TY - JOUR
T1 - Genomic profiles and clinical outcomes of de novo blastoid/pleomorphic MCL are distinct from those of transformed MCL
AU - Jain, Preetesh
AU - Zhang, Shaojun
AU - Kanagal-Shamanna, Rashmi
AU - Ok, Chi Young
AU - Nomie, Krystle
AU - Gonzalez, Graciela Nogueras
AU - Gonzalez-Pagan, Omarya
AU - Hill, Holly A.
AU - Lee, Hun Ju
AU - Fayad, Luis
AU - Westin, Jason
AU - Nastoupil, Loretta
AU - Hagemeister, Frederick
AU - Chen, Wendy
AU - Oriabure, Onyeka
AU - Badillo, Maria
AU - Jiang, Changying
AU - Yixin, Yao
AU - Li, Shaoying
AU - Tang, Guilin
AU - Yin, C. Cameron
AU - Patel, Keyur P.
AU - Medeiros, Leonard Jeffrey
AU - Nair, Ranjit
AU - Ahmed, Sairah
AU - Iyer, Swaminathan P.
AU - Thirumurthi, Selvi
AU - Champlin, Richard
AU - Xu, Guofan
AU - Tinsu, Pan
AU - Santos, David
AU - Wang, Ruiping
AU - Han, Guangchun
AU - Zhang, Jianhua
AU - Song, Xingzhi
AU - Neelapu, Sattva
AU - Romaguera, Jorge
AU - Futreal, Andy
AU - Flowers, Christopher
AU - Fowler, Nathan
AU - Wang, Linghua
AU - Wang, Michael L.
N1 - Funding Information:
Funding for these studies was provided in part by generous philanthropy donated to the MD Anderson Cancer Center B-Cell Lymphoma Moon Shot Program; the National Institutes of Health, National Cancer Institute (R21 CA202104) (M.L.W.); philanthropic funds from The Gary Rogers Foundation and the Fox Family
PY - 2020/3/24
Y1 - 2020/3/24
N2 - Blastoid and pleomorphic mantle cell lymphomas (MCLs) are variants of aggressive histology MCL (AH-MCL). AH-MCL can arise de novo (AH-DN) or transform from prior classic variant MCL (AH-t). This study is the first integrated analysis of clinical and genomic characteristics of AH-MCL. Patient characteristics were collected from diagnosis (AH-DN) and at transformation (AH-t). Survival after initial diagnosis (AH-DN) and after transformation (AH-t) was calculated. Regression tree analysis was performed to evaluate prognostic variables and in univariate and multivariate analyses for survival. Whole-exome sequencing was performed in evaluable biopsy specimens. We identified 183 patients with AH-MCL (108 were AH-DN, and 75 were AH-t; 152 were blastoid, and 31 were pleomorphic). Median survival was 33 months (48 and 14 months for AH-DN and AH-t, respectively; P 5 .001). Factors associated with inferior survival were age (≥72 years), AH-t category, Ki-67 ≥50% and poor performance status. AH-t had a significantly higher degree of aneuploidy compared with AH-DN. Transformed MCL patients exhibited KMT2B mutations. AH-MCL patients with Ki-67 ≥50% had exclusive mutations in CCND1, NOTCH1, TP53, SPEN, SMARCA4, RANBP2, KMT2C, NOTCH2, NOTCH3, and NSD2 compared with low Ki-67 (,50%). AH-t patients have poor outcomes and distinct genomic profile. This is the first study to report that AH-MCL patients with high Ki-67 (≥50%) exhibit a distinct mutation profile and very poor survival.
AB - Blastoid and pleomorphic mantle cell lymphomas (MCLs) are variants of aggressive histology MCL (AH-MCL). AH-MCL can arise de novo (AH-DN) or transform from prior classic variant MCL (AH-t). This study is the first integrated analysis of clinical and genomic characteristics of AH-MCL. Patient characteristics were collected from diagnosis (AH-DN) and at transformation (AH-t). Survival after initial diagnosis (AH-DN) and after transformation (AH-t) was calculated. Regression tree analysis was performed to evaluate prognostic variables and in univariate and multivariate analyses for survival. Whole-exome sequencing was performed in evaluable biopsy specimens. We identified 183 patients with AH-MCL (108 were AH-DN, and 75 were AH-t; 152 were blastoid, and 31 were pleomorphic). Median survival was 33 months (48 and 14 months for AH-DN and AH-t, respectively; P 5 .001). Factors associated with inferior survival were age (≥72 years), AH-t category, Ki-67 ≥50% and poor performance status. AH-t had a significantly higher degree of aneuploidy compared with AH-DN. Transformed MCL patients exhibited KMT2B mutations. AH-MCL patients with Ki-67 ≥50% had exclusive mutations in CCND1, NOTCH1, TP53, SPEN, SMARCA4, RANBP2, KMT2C, NOTCH2, NOTCH3, and NSD2 compared with low Ki-67 (,50%). AH-t patients have poor outcomes and distinct genomic profile. This is the first study to report that AH-MCL patients with high Ki-67 (≥50%) exhibit a distinct mutation profile and very poor survival.
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UR - http://www.scopus.com/inward/citedby.url?scp=85082833951&partnerID=8YFLogxK
U2 - 10.1182/bloodadvances.2019001396
DO - 10.1182/bloodadvances.2019001396
M3 - Article
C2 - 32191807
AN - SCOPUS:85082833951
SN - 2473-9529
VL - 4
SP - 1038
EP - 1050
JO - Blood Advances
JF - Blood Advances
IS - 6
ER -