What is the treatment for Acute Lymphoblastic Leukemia (ALL)?

Treatment of Acute Lymphoblastic Leukemia (ALL)

The treatment of Acute Lymphoblastic Leukemia (ALL) requires intensive multiagent chemotherapy administered in distinct phases (induction, consolidation, and maintenance), with specific modifications based on patient age, disease subtype, and risk stratification. 1, 2

Risk Stratification

• Poor prognostic factors include elevated WBC count (≥30×10⁹/L for B-cell lineage; ≥100×10⁹/L for T-cell lineage), hypodiploidy, and MLL/KMT2A rearrangements 2, 3
• Risk assessment guides treatment intensity and consideration for allogeneic hematopoietic cell transplantation (HCT) 1
• Minimal residual disease (MRD) assessment is crucial for determining subsequent therapy and transplant decisions 2, 3

Treatment Phases

1. Induction Therapy

• For adults <65 years with Ph-negative ALL, multiagent regimens based on a backbone of vincristine, anthracyclines, corticosteroids, and L-asparaginase are recommended 2, 3
• For adults ≥65 years or with substantial comorbidities, lower-intensity options such as vincristine and prednisone or moderate-intensity regimens may be more appropriate 2
• The BFM regimen is a cornerstone protocol that includes a 4-drug induction with vincristine, an anthracycline (daunorubicin/doxorubicin), a corticosteroid (prednisone/dexamethasone), and L-asparaginase 3
• For Philadelphia chromosome (Ph)-positive ALL, tyrosine kinase inhibitors (TKIs) combined with chemotherapy have dramatically improved outcomes 4

2. Consolidation Therapy

• Consolidation typically includes high-dose methotrexate, cytarabine, and other agents 2
• CNS prophylaxis with intrathecal chemotherapy is essential in all treatment regimens 2, 3
• Blinatumomab is FDA-approved for CD19-positive Ph-negative B-cell ALL in the consolidation phase of multiphase chemotherapy 5
• For Ph-positive ALL, continued TKI therapy is incorporated into consolidation 4

3. Maintenance Therapy

• Maintenance therapy typically extends for 2-3 years after achieving complete remission 4
• Standard maintenance regimens include daily mercaptopurine, weekly methotrexate, monthly vincristine, and pulse dexamethasone 1

Novel Targeted Therapies

• Blinatumomab is indicated for:
  • CD19-positive B-cell precursor ALL with minimal residual disease (MRD) ≥0.1% 5
  • Relapsed or refractory CD19-positive B-cell precursor ALL 5
  • CD19-positive Ph-negative B-cell precursor ALL in the consolidation phase 5
• Inotuzumab ozogamicin has improved outcomes in relapsed/refractory ALL and is being incorporated into frontline regimens 4
• For Ph-positive ALL, TKIs combined with reduced-intensity chemotherapy have improved 5-year survival rates to over 80% 4

Special Considerations

• Dexamethasone shows better CNS penetration than prednisone but has higher toxicity risk, including neuropsychiatric events and myopathy 2, 3
• Elderly patients (≥60 years) benefit from less intensive approaches incorporating targeted therapies like blinatumomab and inotuzumab ozogamicin 4
• T-cell ALL requires specific regimens incorporating pegylated asparaginase and nelarabine 4
• Early T-cell precursor (ETP) ALL is a high-risk subgroup for which allogeneic stem cell transplantation should be considered 4

Treatment of Relapsed/Refractory ALL

• Blinatumomab and inotuzumab ozogamicin are approved for relapsed/refractory B-cell ALL 5, 4
• Combination therapy including chemotherapy and immunotherapy followed by CAR T-cell therapy and allogeneic stem cell transplantation offers the best outcomes for relapsed/refractory disease 4
• For Ph-positive relapsed ALL, alternative TKIs may be effective 4

Monitoring

• MRD monitoring is essential to guide therapy intensification and consideration for stem cell transplantation 2, 3
• Achieving MRD negativity, particularly by next-generation sequencing, is an important prognostic indicator 4