What are the key differences in diagnosis and treatment approaches between adult and pediatric patients in hematology, considering conditions such as sickle cell disease, leukemia, anemia, lymphoma, and myeloma?

Key Differences in Diagnosis and Treatment Between Adult and Pediatric Hematology

Pediatric hematologic malignancies require fundamentally different diagnostic workups and treatment approaches than adult cases, with mandatory CNS evaluation at diagnosis, distinct cytogenetic profiles, age-specific drug dosing, and treatment on pediatric-specific protocols that have demonstrated superior outcomes compared to adult regimens. 1

Diagnostic Workup Differences

Leukemia Diagnosis

Pediatric patients require mandatory cerebrospinal fluid examination at diagnosis for all acute leukemias, while this is not routine practice in adults. 1 CNS positivity is defined as >5 × 10⁶/L white blood cells with blasts present in a non-bloody tap, and specific CNS-directed treatment must be initiated immediately in positive cases. 1

• Lumbar puncture should be postponed in patients with severe thrombocytopenia, coagulopathy, or acute promyelocytic leukemia until bleeding risk resolves. 1
• Bone marrow aspiration from the posterior iliac crest remains the gold standard, requiring morphology with cytochemistry, immunophenotyping by flow cytometry, comprehensive cytogenetics and karyotyping, FISH analysis, and molecular genetics. 2
• Optical genome mapping is increasingly used as first-line replacement for FISH in pediatric cases due to the high prevalence of cryptic fusions that are undetectable by conventional karyotyping. 1

Cytogenetic and Molecular Differences

Children have fundamentally different genetic backgrounds in their hematologic malignancies compared to adults, with structural variants and gene fusions predominating over DNA sequence mutations. 1

• Pediatric acute leukemias are characterized by balanced and unbalanced structural variants forming gene fusions as the primary oncogenic drivers, while DNA sequence mutations (SNVs) that predominate in adults are rare in children. 1
• Common cryptic fusions in pediatric B-ALL include t(12;21) forming ETV6::RUNX1, which requires FISH or optical genome mapping for detection. 1
• Pediatric AML features cryptic rearrangements like t(5;11) creating NUP98::NSD1 and inv(16) forming CBFA2T3::GLIS2 fusions. 1
• More than 20 genetic subtypes have been described in pediatric B-ALL, with high heterogeneity requiring comprehensive genome-wide testing rather than targeted approaches. 1

Treatment Approach Differences

Acute Myeloid Leukemia

Pediatric AML requires intensive anthracycline- and cytarabine-based therapy using standard pediatric protocols with at least 4-5 courses, achieving complete remission in >85% of children and adolescents. 2

• Standard induction consists of 3 days of anthracycline (daunorubicin ≥60 mg/m², idarubicin 10-12 mg/m², or mitoxantrone 10-12 mg/m²) and 7-10 days of cytarabine (100-200 mg/m² continuously or twice daily). 2, 3
• Cumulative anthracycline doses >300 mg/m² are associated with significant cardiac toxicity, requiring careful dose monitoring throughout treatment. 2
• CNS prophylaxis with intrathecal chemotherapy is mandatory starting at diagnosis in all pediatric patients, even without detectable CNS involvement. 2, 3

Acute Lymphoblastic Leukemia

Pediatric ALL treatment requires risk-adapted therapy incorporating age, presenting white blood cell count, immunophenotype, cytogenetic/molecular features, and minimal residual disease (MRD) status after induction. 2, 3

• Standard treatment includes induction chemotherapy, consolidation therapy tailored to risk group, and maintenance therapy extending 2-3 years. 2
• MRD testing is essential for risk stratification and treatment decisions, guiding the use of targeted therapy and immunotherapy. 2
• For Philadelphia chromosome-positive ALL, tyrosine kinase inhibitor therapy must be added immediately upon BCR-ABL1 confirmation without delaying until day 15. 2

Chronic Myeloid Leukemia

Pediatric CML presents more aggressively than adult CML, with prognostic scores developed for adults not applying to children, requiring different treatment intensity decisions. 4

• For low-intermediate ELTS score, imatinib 300 mg/m² is recommended; for high ELTS score, second-generation tyrosine kinase inhibitors are preferred. 2
• Response monitoring requires specific BCR-ABL1 transcript targets: <10% at 3 months, <1% at 6 months, and <0.1% at 12 months. 2
• Aggressive eradication strategies with limited duration intensive regimens may be more advantageous in children to avoid lifelong TKI exposure and associated adverse effects during active growth periods. 4

