Secondary cytogenetic abnormalities in core-binding factor AML harboring inv(16) vs t(8;21)

Se Young Han; Krzysztof Mrozek; Jenna Voutsinas; Qian Wu; Elizabeth A. Morgan; Hanne Vestergaard; Robert Ohgami; Philip M. Kluin; Thomas Kielsgaard Kristensen; Sheeja Pullarkat; Michael Boe Moller; Ana-Iris Schiefer; Linda B. Baughn; Young Kim; David Czuchlewski; Jacobien R. Hilberink; Hans-Peter Horny; Tracy George; Michelle Dolan; Nam K. Ku; Cecilia Arana Yi; Vinod Pullarkat; Jessica Kohlschmidt; Amandeep Salhotra; Lori Soma; Clara D. Bloomfield; Dong Chen; Wolfgang R. Sperr; Guido Marcucci; Christina Cho; Cem Akin; Jason Gotlib; Sigurd Broesby-Olsen; Melissa Larson; Michael A. Linden; H. Joachim Deeg; Gregor Hoermann; Miguel-Angel Perales; Jason L. Hornick; Mark R. Litzow; Ryotaro Nakamura; Daniel Weisdorf; Gautam Borthakur; Gerwin Huls; Peter Valent; Celalettin Ustun; Cecilia C. S. Yeung

doi:10.1182/bloodadvances.2020003605

Secondary cytogenetic abnormalities in core-binding factor AML harboring inv(16) vs t(8;21)

Se Young Han, Krzysztof Mrozek, Jenna Voutsinas, Qian Wu, Elizabeth A. Morgan, Hanne Vestergaard, Robert Ohgami, Philip M. Kluin, Thomas Kielsgaard Kristensen, Sheeja Pullarkat, Michael Boe Moller, Ana-Iris Schiefer, Linda B. Baughn, Young Kim, David Czuchlewski, Jacobien R. Hilberink, Hans-Peter Horny, Tracy George, Michelle Dolan, Nam K. KuCecilia Arana Yi, Vinod Pullarkat, Jessica Kohlschmidt, Amandeep Salhotra, Lori Soma, Clara D. Bloomfield, Dong Chen, Wolfgang R. Sperr, Guido Marcucci, Christina Cho, Cem Akin, Jason Gotlib, Sigurd Broesby-Olsen, Melissa Larson, Michael A. Linden, H. Joachim Deeg, Gregor Hoermann, Miguel-Angel Perales, Jason L. Hornick, Mark R. Litzow, Ryotaro Nakamura, Daniel Weisdorf, Gautam Borthakur, Gerwin Huls, Peter Valent, Celalettin Ustun, Cecilia C. S. Yeung^*

^*Corresponding author for this work

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Abstract

Patients with core-binding factor (CBF) acute myeloid leukemia (AML), caused by either t(8; 21)(q22;q22) or inv(16)(p13q22)/t(16;16)(p13;q22), have higher complete remission rates and longer survival than patients with other subtypes of AML. However, similar to 40% of patients relapse, and the literature suggests that patients with inv(16) fare differently from those with t(8;21). We retrospectively analyzed 537 patients with CBF-AML, focusing on additional cytogenetic aberrations to examine their impact on clinical outcomes. Trisomies of chromosomes 8, 21, or 22 were significantly more common in patients with inv(16)/t(16;16): 16% vs 7%, 6% vs 0%, and 17% vs 0%, respectively. In contrast, del(9q) and loss of a sex chromosome were more frequent in patients with t(8;21): 15% vs 0.4% for del(9q), 37% vs 0% for loss of X in females, and 44% vs 5% for loss of Y in males. Hyperdiploidy was more frequent in patients with inv(16) (25% vs 9%, whereas hypodiploidy was more frequent in patients with t(8;21) (37% vs 3%. In multivariable analyses (adjusted for age, white blood counts at diagnosis, and KIT mutation status), trisomy 8 was associated with improved overall survival (OS) in inv(16), whereas the presence of other chromosomal abnormalities (not trisomy 8) was associated with decreased OS. In patients with t(8;21), hypodiploidy was associated with improved disease-free survival; hyperdiploidy and del(9q) were associated with improved OS. KIT mutation (either positive or not tested, compared with negative) conferred poor prognoses in univariate analysis only in patients with t(8;21).

