{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T11:42:39Z","timestamp":1769600559098,"version":"3.49.0"},"reference-count":49,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,10,29]],"date-time":"2021-10-29T00:00:00Z","timestamp":1635465600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Hyponatremia is a well-known adverse event of repeated therapy with vincristine in oncological patients. However, to date, data in pediatric patients with malignant diseases other than acute lymphoblastic leukemia (ALL) are sparse or lacking.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and Methods<\/jats:title><jats:p>A retrospective study of 98 pediatric patients was conducted to analyze the incidence of hyponatremia in a Caucasian cohort of newly diagnosed ALL. For comparison, we further examined five other pediatric oncological cohorts (Hodgkin\u2019s disease, Ewing sarcoma, Wilms tumor, benign glioma of the CNS, Langerhans cell histiocytosis) that receive alkaloids in their induction regimes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We found a high incidence of hyponatremia (14.7%) in our ALL cohort with a trend toward male patients of elementary school age. None of the affected patients showed neurological symptoms. By comparison, patients from other malignancy groups did not show significant hyponatremia, regardless of their comparable therapy with alkaloids. We here show a noticeable coincidence of hyponatremia and hypertriglyceridemia in ALL patients, indicating a possible role of L-asparaginase-related hypertriglyceridemia in the development of severe hyponatremia in such patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We report a higher incidence of hyponatremia following vincristine therapy in Caucasian children with ALL than published before. This hyponatremia could not be demonstrated in other oncologic cohorts treated with alkaloids. L-Asparaginase-induced hypertriglyceridemia may play a role in the certainly multifactorial development of hyponatremia in childhood leukemia.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fonc.2021.708875","type":"journal-article","created":{"date-parts":[[2021,10,29]],"date-time":"2021-10-29T06:32:07Z","timestamp":1635489127000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Hyponatremia During Induction Therapy in Distinct Pediatric Oncological Cohorts: A Retrospective Study"],"prefix":"10.3389","volume":"11","author":[{"given":"Christina","family":"Salvador","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert","family":"Salvador","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Willeit","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christine","family":"Kuntner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexandra","family":"Haid","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"M\u00fcller","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabriele","family":"Kropshofer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roman","family":"Crazzolara","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2021,10,29]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/j.critrevonc.2016.03.010","article-title":"Hyponatremia in Cancer Patients: Time for a New Approach","volume":"102","author":"Berardi","year":"2016","journal-title":"Crit Rev Oncol\/Hematol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1634\/theoncologist.2011-0400","article-title":"Diagnosis and Management of Hyponatremia in Cancer Patients","volume":"17","author":"Castillo","year":"2012","journal-title":"Oncologist"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1177\/0885066617706650","article-title":"Electrolyte Disturbances in Critically Ill Cancer Patients: An Endocrine Perspective","volume":"33","author":"Khan","year":"2018","journal-title":"J Intensive Care Med"},{"key":"B4","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1111\/j.1365-2796.1995.tb00907.x","article-title":"Syndrome of Inappropriate Secretion of Antidiuretic Hormone (SIADH) in Malignant Disease","volume":"238","author":"S\u00f8rensen","year":"1995","journal-title":"J Internal Med"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198405243102104","article-title":"Effective Treatment of Advanced Multiple Myeloma Refractory to Alkylating Agents","volume":"310","author":"Barlogie","year":"1984","journal-title":"New Engl J Med"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1007\/BF01788840","article-title":"Hyponatremia Related to Medical Anticancer Treatment","volume":"4","author":"Berghmans","year":"1996","journal-title":"Supportive Care Cancer"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9343(71)90244-0","article-title":"Inappropriate Secretion of Antidiuretic Hormone Secondary to Vincristine Therapy","volume":"51","author":"Cutting","year":"1971","journal-title":"Am J Med"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.3949\/ccjm.59.6.643","article-title":"Syndrome of Inappropriate Secretion of Antidiuretic Hormone After Infusional Vincristine","volume":"59","author":"Escuro","year":"1992","journal-title":"Cleveland Clinic J Med"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1001\/archpedi.1966.02090120124015","article-title":"Hyponatremia and Vincristine Therapy. Syndrome Possibly Resulting From Inappropriate Antidiuretic Hormone Secretion","volume":"112","author":"Fine","year":"1966","journal-title":"Am J Dis