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
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...
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| Veröffentlicht in: | Pediatric blood & cancer 2018-03, Vol.65 (3), p.n/a |
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| creator | 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. |
| description | 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 |
| doi_str_mv | 10.1002/pbc.26871 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5766393</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1986702349</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4431-a1b425b1738b95ac4f5814407caf134884eb38d5008f398265e17e0cd0c5d0d93</originalsourceid><addsrcrecordid>eNp1kcFu1DAQhi0EoqXlwAsgS5w4bDuO7cThgLQNLa20EqiCs-U4TtdV1g62s6W3PkLfo2_Fk-DtlhUcOI1lf_P_4_kRekPgiAAUx2Orj4pSVOQZ2iec8RkHUj3fnaHeQ69ivM5oCVy8RHtFDTXwAvbRw9xh69YmJnulkvUO-x4n_9Nqm6yJWLkOxyms7VoNGcTnNo7KWY310g5dMO6RUJ0fTNTGpYhvbFri-WLxAV-aOA35pg9-hdPS4E_KqV9392cqtCbgRjmdy4XL3mlKZtOEG--iD8lOKzwGn7z2AwaemwDIIXrRqyGa10_1AH0_O_3WnM8WXz5fNPPFTDNGyUyRlhW8JRUVbc2VZj0XhDGotOoJZUIw01LR5b2IntaiKLkhlQHdgeYddDU9QB-3uuPUrky3-VZQgxyDXalwK72y8t8XZ5fyyq8lr8qS1jQLvHsSCP7HlHcrr_0UXJ5ZklqUFRSUbWzebykdfIzB9DsHAnKTq8y5ysdcM_v275F25J8gM3C8BW7sYG7_ryS_njRbyd-o_7CO</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1986702349</pqid></control><display><type>article</type><title>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</title><source>Wiley Online Library Journals Frontfile Complete</source><creator>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.</creator><creatorcontrib>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.</creatorcontrib><description>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.</description><identifier>ISSN: 1545-5009</identifier><identifier>EISSN: 1545-5017</identifier><identifier>DOI: 10.1002/pbc.26871</identifier><identifier>PMID: 29090520</identifier><language>eng</language><publisher>United States: Wiley Subscription Services, Inc</publisher><subject>Acute lymphoblastic leukemia ; Adolescents ; Cancer ; Children ; Consortia ; Drug delivery ; ethnicity ; Hematology ; Hispanic ; Hispanic people ; Incidence ; Language proficiency ; Leukemia ; Lymphatic leukemia ; Oncology ; Osteonecrosis ; outcomes ; Pediatrics ; Secondary analysis ; Survival ; toxicities ; Toxicity</subject><ispartof>Pediatric blood & cancer, 2018-03, Vol.65 (3), p.n/a</ispartof><rights>2017 Wiley Periodicals, Inc.</rights><rights>2018 Wiley Periodicals, Inc.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4431-a1b425b1738b95ac4f5814407caf134884eb38d5008f398265e17e0cd0c5d0d93</citedby><cites>FETCH-LOGICAL-c4431-a1b425b1738b95ac4f5814407caf134884eb38d5008f398265e17e0cd0c5d0d93</cites><orcidid>0000-0003-3330-6754</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fpbc.26871$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fpbc.26871$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>230,314,776,780,881,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29090520$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kahn, Justine M.</creatorcontrib><creatorcontrib>Cole, Peter D.</creatorcontrib><creatorcontrib>Blonquist, Traci M.</creatorcontrib><creatorcontrib>Stevenson, Kristen</creatorcontrib><creatorcontrib>Jin, Zhezhen</creatorcontrib><creatorcontrib>Barrera, Sergio</creatorcontrib><creatorcontrib>Davila, Randy</creatorcontrib><creatorcontrib>Roberts, Emily</creatorcontrib><creatorcontrib>Neuberg, Donna S.