Infection-related complications during treatment for childhood acute lymphoblastic leukemia

Inaba, Hiroto; D, Pei; Wolf, Joshua; Howard, Scott C.; Hayden, Randall T.; Go, McDONALD; Varechtchouk, Olga; Hahn, Theresa; Buaboonnam, Jassada; Metzger, Monika L.; Rubnitz, Jeffrey E.; Ribeiro, Raul C.; Sandlund, John T.; Jeha, Sima; Cheng, C.; Evans, William E.; Relling, Mary V.; Pui, Ching‐Hon

doi:10.1093/annonc/mdw557

Cited by 134 publications

(158 citation statements)

References 21 publications

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“…There was a significant association between bacteremia and subsequent development of symptomatic osteonecrosis (≥ grade 2 by CTCAE v.3): 29% (20/68) of patients with bacteremia developed symptomatic osteonecrosis versus 18% (54/297) of patients without bacteremia (OR: 1.88; 95% CI, 1.03–3.41, P = 0.038) (Figure ). This association remained significant after adjustment for race and gender ( P = 0.047), which had been associated with bacteremia, although not ( P = 0.087) after additional adjustment to include age, a known risk factor for osteonecrosis. Though most patients with bacteremia had only one documented episode, an increased number of episodes of bacteremia was associated with development of symptomatic osteonecrosis ( P = 0.0073): 8.1% (6/74) of patients with symptomatic osteonecrosis (≥ grade 2) had > 1 episode of bacteremia versus 1.4% (4/291) of patients without symptomatic osteonecrosis (< grade 2).…”

Section: Resultsmentioning

confidence: 93%

“…A retrospective analysis investigating the association between osteonecrosis and bacteremia was performed on patients with ALL ( n = 498) treated on the Total XV (TXV) study from June 2000 to October 2010 at St. Jude Children's Research Hospital . Risk classification and treatment regimens and use of antibiotics have been described elsewhere . Patients ( n = 365) were prospectively screened by magnetic resonance imaging (MRI) of the hips and knees (after reinduction I [weeks 7–9] and II [weeks 17–19] of continuation therapy and at the completion of therapy); additional joints may have been evaluated by MRI on a clinical basis depending on symptoms.…”

Section: Methodsmentioning

confidence: 99%

“…Infection is one of the most common therapy‐related causes of morbidity and mortality in pediatric patients with ALL due to therapy‐related immunosuppression and myelosuppression. Infection remains the most common cause of treatment‐related mortality; a retrospective analysis of the UKALL2003 cohort identified bacterial infections as the most common cause of death .…”

Section: Introductionmentioning

confidence: 99%

“…Older age and higher glucocorticoid exposure are two risk factors consistently associated with osteonecrosis in children with ALL. 3 Infection is one of the most common therapy-related causes of morbidity and mortality in pediatric patients with ALL [12][13][14][15] due to therapyrelated immunosuppression and myelosuppression. Infection remains F I G U R E 1 Dexamethasone and lipopolysaccharide treatment regimens.…”

Section: Introductionmentioning

confidence: 99%

“…12 Likewise, in our recent retrospective study, bacteremia was the most common microbiologically documented infection. 13 Infections are most common during the induction phase of therapy, which includes glucocorticoids. 13,15,19,20 Although severe infections are known to cause end-organ damage, the effect on bone has not been previously studied in patients with ALL.…”

Section: Introductionmentioning

confidence: 99%

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Bloodstream infections exacerbate incidence and severity of symptomatic glucocorticoid‐induced osteonecrosis

Finch

Janke

Smith

et al. 2019

Pediatric Blood & Cancer

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Background Osteonecrosis is a common toxicity associated with glucocorticoid (e.g., dexamethasone and prednisone) treatment of children with acute lymphoblastic leukemia (ALL), but risk factors are incompletely defined. Infections are also a common complication of ALL therapy. Lipopolysaccharide (LPS) is used experimentally to mimic infection‐related systemic effects. To our knowledge, the contribution of systemic infections to the risk of glucocorticoid‐induced osteonecrosis has not been investigated. Procedure Patients with ALL on St. Jude Total Therapy XV (n = 365) were assessed for documented bacteremia prior to development of osteonecrosis, which was confirmed by MRI, and graded using the National Cancer Institute's Common Terminology for Adverse Events (version 3.0). In a preclinical model, Balb/cJ mice treated with dexamethasone plus or minus LPS were assessed for frequency and severity of osteonecrosis and arteriopathy. Results We found that patients with ALL who experienced bacteremia had a higher frequency of symptomatic osteonecrosis (≥grade 2) than those who did not (OR: 1.88; 95% CI, 1.03–3.41, P = 0.038). LPS exacerbated experimental dexamethasone‐induced osteonecrosis. Mice treated with dexamethasone plus LPS had a higher incidence of osteonecrosis (P = 0.00086) and arteriopathy (P = 0.0047) than did those treated with dexamethasone alone, and the severity of osteonecrosis (P = 0.00045) and arteriopathy (P = 0.0048) was also more pronounced with the addition of LPS treatment. The increase in osteonecrosis was not explained by any alteration of dexamethasone pharmacokinetics by LPS. Conclusions These data identify systemic infection during ALL therapy as a novel risk factor in the development of glucocorticoid‐induced osteonecrosis.

