What is the next step in treatment for a patient with Acute Myeloid Leukemia (AML) who has achieved negative Minimal Residual Disease (MRD) status after a second induction cycle, has no sign of FLT3 (Fms-like tyrosine kinase 3) or other genetic mutations, and lacks a matched related or unrelated donor?

Treatment Recommendation for AML with Negative MRD After Second Induction

Continue one more consolidation cycle (for a total of 3-4 cycles) and proceed to haploidentical stem cell transplantation (haplo-SCT). This patient achieved MRD negativity after the second induction, which is a favorable prognostic marker, but the initial MRD positivity (3%) after first induction indicates intermediate-risk disease requiring allogeneic transplantation 1.

Risk Stratification and Rationale

This patient falls into intermediate-risk category based on:

• Absence of FLT3 mutations and other favorable/adverse genetic markers 1
• Initial MRD positivity (3%) after first induction, which indicates suboptimal early response 2
• Achievement of MRD negativity only after second induction cycle 2

The 2017 ELN guidelines specifically recommend allogeneic HCT from matched-related or unrelated donor for intermediate-risk AML in younger patients 1. Since no matched related or unrelated donor is available, haploidentical transplantation becomes the appropriate alternative donor option 1.

Consolidation Strategy Before Transplant

One additional consolidation cycle is recommended before proceeding to haplo-SCT:

• The 2017 ELN guidelines recommend 2-4 cycles of intermediate-dose cytarabine (IDAC) consolidation for intermediate-risk patients 1
• Since this patient has already received 2 induction cycles, one additional consolidation cycle maintains remission during donor preparation without excessive cumulative toxicity 1
• Patients may require at least one cycle of consolidation during donor search to maintain remission 1

Avoid excessive consolidation cycles (3-4 additional cycles) because:

• Prolonged chemotherapy delays definitive transplant and increases relapse risk in intermediate-risk disease 1
• The patient has already achieved MRD negativity, making additional chemotherapy less beneficial than proceeding to transplant 2

Haploidentical Transplantation Justification

Haplo-SCT is the appropriate choice given the donor situation:

• The Chinese Society of Hematology consensus states that haploidentical transplantation should be considered for patients without matched donors who urgently need transplantation 1
• Haploidentical transplantation with appropriate conditioning regimens produces outcomes comparable to matched unrelated donor transplants in intermediate-risk AML 1
• Alternative donor (mismatched-related) SCT should be performed in high and intermediate-risk AML patients without a matched donor 1

The 2017 ELN guidelines emphasize early HLA typing and consideration of allogeneic HCT for intermediate-risk patients 1. Since matched donors are unavailable, haplo-SCT represents the best curative option.

Critical Timing Considerations

Proceed to transplant after one consolidation cycle rather than waiting:

• MRD status after second induction is highly prognostic, and MRD negativity improves transplant outcomes 2, 3
• Delaying transplant with multiple additional consolidation cycles increases risk of MRD recurrence and relapse 2
• Patients achieving CR after ≥2 cycles of induction therapy are specifically recommended for allogeneic HSCT regardless of cytogenetic risk 1

Common Pitfalls to Avoid

Do not continue with chemotherapy-only approach:

• Intermediate-risk AML without favorable molecular markers (NPM1 mutation with FLT3-ITD negative) requires allogeneic transplantation for optimal outcomes 1
• The initial MRD positivity after first induction indicates this patient needs more than chemotherapy alone 2

Do not wait indefinitely for matched unrelated donor:

• Continue donor search in parallel, but proceed with haplo-SCT planning to avoid disease progression 1
• Haploidentical transplantation provides comparable outcomes and should not be considered inferior when matched donors are unavailable 1

Do not proceed directly to transplant without any consolidation:

• At least one consolidation cycle helps maintain remission during transplant preparation 1
• This approach balances disease control with timely progression to definitive therapy 1