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Volume-Outcome Relationships in Pediatric Acute Lymphoblastic Leukemia: Association Between Hospital Pediatric and Pediatric Oncology Volume With Mortality and Intensive Care Resources During Initial Therapy.

ABSTRACT: BACKGROUND:There are few contemporary studies of volume-outcome relationships in pediatric oncology. Children with acute lymphoblastic leukemia (ALL) are treated at a wide variety of hospitals. We investigated if inpatient hospital volume influences outcomes. The objective of this study was to evaluate the relationship between inpatient pediatric and pediatric oncology volume and mortality and intensive care resources (ICU care). We hypothesized an inverse relationship between volume and these outcomes. PATIENTS AND METHODS:This was a retrospective cohort study. Patients 0 to 18 years of age in the Pediatric Health Information System or Perspective Premier Database from 2009 to 2011 with ALL were included. Exposures were considered as the average inpatient pediatric and pediatric oncology volume. The primary outcome was inpatient mortality; secondary outcome was need for ICU care. RESULTS:The included population comprised 3350 patients from 75 hospitals. The inpatient mortality rate was 0.86% (95% confidence interval, 0.58%-1.2%). In the unadjusted analysis, mortality increased as pediatric oncology volume increased from low (0%) to high volume (1.3%) (P = .009). The small number of deaths precluded multivariable analysis of this outcome. Pediatric and pediatric oncology volume was not associated with ICU care when we controlled for potential confounders. CONCLUSION:Induction mortality was low. We did not observe an inverse relationship between volume and mortality or ICU care. This suggests that in a modern treatment era, treatment at a low-volume center might not be associated with increased mortality or ICU care in the first portion of therapy. This relationship should be evaluated in other oncology populations with higher mortality rates and with longer-term outcomes.

SUBMITTER: Wilkes JJ

PROVIDER: S-EPMC4925172 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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Volume-Outcome Relationships in Pediatric Acute Lymphoblastic Leukemia: Association Between Hospital Pediatric and Pediatric Oncology Volume With Mortality and Intensive Care Resources During Initial Therapy.

Wilkes Jennifer J JJ Hennessy Sean S Xiao Rui R Rheingold Susan S Seif Alix E AE Huang Yuan-Shung YS Vendetti Neika N Li Yimei Y Bagatell Rochelle R Aplenc Richard R Fisher Brian T BT

Clinical lymphoma, myeloma & leukemia 20160504 7

<h4>Background</h4>There are few contemporary studies of volume-outcome relationships in pediatric oncology. Children with acute lymphoblastic leukemia (ALL) are treated at a wide variety of hospitals. We investigated if inpatient hospital volume influences outcomes. The objective of this study was to evaluate the relationship between inpatient pediatric and pediatric oncology volume and mortality and intensive care resources (ICU care). We hypothesized an inverse relationship between volume and ...[more]

PMID: 27246140

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Project description:BackgroundContinuous complete clinical remission in T-cell acute lymphoblastic leukemia (T-ALL) is now approaching 80% due to the implementation of aggressive chemotherapy protocols but patients that relapse continue to have a poor prognosis. Such patients could benefit from augmented therapy if their clinical outcome could be more accurately predicted at the time of diagnosis. Gene expression profiling offers the potential to identify additional prognostic markers but has had limited success in generating robust signatures that predict outcome across multiple patient cohorts. This study aimed to identify robust gene classifiers that could be used for the accurate prediction of relapse in independent cohorts and across different experimental platforms.ResultsUsing HG-U133Plus2 microarrays we modeled a five-gene classifier (5-GC) that accurately predicted clinical outcome in a cohort of 50 T-ALL patients. The 5-GC was further tested against three independent cohorts of T-ALL patients, using either qRT-PCR or microarray gene expression, and could predict patients with significantly adverse clinical outcome in each. The 5-GC featured the interleukin-7 receptor (IL-7R), low-expression of which was independently predictive of relapse in T-ALL patients. In T-ALL cell lines, low IL-7R expression was correlated with diminished growth response to IL-7 and enhanced glucocorticoid resistance. Analysis of biological pathways identified the NF-kappaB and Wnt pathways, and the cell adhesion receptor family (particularly integrins) as being predictive of relapse. Outcome modeling using genes from these pathways identified patients with significantly worse relapse-free survival in each T-ALL cohort.ConclusionsWe have used two different approaches to identify, for the first time, robust gene signatures that can successfully discriminate relapse and CCR patients at the time of diagnosis across multiple patient cohorts and platforms. Such genes and pathways represent markers for improved patient risk stratification and potential targets for novel T-ALL therapies.

Project description:Background and objective Philadelphia chromosome-positive acute lymphoblastic leukemia (ALL Ph+) is quite rare among pediatric patients. Its management has undergone significant changes in the past few years, leading to some variability in how it is approached. At the Portuguese Oncology Institute of Porto (IPOP), a tertiary oncological center, the standard of care has been aligned with the guidelines proposed by the European intergroup study of post-induction treatment of ALL Ph+ (EsPhALL). In this study, we aimed to examine the experience and outcomes related to the treatment of pediatric patients with ALL Ph+ at IPOP. Methods This retrospective cohort study involved pediatric patients diagnosed with ALL Ph+ at IPOP between January 2008 and December 2022 and analyzed their outcomes. Results A total of 14 patients were included. IKFZ1 was altered in five patients (out of nine in whom it was searched). Five patients were treated according to EsPhALL 2004, which involved starting imatinib later in a discontinuous manner [resulting in both five-year overall survival (OS) and progression-free survival (PFS) of 60%]. The EsPhALL 2010 (preconizing a continuous imatinib regimen instead) was employed in three patients, with a five-year OS and PFS of 66.7%. All children mentioned above received cranial irradiation therapy (CRT). Finally, six were treated according to the EsPhALL 2015, which stopped including CRT in its backbone. The five-year OS was 100%, whereas every patient progressed with an increase in BCR::ABL1 levels greater than 1-log. Moreover, until 2015, all patients had been recommended to undergo allogeneic hematopoietic stem cell transplantation (alloHSCT). However, since 2015, alloHSCT has been exclusively reserved for relapsed/refractory (R/R) disease or poor responders with positive measurable residual disease (MRD). In total, alloHSCT was performed in nine patients. Conclusions Although initially associated with a poor prognosis, the ALL Ph+ paradigm is drastically shifting. Further studies will hopefully clarify the outcomes in this population and help understand the role of central nervous system (CNS) prophylaxis, alloHSCT, and MRD quantification.

Dataset Information

Volume-Outcome Relationships in Pediatric Acute Lymphoblastic Leukemia: Association Between Hospital Pediatric and Pediatric Oncology Volume With Mortality and Intensive Care Resources During Initial Therapy.

Publications

Volume-Outcome Relationships in Pediatric Acute Lymphoblastic Leukemia: Association Between Hospital Pediatric and Pediatric Oncology Volume With Mortality and Intensive Care Resources During Initial Therapy.

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