</creatorcontrib><creatorcontrib>Athale, Uma H.</creatorcontrib><creatorcontrib>Clavell, Luis A.</creatorcontrib><creatorcontrib>Laverdiere, Caroline</creatorcontrib><creatorcontrib>Leclerc, Jean‐Marie</creatorcontrib><creatorcontrib>Michon, Bruno</creatorcontrib><creatorcontrib>Schorin, Marshall A.</creatorcontrib><creatorcontrib>Welch, Jennifer J.G.</creatorcontrib><creatorcontrib>Sallan, Stephen E.</creatorcontrib><creatorcontrib>Silverman, Lewis B.</creatorcontrib><creatorcontrib>Kelly, Kara M.</creatorcontrib><title>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</title><title>Pediatric blood & cancer</title><addtitle>Pediatr Blood Cancer</addtitle><description>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.</description><subject>Acute lymphoblastic leukemia</subject><subject>Adolescents</subject><subject>Cancer</subject><subject>Children</subject><subject>Consortia</subject><subject>Drug delivery</subject><subject>ethnicity</subject><subject>Hematology</subject><subject>Hispanic</subject><subject>Hispanic people</subject><subject>Incidence</subject><subject>Language proficiency</subject><subject>Leukemia</subject><subject>Lymphatic leukemia</subject><subject>Oncology</subject><subject>Osteonecrosis</subject><subject>outcomes</subject><subject>Pediatrics</subject><subject>Secondary analysis</subject><subject>Survival</subject><subject>toxicities</subject><subject>Toxicity</subject><issn>1545-5009</issn><issn>1545-5017</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><recordid>eNp1kcFu1DAQhi0EoqXlwAsgS5w4bDuO7cThgLQNLa20EqiCs-U4TtdV1g62s6W3PkLfo2_Fk-DtlhUcOI1lf_P_4_kRekPgiAAUx2Orj4pSVOQZ2iec8RkHUj3fnaHeQ69ivM5oCVy8RHtFDTXwAvbRw9xh69YmJnulkvUO-x4n_9Nqm6yJWLkOxyms7VoNGcTnNo7KWY310g5dMO6RUJ0fTNTGpYhvbFri-WLxAV-aOA35pg9-hdPS4E_KqV9392cqtCbgRjmdy4XL3mlKZtOEG--iD8lOKzwGn7z2AwaemwDIIXrRqyGa10_1AH0_O_3WnM8WXz5fNPPFTDNGyUyRlhW8JRUVbc2VZj0XhDGotOoJZUIw01LR5b2IntaiKLkhlQHdgeYddDU9QB-3uuPUrky3-VZQgxyDXalwK72y8t8XZ5fyyq8lr8qS1jQLvHsSCP7HlHcrr_0UXJ5ZklqUFRSUbWzebykdfIzB9DsHAnKTq8y5ysdcM_v275F25J8gM3C8BW7sYG7_ryS_njRbyd-o_7CO</recordid><startdate>201803</startdate><enddate>201803</enddate><creator>Kahn, Justine M.</creator><creator>Cole, Peter D.</creator><creator>Blonquist, Traci M.</creator><creator>Stevenson, Kristen</creator><creator>Jin, Zhezhen</creator><creator>Barrera, Sergio</creator><creator>Davila, Randy</creator><creator>Roberts, Emily</creator><creator>Neuberg, Donna S.</creator><creator>Athale, Uma H.</creator><creator>Clavell, Luis A.</creator><creator>Laverdiere, Caroline</creator><creator>Leclerc, Jean‐Marie</creator><creator>Michon, Bruno</creator><creator>Schorin, Marshall A.</creator><creator>Welch, Jennifer J.G.</creator><creator>Sallan, Stephen E.</creator><creator>Silverman, Lewis B.</creator><creator>Kelly, Kara M.</creator><general>Wiley Subscription Services, Inc</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7T5</scope><scope>7TK</scope><scope>7TO</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>P64</scope><scope>RC3</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0003-3330-6754</orcidid></search><sort><creationdate>201803</creationdate><title>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</title><author>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.