What is the treatment approach for a child diagnosed with B cell Acute Lymphoblastic Leukemia (ALL)?

Treatment of Childhood B-cell Acute Lymphoblastic Leukemia

Children with newly diagnosed B-cell ALL should receive risk-stratified multiagent chemotherapy consisting of induction, consolidation, and maintenance phases, with treatment preferably delivered at a specialized cancer center. 1

Front-line Treatment Approach

Initial Risk Stratification and Induction

• Enroll in a clinical trial whenever possible as the preferred approach 1
• Begin with multiagent induction chemotherapy typically including vincristine, corticosteroids, and asparaginase, with or without an anthracycline 1
• Assess minimal residual disease (MRD) status after induction, which is the most important prognostic factor 1

Post-Induction Management Based on MRD Status

For MRD-negative patients after induction:

• Continue with risk-stratified consolidation chemotherapy 1
• Proceed through interim maintenance and delayed intensification (reinduction) therapy 1
• Complete with maintenance therapy to prevent relapse 1

For MRD-positive patients after induction:

• Undergo intensified consolidation therapy 1
• If MRD remains persistently positive, consider blinatumomab or tisagenlecleucel (category 2B) 1
• Hematopoietic stem cell transplant (HCT) may be considered as part of consolidation or maintenance therapy 1

Recent Evidence for Standard-Risk Disease

Adding blinatumomab to chemotherapy significantly improves outcomes in standard-risk B-cell ALL. A 2025 phase 3 trial demonstrated 3-year disease-free survival of 96.0% with blinatumomab plus chemotherapy versus 87.9% with chemotherapy alone (P<0.001) 2. However, this approach increased catheter-related infections and sepsis rates 2.

Special Populations

Philadelphia Chromosome-Positive B-cell ALL

• Combine intensive chemotherapy with tyrosine kinase inhibitors (TKIs) 1
• Imatinib (340 mg/m²/day) or dasatinib added to chemotherapy achieves 3-year event-free survival rates of 80-86% 1
• The 3-year EFS rates are similar whether patients receive continuous TKI with chemotherapy or proceed to allogeneic HCT from a related donor 1

Infant ALL (Age <12 months)

• Treat with Interfant-based chemotherapy regimens that incorporate elements of both ALL and AML protocols 1
• Assess KMT2A rearrangement status, which is critical for risk stratification 1

For KMT2A-rearranged disease:

• High-risk features include age <6 months, WBC ≥300,000/μL, or persistently MRD-positive after intensive consolidation 1
• High-risk patients should receive maintenance therapy or consider HCT (preferably at ≥6 months of age with non-total body irradiation-based preparative regimen) 1
• Intermediate-risk patients receive maintenance chemotherapy 1

For KMT2A germline (standard-risk):

• May receive Interfant-based consolidation or risk-stratified chemotherapy similar to Ph-negative ALL 1

Relapsed/Refractory Disease Management

First Relapse

For patients achieving second complete remission (CR2):

• If MRD-negative: continue chemotherapy with maintenance therapy or proceed to HCT based on relapse risk 1
• If MRD-positive or relapse after prior HCT: consider blinatumomab 3, tisagenlecleucel, or inotuzumab ozogamicin 4 prior to first or second HCT 1
• Important caveat: Long-term remissions have been reported after tisagenlecleucel without subsequent HCT, with 3-year relapse-free survival of 52% and only 22% proceeding to HCT 1

Multiple Relapse/Refractory Disease

• Treatment options include chemotherapy, blinatumomab (for B-ALL) 3, tisagenlecleucel (for B-ALL), or inotuzumab ozogamicin (for B-ALL) 4 1
• HCT should be pursued as consolidation if disease responds to therapy 1
• For patients with MRD-positive CR2, administer 1-2 additional courses to achieve MRD negativity before allogeneic HCT, though some patients may require proceeding to HCT despite persistent MRD 1

Critical Treatment Principles

CNS-Directed Therapy

• Intensified intrathecal chemotherapy prevents CNS relapse and may protect against late bone marrow relapse 5
• Isolated extramedullary relapse (CNS or testicular) requires systemic therapy to prevent marrow relapse 1

Common Pitfalls to Avoid

• Do not delay treatment at non-specialized centers: The complexity of therapy necessitates treatment at specialized cancer centers with ALL expertise 1
• Do not proceed to HCT with detectable MRD when possible: Additional therapy to achieve MRD negativity before HCT improves outcomes 1
• Monitor for treatment-specific toxicities: Grade 3-4 neutropenia occurs in >80% of patients; infection rates are significant during intensive phases 6
• Recognize blinatumomab risks: Cytokine release syndrome, neurologic problems including seizures, and increased catheter-related infections can occur 3, 2