Malglycemia is associated with poor outcomes in pediatric and adolescent hematopoietic stem cell transplant patients

Abstract

Malglycemia (hypoglycemia, hyperglycemia, and/or glycemic variability) in adult hematopoietic stem cell transplant (HSCT) recipients is associated with increased infection, graft-versus-host disease, organ dysfunction, delayed engraftment, and mortality. Malglycemia has not been studied in pediatric HSCT recipients. This study aimed to characterize the incidence and consequences of malglycemia in this population. Medical records for a cohort of 344 patients, age 0 to 30 years, who underwent first HSCT from 2007 to 2016 at Children’s Hospital Colorado were retrospectively reviewed. Glucose data were analyzed in intervals and assessed for potential risk factors and associated outcomes. Malglycemia occurred in 43.9% of patients. Patients with a day 0 to 100 mean glucose of 100 to 124 mg/dL had a 1.76-fold (95% confidence interval [CI], 1.10-2.82; P = .02) increased risk of death and patients with a day 0 to 100 mean glucose ≥ 125 mg/dL had a 7.06-fold (95% CI, 3.84-12.99; P < .0001) increased risk of death compared with patients with a day 0 to 100 mean glucose < 100 mg/dL. For each 10 mg/dL increase in pre-HSCT glucose, there was a 1.11-fold (95% CI, 1.04-1.18; P = .0013) increased risk of post-HSCT infection. These adverse impacts of malglycemia occurred independent of transplant type, graft-versus-host disease, and steroid therapy. Malglycemia in the pediatric HSCT population is independently associated with significantly increased risk of morbidity and mortality. Further research is required to evaluate the utility of glucose control to mitigate these relationships and improve HSCT outcomes. This trial was registered at www.clinicaltrials.gov as #NCT03482154.

Glycemic variability is associated with poor outcomes in pediatric hematopoietic stem cell transplant patients

“…This retrospective cohort study demonstrates that glycemic variability, as measured by CV, is common in pediatric patients undergoing HSCT, and that it is associated with increased risk of infection and critical illness. These associations are consistent with research describing malglycemia as a whole, both in adult and pediatric HSCT patients 1‐3 . Associations between glucose CV and mortality were less clear.…”

“…It is possible that patients with malignant underlying diagnoses were more tolerant of the stress associated with HSCT preparation due to their prior treatment with chemotherapy, while for nonmalignant HSCT patients, HSCT preparation may have been more disruptive. While our prior research evaluating risk factors for pre‐HSCT malglycemia identified underlying malignant diagnosis and adolescent age as risk factors, these were not associated with pre‐HSCT glucose CV; thus, these findings were likely driven by hyperglycemia and not variability 3 …”

“…Malglycemia, defined as hypoglycemia (blood glucose <70 mg/dL), hyperglycemia (blood glucose≥126 mg/dL), or glycemic variability (standard deviation [SD] ≥29 mg/dL), is associated with adverse outcomes in various adult and pediatric populations, such as those in intensive care units (ICUs) 1,2 . In a prior study, pediatric HSCT patients showed increased risk of mortality and infection, longer hospital stays and more ICU days in association with malglycemia and higher mean glucose 3 . The most common form of malglycemia was glycemic variability (based on the above definition), occurring in 24.1% of patients pre‐HSCT.…”

New‐onset posttransplant diabetes mellitus after haploidentical hematopoietic cell transplantation with posttransplant cyclophosphamide

“…Although further research is required to validate, our proposed model of inflammation-induced PTDM is outlined in Figure S2. (Table S2) [1,2,5,6,12,16]. With the clinical importance now established, it is time to shift focus from examining the incidence of PTDM, and begin to study the mechanistic causes for hyperglycemia and potential therapeutic options to prevent or treat metabolic complications after HCT.…”

“…The development of PTDM was independent of corticosteroids and was associated with a decrease in OS and DFS. At least two other prospective and several retrospective studies have confirmed the high incidence and negative consequences of PTDM after HCT (Table S2) [1,2,5,6,12,16]. With the clinical importance now established, it is time to shift focus from examining the incidence of PTDM, and begin to study the mechanistic causes for hyperglycemia and potential therapeutic options to prevent or treat metabolic complications after HCT.…”