What is the initial treatment recommendation for B cell Acute Lymphoblastic Leukemia (ALL)?

Initial Treatment of B-cell Acute Lymphoblastic Leukemia (ALL)

For adults under 65 years with newly diagnosed B-cell ALL, initiate intensive multiagent induction chemotherapy with a backbone of vincristine, anthracycline (daunorubicin or doxorubicin), corticosteroid (dexamethasone or prednisone), and L-asparaginase. 1, 2, 3

Treatment Approach by Age and Fitness

Adults <65 Years (Fit Patients)

Induction regimens should include the 4-drug backbone mentioned above. 1, 2, 3 Specific evidence-based options include:

• Hyper-CVAD regimen: Hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with high-dose methotrexate and cytarabine 4, 5

  • Achieves 81-86% complete remission rates 4, 5
  • For CD20-positive disease, add rituximab (375 mg/m² on Days 1 and 11), which improves 3-year overall survival to 89% 5

• CALGB 9111, ECOG 1910, or dose-adjusted Hyper-CVAD are classified as high-intensity regimens by NCCN 1

• Modified DFCI 91-01, GMALL, GRAALL, or EWALL regimens are moderate-intensity alternatives 1

  • Add rituximab to GMALL for CD20-positive disease 1

Adults ≥65 Years or With Substantial Comorbidities

Treatment intensity must be reduced but should remain curative-intent when possible. 1

Low-intensity options: 1

• Vincristine and prednisone
• POMP regimen

Moderate-intensity options: 1

• ALLOLD07 (PETHEMA-based)
• EWALL, GMALL, or GRAALL regimens with dose modifications
• Inotuzumab ozogamicin (InO) with dexamethasone (category 2B) 1
• InO mini-hyper-CVD 1

Recent evidence shows dose-dense mini-hyper-CVD with inotuzumab ozogamicin and blinatumomab achieves 100% CR/CRi and MRD negativity by cycle 1 in frontline older adults, with 83% 1-year overall survival. 6

Pediatric Patients

• Standard-risk B-ALL: 3-drug induction (vincristine, corticosteroid, L-asparaginase) without anthracyclines 1, 2, 3
• High-risk B-ALL: 4-drug induction adding anthracycline 2, 3

Critical Treatment Components

CNS Prophylaxis (Essential for All Patients)

• Intrathecal chemotherapy must be administered from the start 1, 2
• Triple intrathecal therapy (methotrexate, cytarabine, dexamethasone) is preferred over methotrexate alone 1, 7
• Prophylactic cranial irradiation is not recommended for B-ALL in the context of effective systemic and intrathecal therapy 1

Corticosteroid Selection

Dexamethasone versus prednisone is a critical decision: 3

• Dexamethasone provides superior CNS penetration and reduces CNS relapse risk 3
• However, dexamethasone carries higher risks of induction mortality, neuropsychiatric events, and myopathy 3
• No conclusive overall survival advantage has been demonstrated 3

Consolidation Therapy

After achieving complete remission: 1, 2

• High-dose methotrexate (1-1.5 g/m² over 24 hours with leucovorin rescue) 1, 7
• High-dose cytarabine 7, 8
• Continue intrathecal chemotherapy 1

For resource-limited settings, intermediate-dose methotrexate (1 g/m² over 24 hours) is acceptable. 1

Maintenance Therapy

Standard maintenance for 2-2.5 years includes: 1, 2

• Daily mercaptopurine 2
• Weekly methotrexate 2
• Monthly vincristine 2
• Pulse dexamethasone 2

Minimal Residual Disease (MRD) Monitoring

MRD assessment is mandatory after induction and guides all subsequent treatment decisions. 1, 2

• MRD-negative patients: Proceed with standard consolidation and maintenance 1
• MRD-positive or rising: Add blinatumomab (preferred) or inotuzumab ozogamicin before consolidation 1
  • Blinatumomab achieves 88% complete MRD response in patients with MRD ≥10⁻³ 1
  • Consider allogeneic hematopoietic cell transplantation for persistent MRD 1

Next-generation sequencing MRD at 10⁻⁶ sensitivity provides the most sensitive assessment, with dose-dense regimens achieving this depth in 60% of patients after cycle 1. 6

High-Risk Features Requiring Treatment Intensification

The following factors mandate more intensive therapy: 1, 9

• Age ≥35 years 1, 9
• WBC >30 × 10⁹/L 1, 9
• Time to complete remission >4 weeks 9
• Poor-risk cytogenetics: complex karyotype, hypodiploidy, MLL/KMT2A rearrangements 1, 2, 3
• Molecular alterations: TP53 mutation, PAX5alt, IKZF1 alterations 1

For these patients, consider allogeneic hematopoietic cell transplantation in first complete remission. 9

Common Pitfalls to Avoid

1. Do not use conventional ALL regimens designed for other ALL subtypes - B-cell ALL requires Burkitt-type intensive short-course therapy 7, 8

2. Do not delay MRD assessment - Perform after induction completion and use results to guide consolidation 1

3. Do not omit CNS prophylaxis - CNS relapse rates drop from 50-57% to 17% with adequate prophylaxis 7

4. Do not use chronologic age alone to determine treatment intensity - Assess performance status, comorbidities, and end-organ function 1, 3

5. Ensure adequate count recovery before transitioning between treatment phases, even with MRD negativity 1