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 - Funding Information:
This work was supported in part by Cancer Prevention and Research Institute of Texas Grant "Defining and Treating Targetable Lesions in AYA Acute Lymphoblastic Leukemia" (N.J. and M.K.), the American Lebanese Syrian Associated Charities of St. Jude Children's Research Hospital, Stand Up to Cancer Innovative Research Grant and St. Baldrick's Foundation Scholar Award (C.G.M.), American Society of Hematology Scholar Award (K.G.R.), and National Institutes of Health, National Cancer Institute Grants CA21765 (St. Jude Cancer Center Support Grant), HHSN261200800001E (C.G.M.), U01 CA157937 (C.L.W.) and CA157937 and CA118100 (UNM Comprehensive Cancer Center), and a Leukemia and Lymphoma Society Specialized Center of Research Grant (St. Jude and UNM Comprehensive Cancer Centers).
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 -