mixed phenotype acute leukemia, T/myeloid

Mixed Phenotype Acute Leukemia (MPAL), T/Myeloid: A Rare and Challenging Condition

Mixed phenotype acute leukemia (MPAL) is a rare and aggressive form of blood cancer that combines characteristics of both myeloid and lymphoid leukemias. The T/myeloid subtype, in particular, is a type of MPAL where the malignant cells express features of both T-cell and myeloid lineages.

Key Features:

• Immunophenotypic features: MPAL-TM cells exhibit co-expression of myeloid and lymphoid antigens, making diagnosis challenging.
• Genetic mutations: High frequency of DNMT3A mutations and other genetic alterations characteristic of both AML and T-ALL.
• Clinical behavior: Aggressive clinical course with poor prognosis.

Diagnosis and Treatment:

Due to its rarity and heterogeneity, MPAL-TM poses a significant diagnostic and therapeutic challenge. Accurate diagnosis requires comprehensive immunophenotyping and molecular analysis. Treatment approaches often involve a combination of therapies typically used for AML or T-ALL, but the optimal treatment strategy remains unclear.

References:

• [1] MP McCormack et al. (2022) - MPAL is a rare leukemia subtype with poor prognosis that is characterized by immunophenotypic features of both myeloid and lymphoid lineages.
• [3] MPAL T-myeloid, NOS: Those with this subtype exhibit further genetic features of both AML and T-ALL.
• [6] Definition. Mixed-phenotype acute leukemia, T/myeloid, not otherwise specified fulfills the criteria for both T-cell and myeloid lineage.

Note: The information provided is based on the search results and may not be an exhaustive or definitive description of MPAL-TM.

Mixed Phenotype Acute Leukemia (MPAL), specifically the T/myeloid type, presents with a range of signs and symptoms that can be similar to other types of acute leukemias. Here are some of the common symptoms:

• Anemia: Fatigue, weakness, dizziness or lightheadedness due to a lack of red blood cells [3].
• Bone or joint pain: Pain in the bones or joints, which can be caused by the accumulation of abnormal white blood cells in these areas [5].
• Easy bruising or bleeding: Easy bruising or bleeding due to a decrease in platelet count or function [5].
• Eczema-like skin symptoms: Some patients may experience eczema-like skin symptoms, although this is not a universal symptom [5].

It's essential to note that the diagnosis of MPAL requires finding both lymphoid and myeloid antigen markers on the same cell. The symptoms mentioned above can be similar to those experienced by patients with other types of acute leukemias.

In terms of prognosis, poor prognostic factors for MPAL include an older age at diagnosis, higher white blood cell (WBC) count at presentation, and a T-lymphoid/myeloid phenotype [9]. However, it's crucial to consult medical professionals for accurate diagnosis and treatment options.

Mixed phenotype acute leukemia (MPAL), specifically the T/myeloid subtype, requires a comprehensive diagnostic approach to confirm its presence. Here are some key diagnostic tests that may be used:

• Flow cytometry: This is a crucial test for diagnosing MPAL, as it can help identify the co-expression of lymphoid and myeloid markers in a single blast population ([4], [9]). A flow cytometry panel should include markers such as CD2, CD7, CD56, and cytoplasmic cluster of differentiation (cCD3) to assign a T-cell lineage ([8]).
• Bone marrow aspiration and biopsy: These tests can help identify the presence of mixed-phenotype blasts in the bone marrow ([6], [10]). The biopsy can also provide information on the cellularity and morphology of the bone marrow.
• Complete blood count (CBC) and other blood tests: A CBC can help identify any abnormalities in the blood cells, such as anemia or thrombocytopenia. Other blood tests may be ordered to rule out other conditions ([6]).
• Immunophenotyping: This involves analyzing the surface markers on the blasts using flow cytometry or immunohistochemistry. It is essential for confirming the diagnosis of MPAL and distinguishing it from other types of leukemia ([4], [9]).
• Cytogenetics and molecular analysis: These tests can help identify any chromosomal abnormalities or genetic mutations that may be present in the blasts ([5], [14]). However, they do not replace conventional cytogenetic analysis.

It's worth noting that a diagnosis of MPAL should only be made after comprehensive examinations, including bone marrow cell morphology, flow cytometry analysis, cytogenetics, and molecular analysis ([5]).

