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 language | English (US) |
|---|---|
| Journal | Pediatric Blood and Cancer |
| DOIs | |
| State | Accepted/In press - 2017 |
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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 journal › Article
}
TY - JOUR
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
UR - http://www.scopus.com/inward/record.url?scp=85032811944&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85032811944&partnerID=8YFLogxK
U2 - 10.1002/pbc.26871
DO - 10.1002/pbc.26871
M3 - Article
AN - SCOPUS:85032811944
JO - Pediatric Blood and Cancer
JF - Pediatric Blood and Cancer
SN - 1545-5009
ER -