Early Injury to Cortical and Cancellous Bone from Induction Chemotherapy for Adolescents and Young Adults Treated for Acute Lymphoblastic Leukemia E. Orgel, N.M. Mueske, T.A.L. Wren, V. Gilsanz, A.M. Butturini, D.R. Freyer, S.D. Mittelman PII: DOI: Reference:
S8756-3282(16)30023-0 doi: 10.1016/j.bone.2016.01.027 BON 10964
To appear in:
Bone
Received date: Revised date: Accepted date:
25 September 2015 14 January 2016 24 January 2016
Please cite this article as: Orgel E, Mueske NM, Wren TAL, Gilsanz V, Butturini AM, Freyer DR, Mittelman SD, Early Injury to Cortical and Cancellous Bone from Induction Chemotherapy for Adolescents and Young Adults Treated for Acute Lymphoblastic Leukemia, Bone (2016), doi: 10.1016/j.bone.2016.01.027
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT Early Injury to Cortical and Cancellous Bone from Induction Chemotherapy for Adolescents and Young Adults Treated for Acute Lymphoblastic
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Leukemia
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E Orgel,a,e,f NM Mueske,b TAL Wren,b,f V Gilsanz,c,f AM Butturini,a,f,1 DR Freyer,a,f SD Mittelmana,d,f Children’s Center for Cancer and Blood Disease, b Children’s Orthopaedic Center, c Department of Radiology, & d Center for Endocrinology, Children’s Hospital Los Angeles, 4650 Sunset Blvd, Los Angeles, CA 90027 USA; e Jonathan Jaques Children’s Cancer Center, Miller Children’s Hospital Long Beach, 2801 Atlantic Avenue, Long Beach, CA, 90806, USA; f University of Southern California, Los Angeles, CA, 90089, USA. 1 Present Address: Agensys, Inc 1800 Steward St, Santa Monica, CA, 90404 USA.
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Manuscript Word Count: Abstract Word Count: # Tables: # Figures: # References: # Supplemental Tables/Figures:
Etan Orgel Division of Hematology, Oncology, BMT Children’s Hospital Los Angeles 4650 Sunset Blvd, MS#54 Los Angeles, CA 90027 Email: [email protected] Fax: 562-933-7802 Office: 562-999-4766
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Corresponding Author:
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These results have not been previously presented Research reported in this publication was supported by: o A Translational Research Program grant (LLS-6249-11) from the Leukemia and Lymphoma Society o The Eunice Kennedy Shriver National Institute of Child Health and Human Development/NIH (5R01HD059826). o The National Center for Advancing Translational Sciences/NIH (UL1TR000130) via the Southern California Clinical and Translational Science Institute at the Children’s Hospital Los Angeles. o The content contained herein is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Clinical Trial Registration # NCT01317940
Disclosure Statement: The authors have nothing to disclose
ACCEPTED MANUSCRIPT Early Bone Changes from ALL Induction Chemotherapy
Page 2 of 17
Abstract Diminished bone density and skeletal fractures are common morbidities during and following therapy for
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acute lymphoblastic leukemia (ALL). While cumulative doses of osteotoxic chemotherapy for ALL have been reported to adversely impact bone density, the timing of onset of this effect as well as other changes
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to bone structure are not well characterized. We therefore conducted a prospective cohort study in pre-
SC
adolescent and adolescent patients (10-21 years) newly diagnosed with ALL (n=38) to explore leukemiarelated changes to bone at diagnosis and the subsequent impact of the first phase of chemotherapy
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(“Induction”). Using quantitative computerized tomography (QCT), we found that pre-chemotherapy
MA
bone properties were similar to age- and sex-matched controls. Subsequently over the one month Induction period, however, cancellous volumetric bone mineral density (vBMD) decreased markedly (26.8%, p
S8756-3282(16)30023-0 doi: 10.1016/j.bone.2016.01.027 BON 10964
To appear in:
Bone
Received date: Revised date: Accepted date:
25 September 2015 14 January 2016 24 January 2016
Please cite this article as: Orgel E, Mueske NM, Wren TAL, Gilsanz V, Butturini AM, Freyer DR, Mittelman SD, Early Injury to Cortical and Cancellous Bone from Induction Chemotherapy for Adolescents and Young Adults Treated for Acute Lymphoblastic Leukemia, Bone (2016), doi: 10.1016/j.bone.2016.01.027
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT Early Injury to Cortical and Cancellous Bone from Induction Chemotherapy for Adolescents and Young Adults Treated for Acute Lymphoblastic
PT
Leukemia
RI
E Orgel,a,e,f NM Mueske,b TAL Wren,b,f V Gilsanz,c,f AM Butturini,a,f,1 DR Freyer,a,f SD Mittelmana,d,f Children’s Center for Cancer and Blood Disease, b Children’s Orthopaedic Center, c Department of Radiology, & d Center for Endocrinology, Children’s Hospital Los Angeles, 4650 Sunset Blvd, Los Angeles, CA 90027 USA; e Jonathan Jaques Children’s Cancer Center, Miller Children’s Hospital Long Beach, 2801 Atlantic Avenue, Long Beach, CA, 90806, USA; f University of Southern California, Los Angeles, CA, 90089, USA. 1 Present Address: Agensys, Inc 1800 Steward St, Santa Monica, CA, 90404 USA.
NU
SC
a
TE
D
AC CE P
Manuscript Word Count: Abstract Word Count: # Tables: # Figures: # References: # Supplemental Tables/Figures:
Etan Orgel Division of Hematology, Oncology, BMT Children’s Hospital Los Angeles 4650 Sunset Blvd, MS#54 Los Angeles, CA 90027 Email: [email protected] Fax: 562-933-7802 Office: 562-999-4766
MA
Corresponding Author:
3,842 263 4 1 42 0/1
These results have not been previously presented Research reported in this publication was supported by: o A Translational Research Program grant (LLS-6249-11) from the Leukemia and Lymphoma Society o The Eunice Kennedy Shriver National Institute of Child Health and Human Development/NIH (5R01HD059826). o The National Center for Advancing Translational Sciences/NIH (UL1TR000130) via the Southern California Clinical and Translational Science Institute at the Children’s Hospital Los Angeles. o The content contained herein is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Clinical Trial Registration # NCT01317940
Disclosure Statement: The authors have nothing to disclose
ACCEPTED MANUSCRIPT Early Bone Changes from ALL Induction Chemotherapy
Page 2 of 17
Abstract Diminished bone density and skeletal fractures are common morbidities during and following therapy for
PT
acute lymphoblastic leukemia (ALL). While cumulative doses of osteotoxic chemotherapy for ALL have been reported to adversely impact bone density, the timing of onset of this effect as well as other changes
RI
to bone structure are not well characterized. We therefore conducted a prospective cohort study in pre-
SC
adolescent and adolescent patients (10-21 years) newly diagnosed with ALL (n=38) to explore leukemiarelated changes to bone at diagnosis and the subsequent impact of the first phase of chemotherapy
NU
(“Induction”). Using quantitative computerized tomography (QCT), we found that pre-chemotherapy
MA
bone properties were similar to age- and sex-matched controls. Subsequently over the one month Induction period, however, cancellous volumetric bone mineral density (vBMD) decreased markedly (26.8%, p
