What is the diagnosis and treatment for Acute Myeloid Leukemia (AML) with core binding factor?

From the Guidelines

The recommended treatment approach for Core Binding Factor Acute Myeloid Leukemia (CBF-AML) includes intensive induction chemotherapy with cytarabine and an anthracycline, specifically 7 days of cytarabine and 3 days of daunorubicin, along with 1-3 days of gemtuzumab ozogamicin (GO) 1.

Diagnosis and Treatment Approach

The diagnosis of CBF-AML is based on specific genetic abnormalities involving the core binding factor complex, primarily t(8;21) or inv(16)/t(16;16).

• The treatment approach for CBF-AML includes:
  • Intensive induction chemotherapy with cytarabine and an anthracycline (typically "7+3" regimen)
  • High-dose cytarabine consolidation therapy
  • Adding gemtuzumab ozogamicin (GO) to standard chemotherapy has shown improved outcomes in CBF-AML patients

Prognosis and Monitoring

• CBF-AML generally has a more favorable prognosis compared to other AML subtypes, with complete remission rates of 85-90% and overall survival rates of 60-70% at 5 years 1.
• Minimal residual disease monitoring using PCR for the fusion transcripts RUNX1-RUNX1T1 or CBFB-MYH11 is essential for early detection of potential relapse.

Role of KIT Mutations

• The presence of KIT mutations, particularly in the tyrosine kinase domain (TKD) at codon 816 (TKD816), has been associated with poorer outcomes in patients with CBF-AML, especially those with t(8;21) 1.
• However, the prognostic influence of KIT mutations in CBF-AML is still being investigated, and their impact on treatment decisions is not yet fully established.

Treatment Recommendations

• The most recent and highest quality study recommends the use of 7 days of cytarabine, 3 days of daunorubicin, and 1-3 days of gemtuzumab ozogamicin (GO) in induction therapy for CBF-AML patients 1.
• High-dose cytarabine consolidation therapy is also recommended, with 3-4 cycles of high-dose cytarabine at 3 g/m² twice daily on days 1,3, and 5 for each consolidation cycle.
• Allogeneic stem cell transplantation is typically reserved for patients who relapse rather than being used in first remission.

From the FDA Drug Label

In the treatment of adult acute nonlymphocytic leukemia, daunorubicin hydrochloride, used as a single agent, has produced complete remission rates of 40 to 50%, and in combination with cytarabine, has produced complete remission rates of 53 to 65%

The diagnosis of Acute Myeloid Leukemia (AML) with core binding factor is not directly addressed in the provided drug labels. However, the treatment of AML is mentioned.

• The treatment for AML may involve daunorubicin hydrochloride as a single agent or in combination with cytarabine.
• Daunorubicin hydrochloride has produced complete remission rates of 40 to 50% as a single agent, and 53 to 65% in combination with cytarabine in adult acute nonlymphocytic leukemia 2.
• Cytarabine is also used in the treatment of AML, but the provided label does not specifically mention its use in AML with core binding factor 3. It is essential to consult the FDA drug label and other relevant medical resources for the most accurate and up-to-date information on diagnosing and treating AML with core binding factor.

From the Research

Diagnosis of Acute Myeloid Leukemia (AML) with Core Binding Factor

• AML with core binding factor (CBF-AML) is characterized by recurrent favorable chromosome translocations, namely t(8;21) and inv(16)/t(16;16) 4
• CBF-AML corresponds to two distinct subtypes of AML, with a relatively good outcome when treated with intensive chemotherapy including high-dose cytarabine 4
• Diagnosis of CBF-AML involves identification of CBF fusion transcripts, such as RUNX1/RUNX1T1 or CBFB/MYH11 5

Treatment of Acute Myeloid Leukemia (AML) with Core Binding Factor

• The optimal treatment strategy for CBF-AML remains to be defined, but may include a combination of chemotherapy, targeted agents, and stem cell transplantation 4
• High-dose cytarabine (HDAC) consolidation is a common treatment approach for CBF-AML, but its effectiveness is still being studied 4
• The use of dasatinib, a multi-kinase inhibitor, in combination with chemotherapy has shown promise in treating CBF-AML, particularly in patients with KIT mutations 5
• Induction therapy with cytarabine and daunorubicin, followed by consolidation with high-dose cytarabine, is a standard treatment approach for AML, including CBF-AML 6, 7
• Allogeneic stem cell transplantation is considered the most effective form of antileukemic therapy in patients with AML in first or subsequent remission 7

Prognosis and Treatment Considerations

• Despite its favorable prognosis, CBF-AML still carries a significant risk of relapse, and optimizing treatment planning is crucial to improving outcomes 8
• The use of measurable residual disease testing is becoming increasingly important for monitoring disease in remission and identifying patients who may benefit from early intervention, such as stem cell transplantation 8
• Ongoing research is focused on evaluating the role of new agents, such as gemtuzumab, hypomethylating agents, and kinase inhibitors, in the treatment of CBF-AML 8