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Section: Resultsmentioning

confidence: 93%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Bloodstream infections exacerbate incidence and severity of symptomatic glucocorticoid‐induced osteonecrosis

Finch

Janke

Smith

et al. 2019

Pediatric Blood & Cancer

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Evaluation of Plasma Microbial Cell-Free DNA Sequencing to Predict Bloodstream Infection in Pediatric Patients With Relapsed or Refractory Cancer

et al. 2020

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IMPORTANCE Bloodstream infection (BSI) is a common, life-threatening complication of treatment for cancer. Predicting BSI before onset of clinical symptoms would enable preemptive therapy, but there is no reliable screening test. OBJECTIVE To estimate sensitivity and specificity of plasma microbial cell-free DNA sequencing (mcfDNA-seq) for predicting BSI in patients at high risk of life-threatening infection. DESIGN, SETTING, AND PARTICIPANTSA prospective pilot cohort study of mcfDNA-seq for predicting BSI in pediatric patients (<25 years of age) with relapsed or refractory cancers at St Jude Children's Research Hospital, a specialist quaternary pediatric hematology-oncology referral center. Remnant clinical blood samples were collected during chemotherapy and hematopoietic cell transplantation. Samples collected during the 7 days before and at onset of BSI episodes, along with negative control samples from study participants, underwent blinded testing using a mcfDNA-seq test in a Clinical Laboratory Improvement Amendments/College of American Pathologists-approved laboratory. MAIN OUTCOMES AND MEASURESThe primary outcomes were sensitivity of mcfDNA-seq for detecting a BSI pathogen during the 3 days before BSI onset and specificity of mcfDNA-seq in the absence of fever or infection in the preceding or subsequent 7 days. RESULTS Between August 9, 2017, and June 4, 2018, 47 participants (27 [57%] male; median age [IQR], 10 [5-14] years) were enrolled; 19 BSI episodes occurred in 12 participants, and predictive samples were available for 16 episodes, including 15 bacterial BSI episodes. In the 3 days before the onset of infection, predictive sensitivity of mcfDNA-seq was 75% for all BSIs (12 of 16; 95% CI, 51%-90%) and 80% (12 of 15; 95% CI, 55%-93%) for bacterial BSIs. The specificity of mcfDNA-seq, evaluated on 33 negative control samples from enrolled participants, was 82% (27 of 33; 95% CI, 66%-91%) for any bacterial or fungal organism and 91% (30 of 33; 95% CI, 76%-97%) for any common BSI pathogen, and the concentration of pathogen DNA was lower in control than predictive samples. CONCLUSIONS AND RELEVANCEA clinically relevant pathogen can be identified by mcfDNA-seq days before the onset of BSI in a majority of episodes, potentially enabling preemptive treatment. Clinical application appears feasible pending further study. TRIAL REGISTRATION ClinicalTrials.gov identifier: NCT03226158JAMA Oncol.

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Medication errors in a cohort of pediatric patients with acute lymphoblastic leukemia on remission induction therapy in a tertiary care hospital in Mexico

et al. 2019

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Introduction Medication errors (MEs) are the main type of preventable adverse events in medical care, as well as safety indicators in the medication processes. Advances in the quality of care in pediatric acute lymphoblastic leukemia (ALL) have enabled to improve clinical outcomes. However, ME epidemiology in pediatric oncology is still incipient in developing countries. In view of this, the objectives of this study were to estimate the incidence of MEs, determine their types and consequences, as well as their preventability in the induction treatment of children with ALL at Hospital Infantil de Mexico Federico Gómez. Methods We reviewed the remission‐induction chemotherapy records of children with ALL between January 2015 and December 2017. A two‐phase review was carried out for ME identification and verification. The consequences of errors were determined by agreement between reviewers. Results We reviewed 1762 chemotherapy orders involving 181 children. MEs were observed in 16.9% of orders and in 57.5% of patients. Prescription errors were the most common (93.3%), with wrong dose errors (90.2%) being predominant. Only 3.7% of wrong dose errors were intercepted, while 12.2% of the children experienced adverse drug events (ADEs) preceded by some wrong dose error. Conclusions MEs were common, since they occurred in 57.5% of children with ALL on induction treatment and involved 16.5% of chemotherapy orders. Only 3.7% of MEs were intercepted, while 12.2% of children had ADEs related to overdose. Measures are required to prevent calculation error in prescriptions, as well as training of the nursing staff to intercept MEs.

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Infection-related complications during treatment for childhood acute lymphoblastic leukemia

Cited by 134 publications

References 21 publications

Bloodstream infections exacerbate incidence and severity of symptomatic glucocorticoid‐induced osteonecrosis

Bloodstream infections exacerbate incidence and severity of symptomatic glucocorticoid‐induced osteonecrosis

Evaluation of Plasma Microbial Cell-Free DNA Sequencing to Predict Bloodstream Infection in Pediatric Patients With Relapsed or Refractory Cancer

Medication errors in a cohort of pediatric patients with acute lymphoblastic leukemia on remission induction therapy in a tertiary care hospital in Mexico

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