TY  - JOUR
A1  - Herold, Tobias
A1  - Schneider, Stephanie
A1  - Metzeler, Klaus Hans
A1  - Neumann, Martin
A1  - Hartmann, Luise
A1  - Roberts, Kathryn G.
A1  - Konstandin, Nikola P.
A1  - Greif, Philipp
A1  - Bräundl, Kathrin
A1  - Ksienzyk, Bianka
A1  - Huk, Natalia
A1  - Schneider, Irene
A1  - Zellmeier, Evelyn
A1  - Jurinovic, Vindi
A1  - Mansmann, Ulrich
A1  - Hiddemann, Wolfgang
A1  - Mullighan, Charles G.
A1  - Bohlander, Stefan Klaus
A1  - Spiekermann, Karsten
A1  - Hoelzer, Dieter
A1  - Brüggemann, Monika
A1  - Baldus, Claudia
A1  - Dreyling, Martin
A1  - Gökbuget, Nicola
T1  - Adults with Philadelphia chromosome-like acute lymphoblastic leukemia frequently have IGH-CRLF2 and JAK2 mutations, persistence of minimal residual disease and poor prognosis
T2  - Haematologica
N2  - 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.
Y1  - 2017
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/44317
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-443173
SN  - 1592-8721
SN  - 0390-6078
N1  - ©2017 Ferrata Storti Foundation. Material published in Haematologica is covered by copyright. All rights reserved to the Ferrata Storti Foundation. Copies of articles are allowed for personal or internal use. Permission in writing from the publisher is required for any other use
VL  - 102
IS  - 1
SP  - 130
EP  - 138
PB  - Ferrata Storti Found
CY  - Pavia
ER  -