Effect of additional cytogenetic abnormalities on survival in arsenic trioxide-treated acute promyelocytic leukemia

Zachary D. Epstein-Peterson; Andriy Derkach; Susan Geyer; Krzysztof Mrózek; Jessica Kohlschmidt; Jae H. Park; Sridevi Rajeeve; Eytan M. Stein; Yanming Zhang; Harry Iland; Lynda J. Campbell; Richard A. Larson; Xavier Poiré; Bayard L. Powell; Wendy Stock; Richard M. Stone; Martin S. Tallman

doi:10.1182/bloodadvances.2021006682

Effect of additional cytogenetic abnormalities on survival in arsenic trioxide-treated acute promyelocytic leukemia

Zachary D. Epstein-Peterson^*, Andriy Derkach, Susan Geyer, Krzysztof Mrózek, Jessica Kohlschmidt, Jae H. Park, Sridevi Rajeeve, Eytan M. Stein, Yanming Zhang, Harry Iland, Lynda J. Campbell, Richard A. Larson, Xavier Poiré, Bayard L. Powell, Wendy Stock, Richard M. Stone, Martin S. Tallman

^*Corresponding author for this work

Medicine, Hematology Oncology Division

Research output: Contribution to journal › Article › peer-review

9 Scopus citations

Abstract

Frontline arsenic trioxide (ATO)–based treatment regimens achieve high rates of long-term relapse-free survival in treating acute promyelocytic leukemia (APL) and form the current standard of care. Refining prognostic estimates for newly diagnosed patients treated with ATO-containing regimens remains important in continuing to improve outcomes and identify patients who achieve suboptimal outcomes. We performed a pooled analysis of exclusively ATO-treated patients at a single academic institution and from the ALLG APML4 and Alliance C9710 studies to determine the prognostic importance of additional cytogenetic abnormalities and/or complex karyotype. We demonstrated inferior event-free survival for patients harboring complex karyotype (hazard ratio [HR], 3.74; 95% confidence interval [CI], 1.63-8.56; P 5 .002), but not for patients harboring additional cytogenetic abnormalities (HR, 2.13; 95% CI, 0.78-5.82; P 5 .142). These data support a role for full karyotypic analysis of all patients with APL and indicate a need for novel treatment strategies to overcome the adverse effect of APL harboring complex karyotype.

Original language	English (US)
Pages (from-to)	3433-3439
Number of pages	7
Journal	Blood Advances
Volume	6
Issue number	11
DOIs	https://doi.org/10.1182/bloodadvances.2021006682
State	Published - Jun 14 2022

Funding

This work was supported by an institutional grant from the National Institutes of Health, National Cancer Institute (NCI) grant P30CA008748; an AACR-AstraZeneca Lymphoma Research Fellowship and support through the Lymphoma Research Foundation’s Lymphoma Scientific Research Mentorship Program and the AIDS Malignancy Consortium’s Domestic Scholar Program (Z.D.EP); and an institutional cancer center grant from the NCI P30 CA008748 (Z.D.E.P., A.D., Y.Z., and M.S.T.). Support for the C9710 trial was provided by a grant from the NCI to Cancer and Leukemia Group B (CALGB; CA31946; Durham, NC) and by NCI grant CA33601 to the CALGB Statistical Center.

ASJC Scopus subject areas

Hematology

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10.1182/bloodadvances.2021006682

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Epstein-Peterson, Z. D., Derkach, A., Geyer, S., Mrózek, K., Kohlschmidt, J., Park, J. H., Rajeeve, S., Stein, E. M., Zhang, Y., Iland, H., Campbell, L. J., Larson, R. A., Poiré, X., Powell, B. L., Stock, W., Stone, R. M., & Tallman, M. S. (2022). Effect of additional cytogenetic abnormalities on survival in arsenic trioxide-treated acute promyelocytic leukemia. Blood Advances, 6(11), 3433-3439. https://doi.org/10.1182/bloodadvances.2021006682

@article{3ec823f2bacf4fb9a1bc0e4db6043820,

title = "Effect of additional cytogenetic abnormalities on survival in arsenic trioxide-treated acute promyelocytic leukemia",

abstract = "Frontline arsenic trioxide (ATO)–based treatment regimens achieve high rates of long-term relapse-free survival in treating acute promyelocytic leukemia (APL) and form the current standard of care. Refining prognostic estimates for newly diagnosed patients treated with ATO-containing regimens remains important in continuing to improve outcomes and identify patients who achieve suboptimal outcomes. We performed a pooled analysis of exclusively ATO-treated patients at a single academic institution and from the ALLG APML4 and Alliance C9710 studies to determine the prognostic importance of additional cytogenetic abnormalities and/or complex karyotype. We demonstrated inferior event-free survival for patients harboring complex karyotype (hazard ratio [HR], 3.74; 95% confidence interval [CI], 1.63-8.56; P 5 .002), but not for patients harboring additional cytogenetic abnormalities (HR, 2.13; 95% CI, 0.78-5.82; P 5 .142). These data support a role for full karyotypic analysis of all patients with APL and indicate a need for novel treatment strategies to overcome the adverse effect of APL harboring complex karyotype.",

author = "Epstein-Peterson, {Zachary D.} and Andriy Derkach and Susan Geyer and Krzysztof Mr{\'o}zek and Jessica Kohlschmidt and Park, {Jae H.} and Sridevi Rajeeve and Stein, {Eytan M.} and Yanming Zhang and Harry Iland and Campbell, {Lynda J.} and Larson, {Richard A.} and Xavier Poir{\'e} and Powell, {Bayard L.} and Wendy Stock and Stone, {Richard M.} and Tallman, {Martin S.}",

