An update on classification, genetics, and clinical approach to mixed phenotype acute leukemia (MPAL)

Khan, Maliha; Siddiqi, Rabbia; Naqvi, Kiran

doi:10.1007/s00277-018-3297-6

Cited by 50 publications

(36 citation statements)

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“…Cases with BCR‐ABL1 or KMT2A rearrangements are allocated to specific categories . The presence of a complex karyotype with MPAL immunophenotype does not classify the case as “AML with MDS‐related features” as suggested in some publications . The only situation when “AML with MDS‐related features” in the context of MPAL immunophenotype can be considered is if the patient had a previously known myelodysplastic (MDS) phase .…”

Section: Cytogeneticsmentioning

confidence: 99%

“…The epidemiology of MPAL remains difficult to establish. A review of the literature and reports from “Surveillance, Epidemiology, and End Results” have been summarized by Khan et al and indicate that MPALs account for about 2% of acute leukemias, with an incidence of 0.35 per million inhabitants. There seems to be a slight male prevalence.…”

Section: Clinical Outlinesmentioning

confidence: 99%

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Multiparameter flow cytometry applications in the diagnosis of mixed phenotype acute leukemia

Porwit

Béné²

2019

Cytometry Part B Clinical

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Mixed phenotype acute leukemias (MPALs) represent a rare subgroup of acute leukemias with a poor prognosis. Proper diagnosis and classification of MPAL is extremely important for patients' outcome. Morphology and flow cytometry recognize two types of MPAL: the “bilineal” MPAL with the coexistence of two blast populations of different lineage and truly “biphenotypic” MPAL coexpressing markers of more than one lineage in a homogenous blast population, respectively. The WHO 2008 classification further delineated three categories: associated with t(9;22)/BCR‐ABL1 fusion gene, associated with KMT2A (mixed lineage leukemia) rearrangements, and nonotherwise specified. These categories remained unchanged in the WHO2016 update. Molecular studies have further underlined the heterogeneity of MPAL. In this review, rules for the correct assignment of acute leukemia to the MPAL category are discussed, including both flow cytometry and immunohistochemistry on bone marrow or other tissues biopsies. Comparison of the immunophenotypic classification proposals is provided outlining the explorations mandatory for definitive diagnosis. An extensive review of published data summarizes the reported cytogenetic and molecular anomalies. New developments in the understanding of the early stages of hematopoiesis provide clues to the possible etiopathology of these diseases. Finally, current treatment recommendations are summarized and referenced for clinical use, pointing out that allogeneic hematopoietic stem cell transplantation at an early stage should be considered (at least in adult patients). © 2019 International Clinical Cytometry Society

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Section: Cytogeneticsmentioning

confidence: 99%

Section: Clinical Outlinesmentioning

confidence: 99%

Multiparameter flow cytometry applications in the diagnosis of mixed phenotype acute leukemia

Porwit

Béné²

2019

Cytometry Part B Clinical

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“…Finally, as seen in this case, MPAL can be particularly difficult to treat and may require novel therapies in order to improve survival [5]. Current leukemia regimens are primarily lineage specific and tailored toward either lymphoid or myeloid disease.…”

Section: Discussionmentioning

confidence: 94%

“…Mixed phenotype acute leukemia (MPAL) is a rare but well-described form of childhood leukemia, with the leukemic blasts expressing features of both lymphoid and myeloid lineage [1][2][3][4][5]. These cases typically have a de novo presentation, with the initiating cell believed to be an early common lineage precursor cell.…”

Section: Introductionmentioning

confidence: 99%

Clonal Evolution of B-Cell Acute Lymphoblastic Leukemia with del(9)(p13p21) into Mixed Phenotype Acute Leukemia Presenting as an Isolated Testicular Relapse

