TY - JOUR
T1 - Characteristics and outcome of patients with acute myeloid leukaemia and t(8;16)(p11;p13)
T2 - results from an International Collaborative Study*
AU - Kayser, Sabine
AU - Hills, Robert K.
AU - Langova, Ralitsa
AU - Kramer, Michael
AU - Guijarro, Francesca
AU - Sustkova, Zuzana
AU - Estey, Elihu H.
AU - Shaw, Carole M.
AU - Ráčil, Zdeněk
AU - Mayer, Jiri
AU - Zak, Pavel
AU - Baer, Maria R.
AU - Brunner, Andrew M.
AU - Szotkowski, Tomas
AU - Cetkovsky, Petr
AU - Grimwade, David
AU - Walter, Roland B.
AU - Burnett, Alan K.
AU - Ho, Anthony D.
AU - Ehninger, Gerhard
AU - Müller-Tidow, Carsten
AU - Platzbecker, Uwe
AU - Thiede, Christian
AU - Röllig, Christoph
AU - Schulz, Angela
AU - Warsow, Gregor
AU - Brors, Benedikt
AU - Esteve, Jordi
AU - Russell, Nigel H.
AU - Schlenk, Richard F.
AU - Levis, Mark J.
N1 - Funding Information:
SK was supported by the Olympia-Morata fellowship program from the Medical Faculty of the Heidelberg University. MJL is supported by a grant from the NCI (NCI Leukemia SPORE P50 CA100632). ZS, ZR, JM, PZ, TS and PC were supported by the Ministry of the Czech Republic, grant No. 15-25809A. Data from the AML10, AML11, AML12, AML15, AML16 and AML17 trials were supplied by Cardiff University HCTU on behalf of the NCRI AMLWG. We thank Jeongbin Park for feedback and testing of the pipelines, and Umut Toprak for discussions and analytical advice.
Funding Information:
SK was supported by the Olympia‐Morata fellowship program from the Medical Faculty of the Heidelberg University. MJL is supported by a grant from the NCI (NCI Leukemia SPORE P50 CA100632). ZS, ZR, JM, PZ, TS and PC were supported by the Ministry of the Czech Republic, grant No. 15‐25809A. Data from the AML10, AML11, AML12, AML15, AML16 and AML17 trials were supplied by Cardiff University HCTU on behalf of the NCRI AMLWG. We thank Jeongbin Park for feedback and testing of the pipelines, and Umut Toprak for discussions and analytical advice.
Publisher Copyright:
© 2021 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/3
Y1 - 2021/3
N2 - In acute myeloid leukaemia (AML) t(8;16)(p11;p13)/MYST3–CREBBP is a very rare abnormality. Previous small series suggested poor outcome. We report on 59 patients with t(8;16) within an international, collaborative study. Median age was 52 (range: 16–75) years. AML was de novo in 58%, therapy-related (t-AML) in 37% and secondary after myelodysplastic syndrome (s-AML) in 5%. Cytogenetics revealed a complex karyotype in 43%. Besides MYST3–CREBBP, whole-genome sequencing on a subset of 10 patients revealed recurrent mutations in ASXL1, BRD3, FLT3, MLH1, POLG, TP53, SAMD4B (n = 3, each), EYS, KRTAP9-1 SPTBN5 (n = 4, each), RUNX1 and TET2 (n = 2, each). Complete remission after intensive chemotherapy was achieved in 84%. Median follow-up was 5·48 years; five-year survival rate was 17%. Patients with s-/t-AML (P = 0·01) and those with complex karyotype (P = 0·04) had an inferior prognosis. Allogeneic haematopoietic cell transplantation (allo-HCT) was performed in 21 (36%) patients, including 15 in first complete remission (CR1). Allo-HCT in CR1 significantly improved survival (P = 0·04); multivariable analysis revealed that allo-HCT in CR1 was effective in de novo AML but not in patients with s-AML/t-AML and less in patients exhibiting a complex karyotype. In summary, outcomes of patients with t(8;16) are dismal with chemotherapy, and may be substantially improved with allo-HCT performed in CR1.
AB - In acute myeloid leukaemia (AML) t(8;16)(p11;p13)/MYST3–CREBBP is a very rare abnormality. Previous small series suggested poor outcome. We report on 59 patients with t(8;16) within an international, collaborative study. Median age was 52 (range: 16–75) years. AML was de novo in 58%, therapy-related (t-AML) in 37% and secondary after myelodysplastic syndrome (s-AML) in 5%. Cytogenetics revealed a complex karyotype in 43%. Besides MYST3–CREBBP, whole-genome sequencing on a subset of 10 patients revealed recurrent mutations in ASXL1, BRD3, FLT3, MLH1, POLG, TP53, SAMD4B (n = 3, each), EYS, KRTAP9-1 SPTBN5 (n = 4, each), RUNX1 and TET2 (n = 2, each). Complete remission after intensive chemotherapy was achieved in 84%. Median follow-up was 5·48 years; five-year survival rate was 17%. Patients with s-/t-AML (P = 0·01) and those with complex karyotype (P = 0·04) had an inferior prognosis. Allogeneic haematopoietic cell transplantation (allo-HCT) was performed in 21 (36%) patients, including 15 in first complete remission (CR1). Allo-HCT in CR1 significantly improved survival (P = 0·04); multivariable analysis revealed that allo-HCT in CR1 was effective in de novo AML but not in patients with s-AML/t-AML and less in patients exhibiting a complex karyotype. In summary, outcomes of patients with t(8;16) are dismal with chemotherapy, and may be substantially improved with allo-HCT performed in CR1.
KW - acute myeloid leukaemia
KW - allogeneic haematopoietic cell transplantation
KW - outcome
KW - t(8;16)(p11;p13)/MYST3–CREBBP
KW - whole-genome sequencing
UR - http://www.scopus.com/inward/record.url?scp=85100218832&partnerID=8YFLogxK
U2 - 10.1111/bjh.17336
DO - 10.1111/bjh.17336
M3 - Article
AN - SCOPUS:85100218832
SN - 0007-1048
VL - 192
SP - 832
EP - 842
JO - British Journal of Haematology
JF - British Journal of Haematology
IS - 5
ER -