An investigation of toxicities and survival in Hispanic children and adolescents with ALL

Results from the Dana-Farber Cancer Institute ALL Consortium protocol 05-001

Justine M. Kahn, Peter D. Cole, Traci M. Blonquist, Kristen Stevenson, Zhezhen Jin, Sergio Barrera, Randy Davila, Emily Roberts, Donna S. Neuberg, Uma H. Athale, Luis A. Clavell, Caroline Laverdiere, Jean Marie Leclerc, Bruno Michon, Marshall A. Schorin, Jennifer J.G. Welch, Stephen E. Sallan, Lewis B. Silverman, Kara M. Kelly

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Purpose: This study compared the relative incidence of treatment-related toxicities and the event-free and overall survival between Hispanic and non-Hispanic children undergoing therapy for acute lymphoblastic leukemia (ALL) on Dana-Farber Cancer Institute ALL Consortium protocol 05-001. Patients and methods: Secondary analysis of prospectively collected data from a phase III multicenter study in children and adolescents of 1-18 years with previously untreated ALL. Results: Between 2005 and 2011, 794 eligible patients enrolled on DFCI 05-001, 730 of whom were included in this analysis (19% [N = 150] Hispanic, 73% [N = 580] non-Hispanic). Hispanic patients were more likely to be ≥10 years of age (32% vs. 24%, P = 0.045) at diagnosis. Toxicity analyses revealed that Hispanic patients had significantly lower cumulative incidence of bone fracture (P < 0.001) and osteonecrosis (ON; P = 0.047). In multivariable risk regression, the risk of ON was significantly lower in Hispanic patients ≥10 years (HR 0.23; P = 0.006). Hispanic patients had significantly lower 5-year event-free survival (EFS) (79.4%; 95% CI: 71.6-85.2) and overall survival (OS) (89.2%; 95% CI: 82.7-93.4) than non-Hispanic patients (EFS: 87.5%; 95% CI: 84.5-90.0, P = 0.004; OS: 92.7%; 95% CI: 90.2-94.6, P = 0.006). Exploratory analyses revealed differences between Hispanic and non-Hispanic patients in the frequency of common variants in genes related to toxicity or ALL outcome. Conclusion: Hispanic children treated for ALL on DFCI 05-001 had fewer bone-related toxicities and inferior survival than non-Hispanic patients. While disease biology is one explanatory variable for outcome disparities, these findings suggest that biologic and non-biologic mechanisms affecting drug delivery and exposure in this population may be important contributing factors as well.

Original languageEnglish (US)
JournalPediatric Blood and Cancer
DOIs
StateAccepted/In press - 2017

Fingerprint

Precursor Cell Lymphoblastic Leukemia-Lymphoma
Hispanic Americans
Survival
Neoplasms
Disease-Free Survival
Osteonecrosis
Bone Fractures
Incidence
Multicenter Studies
Bone and Bones
Therapeutics
Pharmaceutical Preparations
Population
Genes

Keywords

  • Acute lymphoblastic leukemia
  • Ethnicity
  • Hispanic
  • Outcomes
  • Survival
  • Toxicities

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Hematology
  • Oncology

Cite this

An investigation of toxicities and survival in Hispanic children and adolescents with ALL : Results from the Dana-Farber Cancer Institute ALL Consortium protocol 05-001. / Kahn, Justine M.; Cole, Peter D.; Blonquist, Traci M.; Stevenson, Kristen; Jin, Zhezhen; Barrera, Sergio; Davila, Randy; Roberts, Emily; Neuberg, Donna S.; Athale, Uma H.; Clavell, Luis A.; Laverdiere, Caroline; Leclerc, Jean Marie; Michon, Bruno; Schorin, Marshall A.; Welch, Jennifer J.G.; Sallan, Stephen E.; Silverman, Lewis B.; Kelly, Kara M.

In: Pediatric Blood and Cancer, 2017.

