Clinical Significance of Isolated Myeloperoxidase Expression in Pediatric B-Lymphoblastic Leukemia

Oberley, Matthew J.; Li, Sisi; Orgel, Etan; Wee, Choo Phei; Hagiya, Ashley; O’Gorman, Maurice R.G.

doi:10.1093/ajcp/aqx021

Cited by 35 publications

(40 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The COG MPAL cohort described here, the iBFM AMBI2012 registry study, and the few pediatric case series for MPAL all suggest that beginning with ALL therapy results in similar or greater OS in comparison with AML regimens. A recent meta‐analysis of patients with MPAL also reported a survival benefit from starting with ALL therapy, although patient‐level data revealed equivalent OS with AML therapy .…”

Section: Discussionmentioning

confidence: 72%

“…The EGIL system is considered easier to apply in a standardized fashion because the WHO2008 and WHO2016 classifications incorporate the concept of subjective strength of antigen positivity (negative, low, or strong) to delineate lineage specificity . Inherent variability within this approach is evident from the rate of review failure in the COG cohort as well as recent MPAL reports . However, the WHO definition is widely accepted internationally, and its reliance on strongly expressed antigens specific to lineage differentiation is considered most likely to delineate a true MPAL population .…”

Section: Discussionmentioning

confidence: 99%

“…Past reports on MPAL suggest that contemporary ALL treatment regimens may be sufficient to cure many, if not most, pediatric patients with MPAL . However, the majority of these case series have lacked central review and, despite age‐associated differences in survival, included only aggregate pediatric and adult data .…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Mixed‐phenotype acute leukemia: A cohort and consensus research strategy from the Children’s Oncology Group Acute Leukemia of Ambiguous Lineage Task Force

Orgel

Alexander

Wood

et al. 2019

Cancer

Self Cite

View full text Add to dashboard Cite

BACKGROUND:Optimal chemotherapy for treating mixed-phenotype acute leukemia (MPAL) and the role of hematopoietic stem cell transplantation (HSCT) remain uncertain. Major limitations in interpreting available data are MPAL's rarity and the use of definitions other than the currently widely accepted criteria: the World Health Organization 2016 (WHO2016) classification. METHODS: To assess the relative efficacy of chemotherapy types for treating pediatric MPAL, the Children's Oncology Group (COG) Acute Leukemia of Ambiguous Lineage Task Force assembled a retrospective cohort of centrally reviewed WHO2016 MPAL cases selected from banking studies for acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). Patients were not treated in COG trials; treatment and outcome data were captured separately. The findings were then integrated with the available, mixed literature to develop a prospective trial in pediatric MPAL. RESULTS: The central review confirmed that 54 of 70 cases fulfilled WHO2016 criteria for MPAL. ALL induction regimens achieved remission in 72% of the cases (28 of 39), whereas AML regimens achieved remission in 69% (9 of 13). The 5-year event-free survival (EFS) and overall survival (OS) rates for the entire cohort were 72% ± 8% and 77% ± 7%, respectively. EFS and OS were 75% ± 13% and 84% ± 11%, respectively, for those receiving ALL chemotherapy alone without HSCT (n = 21). CONCLUSIONS:The results of the COG MPAL cohort and a literature review suggest that ALL chemotherapy without HSCT may be the preferred initial therapy. A prospective trial within the COG is proposed to investigate this approach; AML chemotherapy and/or HSCT will be reserved for those with treatment failure as assessed by minimal residual disease. Embedded biology studies will provide further insight into MPAL genomics. Cancer 2020;126:593-601.

show abstract

Section: Discussionmentioning

confidence: 72%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Mixed‐phenotype acute leukemia: A cohort and consensus research strategy from the Children’s Oncology Group Acute Leukemia of Ambiguous Lineage Task Force

Orgel

Alexander

Wood

et al. 2019

Cancer

Self Cite

View full text Add to dashboard Cite

show abstract

“…Although current WHO guidelines describe MPO expression as a myeloid‐lineage defining feature, the biologic, prognostic, and therapeutic implications of isolated MPO expression (iMPO) in the absence of other myeloid‐defining or myeloid‐associated antigens in blasts that are otherwise immunophenotypically lymphoid have recently become a subject of increased interest. In the context of MPAL B/M, one retrospective series found that B‐ALL with iMPO (defined as B‐ALL expressing MPO but not CD13, CD14, CD33, CD64, or CD117) was associated with a significantly higher incidence of relapse compared with typical B‐ALL, suggesting that iMPO in B‐ALL should be regarded as a high‐risk feature …”

Section: Discussionmentioning

confidence: 99%

Peripheral blood flow cytometry for the diagnosis of pediatric acute leukemia: Highly reliable with rare exceptions

