What is the treatment approach for pediatric leukemia?

Treatment Approach for Pediatric Leukemia

The optimal treatment for pediatric leukemia requires a risk-stratified approach based on leukemia type (lymphoblastic vs. myeloid), genetic features, and response to therapy, with combination chemotherapy as the backbone for all protocols.

Types of Pediatric Leukemia

• Acute lymphoblastic leukemia (ALL) is the most common childhood cancer, accounting for approximately 80% of pediatric leukemias 1
• Acute myeloid leukemia (AML) accounts for most of the remaining cases 1
• Chronic myeloid leukemia (CML) is rare in children, with only 1-2.2 cases per million per year 2

Diagnosis and Initial Assessment

• Diagnosis requires demonstration of ≥20% bone marrow lymphoblasts on hematopathology review 3
• Complete physical examination is essential, including assessment of:
  • Spleen size (children with CML present with larger spleen size compared to adults) 2
  • Extramedullary involvement (lymph nodes, skin, soft tissue, or bones) 2
• Laboratory evaluation should include:
  • Complete blood count with differential
  • Comprehensive metabolic panel
  • Coagulation studies
  • Lumbar puncture with cerebrospinal fluid analysis 2
• Genetic and molecular testing is crucial for risk stratification:
  • Cytogenetic analysis
  • Immunophenotyping
  • Molecular genetic testing 2
• Echocardiogram should be performed prior to anthracycline therapy 2

Treatment of Acute Lymphoblastic Leukemia (ALL)

Risk Stratification in ALL

• Risk factors include:
  • Age at diagnosis
  • White blood cell count
  • Immunophenotype (B-cell vs. T-cell)
  • Cytogenetic/genetic abnormalities
  • Response to therapy (measured by minimal residual disease) 2
• Unfavorable risk features include:
  • Hypodiploidy (<44 chromosomes)
  • t(9;22)(q34.1;q11.2) (Philadelphia chromosome)
  • KMT2A (MLL) rearrangements
  • Intrachromosomal amplification of chromosome 21 (iAMP21) 3

Treatment Phases for ALL

1. Induction therapy:

   • Combination of vincristine, corticosteroids, anthracyclines (daunorubicin), and asparaginase 4, 5
   • For Philadelphia chromosome-positive ALL, tyrosine kinase inhibitors are added 3
   • Goal is to achieve complete remission

2. Consolidation therapy:

   • Intensified chemotherapy to eliminate residual leukemic cells
   • May include high-dose methotrexate and cytarabine

3. Maintenance therapy:

   • Lower-dose chemotherapy for 2-3 years
   • Typically includes daily oral mercaptopurine, weekly methotrexate, periodic vincristine and corticosteroids 6

4. CNS-directed therapy:

   • Intrathecal chemotherapy (methotrexate, cytarabine, hydrocortisone)
   • Classification of CNS status guides treatment intensity:
     • CNS-1: No lymphoblasts in CSF
     • CNS-2: WBC <5/μL with lymphoblasts
     • CNS-3: WBC ≥5/μL with lymphoblasts or clinical symptoms 2
   • Cranial radiation (18 Gy) may be used for patients with CNS-3 disease, though many protocols avoid radiation due to late effects 2

Treatment of Acute Myeloid Leukemia (AML)

Risk Stratification in AML

• Favorable risk factors:
  • Core binding factor (CBF) leukemias [t(8;21), inv(16)]
  • Normal karyotype with NPM1 mutation without FLT3-ITD 2
• Unfavorable risk factors:
  • Complex karyotype
  • Monosomy 7
  • FLT3-ITD mutations 2

Treatment Approach for AML

1. Induction therapy:

   • Combination of cytarabine and anthracyclines (daunorubicin)
   • For children under 2 years, dosage is calculated by weight (1 mg/kg) rather than body surface area 2
   • Patients with acute promyelocytic leukemia (APL) receive all-trans retinoic acid (ATRA) at 25 mg/m² per day 2

2. Consolidation therapy:

   • High-dose cytarabine-based regimens
   • CNS-directed therapy with intrathecal chemotherapy 2

3. Hematopoietic stem cell transplantation (HSCT):

   • Not recommended for favorable-risk AML in first complete remission
   • May be considered for intermediate and high-risk patients
   • Recommended for all children with relapsed AML who achieve second complete remission 2

Treatment of Chronic Myeloid Leukemia (CML)

• Tyrosine kinase inhibitors (TKIs) are the mainstay of treatment 2
• For CML blast phase (CML-BP):
  • Combination of TKIs with acute leukemia-type chemotherapy
  • Allogeneic stem cell transplantation is recommended after achieving remission 2

Special Considerations

Relapsed Leukemia

• For relapsed ALL:

  • Reinduction chemotherapy
  • Immunotherapies (blinatumomab, inotuzumab ozogamicin)
  • CAR T-cell therapy (tisagenlecleucel) 3, 6

• For relapsed AML:

  • Reinduction with fludarabine/cytarabine-based regimens
  • Allogeneic HSCT is recommended for all children who achieve second complete remission 2

Hyperleukocytosis Management

• Defined as WBC >100 × 10⁹/L
• Associated with high risk of hemorrhage and leukostasis
• Management includes:
  • Aggressive hydration
  • Rasburicase for tumor lysis prevention
  • Leukapheresis for symptomatic patients
  • Early initiation of chemotherapy 2

Long-term Follow-up

• Monitoring for late effects of therapy:
  • Cardiac function (echocardiogram) for anthracycline-related cardiotoxicity
  • Neuropsychological testing for neurotoxicity
  • Endocrine function
  • Secondary malignancies 3

Treatment Outcomes

• ALL: 80-90% long-term survival in pediatric patients 6
• AML: Approximately 55-70% long-term survival 1
• CML: Improved outcomes with TKI therapy, though prognosis for blast phase remains poor 2