myeloid and lymphoid neoplasms associated with PDGFRA rearrangement

Myeloid and lymphoid neoplasms associated with PDGFRA rearrangement are a rare type of cancer that affects the blood and bone marrow. These neoplasms, also known as myeloproliferative neoplasms (MPNs), are characterized by the presence of abnormal cells in the bone marrow and blood.

Types of Presentation

These neoplasms can present in different ways, including:

• Chronic Eosinophilic Leukemia (CEL): This is the most common presentation, where there is an overproduction of eosinophils, a type of white blood cell.
• Acute Myeloid Leukemia (AML): In some cases, these neoplasms can progress to AML, which is a more aggressive form of leukemia.
• T-Lymphoblastic Lymphoma: These neoplasms can also present as T-lymphoblastic lymphoma, a type of cancer that affects the immune system.

Demographics

These neoplasms are rare and have a striking male predominance, with a male-to-female ratio of approximately 16:1 overall [1].

References

• [1] Myeloid/lymphoid neoplasms with eosinophilia and PDGFRA rearrangements is a rare syndrome with striking male predominance (M: F approximately 16:1 overall). [Context 1]
• These neoplasms generally present as chronic eosinophilic leukemia (CEL), but can also present as acute myeloid leukemia, T-lymphoblastic leukemia lymphoma, or ... [Context 2]
• Myeloid neoplasms with PDGFRA rearrangement are rare, and most commonly present with features of chronic eosinophilic leukemia; however, they ... [Context 3]
• Neoplasms associated with rearrangement of PDGFRA can present as acute myeloid leukemia or as T lymphoblastic lymphoma with eosinophilia. [Context 4]

Myeloid and lymphoid neoplasms associated with PDGFRA rearrangement are a type of blood cancer that can present with various signs and symptoms. According to the search results, these conditions often have similar signs and symptoms, which include:

• Eosinophilia: An elevated number of eosinophils in the blood, which is a hallmark of this condition [1].
• Leukocytosis: An increase in the number of white blood cells in the blood [8].
• Anemia: A decrease in the number of red blood cells or hemoglobin in the blood [8].
• Thrombocytopenia: A decrease in the number of platelets in the blood [8].

In addition to these hematological abnormalities, patients with myeloid and lymphoid neoplasms associated with PDGFRA rearrangement may also experience:

• Organ damage: Eosinophilia can lead to life-threatening organ damage, including lung fibrosis, thromboembolism, and eosinophilic gastritis [4].
• Splenomegaly: An enlarged spleen is a common finding in these patients [9].

It's worth noting that the presentation of myeloid and lymphoid neoplasms associated with PDGFRA rearrangement can vary widely among individuals, and not all patients will exhibit all of these signs and symptoms.

References: [1] Sep 1, 2015 — PDGFRA-associated chronic eosinophilic leukemia is a form of blood cell cancer characterized by an elevated number of cells called eosinophils in the blood. [4] by M Abu-Tineh · 2021 · Cited by 4 — Lung fibrosis, thromboembolism, and eosinophilic gastritis are some of the most serious symptoms. In addition to an enlarged spleen and higher ... [8] by A Reiter · 2017 · Cited by 287 — Eosinophilia is observed in a range of reactive and clonal disorders and may be associated with life-threatening organ damage. [9] by M Abu-Tineh · 2021 · Cited by 4 — Lung fibrosis, thromboembolism, and eosinophilic gastritis are some of the most serious symptoms. In addition to an enlarged spleen and higher ...

To determine the diagnostic tests for myeloid and lymphoid neoplasms associated with PDGFRA rearrangement, several tests can be employed.

• Blood chemistry studies can help identify any abnormalities in blood cell counts or chemistry levels.
• Bone marrow aspiration and biopsy are crucial in evaluating the bone marrow's cellular composition and architecture. This test can provide valuable information about the presence of neoplastic cells.
• Complete blood count (CBC) is a basic test that measures various components of the blood, including red and white blood cell counts, hemoglobin levels, and platelet counts.
• Cytogenetic analysis involves examining the chromosomes in bone marrow cells to identify any abnormalities or rearrangements, such as PDGFRA rearrangement.
• Immunophenotyping can help determine the type of neoplastic cells present by analyzing their surface markers.

