Adults with Philadelphia chromosome–like acute lymphoblastic leukemia
frequently have IGH-CRLF2 and JAK2 mutations, persistence of minimal residual
disease and poor prognosis
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