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

Nadia El-Menshawy; Sherin M. Abd-Aziz; Enas M Elkhamisy; Mohammed A. Ebrahim

doi:10.5045/br.2018.53.2.138

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Original Article

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Blood Res 2018; 53(2):

Published online June 25, 2018

https://doi.org/10.5045/br.2018.53.2.138

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

Nadia El-Menshawy¹, Sherin M. Abd-Aziz¹, Enas M Elkhamisy², and Mohammed A. Ebrahim^3*

Author Info. +

¹Clinical Pathology Department, Hematology Unit, Mansoura Medical School, Mansoura University, Mansoura, Egypt.

²Internal Medicine Department, Specialized Medicine Hospital, Mansoura Medical School, Mansoura University, Mansoura, Egypt.

³Medical Oncology, Faculty of Medicine, Oncology Center, Mansoura University, Mansoura, Egypt.

Correspondence to : Mohamed A. Ebrahim, M.D. Faculty of Medicine, Oncology Center, Mansoura University, Mansoura 35516, Egypt. drmohamedawad@gmail.com

Received: November 26, 2017; Revised: January 6, 2018; Accepted: February 22, 2018

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

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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.

Keywords Precursor cell lymphoblastic leukemia-lymphoma, Philadelphia chromosome, Multipotent stem cells

Article

Original Article

Blood Res 2018; 53(2): 138-144

Published online June 25, 2018 https://doi.org/10.5045/br.2018.53.2.138

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

Nadia El-Menshawy¹, Sherin M. Abd-Aziz¹, Enas M Elkhamisy², and Mohammed A. Ebrahim^3*

¹Clinical Pathology Department, Hematology Unit, Mansoura Medical School, Mansoura University, Mansoura, Egypt.

²Internal Medicine Department, Specialized Medicine Hospital, Mansoura Medical School, Mansoura University, Mansoura, Egypt.

³Medical Oncology, Faculty of Medicine, Oncology Center, Mansoura University, Mansoura, Egypt.

Correspondence to:Mohamed A. Ebrahim, M.D. Faculty of Medicine, Oncology Center, Mansoura University, Mansoura 35516, Egypt. drmohamedawad@gmail.com

Received: November 26, 2017; Revised: January 6, 2018; Accepted: February 22, 2018

Abstract

Background

Methods

Results

Conclusion

Keywords: Precursor cell lymphoblastic leukemia-lymphoma, Philadelphia chromosome, Multipotent stem cells

Abstract

Fig 1.

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Figure 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.

Blood Research 2018; 53: 138-144https://doi.org/10.5045/br.2018.53.2.138

Fig 2.

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Figure 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.

Blood Research 2018; 53: 138-144https://doi.org/10.5045/br.2018.53.2.138

Fig 3.

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Figure 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.

Blood Research 2018; 53: 138-144https://doi.org/10.5045/br.2018.53.2.138

Table 1 . Patients' characteristics in all studied groups..

^a)Two patients died because of post-transplant complications..

Abbreviations: CR, complete remission; FAB, French American British classification; WBC, white blood cell..

Table 2 . Comparison of Ph+ ALL subjects with CD34+CD38−CD58− versus other phenotype at diagnosis..

Abbreviations: CR, complete remission; ECOG, Eastern Cooperative Oncology Group; FAB, French American British classification; Hb, hemoglobin; LDH, lactate dehydrogenase; Ph+ ALL, Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia; WBC, white blood cell..

Table 3 . Univariate and multivariate analysis of the impact of prognostic factors on overall survival..

Abbreviations: 95% CI, 95% confidence nterval; ECOG, Eastern Cooperative Oncology Group; HR, hazard ratio MR, molecular response; OS, overall survival..