TY - JOUR
T1 - Ph-like acute lymphoblastic leukemia
T2 - A high-risk subtype in adults
AU - Jain, Nitin
AU - Roberts, Kathryn G.
AU - Jabbour, Elias
AU - Patel, Keyur
AU - Eterovic, Agda Karina
AU - Chen, Ken
AU - Zweidler-McKay, Patrick
AU - Lu, Xinyan
AU - Fawcett, Gloria
AU - Wang, Sa A.
AU - Konoplev, Sergej
AU - Harvey, Richard C.
AU - Chen, I. Ming
AU - Payne-Turner, Debbie
AU - Valentine, Marcus
AU - Thomas, Deborah
AU - Garcia-Manero, Guillermo
AU - Ravandi, Farhad
AU - Cortes, Jorge
AU - Kornblau, Steven
AU - O'Brien, Susan
AU - Pierce, Sherry
AU - Jorgensen, Jeffrey
AU - Mills Shaw, Kenna R.
AU - Willman, Cheryl L.
AU - Mullighan, Charles G.
AU - Kantarjian, Hagop
AU - Konopleva, Marina
N1 - Publisher Copyright:
© 2017 by The American Society of Hematology.
PY - 2017/2/2
Y1 - 2017/2/2
N2 - Philadelphia chromosome (Ph)-like acute lymphoblastic leukemia (ALL) is a high-risk subtype of ALL in children. There are conflicting data on the incidence and prognosis of Ph-like ALL in adults. Patients with newly diagnosed B-cell ALL (B-ALL) who received frontline chemotherapy at MD Anderson Cancer Center underwent gene expression profiling of leukemic cells. Of 148 patients, 33.1% had Ph-like, 31.1% had Ph+, and 35.8% had other B-ALL subtypes (B-other). Within the Ph-like ALL cohort, 61% had cytokine receptor-like factor 2 (CRLF2) overexpression. Patients with Ph-like ALL had significantly worse overall survival (OS), and event-free survival compared with B-other with a 5-year survival of 23% (vs 59% for B-other, P = .006). Sixty-eight percent of patients with Ph-like ALL were of Hispanic ethnicity. The following were associated with inferior OS on multivariable analysis: age (hazard ratio [HR], 3.299; P < .001), white blood cell count (HR, 1.910; P = .017), platelet count (HR, 7.437; P = .005), and Ph-like ALL (HR, 1.818; P = .03). Next-generation sequencing of the CRLF2+ group identified mutations in the JAK-STAT and Ras pathway in 85% of patients, and 20% had a CRLF2 mutation. Within the CRLF2+ group, JAK2 mutation was associated with inferior outcomes. Our findings show high frequency of Ph-like ALL in adults, an increased frequency of Ph-like ALL in adults of Hispanic ethnicity, significantly inferior outcomes of adult patients with Ph-like ALL, and significantly worse outcomes in the CRLF2+ subset of Ph-like ALL. Novel strategies are needed to improve the outcome of these patients.
AB - Philadelphia chromosome (Ph)-like acute lymphoblastic leukemia (ALL) is a high-risk subtype of ALL in children. There are conflicting data on the incidence and prognosis of Ph-like ALL in adults. Patients with newly diagnosed B-cell ALL (B-ALL) who received frontline chemotherapy at MD Anderson Cancer Center underwent gene expression profiling of leukemic cells. Of 148 patients, 33.1% had Ph-like, 31.1% had Ph+, and 35.8% had other B-ALL subtypes (B-other). Within the Ph-like ALL cohort, 61% had cytokine receptor-like factor 2 (CRLF2) overexpression. Patients with Ph-like ALL had significantly worse overall survival (OS), and event-free survival compared with B-other with a 5-year survival of 23% (vs 59% for B-other, P = .006). Sixty-eight percent of patients with Ph-like ALL were of Hispanic ethnicity. The following were associated with inferior OS on multivariable analysis: age (hazard ratio [HR], 3.299; P < .001), white blood cell count (HR, 1.910; P = .017), platelet count (HR, 7.437; P = .005), and Ph-like ALL (HR, 1.818; P = .03). Next-generation sequencing of the CRLF2+ group identified mutations in the JAK-STAT and Ras pathway in 85% of patients, and 20% had a CRLF2 mutation. Within the CRLF2+ group, JAK2 mutation was associated with inferior outcomes. Our findings show high frequency of Ph-like ALL in adults, an increased frequency of Ph-like ALL in adults of Hispanic ethnicity, significantly inferior outcomes of adult patients with Ph-like ALL, and significantly worse outcomes in the CRLF2+ subset of Ph-like ALL. Novel strategies are needed to improve the outcome of these patients.
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U2 - 10.1182/blood-2016-07-726588
DO - 10.1182/blood-2016-07-726588
M3 - Article
C2 - 27919910
AN - SCOPUS:85014854171
SN - 0006-4971
VL - 129
SP - 572
EP - 581
JO - Blood
JF - Blood
IS - 5
ER -