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

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 child...

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Veröffentlicht in:European journal of pediatrics 2024-01, Vol.183 (1), p.185-202
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description 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 pres
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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.</description><identifier>ISSN: 1432-1076</identifier><identifier>ISSN: 0340-6199</identifier><identifier>EISSN: 1432-1076</identifier><identifier>DOI: 10.1007/s00431-023-05273-w</identifier><identifier>PMID: 37855927</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>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 &amp; 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</subject><ispartof>European journal of pediatrics, 2024-01, Vol.183 (1), p.185-202</ispartof><rights>The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.</rights><rights>2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c326t-8f983c0c82c63ff2af71cc2fde6671c011f6408d252b581b8f9f6f91e7640ac43</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00431-023-05273-w$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00431-023-05273-w$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,27924,27925,41488,42557,51319</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/37855927$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Du, Jiaxi</creatorcontrib><creatorcontrib>Yuan, Xiaojun</creatorcontrib><title>Analysis of the incidence, characteristics, and risk factors of complications during induction chemotherapy in children with high-risk neuroblastoma</title><title>European journal of pediatrics</title><addtitle>Eur J Pediatr</addtitle><addtitle>Eur J Pediatr</addtitle><description>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.</description><subject>Bacterial infections</subject><subject>Bone marrow</subject><subject>Bone Marrow Neoplasms - drug therapy</subject><subject>Chemotherapy</subject><subject>Child</subject><subject>Children</subject><subject>Hemorrhage</subject><subject>Humans</subject><subject>Incidence</subject><subject>Induction Chemotherapy - adverse effects</subject><subject>Infant</subject><subject>Infections</subject><subject>Medical prognosis</subject><subject>Medicine</subject><subject>Medicine &amp; Public Health</subject><subject>Metastases</subject><subject>Metastasis</subject><subject>Myelosuppression</subject><subject>Neuroblastoma</subject><subject>Neuroblastoma - drug therapy</subject><subject>Neuroblastoma - pathology</subject><subject>Patients</subject><subject>Pediatrics</subject><subject>Phosphopyruvate hydratase</subject><subject>Prognosis</subject><subject>Quality of Life</subject><subject>Retrospective Studies</subject><subject>Risk Factors</subject><subject>Side effects</subject><issn>1432-1076</issn><issn>0340-6199</issn><issn>1432-1076</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNp9kc1u1DAUhS0EomXgBVggS2xYNOCfJHaWVVUoUiU2sLY8N3bjktjBTjSa9-gDc2em_IgF3tj36JzP0j2EvObsPWdMfSiM1ZJXTMiKNULJaveEnPNaiooz1T79631GXpRyzzDUcf2cnEmlm6YT6pw8XEY77ksoNHm6DI6GCKF3EdwFhcFmC4vLoSwBygW1sac4fKce5ZSPGUjTPAawS0ix0H7NId4hpF_hoCDDTQm52c57lHEOY59dpLuwDHQId0N1JEa35rQdbVnSZF-SZ96Oxb16vDfk28frr1c31e2XT5-vLm8rkKJdKu07LYGBFtBK74X1igMI37u2xRfj3Lc1071oxLbRfIt-3_qOO4WyhVpuyLsTd87px-rKYqZQwI2jjS6txQituprVSiu0vv3Hep_WjLtDVydqppjEsyHi5IKcSsnOmzmHyea94cwcOjOnzgx2Zo6dmR2G3jyi1-3k-t-RXyWhQZ4MZT5s1-U_f_8H-xNd3KVR</recordid><startdate>20240101</startdate><enddate>20240101</enddate><creator>Du, Jiaxi</creator><creator>Yuan, Xiaojun</creator><general>Springer Berlin Heidelberg</general><general>Springer Nature B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7RV</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8C1</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9-</scope><scope>K9.</scope><scope>KB0</scope><scope>M0R</scope><scope>M0S</scope><scope>M1P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>7X8</scope></search><sort><creationdate>20240101</creationdate><title>Analysis of the incidence, characteristics, and risk factors of complications during induction chemotherapy in children with high-risk neuroblastoma</title><author>Du, Jiaxi ; 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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.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><pmid>37855927</pmid><doi>10.1007/s00431-023-05273-w</doi><tpages>18</tpages></addata></record>
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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
title Analysis of the incidence, characteristics, and risk factors of complications during induction chemotherapy in children with high-risk neuroblastoma
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