Clinical Characteristics and Outcome of Biphenotypic Acute Leukemia: 10 Cases Report and Literature Review

Background: Based on the cells' antigen differentiation expression patterns, most cases of acute leukemia (AL) are classified as either myeloid or lymphoid lineage. However, there are patients with leukemic blast population that co-express both lymphoid and myeloid characteristics, known as biphenotypic acute leukemia (BAL) or mixed-phenotype acute leukemia (MPAL). BAL is a rare subgroup of acute leukemia with a poor prognosis. Currently, a standard chemotherapy treatment has yet to be established. Aims: This study aims to retrospectively investigate the incidence, pathological characteristics, and clinical outcome of BAL patients from the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China, between January, 2014 and June 2019. Methods: From January 2014 to June 2019, the medical records of newly diagnosed BAL based on the EGIL criteria, or ALAL based on the 2008/2016 WHO criteria and who were admitted at the First Affiliated Hospital of Zhengzhou University (Zhengzhou, China) were retrospectively reviewed. The diagnostic workup of BAL was based on initial morphological, cytochemical, and immunophenotypic evaluation of the BM. Using the EGIL scoring system and 2008/2016 WHO criteria, treatment methods and outcome data, including induction chemotherapy, complete remission (CR), relapse, and death, were collected and reviewed. This study was an observational, retrospective, and descriptive study of the clinical aspects of BAL, which was approved by the Ethics Committee of the First Affiliated Hospital of Zhengzhou University. Results: Among a total of 6100 newly diagnosed patients with AL, 10 (0.16%) patients satisfied the definition of BAL based on the EGIL criteria, or MPAL based on the WHO criteria, including 7 males and 3 females. The median age of these patients at diagnosis was 19 years (range 3-67 years). One patient (Pt #1) had extramedullary invasion, including neck, mediastinum (area 8), posterior septal group, left axillary, peritoneal and retroperitoneal lymph nodes. Another patient (Pt #7) had extramedullary invasion with central nervous system leukemia. Immunophenotypic characteristics showed that among 10 BAL patients, 4 cases carried B/Myeloid phenotype, 4 cases carried T/Myeloid phenotype and 2 case carried T/B phenotype. For 8 patients with myeloid lineage differentiation, MPO was positive in 6 (75%), CD13 in 4 (50%), CD33 in 4 (50%), CD38 in 6 (75%), CD58 in 3 (37.5%), CD117 in 4 (50%) patients. In 5 patients with B-lymphoid lineage differentiation, CD19 was positive in 4 (80%), CD79a in 5 (100%) patients. The most frequently T-lymphoid lineage positive markers were CD7 and cCD3, which were positive in 4 of 5 (80%) patients. The stem cell markers HLA-DR and CD34 were both positive in 7 (7/10, 70%) patients, while CD117 was positive in 4 (4/10, 40%) patients. Cytogenetic analysis results showed that 7 of 10 patients had normal karyotypes (Pt#1, 2, 6, 7, 8, 9,10) while the other 3 patients had clonal abnormalities. Pt#4 had 46, xx, t(9;22)(q34;q11) aberration; Pt#6 had 45, XY, -7/46, idem,+8 aberration; and Pt#7 had 45, X,-Y, del(7)q32, t(8,21) (q22;q22) aberration. Two patients (Pt# 3, 5) had RUNX1 gene mutation, one patient (Pt#4) had BCR/ABL fusion gene mutation, and one patient (Pt#9) had JAK1, JAK3, FBXW7 mutation. Six patients received ALL-directed induction therapy (VDLP), whereas two patients received AML-directed induction therapy (MEA and IA regimens). Overall, 4 of 8 (50%) patients with chemotherapy achieved complete remission (CR) after initial induction therapy. In the AML-directed therapy group, 1 of 2 (50%) patients achieved CR. Meanwhile, 3 of 6 (50%) patients achieved CR after ALL-directed induction chemotherapy. Two patients received HSCT after initial CRs, one patient (Pt#7) died two months after transplantation due to the infection, and another patient (Pt#5) is still alive. With an average of 14.3 (4.0-42.0) months follow-up, the median survival time was 7 months. Conclusion: We reported 10 cases of BAL, including 4 cases of B/Myeloid phenotype, 4 cases of T/Myeloid phenotype and 2 case of T/B phenotype. 4 of 8 patients achieved CR (50%) after initial chemotherapy. Although many patients achieved CR after initial chemotherapy, but the relapse rate was very high and the CR rate after relapse was very low. Our results confirmed that BAL is a rare malignancy with a very poor prognosis. Disclosures No relevant conflicts of interest to declare.

Mixed Phenotype Acute Leukemia that Evolved from Myelodysplastic Syndrome with Excess Blasts

Myelodysplastic syndrome (MDS) that evolves into acute leukemia with blasts of mixed phenotypes has rarely been reported and has no distinct diagnostic category. Herein, we describe a 79-year-old Korean female patient with MDS–excess blasts (MDS-EB) that evolved into acute leukemia; the blasts simultaneously expressed B-lymphoid and myeloid antigens. The patient was diagnosed with MDS-EB with blasts of myeloid lineage coexpressing a few B-lymphoid antigens with 7q and 20q abnormalities. The disease progressed to acute leukemia with blasts carrying more B-lymphoid antigens, which was immunophenotypically compatible with B-lymphoid/myeloid acute leukemia. Unlike previously reported patients whose blast populations are bilineal, our patient is the first with biphenotypic acute leukemia that progressed from MDS. The diagnosis of our patient introduces the possibility that many other types of biphenotypic acute leukemia may have gone undiagnosed and encourages hematologists to designate a specific diagnostic category for this type of disease, so that it can more readily be detected and studied in the future.

Biphenotypic Acute Leukemia versus Myeloid Antigen-Positive ALL: Clinical Relevance of WHO Criteria for Mixed Phenotype Acute Leukemia

Updated WHO criteria define mixed phenotype acute leukemia (MPAL) with more stringent diagnostic criteria than the formerly described entity biphenotypic acute leukemia (BAL). The changes in diagnostic criteria influence management by assigning weight to aberrantly expressed markers and minimizing expression of myeloid markers other than myeloperoxidase (MPO), potentially foregoing consolidative allogeneic transplant for an otherwise “favorable” lymphoid phenotypic leukemia. We present a case of MPO-negative, myeloid antigen-positive acute lymphoblastic leukemia who progressed with refractory phenotypic acute myeloid leukemia while receiving lymphoid-directed therapy and discuss concerns raised by the adoption of the new, more stringent diagnostic criteria for BAL.