CML Blast Phase Management

For CML blast phase lymphoid phenotype, initial therapy must follow institutional ALL induction standards combined with a TKI, with prophylactic intrathecal therapy being mandatory. 1

• For myeloid blast phase, AML induction according to national standards is recommended, with TKI therapy administered after chemotherapy completion rather than in parallel to avoid drug interactions. 1
• CNS prophylaxis following the AML induction protocol is recommended, with weekly intrathecal chemotherapy until blast clearance in CNS-status 3 cases. 1

Age-Specific Dosing and Pharmacokinetics

Children under 2 years represent a distinct biological subgroup requiring drug dosing by body weight (mg/kg) rather than body surface area due to organ immaturity and different pharmacokinetic profiles. 3

• Infants have higher rates of MLL gene rearrangements (≥50%) requiring specific testing and treatment modifications. 3
• Adolescents and young adults (ages 15-39) have worse outcomes than pediatric patients, with treatment on pediatric or pediatric-inspired protocols at pediatric cancer centers associated with improved survival. 5

Supportive Care Differences

Tumor Lysis Syndrome

Aggressive prophylaxis with vigorous hydration at 2.5-3 liters/m²/day, allopurinol or rasburicase, and continuous electrolyte monitoring must be initiated immediately in pediatric patients with hyperleucocytosis. 2, 3

• Hydroxyurea 50-60 mg/kg/day should be considered to rapidly reduce WBC counts if signs of leukostasis (respiratory symptoms, neurological changes) develop. 3

Transfusion Management

Pediatric transfusion thresholds and strategies differ from adults, with restrictive strategies maintaining hemoglobin >7-8 g/dL and platelets >10,000-20,000/μL in stable patients. 6

• Transfusion decisions, indications, and doses in neonates and children are fundamentally different from adults and cannot be uniformly applied. 7
• Adult patient blood management standards require modification for pediatric populations, with further research needed for patients with active bleeding, hemodynamic instability, or cyanotic cardiac disease. 7

Venous Thromboembolism Management

Anticoagulation is strongly recommended for pediatric patients with symptomatic deep vein thrombosis or pulmonary embolism, despite limited direct pediatric evidence, based on extrapolation from adult data and the life-threatening nature of VTE in sick hospitalized children. 1

• Direct oral anticoagulants remain investigational in children with no published pharmacokinetics, safety, or efficacy studies, and should only be used within formal clinical trials. 1
• Treatment options are limited to unfractionated heparin, low-molecular-weight heparin, fondaparinux, or vitamin K antagonists with published pediatric safety data. 1

Sickle Cell Disease Considerations

Cardiopulmonary and renal complications in pediatric sickle cell disease require specific screening protocols distinct from adult management, though most recommendations remain conditional due to limited high-quality pediatric evidence. 1

Relapsed Disease Management

Prognosis in relapsed pediatric leukemia depends primarily on duration of first remission and site of relapse, with treatment options including clinical trials, intensive re-induction, allogeneic stem cell transplantation, and supportive care. 2

• Fludarabine/cytarabine-based regimens achieve second complete remission rates of 59-69% with overall survival of 38% in pediatric relapsed AML. 2
• Allogeneic stem cell transplantation is recommended for high-risk disease features at diagnosis, poor MRD response to induction, and relapsed AML achieving second complete remission. 2

Long-Term Surveillance

Pediatric patients require monitoring every 3-6 months during the first two years after treatment completion, including physical examination, blood tests, echocardiogram, neuropsychological testing, and screening for secondary malignancies. 2

• Long-term monitoring must address late effects including cardiotoxicity, neurotoxicity, and obesity specific to pediatric treatment exposures. 2

Critical Pitfalls to Avoid

• Never misdiagnose pediatric acute leukemia as aplastic anemia, even if initial bone marrow appears hypoplastic. 3
• Never omit CNS-directed therapy in pediatric patients, regardless of detectable CNS involvement at diagnosis. 3
• Never treat pediatric leukemia outside specialized centers with multidisciplinary expertise and adequate infrastructure; clinical trials should be considered whenever possible. 2, 3
• Never apply adult prognostic scores or treatment intensity decisions to pediatric CML, as these do not correlate with pediatric outcomes. 4