Clinical and laboratory features associated with myeloperoxidase expression in pediatric B‐lymphoblastic leukemia

Abstract

Background: B-lymphoblastic leukemia (B-ALL) is the most common childhood malignancy, and its diagnosis requires immunophenotypically demonstrating blast B cell lineage differentiation. Expression of myeloperoxidase (MPO) in B-ALL is well-described and it has been recognized that a diagnosis of mixed phenotype acute leukemia should be made cautiously if MPO expression is the sole myeloid feature in these cases. We sought to determine whether MPO expression in pediatric B-ALL was associated with differences in laboratory, immunophenotypic, or clinical features.Methods: We reviewed clinical, diagnostic bone marrow flow cytometry, and laboratory data for all new B-ALL diagnoses at our pediatric institution in 5 years. Cases were categorized as MPO positive (MPO+) or negative (MPO−) using a threshold of ≥20% blasts expressing MPO at intensity greater than the upper limit of normal lymphocytes on diagnostic bone marrow flow cytometry.Results: A total of 148 cases were reviewed, 32 of which (22%) were MPO+. MPO+ B-ALL was more frequently hyperdiploid and less frequently harbored ETV6-RUNX1; no MPO+ cases had KMT2A rearrangements or BCR-ABL1. Although not significantly so, MPO+ B-ALL was less likely than MPO− B-ALL to have positive end-of-induction minimal residual disease studies (9.4 and 24%, respectively), but relapse rates and stem cell transplantation rates were similar between groups. Aberrant expression of other more typically myeloid markers was similar between these groups. Conclusion:In our study cohort, MPO+ B-ALL showed minimal residual disease persistence less often after induction chemotherapy but otherwise had similar clinical outcomes to MPO− B-ALL, with similar rates of additional myeloid antigen aberrancy.

Isolated Myeloperoxidase Immunohistochemical Expression in Bone Marrow Biopsy Depicts Clinical Outcomes in Adults with Typical B-Acute Lymphoblastic Leukemia

“…In one study, MPO+ve patients tended to be older males without increased WBC counts or common B-ALL-related karyotypic findings, and showed an increased rate of relapse and a worse event-free survival than the patients with B-ALL who did not express MPO (Oberley et al, 2017). But another study that demonstrated a higher frequency of isoMPO expression, identified similar aberrant expression of myeloid markers and similar or even better clinical outcomes (as indicated by minimal residual disease) in the MPO+ve and -ve B-ALL, suggesting that these cases are not necessarily high-risk as a group and remain best classified as B-ALL rather than a separate entity (McGinnis et al, 2020).…”

“…Some investigators considered MPO expression in B-ALL as a diagnostic confounder in IHC (Du et al, 2020), or as a false positive FCM finding (Savasan et al, 2018). Nevertheless, the prognostic relations of this phenomenon were recently studied in pediatric B-ALL, and the data were controversial suggesting an association with higher risk and relapsing disease in some cohorts (Oberley et al, 2017, or better clinical outcomes in other cohorts (Raikar et al, 2018;McGinnis et al, 2020). To the best of our knowledge, a limited number of studies have investigated isoMPO in adult patients with B-ALL using IHC (Arber et al, 2001), therefore it may be of importance to address further studies in this field.…”

Case Report: Myeloid Sarcoma Development During Treatment for B Cell Lymphoblastic Lymphoma in a Boy with KRAS/NRAS Gene Mutations

“…In fact, MPO expression could be observed in up to 22% of pediatric BALL patients. 14 Another concern in the diagnosis of this patient was the use of methylprednisolone before admission that might have lysed part of the blasts. Thus, the percentage of blasts in the bone marrow (15%) could have been underestimated hence suggestive of a diagnosis of mixed phenotypic acute leukemia (MPAL) according to the 2016 WHO guideline.…”

Issue Highlights—July 2021

“…Also in this issue, McGinnis and colleagues describe the clinical and laboratory correlates of myeloperoxidase (MPO) positivity by flow cytometry in a series of cases of B‐lymphoblastic leukemia (McGinnis et al, 2021). Although MPO is typically regarded as a specific marker of myeloid lineage, and in conjunction with B‐lineage antigens would raise the consideration of mixed phenotype acute leukemia (Porwit & Béné, 2019), MPO immunoreactivity should not automatically exclude a diagnosis of B‐lymphoblastic leukemia in an otherwise‐typical case (DiGiuseppe & Wood, 2019).…”

“…Moreover, artifactual MPO positivity, which is well described in B‐lymphoblastic leukemia (Savaşan et al, 2018), should be excluded. Among the authors' findings were a higher proportion of hyperdiploidy and a lower proportion of ETV6‐RUNX1 among MPO‐positive cases compared with MPO‐negative cases (McGinnis et al, 2021). These findings complement other recently described immunophenotypic‐genotypic correlations in B‐lymphoblastic leukemia (Collins et al, 2021; Gudapati et al, 2020).…”