDH ≥ 1000 U/L (60%). (4) Non-myelosuppressive adverse effects were observed in 75.9% children (82/108), with the highest incidence occurring in the third cycle at 42.6%. (5) Patients who experienced three types of complications had a lower median survival time (MST) of 54.4 months, a 3-year event-free survival (EFS) rate of (44.2 ± 10.7)%, and a 3-year overall survival (OS) rate of (75.8 ± 8.6)%, in comparison to those with only one or two complications, who had a higher MST of 59.5 months, a 3-year EFS rate of (73.5 ± 5.2)% ( X 2  = 10.457, P  =  0.001 ), and a 3-year OS rate of (84.8 ± 4.1)% ( X 2  = 10.511, P  =  0.001 ). Conclusion : The presence of bone marrow involved and increased VMA were high-risk factors for infection, while NSE ≥ 200 µg/L and LDH ≥ 1000 U/L were high-risk factors for hemorrhage. For those children who had experienced severe myelosuppression, the presence of bone marrow metastases, increased VMA, and LDH ≥ 1000 U/L were their risk factors. The presence of bone involvement was a high-risk factor for children to have non-myelosuppressive adverse effects. Complications that arise during induction chemotherapy could negatively impact the children’s prognosis and overall quality of life. What is Known: • The high-risk neuroblastoma (HR-NB) had a worse prognosis; there was a general international preference for high-intensity chemotherapeutic regimens in the induction phase to these children. What is New: • We analyzed the incidence and risk factors of complications during induction chemotherapy in children with HR-NB and tried to help clinicians predict such complications and adopt optimized therapeutic strategy.