Characteristics and outcome of patients with acute myeloid leukaemia and t(8;16)(p11;p13): results from an International Collaborative Study.
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.
['Kayser|Sabine|S|0000-0003-3796-8843', 'Hills|Robert K|RK|0000-0003-0166-0062', 'Langova|Ralitsa|R|', 'Kramer|Michael|M|', 'Guijarro|Francesca|F|', 'Sustkova|Zuzana|Z|', 'Estey|Elihu H|EH|', 'Shaw|Carole M|CM|', 'Ráčil|Zdeněk|Z|0000-0003-3511-4596', 'Mayer|Jiri|J|', 'Zak|Pavel|P|', 'Baer|Maria R|MR|', 'Brunner|Andrew M|AM|', 'Szotkowski|Tomas|T|', 'Cetkovsky|Petr|P|', 'Grimwade|David|D|', 'Walter|Roland B|RB|0000-0002-9268-3341', 'Burnett|Alan K|AK|', 'Ho|Anthony D|AD|', 'Ehninger|Gerhard|G|', 'Müller-Tidow|Carsten|C|', 'Platzbecker|Uwe|U|', 'Thiede|Christian|C|', 'Röllig|Christoph|C|', 'Schulz|Angela|A|', 'Warsow|Gregor|G|', 'Brors|Benedikt|B|', 'Esteve|Jordi|J|', 'Russell|Nigel H|NH|', 'Schlenk|Richard F|RF|', 'Levis|Mark J|MJ|0000-0003-0473-6982']
D059786:Abnormal Karyotype D000293:Adolescent D000328:Adult D000368:Aged D000971:Antineoplastic Combined Chemotherapy Protocols D002885:Chromosomes, Human, Pair 16 D002898:Chromosomes, Human, Pair 8 D003131:Combined Modality Therapy D060830:Consolidation Chemotherapy D018450:Disease Progression D018572:Disease-Free Survival D005260:Female D005500:Follow-Up Studies D018380:Hematopoietic Stem Cell Transplantation D006801:Humans D007391:International Cooperation D015470:Leukemia, Myeloid, Acute D008297:Male D008875:Middle Aged D009154:Mutation D009190:Myelodysplastic Syndromes D016609:Neoplasms, Second Primary D015514:Oncogene Proteins, Fusion D012074:Remission Induction D016019:Survival Analysis D014178:Translocation, Genetic D000073336:Whole Genome Sequencing
outcome acute myeloid leukaemia whole-genome sequencing allogeneic haematopoietic cell transplantation t(8 16)(p11 p13)/MYST3-CREBBP