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4431-a1b425b1738b95ac4f5814407caf134884eb38d5008f398265e17e0cd0c5d0d93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Acute lymphoblastic leukemia</topic><topic>Adolescents</topic><topic>Cancer</topic><topic>Children</topic><topic>Consortia</topic><topic>Drug delivery</topic><topic>ethnicity</topic><topic>Hematology</topic><topic>Hispanic</topic><topic>Hispanic people</topic><topic>Incidence</topic><topic>Language proficiency</topic><topic>Leukemia</topic><topic>Lymphatic leukemia</topic><topic>Oncology</topic><topic>Osteonecrosis</topic><topic>outcomes</topic><topic>Pediatrics</topic><topic>Secondary analysis</topic><topic>Survival</topic><topic>toxicities</topic><topic>Toxicity</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kahn, Justine M.</creatorcontrib><creatorcontrib>Cole, Peter D.</creatorcontrib><creatorcontrib>Blonquist, Traci M.</creatorcontrib><creatorcontrib>Stevenson, Kristen</creatorcontrib><creatorcontrib>Jin, Zhezhen</creatorcontrib><creatorcontrib>Barrera, Sergio</creatorcontrib><creatorcontrib>Davila, Randy</creatorcontrib><creatorcontrib>Roberts, Emily</creatorcontrib><creatorcontrib>Neuberg, Donna S.</creatorcontrib><creatorcontrib>Athale, Uma H.</creatorcontrib><creatorcontrib>Clavell, Luis A.</creatorcontrib><creatorcontrib>Laverdiere, Caroline</creatorcontrib><creatorcontrib>Leclerc, Jean‐Marie</creatorcontrib><creatorcontrib>Michon, Bruno</creatorcontrib><creatorcontrib>Schorin, Marshall A.</creatorcontrib><creatorcontrib>Welch, Jennifer J.G.</creatorcontrib><creatorcontrib>Sallan, Stephen E.</creatorcontrib><creatorcontrib>Silverman, Lewis B.</creatorcontrib><creatorcontrib>Kelly, Kara M.</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Pediatric blood & cancer</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kahn, Justine M.</au><au>Cole, Peter D.</au><au>Blonquist, Traci M.</au><au>Stevenson, Kristen</au><au>Jin, Zhezhen</au><au>Barrera, Sergio</au><au>Davila, Randy</au><au>Roberts, Emily</au><au>Neuberg, Donna S.</au><au>Athale, Uma H.</au><au>Clavell, Luis A.</au><au>Laverdiere, Caroline</au><au>Leclerc, Jean‐Marie</au><au>Michon, Bruno</au><au>Schorin, Marshall A.</au><au>Welch, Jennifer J.G.</au><au>Sallan, Stephen E.</au><au>Silverman, Lewis B.</au><au>Kelly, Kara M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>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</atitle><jtitle>Pediatric blood & cancer</jtitle><addtitle>Pediatr Blood Cancer</addtitle><date>2018-03</date><risdate>2018</risdate><volume>65</volume><issue>3</issue><epage>n/a</epage><issn>1545-5009</issn><eissn>1545-5017</eissn><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.</abstract><cop>United States</cop><pub>Wiley Subscription Services, Inc</pub><pmid>29090520</pmid><doi>10.1002/pbc.26871</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0003-3330-6754</orcidid><oa>free_for_read</oa></addata></record> |
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| source | Wiley Online Library Journals Frontfile Complete |
| subjects | Acute lymphoblastic leukemia Adolescents Cancer Children Consortia Drug delivery ethnicity Hematology Hispanic Hispanic people Incidence Language proficiency Leukemia Lymphatic leukemia Oncology Osteonecrosis outcomes Pediatrics Secondary analysis Survival toxicities Toxicity |
| title | 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 |
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