Cheng

Klairmont

Choi

2018

Pediatric Blood & Cancer

View full text Add to dashboard Cite

Background: Recent data have demonstrated the high sensitivity and specificity of peripheral blood flow cytometry (PBFC) for the diagnosis of pediatric leukemia; however, diagnostically significant immunophenotypic discrepancies between PBFC and bone marrow (BM) evaluation, which result in different lineage assignment and treatment protocols, can rarely occur. Here, we sought to further characterize the performance of PBFC for pediatric leukemia and highlight the exceptions when PBFC can result in misdiagnosis. Methods: An institutional database was searched between 2012 and 2016 for cases of acute leukemia with concurrent PBFC and BM evaluation. Immunophenotyping results from the peripheral blood and BM using four or eight color flow cytometry, as well as BM cytochemical staining and immunohistochemistry, were compared. Results: Two hundred ninety PBFC samples with concurrent BM evaluation were identified. Based on the final immunophenotypic classification, the cases were distributed as follows: 108 B-lymphoblastic leukemia (B-ALL), 57 T-lymphoblastic leukemia (T-ALL), 116 acute myeloid leukemia (AML), and 9 mixed-phenotype acute leukemia (MPAL). Among all cases, five had a diagnostically significant discrepancy between PBFC and BM evaluation. In three cases, the immunophenotype by PBFC was consistent with early T-cell precursor ALL (ETP-ALL), whereas BM evaluation demonstrated MPAL. Two cases were suspicious for acute megakaryoblastic leukemia (AMKL) and MPAL, T/myeloid by PBFC but were diagnosed as B-ALL and T-ALL in the BM. Conclusion: Immunophenotypic classification by PBFC is accurate (>98%) in almost all cases of pediatric leukemia with the rare exceptions of suspected ETP-ALL, MPAL, and AMKL. These PBFC diagnoses should be confirmed with BM immunophenotyping. K E Y W O R D S acute lymphoblastic leukemia, acute myeloid leukemia, early T-cell precursor acute lymphoblastic leukemia, mixed-phenotype acute leukemia, pediatric leukemia, peripheral blood flow cytometry

show abstract

“…It is suggested that the development of chemoresistance is a key regulator for relapse among children (4,5). Therefore, further understanding of the pathogenesis of B-ALL is of great significance to improve the survival rate of patients (6).…”

Section: Introductionmentioning

confidence: 99%

MicroRNA‑31 is a potential biomarker for screening B‑lymphoblastic leukemia in children

Zhang

Bai

et al. 2019

Oncol Lett

View full text Add to dashboard Cite

The present study aimed to investigate the expression and significance of microRNA-31 (miR-31) in children with acute B-lymphoblastic leukemia (B-ALL). Bone marrow specimens and peripheral blood were collected from children with BALL (n=38) and healthy controls (n=18). Total RNA was extracted and the expression levels of miR-31 were measured using quantitative PCR. In addition, a receiver operating characteristic curve was generated, and the area under the curve (AUC) was calculated to evaluate the diagnostic value of miR-31 for the development of BALL. miR-31 expression was significantly lower in the BALL group compared with in the control group (P<0.05). Additionally, the expression levels of miR-31 in the BALL group before treatment were markedly lower than in the BALL group after treatment, and miR-31 expression was significantly lower after 30 days of treatment compared with after 12 weeks of treatment. Furthermore, miR-31 expression in the group of children ≥10 years of age was higher than that in the group of children <10 years of age. Furthermore, the expression levels of miR-31 were higher in the low-risk group compared with in the medium-and high-risk groups (P<0.05). When the cutoff value was set at 1.8, the AUC of miR-31 for BALL diagnosis was 0.915 (95% CI, 0.828-1.000; P<0.0001), with a sensitivity and specificity of 80.8 and 100%, respectively. In conclusion, miR-31 may exert an anticancer role in BALL in children and may be a potential marker to assist in diagnosis and prognostic prediction.

show abstract

Clinical Significance of Isolated Myeloperoxidase Expression in Pediatric B-Lymphoblastic Leukemia

Cited by 35 publications

References 18 publications

Mixed‐phenotype acute leukemia: A cohort and consensus research strategy from the Children’s Oncology Group Acute Leukemia of Ambiguous Lineage Task Force

Mixed‐phenotype acute leukemia: A cohort and consensus research strategy from the Children’s Oncology Group Acute Leukemia of Ambiguous Lineage Task Force

Peripheral blood flow cytometry for the diagnosis of pediatric acute leukemia: Highly reliable with rare exceptions

MicroRNA‑31 is a potential biomarker for screening B‑lymphoblastic leukemia in children

Contact Info

Product

Resources

About