What is the treatment for acute leukemia?

Treatment for Acute Leukemia

The standard treatment for acute leukemia consists of induction chemotherapy with an anthracycline and cytarabine, followed by consolidation therapy, with treatment approaches varying based on leukemia subtype and patient risk factors. 1

Types of Acute Leukemia and Risk Assessment

• Acute leukemia is classified into two main types: Acute Myeloid Leukemia (AML) and Acute Lymphoblastic Leukemia (ALL), each requiring different treatment approaches 1
• Risk assessment includes patient's age, initial leukocyte count, leukemia subtype, karyotype data, and medical history 1
• Favorable prognostic factors in AML include chromosomal translocations t(15;17) (acute promyelocytic leukemia), t(8;21), and inv(16) 1
• Poor prognostic factors include advanced age (>60 years), antecedent myelodysplastic syndrome, and complex aberrant karyotypes 1

Treatment Phases

Induction Therapy

• Induction therapy aims to reduce tumor burden by clearing leukemic cells from bone marrow 1

• For AML in adults under 65 years:

  • Standard regimen includes an anthracycline (e.g., daunorubicin) and cytarabine 1, 2
  • Typical dosing: daunorubicin 45 mg/m²/day IV on days 1,2, and 3 of first course and days 1,2 of subsequent courses 2
  • Cytarabine 100 mg/m²/day IV infusion for 7 days in first course and 5 days in subsequent courses 2, 3
  • Dose reduction for patients ≥60 years: daunorubicin 30 mg/m²/day 2

• For ALL:

  • Induction typically includes vincristine, anthracyclines, corticosteroids, with or without L-asparaginase and/or cyclophosphamide 1
  • For adult ALL: daunorubicin 45 mg/m²/day IV on days 1,2, and 3, vincristine 2 mg IV on days 1,8, and 15, prednisone 40 mg/m²/day, and L-asparaginase 2
  • For pediatric ALL: daunorubicin 25 mg/m² IV weekly, vincristine 1.5 mg/m² IV weekly, and prednisone 40 mg/m² daily 2

• For Acute Promyelocytic Leukemia (APL):

  • Induction should include an anthracycline and all-trans retinoic acid (ATRA) 1

Consolidation Therapy

• Patients achieving complete remission should receive one to two cycles of post-remission therapy 1
• Treatment strategy varies based on risk factors:
  • Good risk patients should receive chemotherapy only, preferably including high-dose cytarabine 1
  • Patients with HLA-identical siblings are candidates for allogeneic stem cell transplantation in first remission 1
  • Patients with poor risk features and no family donor may qualify for unrelated matched donor transplant 1
  • For APL, consolidation should include ATRA 1

Maintenance Therapy

• Maintenance chemotherapy and ATRA are beneficial in APL 1
• Most ALL patients benefit from maintenance therapy 4

Central Nervous System (CNS) Prophylaxis

• All treatment regimens for ALL include CNS prophylaxis and/or treatment 1
• Antimetabolites such as methotrexate, cytarabine, and/or mercaptopurine are often included during induction therapy for CNS prophylaxis 1

Treatment of Relapsed or Refractory Disease

• Patients in second or subsequent remission may qualify for allogeneic transplantation with an unrelated donor 1
• In relapsed APL, arsenic trioxide can induce remission even if patients have become refractory to ATRA 1

Response Evaluation

• Response to induction is monitored through clinical examination, serial peripheral blood counts, and bone marrow aspirates 1
• During induction-induced aplasia, a bone marrow aspirate should be obtained to monitor for early marrow response 1
• Complete remission requires normal cellularity of bone marrow, morphologically normal hematopoiesis, and blast levels <5% 1

Special Considerations

• Untreated acute leukemia is uniformly fatal with median survival less than 3 months 5
• Dose adjustments are necessary for patients with hepatic or renal impairment 2:
  • Serum bilirubin 2-3 mg%: reduce dose by 25%
  • Serum bilirubin >3 mg%: reduce dose by 50%
  • Serum creatinine >3 mg%: reduce dose by 50%
• Infectious complications are common and may require prophylaxis, especially with combination therapies 1
• Treatment should be conducted in centers with multidisciplinary expertise and adequate infrastructure 1

Recent Advances

• Since 2017, nine new agents have been approved for different AML treatment indications 6
• Low-intensity therapy with hypomethylating agents and venetoclax is now the standard of care for older/unfit patients with AML 6
• Targeted therapies including FLT3 and IDH inhibitors are being incorporated into traditional chemotherapy regimens 6