Overview
Definition:
Leukemia is a malignant proliferation of hematopoietic stem cells, characterized by the uncontrolled growth of immature white blood cells (blasts) in the bone marrow, peripheral blood, and other organs
In pediatrics, acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) are the most common types.
Epidemiology:
Leukemia is the most common childhood cancer, accounting for approximately 25% of all pediatric cancers
The incidence of ALL peaks between ages 2-5 years, while AML is more common in infants and adolescents
Survival rates have significantly improved with advancements in treatment.
Clinical Significance:
Early recognition of leukemia signs and symptoms is crucial for timely diagnosis and initiation of therapy, which significantly impacts prognosis
Understanding the high risk of tumor lysis syndrome (TLS) and appropriate central venous access are critical components of immediate patient management in pediatric leukemia.
Clinical Presentation
Symptoms:
Nonspecific symptoms
Bone pain or joint pain due to marrow infiltration
Fever and recurrent infections due to neutropenia
Easy bruising or bleeding (petechiae, purpura, epistaxis) due to thrombocytopenia
Pallor and fatigue due to anemia
Abdominal distension or palpable masses due to hepatosplenomegaly or organ infiltration
Lymphadenopathy
Weight loss and poor feeding
Neurological symptoms (headache, vomiting, cranial nerve palsies) if central nervous system involvement.
Signs:
Pallor
Petechiae, ecchymoses, or purpura
Hepatosplenomegaly
Lymphadenopathy
Signs of infection
Signs of anemia (tachycardia, tachypnea)
Bone tenderness on palpation
In rare cases, testicular enlargement or mediastinal mass.
Diagnostic Criteria:
Diagnosis is primarily based on peripheral blood smear morphology and bone marrow examination
Key criteria include: identification of >=20% blasts in the bone marrow or peripheral blood for acute leukemia (WHO classification)
Immunophenotyping to determine lineage (B-cell vs
T-cell ALL, myeloid lineage for AML)
Cytogenetic and molecular studies for risk stratification.
Diagnostic Approach
History Taking:
Detailed history of symptom onset and progression
History of prior infections or bleeding tendencies
Family history of hematologic malignancies
Review of systems to elicit organ-specific involvement
Red flags include prolonged fever, unexplained bleeding, bone pain, and pallor.
Physical Examination:
Complete physical examination with emphasis on: vital signs, skin for bruising/petechiae, lymph nodes (cervical, axillary, inguinal), abdomen for hepatosplenomegaly, musculoskeletal system for bone tenderness, neurological examination
Evaluation for signs of CNS involvement (papilledema, cranial nerve deficits).
Investigations:
Complete blood count (CBC) with differential: often shows anemia, thrombocytopenia, and leukocytosis or leukopenia with a significant blast count
Peripheral blood smear: examination for morphology and presence of blasts
Bone marrow aspiration and biopsy: crucial for definitive diagnosis, blast percentage, immunophenotyping, cytogenetics, and molecular studies
Coagulation profile (PT, PTT, INR, fibrinogen): to assess for disseminated intravascular coagulation (DIC)
Serum electrolytes, calcium, phosphorus, uric acid: for baseline assessment and TLS risk
Renal and liver function tests: to assess organ function
Chest X-ray: to evaluate for mediastinal mass or infection
Lumbar puncture: to assess for CNS involvement.
Differential Diagnosis:
Other causes of cytopenias (aplastic anemia, immune thrombocytopenia)
Infectious causes of fever and lymphadenopathy (viral infections, bacterial sepsis)
Other malignancies (neuroblastoma, Wilms tumor)
Reactive lymphocytosis or leukemoid reaction.
Tumor Lysis Syndrome Prevention
Definition:
TLS is a life-threatening complication characterized by rapid tumor cell lysis, leading to the release of intracellular contents into the bloodstream
This can cause hyperuricemia, hyperkalemia, hyperphosphatemia, and hypocalcemia, resulting in acute kidney injury (AKI) and arrhythmias.
Risk Stratification:
Risk factors include high tumor burden, high blast count, bulky disease, rapid proliferation rate, and pre-existing renal impairment
Pediatric leukemias, particularly AML and high-risk ALL, are associated with a high risk of TLS.
Prevention Strategies:
Aggressive hydration: intravenous fluids (e.g., normal saline) initiated prior to chemotherapy to maintain high urine output (2-4 mL/kg/hr)
Alkalinization of urine: with sodium bicarbonate if urine pH < 7.0 to enhance uric acid solubility
Urate oxidase enzyme (rasburicase): a recombinant urate oxidase that rapidly degrades uric acid to more soluble allantoin
Administered intravenously based on weight
Allopurinol: a xanthine oxidase inhibitor that reduces uric acid production, often used for prophylaxis or mild cases
however, rasburicase is preferred for high-risk patients due to faster action
Close monitoring: frequent monitoring of electrolytes, renal function, and uric acid levels
Management of electrolyte abnormalities: prompt correction of hyperkalemia and hyperphosphatemia
calcium supplementation for hypocalcemia.
Tls Management:
If TLS occurs, aggressive hydration and electrolyte correction are paramount
Rasburicase is the treatment of choice for severe hyperuricemia
Hemodialysis may be required for refractory AKI and severe electrolyte derangements
Discontinuation or dose adjustment of chemotherapy may be necessary.
Central Line Access
Indications:
Essential for administration of chemotherapy, fluids, blood products, and antibiotics
Enables frequent blood sampling for monitoring
Minimizes the need for repeated peripheral venipunctures, reducing pain and risk of infection
Provides a secure route for long-term venous access in intensive chemotherapy regimens.
Types Of Lines:
Peripherally Inserted Central Catheters (PICC lines): inserted in a peripheral vein of the arm and threaded to a central vein
Surgically implanted ports (e.g., Port-a-Cath): placed entirely under the skin, with a reservoir accessed by a needle
Tunneled catheters (e.g., Hickman, Broviac): inserted in a peripheral vein and tunneled under the skin to exit on the chest wall.
Insertion Considerations:
Requires experienced personnel and aseptic technique
Choice of line depends on duration of therapy, patient factors, and institutional protocols
Pre-procedure assessment of coagulation status and platelet count is vital
Ultrasound guidance improves success rates and reduces complications.
Care And Maintenance:
Strict aseptic technique for all manipulations (dressing changes, flushing, accessing)
Regular flushing with saline and heparinized saline to maintain patency
Monitoring for signs of infection (fever, erythema, purulence at site) and thrombosis (swelling, pain)
Education of patient and family on care and recognizing complications.
Key Points
Exam Focus:
Recognize leukemia signs/symptoms in children
Understand blast morphology on peripheral smear
Know the criteria for acute leukemia diagnosis
Identify high-risk features for TLS
Know the components of TLS prophylaxis (hydration, alkalinization, rasburicase)
Understand indications and types of central venous access in pediatric oncology
Recognize complications of TLS and central lines.
Clinical Pearls:
Always consider leukemia in a child with persistent fever, bone pain, or unexplained bleeding
Aggressive hydration and rasburicase are cornerstones of TLS prevention in high-risk leukemias
Central lines are a lifeline for pediatric oncology patients, requiring meticulous care
Early consultation with pediatric hematology-oncology is essential.
Common Mistakes:
Delaying diagnosis due to attributing symptoms to benign causes
Underestimating the risk and severity of TLS
Inadequate hydration or delayed administration of rasburicase for TLS prevention
Poor aseptic technique leading to line infections
Inappropriate management of electrolyte imbalances during TLS.