Leukemia, Acute Lymphoblastic (All)

Key Features

Essentials of Diagnosis

• Bruising, pallor, petechiae, and purpura

• Hepatomegaly

• Splenomegaly

• Lymphadenopathy

General Considerations

• Defined by the presence of > 25% malignant hematopoietic cells (blasts) in the bone marrow aspirate

• Accounts for about 25% of all cancer diagnoses in patients younger than 15 years

• Worldwide incidence is about 1:25,000 children per year, including 3000 children per year in the United States

• Peak age at onset is 4 years; 85% of patients are diagnosed between ages 2 and 10 years

• Children with Down syndrome have a 14-fold increase in the overall rate of leukemia

Clinical Findings

Symptoms and Signs

• Pallor, petechiae, and purpura

• Intermittent fevers are common

• Bone pain, especially in the pelvis, vertebral bodies, and legs

• Hepatomegaly and splenomegaly

• Lymphadenopathy is common, either localized or generalized to cervical, axillary, and inguinal regions

• Testes may occasionally be unilaterally or bilaterally enlarged secondary to leukemic infiltration

• Superior vena cava syndrome is caused by mediastinal adenopathy compressing the superior vena cava

• Neck may feel full from venous engorgement

• Face may appear plethoric, and the periorbital area may be edematous

Differential Diagnosis

• Epstein-Barr virus

• Cytomegalovirus

• Immune thrombocytopenic purpura

• Transient erythroblastopenia of childhood

• Autoimmune hemolytic anemias

• Aplastic anemia

• Juvenile rheumatoid arthritis

Diagnosis

Laboratory Findings

• Complete blood count (CBC) with differential is the most useful initial test

• WBC count

  • Low or normal (= 10,000/μL) in 50% of patients, but the differential shows neutropenia (absolute neutrophil count < 1000/μL) along with a small percentage of blasts amid normal lymphocytes

  • Between 10,000/μL and 50,000/μL in 30%

  • Over 50,000/μL, occasionally higher than 300,000/μL in 20%

• Peripheral blood smears also show abnormalities in RBCs

• Most patients have decreased platelet counts (< 150,000/μL) and decreased hemoglobin (< 11 g/dL) at diagnosis

• Serum chemistries, particularly uric acid and lactate dehydrogenase, are often elevated as a result of cell breakdown

• Bone marrow examination confirm diagnosis

Imaging

• Chest radiograph may show mediastinal widening or an anterior mediastinal mass and tracheal compression secondary to lymphadenopathy or thymic infiltration, especially in T-cell ALL

• Plain radiographs of the long bones and spine may show demineralization, periosteal elevation, growth arrest lines, or compression of vertebral bodies

• Abdominal ultrasound may show kidney enlargement from leukemic infiltration or uric acid nephropathy as well as intra-abdominal adenopathy

Treatment

Specific Therapy

• Medications used most commonly in induction

  • Oral prednisone or dexamethasone

  • Intravenous vincristine

  • Daunorubicin

  • Intramuscular or intravenous asparaginase

  • Intrathecal methotrexate

• Consolidation is the second phase of treatment, during which intrathecal chemotherapy along with continued systemic therapy and sometimes cranial radiation therapy are given to kill lymphoblasts "hiding" in the meninges

• Several months of intensive chemotherapy follows consolidation, often referred to as intensification

• Maintenance therapy can include

  • Daily oral mercaptopurine

  • Weekly oral methotrexate

  • Monthly pulses of intravenous vincristine and oral prednisone or dexamethasone

• Intrathecal chemotherapy, either with methotrexate alone ...