Research output: Contribution to journalArticle

Kahn, JM, Cole, PD, Blonquist, TM, Stevenson, K, Jin, Z, Barrera, S, Davila, R, Roberts, E, Neuberg, DS, Athale, UH, Clavell, LA, Laverdiere, C, Leclerc, JM, Michon, B, Schorin, MA, Welch, JJG, Sallan, SE, Silverman, LB & Kelly, KM 2017, 'An investigation of toxicities and survival in Hispanic children and adolescents with ALL: Results from the Dana-Farber Cancer Institute ALL Consortium protocol 05-001', Pediatric Blood and Cancer. https://doi.org/10.1002/pbc.26871
Kahn, Justine M. ; Cole, Peter D. ; Blonquist, Traci M. ; Stevenson, Kristen ; Jin, Zhezhen ; Barrera, Sergio ; Davila, Randy ; Roberts, Emily ; Neuberg, Donna S. ; Athale, Uma H. ; Clavell, Luis A. ; Laverdiere, Caroline ; Leclerc, Jean Marie ; Michon, Bruno ; Schorin, Marshall A. ; Welch, Jennifer J.G. ; Sallan, Stephen E. ; Silverman, Lewis B. ; Kelly, Kara M. / An investigation of toxicities and survival in Hispanic children and adolescents with ALL : Results from the Dana-Farber Cancer Institute ALL Consortium protocol 05-001. In: Pediatric Blood and Cancer. 2017.
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abstract = "Purpose: This study compared the relative incidence of treatment-related toxicities and the event-free and overall survival between Hispanic and non-Hispanic children undergoing therapy for acute lymphoblastic leukemia (ALL) on Dana-Farber Cancer Institute ALL Consortium protocol 05-001. Patients and methods: Secondary analysis of prospectively collected data from a phase III multicenter study in children and adolescents of 1-18 years with previously untreated ALL. Results: Between 2005 and 2011, 794 eligible patients enrolled on DFCI 05-001, 730 of whom were included in this analysis (19{\%} [N = 150] Hispanic, 73{\%} [N = 580] non-Hispanic). Hispanic patients were more likely to be ≥10 years of age (32{\%} vs. 24{\%}, P = 0.045) at diagnosis. Toxicity analyses revealed that Hispanic patients had significantly lower cumulative incidence of bone fracture (P < 0.001) and osteonecrosis (ON; P = 0.047). In multivariable risk regression, the risk of ON was significantly lower in Hispanic patients ≥10 years (HR 0.23; P = 0.006). Hispanic patients had significantly lower 5-year event-free survival (EFS) (79.4{\%}; 95{\%} CI: 71.6-85.2) and overall survival (OS) (89.2{\%}; 95{\%} CI: 82.7-93.4) than non-Hispanic patients (EFS: 87.5{\%}; 95{\%} CI: 84.5-90.0, P = 0.004; OS: 92.7{\%}; 95{\%} CI: 90.2-94.6, P = 0.006). Exploratory analyses revealed differences between Hispanic and non-Hispanic patients in the frequency of common variants in genes related to toxicity or ALL outcome. Conclusion: Hispanic children treated for ALL on DFCI 05-001 had fewer bone-related toxicities and inferior survival than non-Hispanic patients. While disease biology is one explanatory variable for outcome disparities, these findings suggest that biologic and non-biologic mechanisms affecting drug delivery and exposure in this population may be important contributing factors as well.",
keywords = "Acute lymphoblastic leukemia, Ethnicity, Hispanic, Outcomes, Survival, Toxicities",
author = "Kahn, {Justine M.} and Cole, {Peter D.} and Blonquist, {Traci M.} and Kristen Stevenson and Zhezhen Jin and Sergio Barrera and Randy Davila and Emily Roberts and Neuberg, {Donna S.} and Athale, {Uma H.} and Clavell, {Luis A.} and Caroline Laverdiere and Leclerc, {Jean Marie} and Bruno Michon and Schorin, {Marshall A.} and Welch, {Jennifer J.G.} and Sallan, {Stephen E.} and Silverman, {Lewis B.} and Kelly, {Kara M.}",
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T1 - An investigation of toxicities and survival in Hispanic children and adolescents with ALL

T2 - Results from the Dana-Farber Cancer Institute ALL Consortium protocol 05-001

AU - Kahn, Justine M.

AU - Cole, Peter D.

AU - Blonquist, Traci M.

AU - Stevenson, Kristen

AU - Jin, Zhezhen

AU - Barrera, Sergio

AU - Davila, Randy

AU - Roberts, Emily

AU - Neuberg, Donna S.

AU - Athale, Uma H.

AU - Clavell, Luis A.

