Hyponatremia During Induction Therapy in Distinct Pediatric Oncological Cohorts: A Retrospective Study

Abstract

Background: 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.

Materials and methods: 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's disease, Ewing sarcoma, Wilms tumor, benign glioma of the CNS, Langerhans cell histiocytosis) that receive alkaloids in their induction regimes.

Results: 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.

Conclusion: 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.

Keywords: alkaloids; children; hyponatremia; leukemia; triglycerides; vincristine.

Figure 1

Induction therapy protocols using vincristine or vinblastine: (A) ALL cohort: ALL-BFM 2009 (Protocol I, induction), (B) Hodgkin’s cohort: EuroNet-PHL-C2 protocol and GPOH Register (OEPA scheme), (C) Ewing sarcoma cohort: EuroEWING 2008 (VIDE cycle), (D) Wilms tumor cohort: SIOP 2001 Wilms and SIOP 2014 Wilms Register (preoperative chemotherapy), (E) benign CNS glioma cohort: SIOP-LGG 2004, and (F) Langerhans cell histiocytosis cohort: LCH-III and LCH-IV protocol.

Figure 2

(A) Prevalence of hyponatremia in the studied ALL cohort: a considerable group of ALL patients showed statistically significant hyponatremia during induction therapy (solid line, ± standard deviation) compared to the rest of the ALL cohort (dashed line), which remained within the standard range of sodium in childhood (132–145 mmol/l). The start of the first hyponatremic episode was on average between days 27 and 28 (average day 27.6, curly brackets), although there was a statistically significant difference between hyponatremic and non-hyponatremic patients from day 12 (p = 0.014, F test and T test, curly brackets). (B) Mean sodium levels of all patients with the following diagnoses during the first 40 days of their initial therapy. Patients with Hodgkin’s lymphoma, Ewing sarcoma, Wilms tumor, benign brain tumors, and Langerhans cell histiocytosis do not show hyponatremia during therapy with alkaloids (sodium levels within standard range).