Blood Res.  2018 Jun;53(2):138-144. 10.5045/br.2018.53.2.138.

Leukemia propagating cells in Philadelphia chromosome-positive ALL: a resistant phenotype with an adverse prognosis

• El-Menshawy N
• Abd-Aziz S
• Elkhamisy
• Ebrahim MA

• KMID: 2451032
• DOI: http://doi.org/10.5045/br.2018.53.2.138

Abstract

BACKGROUND
Targeted therapy has revolutionized the management of Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL); however, relapse still occurs because of the presence of quiescent stem cells, termed leukemia propagating cells (LPCs). This study aimed to assess the phenotypic diversity of LPCs in adult patients with Ph+ B-Acute ALL (B-ALL) and to assess its prognostic impact.
METHODS
Seventy adults with newly diagnosed Ph+ B-ALL were recruited at the Mansoura Oncology Center. Multiparameter flow cytometry studies of mononuclear blast cells for cluster of differentiation (CD)34, CD38, and CD58 were performed.
RESULTS
Seventeen patients had blasts with the pattern of LPCs (CD34+CD38−CD58−), while 53 cases had other diverse phenotypic patterns. The rate of complete response was significantly lower in patients with the LPC phenotype (47% vs. 81%, P=0.006). The median time to achieve a complete response was prolonged in patients with the CD34+CD38−CD58− phenotype (48 vs. 32 days, P=0.016). The three-year overall survival was significantly lower in patients with the CD34+CD38−CD58− phenotype (37% vs. 55% respectively, P=0.028). Multivariate analysis showed that the CD34+CD38− CD58− phenotype was an independent risk factor for overall survival.
CONCLUSION
The presence of CD34+CD38−CD58− LPCs at diagnosis allows rapid identification of higher risk patients. Risk stratification of these patients is needed to further guide therapy and develop effective LPCs-targeted therapy to improve treatment outcome.

Keyword

Precursor cell lymphoblastic leukemia-lymphoma; Philadelphia chromosome; Multipotent stem cells

MeSH Terms

Adult
Diagnosis
Flow Cytometry
Humans
Leukemia*
Multipotent Stem Cells
Multivariate Analysis
Phenotype*
Philadelphia Chromosome
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Prognosis*
Recurrence
Risk Factors
Stem Cells
Treatment Outcome

Figure

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  Fig. 1 Comparison of Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (Ph+ ALL) subjects with the CD34+CD38−CD58− phenotype versus other phenotypes regarding the rate of complete remission (CR) after induction chemotherapy.

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  Fig. 2 Comparison of Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (Ph+ ALL) subjects with the CD34+CD38−CD58− phenotype versus other phenotypes regarding the time to complete remission (CR; in days) after induction chemotherapy.

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  Fig. 3 Overall survival of studied cases as classified by their phenotypic pattern. The median survival time of patients with the CD34+CD38−CD58− phenotype was 15 months (95% CI, 11–25 mo); the median survival for other phenotypes was not reached.

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