Induction Chemotherapy for AML (other than acute promyelocytic leukemia [APL])

• Offer all patients enrolment in a clinical trial
• For patients < 60 years old eligible for intensive induction:
  • Discuss treatment options with either anthracycline plus cytarabine in “7+3” regimen
  • Consider other treatment options such as high-dose cytarabine 2 g/m² plus either idarubicin or daunorubicin, daunorubicin plus cladribine plus standard dose cytarabine or another combination of anthracycline plus cytarabine such as timed sequential therapy
• For patients ≥ 60 years old:
  • If performance status (PS) 0-2 and eligible for intensive induction, consider either:
    • Standard-dose cytarabine plus anthracycline (idarubicin, daunorubicin, or mitoxantrone)
    • Low-intensity therapy with cytarabine subcutaneously, 5-azacytidine, or decitabine
  • If PS > 2 or if PS 0-3 with significant comorbidities or if patient ≥ 75 years old, consider
    • Low-dose cytarabine subcutaneously, 5-azacytidine, or decitabine
    • Best supportive care, including transfusion support and/or hydroxyurea

Other Supportive Care:

• Central access catheter required for frequent phlebotomy and chemotherapy (vesicant) administration
• Monitoring for bleeding diatheses (disseminated intravascular coagulation)
• Transfusional support per institutional standards (red cells, platelets, cryoprecipitate)
• Growth factors rarely have a role in AML therapy (except in select regimens)
• Lumbar punctures to evaluate for central nervous system involvement by leukemia
• Monitoring for infection
  • Perform exam of mouth or throat to detect infections, including thrush
  • Look at skin for signs of focal infections, and at catheter sites
  • Imaging studies
    • Regular chest x-rays or high-resolution computerized tomography (CT) scans should be considered to detect pulmonary infection, including pulmonary aspergillosis
    • X-rays or CT scans of sinuses may detect occult fungal infections

Postinduction Therapy

• Follow-up bone marrow assessment is typically performed at 7-10 days after completing induction with standard-dose cytarabine regimen or 7-14 days after completing induction with high-dose cytarabine regimen. (This may vary with treatment facility and patient condition)
• Next therapy pathways based on the above results (degree of cytoreduction or residual disease versus clearance of disease)
  • After standard-dose cytarabine regimen, consider any of high-dose cytarabine, standard-dose cytarabine plus idarubicin or daunorubicin, other treatment options for postremission therapy after induction failure, or waiting for hematologic recovery
  • After high-dose cytarabine regimen, offer patients enrolment in a clinical trial
  • Clinical trial if response inadequate and patient performance status adequate

Postremission Therapy

• Response assessment is typically performed after postinduction therapy and hematologic recovery, and is based on cytogenetics and molecular studies.
• Allogeneic stem cell transplantation in appropriate patients (conditioning and graft versus host disease prophylaxis regimen based on patient and disease characteristics as well as donor availability)
• For patients < 60 years old:
  • If complete remission is achieved, consider consolidation therapy according to risk status:
    • In patients with favorable risk, either high- or intermediate-dose cytarabine
    • In patients with intermediate risk, consider allogeneic stem cell transplantation or high-dose cytarabine
    • In patients with poor risk or treatment-related disease or those with antecedent hematologic disorders, consider allogeneic stem cell transplantation
  • If no complete remission:
    • Clinical trial versus supportive care

• For patients ≥ 60 years old:
  • If complete remission:
    • Consider any of reduced-intensity allogeneic stem cell transplantation, standard-dose cytarabine with or without either idarubicin or daunorubicin, low-intensity therapy with hypomethylating agents (azacitidine or decitabine), or observation (evaluate options in context of patient’s performance status and medical comorbidities)
    • Multiple courses of high-dose cytarabine does not appear to increase survival compared to lower doses in patients > 60 years old, and may increase toxicity.
  • If no complete remission:
    • Clinical trial versus supportive care

Therapy for Relapsed Disease

• R > 50% after primary treatment for AML
• Definitions of relapse
  • Often based on hematologic or bone marrow evaluation
  • Molecular monitoring has shown good correlation with other definitions of relapse, but is currently limited by a lack of standardization
• No standard of care for relapse of AML
  • Consider clinical trials for all patients at relapse
  • Relapse < 1 year
    • Encourage trial participation
    • Consider alternative chemotherapy (from induction), then allogeneic stem cell transplantation
    • Supportive care if performance status does not allow further therapy
  • Relapse ≥ 1 year
    • Consider trial participation
    • Consider alternative chemotherapy (from induction), then allogeneic stem cell transplantation
    • Consider repeating the initial successful induction therapy, then allogeneic stem cell transplantation
    • Supportive care  if performance status does not allow further therapy

In 2017, midostaurin (Rydapt) was approved for the treatment of adult patients with newly diagnosed FLT3-positive AML in combination with standard cytarabine and daunorubicin induction and cytarabine consolidation.