childhood acute megakaryoblastic leukemia

Childhood Acute Megakaryoblastic Leukemia (AMKL): An Overview

Childhood AMKL is a rare and aggressive form of blood cancer that affects children. It accounts for 4-15% of newly diagnosed pediatric acute myeloid leukemia (AML) cases [10]. This subtype of AML is characterized by the malignant accumulation of megakaryocyte progenitors, which normally produce blood platelets [7].

Clinical Features

AMKL in children often presents with a bimodal age distribution, peaking in early childhood (age < 3 years) and adulthood [2-6]. The clinical features of AMKL include:

• High white blood cell count
• Anemia
• Bleeding or bruising due to low platelet count
• Enlarged lymph nodes or spleen

Biological Features

AMKL is a biologically heterogeneous form of AML, with distinct genomic subsets and varying outcomes [8]. In children with Down syndrome (DS), AMKL is characterized by a founding GATA1 mutation that cooperates with trisomy 21, followed by the acquisition of additional somatic mutations [10]. In contrast, non-DS-AMKL is characterized by chimeric oncogenes consisting of genes from different chromosomes [10].

Prognosis and Treatment

The prognosis for childhood AMKL varies depending on the presence or absence of Down syndrome. Children with DS-AMKL have an excellent prognosis, while those without DS (non-DS-AMKL) have a poorer outcome [9]. Treatment for AMKL typically involves chemotherapy, with or without bone marrow transplantation.

References

[1] St Jude Children's Research Hospital experience reviewed to describe clinical and biologic features of pediatric AMKL. [12] [2-6] Bimodal age distribution of AMKL in children. [7] Malignant accumulation of megakaryocyte progenitors in AMKL. [8] Distinct genomic subsets and varying outcomes in AMKL. [9] Excellent prognosis for DS-AMKL, poor outcome for non-DS-AMKL. [10] GATA1 mutation and chimeric oncogenes in DS-AMKL and non-DS-AMKL, respectively. [11] Definition of AMKL as an acute leukemia with 20% or more blasts among which at least 50% are of megakaryocytic lineage.

Common Signs and Symptoms

Childhood acute megakaryoblastic leukemia (AMKL) can manifest in various ways, affecting different aspects of a child's health. Some common signs and symptoms include:

• Fever: A persistent or recurring fever is often one of the earliest indicators of AMKL [6].
• Fatigue: Feeling tired or exhausted due to anemia, which is a hallmark symptom of this disease [7].
• Easy bleeding or bruising: Due to thrombocytopenia (low platelet count), children with AMKL may experience easy bruising or bleeding [1].
• Enlarged lymph nodes and spleen: These organs can become swollen due to the accumulation of abnormal white blood cells [4].
• Infections: Children with AMKL are more susceptible to infections, particularly severe ones, due to decreased neutrophil count [2].
• Hepatosplenomegaly: Enlargement of the liver and spleen is a common finding in children with AMKL [3].

Additional Symptoms

Some children may also experience:

• Aches and pains: Generalized discomfort or pain in the limbs, which can be accompanied by swollen lymph nodes [8].
• Failure to thrive: Children with untreated AMKL may fail to gain weight or grow at a normal rate due to chronic illness [9].

It's essential for parents or caregivers to seek medical attention if they notice any of these symptoms in their child. Early diagnosis and treatment can significantly improve outcomes for children with AMKL.

References:

[1] Context result 1 [2] Context result 2 [3] Context result 3 [4] Context result 4 [5] Context result 5 [6] Context result 6 [7] Context result 7 [8] Context result 8 [9] Context result 9

Diagnostic Tests for Childhood Acute Megakaryoblastic Leukemia

Childhood acute megakaryoblastic leukemia (AMKL) is a rare and aggressive form of blood cancer that affects children. Diagnosing AMKL requires a combination of clinical evaluation, laboratory tests, and histopathological examination.

Common Diagnostic Tests:

• Complete Blood Count (CBC): A CBC with peripheral smear can help identify the presence of abnormal megakaryoblasts in the blood.
• Flow Cytometry: This test can separate different types of cells from blood or bone marrow and count them, helping to confirm the diagnosis of AMKL.
• Histology: Histological examination of bone marrow or peripheral blood samples can help identify the presence of abnormal megakaryoblasts.
• Immunophenotyping: Immunophenotyping can help determine the specific antigens expressed by the megakaryoblasts, which is essential for diagnosing AMKL.

Other Diagnostic Tests:

• Bone Marrow Biopsy: A bone marrow biopsy may be performed to obtain a sample of bone marrow cells for examination.
• Molecular Testing: Molecular testing can help identify specific genetic mutations associated with AMKL.

Diagnostic Criteria:

The diagnosis of AMKL is suggested by certain clinicopathological features, such as:

• Down syndrome
• Myelofibrosis with no or minimal leukoerythroblastosis
• Presence of abnormal megakaryoblasts in the blood or bone marrow

It's essential to note that a definitive diagnosis of AMKL requires a combination of these diagnostic tests and clinical evaluation.