These tests are useful for detecting a neoplastic clone associated with common chromosome abnormalities seen in patients with myeloid/lymphoid neoplasms with eosinophilia [4]. A diagnosis of myeloid/lymphoid neoplasm with eosinophilia (M/LN-eo) and FIP1L1::PDGFRA rearrangement was made using these diagnostic exams [7].

In patients with PDGFRA/PDGFRB fusion genes, secondary BP only occurred in 6% of patients after a median of 87 months because >90% of patients had no evidence of secondary malignancies [9].

Treatment Options for Myeloid and Lymphoid Neoplasms Associated with PDGFRA Rearrangement

Myeloid and lymphoid neoplasms (MLNs) associated with PDGFRA rearrangement are a type of rare, malignant disease characterized by clonal proliferation of myeloid and/or lymphoid precursors harboring rearrangements in the PDGFRA gene [5]. The treatment of MLNs associated with PDGFRA rearrangement typically involves targeted therapy with tyrosine kinase inhibitors (TKIs) such as imatinib.

Imatinib: A First-Line Therapy

Imatinib is a TKI that has been shown to be highly effective in patients with PDGFRA and PDGFRB fusion genes, including those with MLNs associated with PDGFRA rearrangement [4]. Studies have demonstrated that imatinib can induce high rates of treatment response and remission in these patients [3].

Other Treatment Options

While imatinib is a first-line therapy for MLNs associated with PDGFRA rearrangement, other TKIs may also be effective in some cases. For example, dasatinib has been shown to be active against PDGFRA/B fusion genes, although its efficacy compared to imatinib is not well established [7].

Steroid-Sparing Agents

In addition to TKIs, corticosteroids such as prednisone may also be used in the treatment of MLNs associated with PDGFRA rearrangement. However, the use of corticosteroids along with low-dose oral cyclophosphamide or methotrexate as steroid-sparing agents has been reported [1].

Pediatric Cases

In pediatric cases, myeloid/lymphoid neoplasm with PDGFRA rearrangement presenting with synchronous myeloproliferative disease and B-LBL has been described. This is a rare occurrence, and the treatment of these patients may require a multidisciplinary approach [9].

References:

[1] P Kaur (2022) - Cited by 4 [3] G Metzgeroth (2020) - Cited by 35 [4] G Metzgeroth (2023) - Cited by 10 [5] A rare, malignant, neoplastic disease characterized by clonal proliferation of myeloid and/or lymphoid precursors harboring rearrangements in the PDGFRA gene. [6] Myeloid/lymphoid neoplasms with PDGFRA rearrangement is the most common neoplasm associated with PDGFRA and is associated with FIP1L1-PDGFRA gene fusion. [7] A Reiter (2017) - Cited by 287 [8] N Savage (2013) - Cited by 76 [9] R Akiely (2022) - Cited by 2

The differential diagnosis for myeloid and lymphoid neoplasms associated with PDGFRA rearrangement may include other myeloid neoplasms with associated eosinophilia, such as systemic mastocytosis [1]. Additionally, diagnostic criteria for myeloid/lymphoid neoplasms associated with ETV6-PDGFRB fusion gene or other rearrangement of PDGFRB should be considered [2].

Other conditions that may be part of the differential diagnosis include:

• Myeloid and lymphoid neoplasms with eosinophilia and PCM1::JAK2 rearrangement or FGFR1 rearrangement, which have a high transformation rate to acute leukemias [3].
• Molecular genetic characterization of myeloid/lymphoid neoplasms associated with eosinophilia and rearrangement of PDGFRA, PDGFRB, FGFR1 or PCM1, as described in the literature [4].

It is also worth noting that myeloid/Lymphoid neoplasms with eosinophilia (M/LN-Eo) harboring gene rearrangements of PDGFRA, PDGFRB, FGFR1, JAK2 were first recognized as a distinct entity in the medical literature [5]. Furthermore, myeloid, lymphoid or combined myeloid / lymphoid neoplasms often accompanied with eosinophilia and associated with FIP1L1-PDGFRA fusion have been reported [6].

The differential diagnosis for PDGFRA rearrangement-associated myeloid and lymphoid neoplasms is complex and requires careful consideration of various conditions. A comprehensive evaluation, including cytogenetics/FISH study, may be necessary to detect all PDGFRB rearrangements critical for patient management [8].