Children"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9343(67)90091-5","article-title":"Metabolism of Antidiuretic Hormones","volume":"42","author":"Lauson","year":"1967","journal-title":"Am J Med"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1007\/s00520-007-0309-9","article-title":"Diagnosis and Management of Hyponatremia in Cancer Patients","volume":"15","author":"Raftopoulos","year":"2007","journal-title":"Supportive Care Cancer"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1002\/jso.2930240322","article-title":"The Syndrome of Inappropriate ADH Secretion Secondary to Vinblastine-Bleomycin Therapy","volume":"24","author":"Ravikumar","year":"1983","journal-title":"J Surg Oncol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1001\/archinte.1973.03650110061013","article-title":"Vincristine Neurotoxicity and Abnormal Secretion of Antidiuretic Hormone","volume":"132","author":"Robertson","year":"1973","journal-title":"Arch Internal Med"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-80-6-733","article-title":"Vincristine Neurotoxicity","volume":"80","author":"Rosenthal","year":"1974","journal-title":"Ann Internal Med"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9343(57)90224-3","article-title":"A Syndrome of Renal Sodium Loss and Hyponatremia Probably Resulting From Inappropriate Secretion of Antidiuretic Hormone","volume":"23","author":"Schwartz","year":"1957","journal-title":"Am J Med"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(196901)23:1<122::AID-CNCR2820230114>3.0.CO;2-E","article-title":"Vincristine Neurotoxicity With Hyponatremia","volume":"23","author":"Slater","year":"1969","journal-title":"Cancer"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V45.3.315.315","article-title":"Syndrome of Recurrent Increased Secretion of Antidiuretic Hormone Following Multiple Doses of Vincristine","volume":"45","author":"Stuart","year":"1975","journal-title":"Blood"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(72)80381-0","article-title":"Syndrome of Inappropriate Secretion of Antidiuretic Hormone Produced by Vincristine Toxicity (With Bioassay of ADH Level)","volume":"81","author":"Suskind","year":"1972","journal-title":"J Pediatr"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1007\/BF00313556","article-title":"Syndrome of Inappropriate Secretion of Antidiuretic Hormone Caused by Vincristine Therapy: A Case Report of the Neuropathology","volume":"229","author":"Tomiwa","year":"1983","journal-title":"J Neurol"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1007\/BF03003183","article-title":"Life-Threatening Hyponatremia Caused by Vinblastine","volume":"5","author":"Zavagli","year":"1988","journal-title":"Med Oncol Tumor Pharmacother"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/37.3.331","article-title":"A Note on the Selective Toxicity of Vincristine Sulfate on Chick-Embryo Sensory Ganglia in Tissue Culture","volume":"37","author":"Burdman","year":"1966","journal-title":"J Natl Cancer Inst"},{"key":"B22","article-title":"Effect of Vincristine on the Rat Posterior Pituitary In Vitro","volume":"18","author":"Rufener","year":"1972","journal-title":"Neuro-Chirurgie"},{"key":"B23","volume-title":"2., Vollst\u00e4ndig \u00dcberarbeitete Auflage, Duale Reihe MLP, Thieme, Stuttgart, Tbl. 25.1, S. 967","author":"Sitzmann","year":""},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1097\/MPH.0000000000000758","article-title":"Severe Hyponatremia in a Single-Center Series of 84 Homogenously Treated Children With Acute Lymphoblastic Leukemia","volume":"39","author":"Janczar","year":"2017","journal-title":"J Pediatr Hematol\/Oncol"},{"key":"B25","article-title":"Higher Incidence of Syndrome of Inappropriate Antidiuretic Hormone Secretion During Induction Chemotherapy of Acute Lymphoblastic Leukemia in Indian Children","volume":"56","author":"Seetharam","year":"2019","journal-title":"Indian J Cancer"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.23536","article-title":"An Integrated Analysis of Hyponatremia in Cancer Patients Receiving Platinum-Based or Nonplatinum-Based Chemotherapy in Clinical Trials (JCOG1405-A)","volume":"9","author":"Ezoe","year":"2018","journal-title":"Oncotarget"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.17925\/EE.2020.16.2.122","article-title":"Anticancer Medications and Sodium Dysmetabolism","volume":"16","author":"Krishnamurthy","year":"2020","journal-title":"Eur Endocrinol"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0215(200002)9999:9999<::AID-IJC1048>3.0.CO;2-F","article-title":"Childhood Cancer Registrations in the Developing World: Still More Boys Than Girls","volume":"91","author":"Pearce","year":"2001","journal-title":"Int J Cancer"},{"key":"B29","article-title":"Vincristine-Induced Acute Life-Threatening Hyponatremia Resulting in Seizure and Coma","volume":"13","author":"Nagappa","year":"2009","journal-title":"Indian J Crit Care Med"},{"key":"B30","article-title":"Pseudohyponatremia in Multiple Myeloma","volume":"58","author":"Giri","year":"2010","journal-title":"J Assoc Phys India"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1373\/clinchem.2017.276501","article-title":"Atypical Pseudohyponatremia","volume":"64","author":"Girot","year":"2018","journal-title":"Clin Chem"},{"key":"B32","doi-asserted-by":"publisher","first-page":"77","DOI":"10.5049\/EBP.2006.4.2.77","article-title":"Pseudohyponatremia: Does it Matter in Current Clinical