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. 2017 Feb 2;129(5):572-581.
doi: 10.1182/blood-2016-07-726588. Epub 2016 Dec 5.

Ph-like acute lymphoblastic leukemia: a high-risk subtype in adults

Nitin Jain  1 , Kathryn G Roberts  2 , Elias Jabbour  1 , Keyur Patel  3 , Agda Karina Eterovic  4 , Ken Chen  4 , Patrick Zweidler-McKay  5 , Xinyan Lu  3 , Gloria Fawcett  4 , Sa A Wang  3 , Sergej Konoplev  3 , Richard C Harvey  6 , I-Ming Chen  6 , Debbie Payne-Turner  2 , Marcus Valentine  2 , Deborah Thomas  1 , Guillermo Garcia-Manero  1 , Farhad Ravandi  1 , Jorge Cortes  1 , Steven Kornblau  1 , Susan O'Brien  7 , Sherry Pierce  1 , Jeffrey Jorgensen  3 , Kenna R Mills Shaw  4 , Cheryl L Willman  6 , Charles G Mullighan  2 , Hagop Kantarjian  1 , Marina Konopleva  1
Affiliations

Ph-like acute lymphoblastic leukemia: a high-risk subtype in adults

Nitin Jain et al. Blood. .

Abstract

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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Figures

Figure 1.
Figure 1.
Frequency of B-ALL subtypes in adults (N = 148).
Figure 2.
Figure 2.
Clinical outcomes of patients with Ph-like ALL and B-other ALL. (A) OS, (B) EFS, and (C) remission duration of Ph-like ALL and B-other ALL.
Figure 3.
Figure 3.
OS of Ph-like ALL and B-other ALL (hyper-CVAD–based treatment only).
Figure 4.
Figure 4.
Clinical outcomes of patients with CRLF2+ Ph-like ALL, non-CRLF2 Ph-like ALL, Ph+ ALL, and B-other ALL. (A) OS, (B) EFS, and (C) remission duration of CRLF2+ Ph-like ALL, non-CRLF2 Ph-like ALL, Ph+ ALL, and B-other ALL. (A) For OS, P for comparison between Ph-like CRLF2+ vs B-other was .001; P for comparison between Ph-like CRLF2+ vs Ph-like non-CRLF2 was .01; all other comparisons were not significant. (B) For EFS, P for comparison between Ph-like CRLF2+ vs B-other was <.001; P for comparison between Ph-like CRLF2+ vs Ph-like non-CRLF2 was .01; P for comparison between Ph-like CRLF2+ vs Ph+ was .02; all other comparisons were not significant. (C) For remission duration, P for comparison between Ph-like CRLF2+ vs B-other was <.001; P for comparison between Ph-like CRLF2+ vs Ph+ was .001; P for comparison between Ph-like non-CRLF2 vs B-other was .03; all other comparisons were not significant.
Figure 5.
Figure 5.
Mutational landscape in CRLF2+ Ph-like ALL (n = 40), categorized by JAK2 mutation status. *Patients with paired tumor and germ line samples. #Relapsed samples.
See this image and copyright information in PMC

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