AU - Laverdiere, Caroline

AU - Leclerc, Jean Marie

AU - Michon, Bruno

AU - Schorin, Marshall A.

AU - Welch, Jennifer J.G.

AU - Sallan, Stephen E.

AU - Silverman, Lewis B.

AU - Kelly, Kara M.

PY - 2017

Y1 - 2017

N2 - Purpose: This study compared the relative incidence of treatment-related toxicities and the event-free and overall survival between Hispanic and non-Hispanic children undergoing therapy for acute lymphoblastic leukemia (ALL) on Dana-Farber Cancer Institute ALL Consortium protocol 05-001. Patients and methods: Secondary analysis of prospectively collected data from a phase III multicenter study in children and adolescents of 1-18 years with previously untreated ALL. Results: Between 2005 and 2011, 794 eligible patients enrolled on DFCI 05-001, 730 of whom were included in this analysis (19% [N = 150] Hispanic, 73% [N = 580] non-Hispanic). Hispanic patients were more likely to be ≥10 years of age (32% vs. 24%, P = 0.045) at diagnosis. Toxicity analyses revealed that Hispanic patients had significantly lower cumulative incidence of bone fracture (P < 0.001) and osteonecrosis (ON; P = 0.047). In multivariable risk regression, the risk of ON was significantly lower in Hispanic patients ≥10 years (HR 0.23; P = 0.006). Hispanic patients had significantly lower 5-year event-free survival (EFS) (79.4%; 95% CI: 71.6-85.2) and overall survival (OS) (89.2%; 95% CI: 82.7-93.4) than non-Hispanic patients (EFS: 87.5%; 95% CI: 84.5-90.0, P = 0.004; OS: 92.7%; 95% CI: 90.2-94.6, P = 0.006). Exploratory analyses revealed differences between Hispanic and non-Hispanic patients in the frequency of common variants in genes related to toxicity or ALL outcome. Conclusion: Hispanic children treated for ALL on DFCI 05-001 had fewer bone-related toxicities and inferior survival than non-Hispanic patients. While disease biology is one explanatory variable for outcome disparities, these findings suggest that biologic and non-biologic mechanisms affecting drug delivery and exposure in this population may be important contributing factors as well.

AB - Purpose: This study compared the relative incidence of treatment-related toxicities and the event-free and overall survival between Hispanic and non-Hispanic children undergoing therapy for acute lymphoblastic leukemia (ALL) on Dana-Farber Cancer Institute ALL Consortium protocol 05-001. Patients and methods: Secondary analysis of prospectively collected data from a phase III multicenter study in children and adolescents of 1-18 years with previously untreated ALL. Results: Between 2005 and 2011, 794 eligible patients enrolled on DFCI 05-001, 730 of whom were included in this analysis (19% [N = 150] Hispanic, 73% [N = 580] non-Hispanic). Hispanic patients were more likely to be ≥10 years of age (32% vs. 24%, P = 0.045) at diagnosis. Toxicity analyses revealed that Hispanic patients had significantly lower cumulative incidence of bone fracture (P < 0.001) and osteonecrosis (ON; P = 0.047). In multivariable risk regression, the risk of ON was significantly lower in Hispanic patients ≥10 years (HR 0.23; P = 0.006). Hispanic patients had significantly lower 5-year event-free survival (EFS) (79.4%; 95% CI: 71.6-85.2) and overall survival (OS) (89.2%; 95% CI: 82.7-93.4) than non-Hispanic patients (EFS: 87.5%; 95% CI: 84.5-90.0, P = 0.004; OS: 92.7%; 95% CI: 90.2-94.6, P = 0.006). Exploratory analyses revealed differences between Hispanic and non-Hispanic patients in the frequency of common variants in genes related to toxicity or ALL outcome. Conclusion: Hispanic children treated for ALL on DFCI 05-001 had fewer bone-related toxicities and inferior survival than non-Hispanic patients. While disease biology is one explanatory variable for outcome disparities, these findings suggest that biologic and non-biologic mechanisms affecting drug delivery and exposure in this population may be important contributing factors as well.

KW - Acute lymphoblastic leukemia

KW - Ethnicity

KW - Hispanic

KW - Outcomes

KW - Survival

KW - Toxicities

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DO - 10.1002/pbc.26871

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