Practice","volume":"4","author":"Kim","year":"2006","journal-title":"Electrolyte Blood Pressure: E BP"},{"key":"B33","doi-asserted-by":"publisher","first-page":"31808","DOI":"10.3402\/jchimp.v6.31808","article-title":"Hypertriglyceridemic Pancreatitis Associated With Confounding Laboratory Abnormalities","volume":"6","author":"Melnick","year":"2016","journal-title":"J Community Hosp Internal Med Perspect"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.3109\/10428194.2011.596963","article-title":"Prevention and Management of Asparaginase\/Pegasparaginase-Associated Toxicities in Adults and Older Adolescents: Recommendations of an Expert Panel","volume":"52","author":"Stock","year":"2011","journal-title":"Leukemia Lymphoma"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacl.2018.05.021","article-title":"Combination Therapy of Omega-3 Fatty Acids and Acipimox for Children With Hypertriglyceridemia and Acute Lymphoblastic Leukemia","volume":"12","author":"Salvador","year":"2018","journal-title":"J Clin Lipidol"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2013.07.020","article-title":"Association Between Maintenance Fluid Tonicity and Hospital-Acquired Hyponatremia","volume":"163","author":"Carandang","year":"2013","journal-title":"J Pediatr"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2018-3083","article-title":"Clinical Practice Guideline: Maintenance Intravenous Fluids in Children","volume":"142","author":"Feld","year":"2018","journal-title":"Pediatrics"},{"key":"B38","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1016\/j.jpeds.2014.01.040","article-title":"Hypotonic Versus Isotonic Fluids in Hospitalized Children: A Systematic Review and Meta-Analysis","volume":"165","author":"Foster","year":"2014","journal-title":"J Pediatr"},{"key":"B39","doi-asserted-by":"publisher","first-page":"Cd009457","DOI":"10.1002\/14651858.CD009457.pub2","article-title":"Isotonic Versus Hypotonic Solutions for Maintenance Intravenous Fluid Administration in Children","volume":"2014","author":"McNab","year":"","journal-title":"Cochrane Database Syst Rev"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1412877","article-title":"Maintenance Intravenous Fluids in Acutely Ill Patients","volume":"373","author":"Moritz","year":"2015","journal-title":"New Engl J Med"},{"key":"B41","article-title":"Hyponatraemia Despite Isotonic Maintenance Fluid Therapy: A Time Series Intervention Study","volume":"106","author":"Chromek","year":"2020","journal-title":"Arch Dis Childhood"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1097\/MJT.0000000000000880","article-title":"Paralytic Ileus and Syndrome of Inappropriate Antidiuretic Hormone Secretion Potentially Due to an Interaction Between Vincristine and Voriconazole\/Posaconazole","volume":"26","author":"Castells","year":"2019","journal-title":"Am J Ther"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2257.1998.00103.x","article-title":"Severe Vincristine Toxicity in Combination With Itraconazole","volume":"20","author":"Gillies","year":"1998","journal-title":"Clin Lab Haematol"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1016\/S0268-960X(02)00042-5","article-title":"Endocrine Complications in Pediatric Patients With Acute Lymphoblastic Leukemia","volume":"16","author":"Howard","year":"2002","journal-title":"Blood Rev"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1111\/j.1439-0507.2011.02158.x","article-title":"Adverse Interactions Between Antifungal Azoles and Vincristine: Review and Analysis of Cases","volume":"55","author":"Moriyama","year":"2012","journal-title":"Mycoses"},{"key":"B46","doi-asserted-by":"publisher","first-page":"591","DOI":"10.1097\/00043426-200210000-00023","article-title":"Vincristine-Itraconazole Interaction: Cause for Increasing Concern","volume":"24","author":"Sathiapalan","year":"2002","journal-title":"J\u00a0Pediatr Hematol\/Oncol"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1111\/jcpt.12598","article-title":"Syndrome of Inappropriate Antidiuretic Hormone Secretion From Concomitant Use of Itraconazole and Vindesine","volume":"43","author":"Zhou","year":"2018","journal-title":"J\u00a0Clin Pharm Ther"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1111\/j.1651-2227.2001.tb03257.x","article-title":"Potentiation of Vincristine Toxicity by Itraconazole in Children With Lymphoid Malignancies","volume":"90","author":"Kamaluddin","year":"2001","journal-title":"Acta Paediatr (Oslo Norway: 1992)"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.22442","article-title":"Syndrome of Inappropriate Secretion of Antidiuretic Hormone as a Leading Cause of Hyponatremia in Children Who Underwent Chemotherapy or Stem Cell Transplantation","volume":"54","author":"Lim","year":"2010","journal-title":"Pediatr Blood Cancer"}],"container-title":["Frontiers in Oncology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2021.708875\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,10,29]],"date-time":"2021-10-29T06:32:16Z","timestamp":1635489136000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2021.708875\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,29]]},"references-count":49,"alternative-id":["10.3389\/fonc.2021.708875"],"URL":"https:\/\/doi.org\/10.3389\/fonc.2021.708875","relation":{},"ISSN":["2234-943X"],"issn-type":[{"value":"2234-943X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,29]]},"article-number":"708875"}}