Original language	English
Pages (from-to)	2481-2489
Number of pages	9
Journal	Blood
Volume	5
Issue number	10
Early online date	18-May-2021
DOIs	https://doi.org/10.1182/bloodadvances.2020003605
Publication status	Published - 25-May-2021

Keywords

ACUTE MYELOID-LEUKEMIA
MINIMAL RESIDUAL DISEASE
C-KIT MUTATIONS
PROGNOSTIC IMPACT
GENE
SURVIVAL
EXPRESSION
RELAPSE
CANCER

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Secondary cytogenetic abnormalities in core-binding factor AML harboring inv(16) vs t(8;21)Final publisher's version, 0.98 MBLicence: Taverne

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Han, S. Y., Mrozek, K., Voutsinas, J., Wu, Q., Morgan, E. A., Vestergaard, H., Ohgami, R., Kluin, P. M., Kristensen, T. K., Pullarkat, S., Moller, M. B., Schiefer, A.-I., Baughn, L. B., Kim, Y., Czuchlewski, D., Hilberink, J. R., Horny, H.-P., George, T., Dolan, M., ... Yeung, C. C. S. (2021). Secondary cytogenetic abnormalities in core-binding factor AML harboring inv(16) vs t(8;21). Blood, 5(10), 2481-2489. https://doi.org/10.1182/bloodadvances.2020003605

@article{41555cb2e32049c6aae6901adc6fa7a5,

title = "Secondary cytogenetic abnormalities in core-binding factor AML harboring inv(16) vs t(8;21)",

abstract = "Patients with core-binding factor (CBF) acute myeloid leukemia (AML), caused by either t(8; 21)(q22;q22) or inv(16)(p13q22)/t(16;16)(p13;q22), have higher complete remission rates and longer survival than patients with other subtypes of AML. However, similar to 40% of patients relapse, and the literature suggests that patients with inv(16) fare differently from those with t(8;21). We retrospectively analyzed 537 patients with CBF-AML, focusing on additional cytogenetic aberrations to examine their impact on clinical outcomes. Trisomies of chromosomes 8, 21, or 22 were significantly more common in patients with inv(16)/t(16;16): 16% vs 7%, 6% vs 0%, and 17% vs 0%, respectively. In contrast, del(9q) and loss of a sex chromosome were more frequent in patients with t(8;21): 15% vs 0.4% for del(9q), 37% vs 0% for loss of X in females, and 44% vs 5% for loss of Y in males. Hyperdiploidy was more frequent in patients with inv(16) (25% vs 9%, whereas hypodiploidy was more frequent in patients with t(8;21) (37% vs 3%. In multivariable analyses (adjusted for age, white blood counts at diagnosis, and KIT mutation status), trisomy 8 was associated with improved overall survival (OS) in inv(16), whereas the presence of other chromosomal abnormalities (not trisomy 8) was associated with decreased OS. In patients with t(8;21), hypodiploidy was associated with improved disease-free survival; hyperdiploidy and del(9q) were associated with improved OS. KIT mutation (either positive or not tested, compared with negative) conferred poor prognoses in univariate analysis only in patients with t(8;21).",

keywords = "ACUTE MYELOID-LEUKEMIA, MINIMAL RESIDUAL DISEASE, C-KIT MUTATIONS, PROGNOSTIC IMPACT, GENE, SURVIVAL, EXPRESSION, RELAPSE, CANCER",