note = "Funding Information: This work was supported by an institutional grant from the National Institutes of Health, National Cancer Institute (NCI) grant P30CA008748; an AACR-AstraZeneca Lymphoma Research Fellowship and support through the Lymphoma Research Foundation{\textquoteright}s Lymphoma Scientific Research Mentorship Program and the AIDS Malignancy Consortium{\textquoteright}s Domestic Scholar Program (Z.D.EP); and an institutional cancer center grant from the NCI P30 CA008748 (Z.D.E.P., A.D., Y.Z., and M.S.T.). Support for the C9710 trial was provided by a grant from the NCI to Cancer and Leukemia Group B (CALGB; CA31946; Durham, NC) and by NCI grant CA33601 to the CALGB Statistical Center. Publisher Copyright: {\textcopyright} 2022 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.",

year = "2022",

month = jun,

day = "14",

doi = "10.1182/bloodadvances.2021006682",

language = "English (US)",

volume = "6",

pages = "3433--3439",

journal = "Blood Advances",

issn = "2473-9529",

publisher = "American Society of Hematology",

number = "11",

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Epstein-Peterson, ZD, Derkach, A, Geyer, S, Mrózek, K, Kohlschmidt, J, Park, JH, Rajeeve, S, Stein, EM, Zhang, Y, Iland, H, Campbell, LJ, Larson, RA, Poiré, X, Powell, BL, Stock, W, Stone, RM & Tallman, MS 2022, 'Effect of additional cytogenetic abnormalities on survival in arsenic trioxide-treated acute promyelocytic leukemia', Blood Advances, vol. 6, no. 11, pp. 3433-3439. https://doi.org/10.1182/bloodadvances.2021006682

TY - JOUR

T1 - Effect of additional cytogenetic abnormalities on survival in arsenic trioxide-treated acute promyelocytic leukemia

AU - Epstein-Peterson, Zachary D.

AU - Derkach, Andriy

AU - Geyer, Susan

AU - Mrózek, Krzysztof

AU - Kohlschmidt, Jessica

AU - Park, Jae H.

AU - Rajeeve, Sridevi

AU - Stein, Eytan M.

AU - Zhang, Yanming

AU - Iland, Harry

AU - Campbell, Lynda J.

AU - Larson, Richard A.

AU - Poiré, Xavier

AU - Powell, Bayard L.

AU - Stock, Wendy

AU - Stone, Richard M.

AU - Tallman, Martin S.

N1 - Funding Information: This work was supported by an institutional grant from the National Institutes of Health, National Cancer Institute (NCI) grant P30CA008748; an AACR-AstraZeneca Lymphoma Research Fellowship and support through the Lymphoma Research Foundation’s Lymphoma Scientific Research Mentorship Program and the AIDS Malignancy Consortium’s Domestic Scholar Program (Z.D.EP); and an institutional cancer center grant from the NCI P30 CA008748 (Z.D.E.P., A.D., Y.Z., and M.S.T.). Support for the C9710 trial was provided by a grant from the NCI to Cancer and Leukemia Group B (CALGB; CA31946; Durham, NC) and by NCI grant CA33601 to the CALGB Statistical Center. Publisher Copyright: © 2022 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.

PY - 2022/6/14

Y1 - 2022/6/14

N2 - Frontline arsenic trioxide (ATO)–based treatment regimens achieve high rates of long-term relapse-free survival in treating acute promyelocytic leukemia (APL) and form the current standard of care. Refining prognostic estimates for newly diagnosed patients treated with ATO-containing regimens remains important in continuing to improve outcomes and identify patients who achieve suboptimal outcomes. We performed a pooled analysis of exclusively ATO-treated patients at a single academic institution and from the ALLG APML4 and Alliance C9710 studies to determine the prognostic importance of additional cytogenetic abnormalities and/or complex karyotype. We demonstrated inferior event-free survival for patients harboring complex karyotype (hazard ratio [HR], 3.74; 95% confidence interval [CI], 1.63-8.56; P 5 .002), but not for patients harboring additional cytogenetic abnormalities (HR, 2.13; 95% CI, 0.78-5.82; P 5 .142). These data support a role for full karyotypic analysis of all patients with APL and indicate a need for novel treatment strategies to overcome the adverse effect of APL harboring complex karyotype.

AB - Frontline arsenic trioxide (ATO)–based treatment regimens achieve high rates of long-term relapse-free survival in treating acute promyelocytic leukemia (APL) and form the current standard of care. Refining prognostic estimates for newly diagnosed patients treated with ATO-containing regimens remains important in continuing to improve outcomes and identify patients who achieve suboptimal outcomes. We performed a pooled analysis of exclusively ATO-treated patients at a single academic institution and from the ALLG APML4 and Alliance C9710 studies to determine the prognostic importance of additional cytogenetic abnormalities and/or complex karyotype. We demonstrated inferior event-free survival for patients harboring complex karyotype (hazard ratio [HR], 3.74; 95% confidence interval [CI], 1.63-8.56; P 5 .002), but not for patients harboring additional cytogenetic abnormalities (HR, 2.13; 95% CI, 0.78-5.82; P 5 .142). These data support a role for full karyotypic analysis of all patients with APL and indicate a need for novel treatment strategies to overcome the adverse effect of APL harboring complex karyotype.

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DO - 10.1182/bloodadvances.2021006682

M3 - Article

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AN - SCOPUS:85132347506

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JO - Blood Advances

JF - Blood Advances

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ER -

Effect of additional cytogenetic abnormalities on survival in arsenic trioxide-treated acute promyelocytic leukemia

Abstract

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