References:

[4] Mixed-phenotype acute leukemia (MPAL) is a heterogeneous category in the World Health Organization classification... [context 4] [8] Cytoplasmic cluster of differentiation (cCD3) is essential to assign a T-cell lineage in MPAL. CD2, CD7, and CD56 are also important markers. [context 8] [9] The flow cytometry panel should be sufficient to distinguish acute myeloid leukemia, T-ALL (including early T-cell precursor leukemia), B-ALL, and acute leukemia of ambiguous lineage on all patients diagnosed with acute leukemia. [context 14] [10] Extensive immunophenotypic analysis is required for evaluation of these neoplasms... [context 10]

Treatment Options for Mixed Phenotype Acute Leukemia (MPAL), T/Myeloid

Mixed phenotype acute leukemia (MPAL) is a rare subtype of acute leukemia characterized by differentiation along more than one lineage. In the absence of eosinophilia and/or stereotypical tyrosine kinase gene fusions, there is no established optimal therapy for adults with MPAL.

Chemotherapy

Treatment was classified as either AML-type (anthracycline-based chemotherapy) or ALL-type (chemotherapy regimens used in acute lymphoblastic leukemia). Some patients received a combination of both therapies. For example, high-dose cytarabine plus mitoxantrone ("ALL-2") is one of the most utilized induction regimens for MPAL.

Targeted Therapy

Venetoclax, which targets BCL-2, combined with various chemotherapies in MPAL, has shown encouraging results in recent case series. Additionally, transplanting stem cells (bone marrow) after chemotherapy may be an option for some patients.

Other Therapeutic Options

Therapeutic options include using acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), or a combination of both therapies. Two subjects died before starting chemotherapy, and ten patients (25%) received ALL induction, with all achieving complete remission.

Post-Remission Therapy

Post-remission therapy for Philadelphia chromosome-negative acute lymphoblastic leukemia in adults may also be applicable to MPAL patients.

References:

• [10] Mixed phenotype acute leukemia (MPAL) is a rare subtype of acute leukemia characterized by differentiation along more than one lineage.
• [9] Ten patients (25%) received acute lymphoblastic leukemia (ALL) induction, and all achieved complete remission.
• [8] The most utilized induction regimen for MPAL is high dose cytarabine plus mitoxantrone (“ALL-2”), though outcomes with this regimen are not well described.
• [6] Venetoclax, which targets BCL-2, combined with various chemotherapies in MPAL, has shown encouraging results in recent case series.
• [7] Therapeutic options include using acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), or a combination of both therapies.

The differential diagnosis of mixed phenotype acute leukemia (MPAL) with a T/myeloid lineage can be challenging due to its complex immunophenotype.

Key Considerations

• The presence of both T-cell and myeloid markers in the blasts suggests a mixed phenotype, which can make it difficult to distinguish from other types of acute leukemias.
• The differential diagnosis includes:
  • Acute T-lymphoblastic leukemia (T-ALL) with myeloid antigen expression
  • T/myeloid MPAL
  • Myeloid-B and myeloid-T MPAL show distinct genetic features [7]
• It is essential to perform a thorough immunophenotypic analysis, including flow cytometry and molecular studies, to confirm the diagnosis.
• The presence of specific genetic abnormalities, such as t(3;3), can also aid in the differential diagnosis [2][8]

Differential Diagnosis

The differential diagnosis between ETP ALL with myeloid antigen expression and T/myeloid MPAL is tricky [5]. A careful analysis of the immunophenotype, including the expression of specific markers such as CD117 and CD33, can help distinguish between these two entities.

• Acute T-lymphoblastic leukemia (T-ALL) with myeloid antigen expression:
  • Typically presents with a T-cell immunophenotype
  • May express myeloid antigens, but the T-cell markers are more prominent
• T/myeloid MPAL:
  • Presents with a mixed phenotype of both T-cell and myeloid markers
  • The myeloid markers may be more pronounced than in T-ALL

Rare Features

Some cases of T/myeloid MPAL can present with rare features, such as monocytic differentiation [6] or isolated 17p deletion [6]. These features can aid in the differential diagnosis and provide additional clues for the diagnosis.

In summary, the differential diagnosis of mixed phenotype acute leukemia (MPAL) with a T/myeloid lineage requires a thorough analysis of the immunophenotype, including flow cytometry and molecular studies. The presence of specific genetic abnormalities and rare features can also aid in the differential diagnosis.

References:

[1] A Porwit · 2015 · Cited by 65 [2] Y Jia · 2022 · Cited by 3 [3] NJ Charles · 2017 · Cited by 90 [4] T Carll · 2020 · Cited by 14 [5] RN Pawar · 2023 [6] GS Lopes · 2014 · Cited by 2 [7] K Takahashi · 2018 · Cited by 102 [8] Y Jia · 2022 · Cited by 3 [9] BS George · 2022 · Cited by 16