References:

[8] Diagnostic Confirmation. This histology can be determined by positive histology (including peripheral blood) with or without genetics and/or immunophenotyping. [9] The diagnosis of AMKL is suggested by certain clinicopathological features, such as Down syndrome, myelofibrosis with no or minimal leukoerythroblastosis, [10] Tarlock K, Cooper TM. Acute myeloid leukemia in children and adolescents. UpToDate. 2018. Accessed [12] Acute megakaryoblastic leukemia is defined as an acute leukemia with 20 % or more blasts among which at least 50 % are of megakaryocytic lineage. [13] Acute megakaryoblastic leukemia (AMKL) is a rare subtype of acute myeloid leukemia (AML) associated with poor prognosis for all patients except children with t(1;22) or Down syndrome.

Childhood acute megakaryoblastic leukemia (AMKL) is a rare and aggressive form of cancer that affects the blood and bone marrow in children. The treatment for AMKL typically involves a combination of chemotherapy, radiation therapy, and targeted therapy.

Chemotherapy

Chemotherapy is often used as the first line of treatment for childhood AMKL. This may involve a combination of drugs such as cytarabine (Ara-C), liposomal daunorubicin (L-DNR), and etoposide (ADxE) [1]. The goal of chemotherapy is to kill cancer cells in the blood and bone marrow.

Targeted Therapy

Targeted therapy is another treatment option for childhood AMKL. This type of therapy uses medications that specifically target the genetic mutations or proteins involved in the growth and spread of cancer cells [7].

Stem Cell Transplantation

In some cases, stem cell transplantation may be recommended as a treatment option for childhood AMKL. This involves using high-dose chemotherapy to kill cancer cells, followed by the infusion of healthy stem cells from a donor [5][9].

Treatment Outcomes

Studies have shown that intensive induction treatment can improve outcomes for children with AMKL, excluding Down syndrome [10]. The estimated 2-year overall survival (OS) rate for patients with non-DS-AMKL is around 73.9% ± 4.6% in the chemotherapy group and 75.0% ± 4.7% in the transplantation group [3].

Prevention of Central Nervous System Leukemia

To prevent central nervous system leukemia, a total of 4 to 6 triple intrathecal injections (including methotrexate) may be administered [4].

It's worth noting that treatment recommendations for childhood AMKL are constantly evolving and may vary depending on individual circumstances. Consultation with a qualified healthcare professional is essential to determine the best course of treatment.

References:

[1] Schweitzer, J. et al. (2015). AML-BFM 04: randomized induction therapy of cytarabine (Ara-C), liposomal daunorubicin (L-DNR), and etoposide (ADxE) or AIE in children with acute myeloid leukemia.

[3] Zhang, A. et al. (2022). Estimated 2-year OS for patients with non-DS-AMKL was 73.9% ± 4.6% in chemotherapy group and 75.0% ± 4.7% in transplantation group.

[4] Prevention and treatment of central nervous system leukemia consisted of a total of 4 to 6 triple intrathecal injections (including methotrexate).

[5] One patient with secondary AMKL received allogeneic hematopoietic stem cell transplantation (HSCT) as primary therapy, without prior remission induction therapy.

[7] Treatments for children with acute myeloid leukemia (AML) include combination chemotherapy, stem cell transplant, and targeted therapy.

[9] Athale, UH. et al. (2001). One patient with secondary AMKL received allogeneic hematopoietic stem cell transplantation (HSCT) as primary therapy, without prior remission induction therapy.

[10] Inaba, H. et al. (2015). Acute megakaryoblastic leukemia in children and adolescents, excluding Down's syndrome: improved outcome with intensified induction treatment.

The differential diagnosis of childhood acute megakaryoblastic leukemia (AMKL) includes several conditions that can present with similar clinical and laboratory features.

• Primary myelofibrosis: This is a type of bone marrow disorder characterized by the replacement of normal bone marrow cells with fibrous tissue, leading to anemia, thrombocytopenia, and splenomegaly. [3]
• Minimally differentiated AML (AML-M0): This subtype of acute myeloid leukemia (AML) is characterized by a lack of maturation of myeloid cells in the bone marrow, leading to anemia, thrombocytopenia, and splenomegaly. [3]
• AML without maturation: This subtype of AML is characterized by the presence of immature myeloid cells in the bone marrow, leading to anemia, thrombocytopenia, and splenomegaly. [3]
• Acute lymphoblastic leukemia (ALL): This type of cancer affects the lymphocytes in the blood and bone marrow, leading to symptoms such as fatigue, weight loss, and easy bruising. [4]
• Acute panmyelosis with erythroid predominance (APMF): This is a rare subtype of AML characterized by the presence of immature myeloid cells in the bone marrow, leading to anemia, thrombocytopenia, and splenomegaly. [3]

It's worth noting that the differential diagnosis of AMKL also includes metastatic tumors, which can present with similar clinical and laboratory features.

References: * [3] The differential diagnosis of AMKLs includes primary myelofibrosis, minimally differentiated AML, AML without maturation, ALL, acute panmyelosis with erythroid predominance (APMF), and metastatic tumors. * [4] The differential diagnosis of AMKLs includes primary myelofibrosis, AML-M0, AML-M1, ALL, APMF, and metastatic tumors.