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. 2022 Jan;69(1):e29341.
doi: 10.1002/pbc.29341. Epub 2021 Sep 17.

Prognostic significance of chromosomal abnormalities at relapse in children with relapsed acute myeloid leukemia: A retrospective cohort study of the Relapsed AML 2001/01 Study

Kim Klein  1   2 , H Berna Beverloo  3 , Martin Zimmermann  4 , Susana C Raimondi  5 , Christine von Neuhoff  6 , Valérie de Haas  7   2 , Romy van Weelderen  1   2 , Jacqueline Cloos  1 , Jonas Abrahamsson  8 , Yves Bertrand  9 , Michael Dworzak  10 , Alcira Fynn  11 , Brenda Gibson  12 , Shau-Yin Ha  13 , Christine J Harrison  14 , Henrik Hasle  15 , Sarah Elitzur  16 , Guy Leverger  17 , Alexei Maschan  18 , Bassem Razzouk  19 , Dirk Reinhardt  6 , Carmelo Rizzari  20 , Pter Smisek  21 , Ursula Creutzig  4 , Gertjan J L Kaspers  1   7   2
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Prognostic significance of chromosomal abnormalities at relapse in children with relapsed acute myeloid leukemia: A retrospective cohort study of the Relapsed AML 2001/01 Study

Kim Klein et al. Pediatr Blood Cancer. 2022 Jan.

Abstract

Background: In addition to treatment response, cytogenetic and molecular aberrations are the most important prognostic factors in children with de novo acute myeloid leukemia (AML). However, little is known about cytogenetics at the time of relapse.

Methods: This international study analyzed the prognostic value of cytogenetic profiles and karyotypic changes in pediatric relapsed AML in relation to the probability of event-free (pEFS) and overall survival (pOS). For this purpose, cytogenetic reports from all patients registered on the Relapsed AML 2001/01 Study were reviewed and classified.

Results: Cytogenetic information at relapse was available for 403 (71%) of 569 registered patients. Frequently detected aberrations at relapse were t(8;21)(q22;q22) (n = 60) and inv(16)(p13.1q22)/t(16;16)(p13.1;q22) (n = 24), both associated with relatively good outcome (4-year pOS 59% and 71%, respectively). Monosomy 7/7q-, t(9;11)(p22;q23), t(10;11)(p12;q23), and complex karyotypes were associated with poor outcomes (4-year pOS 17%, 19%, 22%, and 22%, respectively). Of 261 (65%) patients for whom cytogenetic data were reliable at both diagnosis and relapse, pEFS was inferior for patients with karyotypic instability (n = 128, 49%), but pOS was similar. Unstable karyotypes with both gain and loss of aberrations were associated with inferior outcome. Early treatment response, time to relapse, and cytogenetic profile at time of relapse were the most important prognostic factors, both outweighing karytoypic instability per se.

Conclusion: The cytogenetic subgroup at relapse is an independent risk factor for (event-free) survival. Cytogenetic assessment at the time of relapse is of high importance and may contribute to improved risk-adapted treatment for children with relapsed AML.

Keywords: chromosomal instability; clonal evolution; core-binding factor leukemia; cytogenetics; karyotypic change(s); pediatric acute myeloid leukemia/pediatric AML; relapsed AML.

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References

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