author = "Han, {Se Young} and Krzysztof Mrozek and Jenna Voutsinas and Qian Wu and Morgan, {Elizabeth A.} and Hanne Vestergaard and Robert Ohgami and Kluin, {Philip M.} and Kristensen, {Thomas Kielsgaard} and Sheeja Pullarkat and Moller, {Michael Boe} and Ana-Iris Schiefer and Baughn, {Linda B.} and Young Kim and David Czuchlewski and Hilberink, {Jacobien R.} and Hans-Peter Horny and Tracy George and Michelle Dolan and Ku, {Nam K.} and Yi, {Cecilia Arana} and Vinod Pullarkat and Jessica Kohlschmidt and Amandeep Salhotra and Lori Soma and Bloomfield, {Clara D.} and Dong Chen and Sperr, {Wolfgang R.} and Guido Marcucci and Christina Cho and Cem Akin and Jason Gotlib and Sigurd Broesby-Olsen and Melissa Larson and Linden, {Michael A.} and Deeg, {H. Joachim} and Gregor Hoermann and Miguel-Angel Perales and Hornick, {Jason L.} and Litzow, {Mark R.} and Ryotaro Nakamura and Daniel Weisdorf and Gautam Borthakur and Gerwin Huls and Peter Valent and Celalettin Ustun and Yeung, {Cecilia C. S.}",

year = "2021",

month = may,

day = "25",

doi = "10.1182/bloodadvances.2020003605",

language = "English",

volume = "5",

pages = "2481--2489",

journal = "Blood",

issn = "0000-0000",

publisher = "AMER SOC HEMATOLOGY",

number = "10",

}

Han, SY, Mrozek, K, Voutsinas, J, Wu, Q, Morgan, EA, Vestergaard, H, Ohgami, R, Kluin, PM, Kristensen, TK, Pullarkat, S, Moller, MB, Schiefer, A-I, Baughn, LB, Kim, Y, Czuchlewski, D, Hilberink, JR, Horny, H-P, George, T, Dolan, M, Ku, NK, Yi, CA, Pullarkat, V, Kohlschmidt, J, Salhotra, A, Soma, L, Bloomfield, CD, Chen, D, Sperr, WR, Marcucci, G, Cho, C, Akin, C, Gotlib, J, Broesby-Olsen, S, Larson, M, Linden, MA, Deeg, HJ, Hoermann, G, Perales, M-A, Hornick, JL, Litzow, MR, Nakamura, R, Weisdorf, D, Borthakur, G, Huls, G, Valent, P, Ustun, C & Yeung, CCS 2021, 'Secondary cytogenetic abnormalities in core-binding factor AML harboring inv(16) vs t(8;21)', Blood, vol. 5, no. 10, pp. 2481-2489. https://doi.org/10.1182/bloodadvances.2020003605

TY - JOUR

T1 - Secondary cytogenetic abnormalities in core-binding factor AML harboring inv(16) vs t(8;21)

AU - Han, Se Young

AU - Mrozek, Krzysztof

AU - Voutsinas, Jenna

AU - Wu, Qian

AU - Morgan, Elizabeth A.

AU - Vestergaard, Hanne

AU - Ohgami, Robert

AU - Kluin, Philip M.

AU - Kristensen, Thomas Kielsgaard

AU - Pullarkat, Sheeja

AU - Moller, Michael Boe

AU - Schiefer, Ana-Iris

AU - Baughn, Linda B.

AU - Kim, Young

AU - Czuchlewski, David

AU - Hilberink, Jacobien R.

AU - Horny, Hans-Peter

AU - George, Tracy

AU - Dolan, Michelle

AU - Ku, Nam K.

AU - Yi, Cecilia Arana

AU - Pullarkat, Vinod

AU - Kohlschmidt, Jessica

AU - Salhotra, Amandeep

AU - Soma, Lori

AU - Bloomfield, Clara D.

AU - Chen, Dong

AU - Sperr, Wolfgang R.

AU - Marcucci, Guido

AU - Cho, Christina

AU - Akin, Cem

AU - Gotlib, Jason

AU - Broesby-Olsen, Sigurd

AU - Larson, Melissa

AU - Linden, Michael A.

AU - Deeg, H. Joachim

AU - Hoermann, Gregor

AU - Perales, Miguel-Angel

AU - Hornick, Jason L.

AU - Litzow, Mark R.

AU - Nakamura, Ryotaro

AU - Weisdorf, Daniel

AU - Borthakur, Gautam

AU - Huls, Gerwin

AU - Valent, Peter

AU - Ustun, Celalettin

AU - Yeung, Cecilia C. S.

