What are the differences in treatment between Acute Lymphoblastic Leukemia (ALL) and Chronic Lymphocytic Leukemia (CLL)?

Treatment Differences Between Acute Lymphoblastic Leukemia (ALL) and Chronic Lymphocytic Leukemia (CLL)

The treatment approaches for ALL and CLL differ fundamentally, with ALL requiring intensive multi-agent chemotherapy administered in distinct phases (induction, consolidation, maintenance), while CLL typically follows a "watch and wait" approach for asymptomatic patients and less intensive targeted therapies for those requiring treatment.

Acute Lymphoblastic Leukemia (ALL) Treatment

Treatment Phases

ALL treatment follows a complex, intensive approach with distinct phases:

1. Induction Phase

   • Goal: Achieve complete remission by clearing leukemic cells from bone marrow 1
   • Regimens:
     • B-ALL: Typically 3-4 drug combination including:
       • Vincristine
       • Corticosteroids (dexamethasone or prednisone)
       • Asparaginase
       • ± Anthracyclines (daunorubicin, doxorubicin) 1
     • T-ALL: Usually 4-drug regimen 1
     • Ph+ ALL: TKI (imatinib, dasatinib, ponatinib) added to standard regimen 1, 2

2. Consolidation/Intensification Phase

   • Goal: Eliminate residual leukemic cells after induction 1
   • Components:
     • High-dose methotrexate
     • Cytarabine
     • Mercaptopurine
     • L-asparaginase 1
     • For Ph+ ALL: Continued TKI therapy 1

3. Maintenance Phase

   • Duration: 2-3 years 2
   • Typically includes:
     • Oral methotrexate
     • Mercaptopurine 2

4. CNS Prophylaxis (throughout treatment)

   • Methods:
     • Intrathecal chemotherapy (methotrexate, cytarabine, corticosteroids)
     • High-dose systemic chemotherapy
     • ± Cranial irradiation 1

Risk-Adapted Therapy

Treatment intensity is adjusted based on:

• Age (pediatric vs. AYA vs. adult)
• WBC count at diagnosis
• Immunophenotype (B vs. T cell)
• Cytogenetics (Ph+, hypodiploidy, etc.)
• Minimal Residual Disease (MRD) status 1, 2

Novel Targeted Approaches

• Ph+ ALL: TKIs (imatinib, dasatinib, ponatinib) + chemotherapy or blinatumomab 1
• CD19+ B-ALL: Blinatumomab, CAR-T cell therapy 1, 2, 3
• CD22+ B-ALL: Inotuzumab ozogamicin 2, 3

Role of Stem Cell Transplantation

• Considered for high-risk features:
  • Ph+ ALL
  • Persistent MRD ≥0.01% post-consolidation
  • Induction failure
  • Relapsed disease 1

Chronic Lymphocytic Leukemia (CLL) Treatment

Treatment Approach

• Initial Management: "Watch and wait" for asymptomatic patients
• Treatment Indications:
  • Progressive cytopenias
  • Symptomatic or massive lymphadenopathy/splenomegaly
  • Disease-related symptoms (fatigue, night sweats, weight loss)
  • Rapidly increasing lymphocyte count

First-Line Treatment Options

• Standard Risk CLL:

  • BTK inhibitors (ibrutinib, acalabrutinib, zanubrutinib)
  • Venetoclax + obinutuzumab
  • For older/comorbid patients: Obinutuzumab + chlorambucil

• High-Risk CLL (del17p/TP53 mutation):

  • BTK inhibitors preferred
  • Venetoclax + obinutuzumab

Relapsed/Refractory CLL

• Switch to alternative targeted therapy:
  • BTK inhibitor if previously on venetoclax
  • Venetoclax if previously on BTK inhibitor
  • PI3K inhibitors (idelalisib, duvelisib)

Key Differences from ALL

• No distinct treatment phases (induction, consolidation, maintenance)
• Less intensive therapy with targeted agents rather than multi-agent chemotherapy
• Continuous treatment or fixed-duration approaches rather than 2-3 year protocols
• No routine CNS prophylaxis needed
• Stem cell transplantation rarely used in first remission

Practical Treatment Algorithm

1. Diagnosis Confirmation

   • ALL: >20% lymphoblasts in bone marrow 2
   • CLL: ≥5,000 B-lymphocytes/μL with characteristic immunophenotype

2. Risk Stratification

   • ALL: Age, WBC count, immunophenotype, cytogenetics, MRD 1
   • CLL: FISH analysis (del17p, del11q), IGHV mutation status, TP53 mutation

3. Treatment Selection

   • ALL: Multi-agent chemotherapy by phase with risk-adapted intensity
   • CLL: Observe or targeted therapy based on symptoms and risk factors

4. Response Assessment

   • ALL: MRD monitoring crucial for prognosis and treatment decisions 1, 2
   • CLL: CT scans, blood counts, bone marrow examination as needed

5. Post-Remission Decisions

   • ALL: Consider transplant for high-risk features 1
   • CLL: Continue therapy or observe based on response and treatment type

Common Pitfalls to Avoid

1. For ALL:

   • Inadequate CNS prophylaxis leading to CNS relapse
   • Insufficient treatment intensity in adolescents and young adults
   • Failure to incorporate TKIs early for Ph+ ALL
   • Not monitoring MRD to guide treatment decisions

2. For CLL:

   • Treating asymptomatic patients without indications
   • Using intensive chemotherapy in elderly or comorbid patients
   • Not testing for TP53/17p status before treatment selection
   • Overlooking drug interactions with targeted agents