| Literature DB >> 27561722 |
Tobias Herold1,2,3, Stephanie Schneider4, Klaus H Metzeler4,2,3, Martin Neumann2,3,5, Luise Hartmann4,2,3, Kathryn G Roberts6, Nikola P Konstandin4, Philipp A Greif4,2,3, Kathrin Bräundl4,2,3, Bianka Ksienzyk4, Natalia Huk4, Irene Schneider4, Evelyn Zellmeier4, Vindi Jurinovic7, Ulrich Mansmann7, Wolfgang Hiddemann4,2,3, Charles G Mullighan6, Stefan K Bohlander8, Karsten Spiekermann4,2,3, Dieter Hoelzer9, Monika Brüggemann10, Claudia D Baldus2,3,5, Martin Dreyling4, Nicola Gökbuget9.
Abstract
Philadelphia-like B-cell precursor acute lymphoblastic leukemia (Ph-like ALL) is characterized by distinct genetic alterations and inferior prognosis in children and younger adults. The purpose of this study was a genetic and clinical characterization of Ph-like ALL in adults. Twenty-six (13%) of 207 adult patients (median age: 42 years) with B-cell precursor ALL (BCP-ALL) were classified as having Ph-like ALL using gene expression profiling. The frequency of Ph-like ALL was 27% among 95 BCP-ALL patients negative for BCR-ABL1 and KMT2A-rearrangements. IGH-CRLF2 rearrangements (6/16; P=0.002) and mutations in JAK2 (7/16; P<0.001) were found exclusively in the Ph-like ALL subgroup. Clinical and outcome analyses were restricted to patients treated in German Multicenter Study Group for Adult ALL (GMALL) trials 06/99 and 07/03 (n=107). The complete remission rate was 100% among both Ph-like ALL patients (n=19) and the "remaining BCP-ALL" cases (n=40), i.e. patients negative for BCR-ABL1 and KMT2A-rearrangements and the Ph-like subtype. Significantly fewer Ph-like ALL patients reached molecular complete remission (33% versus 79%; P=0.02) and had a lower probability of continuous complete remission (26% versus 60%; P=0.03) and overall survival (22% versus 64%; P=0.006) at 5 years compared to the remaining BCP-ALL patients. The profile of genetic lesions in adults with Ph-like ALL, including older adults, resembles that of pediatric Ph-like ALL and differs from the profile in the remaining BCP-ALL. Our study is the first to demonstrate that Ph-like ALL is associated with inferior outcomes in intensively treated older adult patients. Ph-like adult ALL should be recognized as a distinct, high-risk entity and further research on improved diagnostic and therapeutic approaches is needed. (NCT00199056, NCT00198991). Copyright© Ferrata Storti Foundation.Entities:
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Year: 2016 PMID： 27561722 PMCID： PMC5210243 DOI： 10.3324/haematol.2015.136366
Source DB: PubMed Journal: Haematologica ISSN： 0390-6078 Impact factor: 9.941