Miller

Park

Saxe

et al. 2019

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Lineage switch in acute leukemias is a well-reported occurrence; however, most of these cases involve a switch from either lymphoid to myeloid or myeloid to lymphoid lineage. Here, we report a case of a 14-year-old male with B-cell acute lymphoblastic leukemia (B-ALL) who initially responded well to standard chemotherapy but then later developed mixed phenotype acute leukemia (MPAL) at relapse, likely reflecting a clonal evolution of the original leukemia with a partial phenotypic shift. The patient had a del(9)(p13p21) in his leukemia blasts at diagnosis, and the deletion persisted at relapse along with multiple additional cytogenetic aberrations. Interestingly, the patient presented with an isolated testicular lesion at relapse, which on further analysis revealed both a lymphoid and myeloid component. Unfortunately, the patient did not respond well to treatment at relapse and eventually succumbed to his disease. To our knowledge, an isolated extramedullary MPAL at relapse in a patient with previously diagnosed B-ALL has not been reported in the literature before.

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“…In 2008, new World Health Organization (WHO) classifications of hematopoietic and lymphoid tumors were proposed, in which mixed phenotype acute leukemia (MPAL) was defined as a new disease entity representing the rare subtype of AL that has blast cells co‐expressing certain antigens of more than one lineage on the same cells or that has separate populations of blasts of different lineages, that is, biphenotypic or bilineal AL. Thus, MPAL may show a B/T lymphoid, B/myeloid, T/myeloid, or B/T/myeloid phenotype, irrespective of whether one or more than one population of blasts were found 5,6 . Moreover, cases with no lineage‐specific markers, which often express CD34, HLA‐DR, and/or CD38, and sometimes TdT, but lack‐specific myeloid or lymphoid antigens, were designated as acute undifferentiated leukemia (AUL) and also included into MPAL definition.…”

Section: Introductionmentioning

confidence: 99%

Mixed phenotype acute leukemia: Biological profile, clinical characteristic and treatment outcomes: Report of the population‐based study

Zając‐Spychała

Irga‐Jaworska

Drożyńska

et al. 2020

European J of Haematology

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Objectives The aim of this population‐based, retrospective study was to analyze biological and clinical features and treatment results in children diagnosed with MPAL in all Polish pediatric oncology centers between 2007 and 2018. Methods Among 2893 children and adolescents diagnosed and treated for acute leukemia, 39 (1.35%) patients fulfilled the WHO criteria of MPAL. The T/myeloid phenotype was most prevalent. Results Cytogenetics findings were seen in 2 (5.1%), while chromosomal abnormalities were found in 14 (35.9%) patients. Thirty‐two patients achieved CR‐1, including 23 (92.0%) treated with ALL‐directed chemotherapy and 9 (64.3%) treated with AML‐type induction regimens. Within these patients, 4 (12.5%) died due to treatment‐related complications and 11 (34.4%) relapsed. Nineteen (63.3%) patients underwent allo‐HSCT in CR‐1 and 14 (73.7%) of them have been in CR‐1. In total, 17 (43.6%) patients remain in CR‐1 for 1‐12 years, including 14 (58.3%) with T/myeloid MPAL. The 5‐year pOS and pEFS were 51.8% and 44.2%, respectively. The overall survival for ALL‐directed therapy was significantly better than the one for AML‐type chemotherapy (P = .001). It was also better for patients who underwent HSCT in CR‐1 (P = .001). Conclusions The prognosis of MPAL is unsatisfactory, but initial treatment with ALL‐directed chemotherapy consolidated with allo‐HSCT improves the outcomes in MPAL.

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An update on classification, genetics, and clinical approach to mixed phenotype acute leukemia (MPAL)

Cited by 50 publications

References 55 publications

Multiparameter flow cytometry applications in the diagnosis of mixed phenotype acute leukemia

Multiparameter flow cytometry applications in the diagnosis of mixed phenotype acute leukemia

Clonal Evolution of B-Cell Acute Lymphoblastic Leukemia with del(9)(p13p21) into Mixed Phenotype Acute Leukemia Presenting as an Isolated Testicular Relapse

Mixed phenotype acute leukemia: Biological profile, clinical characteristic and treatment outcomes: Report of the population‐based study

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