PY - 2021/5/25

Y1 - 2021/5/25

N2 - Patients with core-binding factor (CBF) acute myeloid leukemia (AML), caused by either t(8; 21)(q22;q22) or inv(16)(p13q22)/t(16;16)(p13;q22), have higher complete remission rates and longer survival than patients with other subtypes of AML. However, similar to 40% of patients relapse, and the literature suggests that patients with inv(16) fare differently from those with t(8;21). We retrospectively analyzed 537 patients with CBF-AML, focusing on additional cytogenetic aberrations to examine their impact on clinical outcomes. Trisomies of chromosomes 8, 21, or 22 were significantly more common in patients with inv(16)/t(16;16): 16% vs 7%, 6% vs 0%, and 17% vs 0%, respectively. In contrast, del(9q) and loss of a sex chromosome were more frequent in patients with t(8;21): 15% vs 0.4% for del(9q), 37% vs 0% for loss of X in females, and 44% vs 5% for loss of Y in males. Hyperdiploidy was more frequent in patients with inv(16) (25% vs 9%, whereas hypodiploidy was more frequent in patients with t(8;21) (37% vs 3%. In multivariable analyses (adjusted for age, white blood counts at diagnosis, and KIT mutation status), trisomy 8 was associated with improved overall survival (OS) in inv(16), whereas the presence of other chromosomal abnormalities (not trisomy 8) was associated with decreased OS. In patients with t(8;21), hypodiploidy was associated with improved disease-free survival; hyperdiploidy and del(9q) were associated with improved OS. KIT mutation (either positive or not tested, compared with negative) conferred poor prognoses in univariate analysis only in patients with t(8;21).

AB - Patients with core-binding factor (CBF) acute myeloid leukemia (AML), caused by either t(8; 21)(q22;q22) or inv(16)(p13q22)/t(16;16)(p13;q22), have higher complete remission rates and longer survival than patients with other subtypes of AML. However, similar to 40% of patients relapse, and the literature suggests that patients with inv(16) fare differently from those with t(8;21). We retrospectively analyzed 537 patients with CBF-AML, focusing on additional cytogenetic aberrations to examine their impact on clinical outcomes. Trisomies of chromosomes 8, 21, or 22 were significantly more common in patients with inv(16)/t(16;16): 16% vs 7%, 6% vs 0%, and 17% vs 0%, respectively. In contrast, del(9q) and loss of a sex chromosome were more frequent in patients with t(8;21): 15% vs 0.4% for del(9q), 37% vs 0% for loss of X in females, and 44% vs 5% for loss of Y in males. Hyperdiploidy was more frequent in patients with inv(16) (25% vs 9%, whereas hypodiploidy was more frequent in patients with t(8;21) (37% vs 3%. In multivariable analyses (adjusted for age, white blood counts at diagnosis, and KIT mutation status), trisomy 8 was associated with improved overall survival (OS) in inv(16), whereas the presence of other chromosomal abnormalities (not trisomy 8) was associated with decreased OS. In patients with t(8;21), hypodiploidy was associated with improved disease-free survival; hyperdiploidy and del(9q) were associated with improved OS. KIT mutation (either positive or not tested, compared with negative) conferred poor prognoses in univariate analysis only in patients with t(8;21).

KW - ACUTE MYELOID-LEUKEMIA

KW - MINIMAL RESIDUAL DISEASE

KW - C-KIT MUTATIONS

KW - PROGNOSTIC IMPACT

KW - GENE

KW - SURVIVAL

KW - EXPRESSION

KW - RELAPSE

KW - CANCER

U2 - 10.1182/bloodadvances.2020003605

DO - 10.1182/bloodadvances.2020003605

M3 - Article

SN - 0000-0000

VL - 5

SP - 2481

EP - 2489

JO - Blood

JF - Blood

IS - 10

ER -

Secondary cytogenetic abnormalities in core-binding factor AML harboring inv(16) vs t(8;21)

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Keywords

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