What is the best course of treatment for a middle-aged adult patient with a history of acute myeloblastic leukemia (AML) who has not achieved remission, has undergone a bone marrow transplant, and has cytogenetic results showing a CBFB (16q22) gene rearrangement and an extra signal for the RUNX1T1 (8q21.3) gene region?

Treatment of Relapsed/Refractory Core Binding Factor AML Post-Transplant

This patient with persistent/relapsed CBFB-rearranged AML after prior allogeneic transplant requires immediate re-induction chemotherapy followed by consideration of a second allogeneic transplant from an alternative donor if remission is achieved. 1, 2

Critical Context: Why This Case is High-Risk

The cytogenetic findings reveal persistent disease with concerning features:

• CBFB rearrangement (42% of cells) confirms core binding factor AML, typically favorable-risk, but this patient has already failed both initial therapy and transplant 3, 4
• Extra RUNX1T1 signal (7% of cells) suggests clonal evolution and genomic instability 4
• New der(1;18) translocation represents clonal evolution with gain of 1q, an independent poor prognostic factor that signals transformation and treatment resistance 1
• Trisomy 8 in second clone further confirms aggressive disease biology 4

This is relapsed disease post-transplant, not minimal residual disease—the patient never achieved durable remission. 5, 2

Immediate Management Algorithm

Step 1: Re-Induction Chemotherapy

Initiate salvage chemotherapy immediately with high-dose cytarabine-based regimen. 1

• Standard re-induction should include an anthracycline plus cytarabine (same backbone as initial induction) 1
• High-dose cytarabine (3 g/m² every 12 hours on days 1,3,5) is particularly effective in core binding factor AML 6, 3
• Critical pitfall: Do not delay chemotherapy for additional testing—the blast burden and clonal evolution demand urgent cytoreduction 1

Step 2: Assess Response After Re-Induction

Perform bone marrow aspirate and biopsy after count recovery to document remission status. 1, 5

• Complete remission requires <5% blasts, normal cellularity, and morphologically normal hematopoiesis 1, 7
• If remission achieved: Proceed immediately to Step 3 2, 8
• If refractory: Consider investigational therapies or palliative care, as outcomes are dismal 2, 8

Step 3: Second Allogeneic Transplant (If Remission Achieved)

Patients achieving second remission should proceed to allogeneic transplantation with an unrelated matched donor or alternative donor source. 1, 2

• This is the only potentially curative option for relapsed AML post-transplant 2, 8
• Alternative donor sources (matched unrelated donor, haploidentical, cord blood) are acceptable given urgency 1, 2
• Reduced-intensity conditioning may be appropriate given prior transplant and middle age 1
• Approximately 30% of patients with refractory/relapsed AML can achieve durable remission with allogeneic transplant, though outcomes are worse than primary refractory disease 2, 8

Why Standard Approaches Don't Apply Here

This patient cannot be managed with surveillance or consolidation chemotherapy alone:

• Patients not entering complete remission after induction (or losing remission post-transplant) are at extremely high risk and require allogeneic transplantation 1
• The favorable prognosis typically associated with CBFB-rearranged AML does not apply to relapsed disease post-transplant 3, 4
• High-dose cytarabine consolidation alone (the standard for favorable-risk CBF-AML) is insufficient for relapsed disease 1, 6
• Maintenance therapy and ATRA are beneficial only in acute promyelocytic leukemia (APL), not this patient's CBFB-rearranged AML 1

Prognostic Reality

Patients with relapsed AML after allogeneic transplant have limited curative options, with long-term survival rates of approximately 20-30% even with aggressive salvage therapy and second transplant. 2, 8

• Primary refractory AML has better outcomes than relapsed disease post-transplant 2
• The new der(1;18) translocation with 1q gain is an independent poor prognostic factor 1
• Only 3 of 27 patients in one series relapsed beyond 2 years post-transplant, suggesting that achieving durable remission is possible but uncommon 8

Critical Pitfalls to Avoid

• Do not pursue "watchful waiting"—the cytogenetics show active disease requiring immediate treatment 1, 5
• Do not treat this as favorable-risk CBF-AML—relapsed disease post-transplant negates the favorable prognosis 3, 4
• Do not delay donor search—initiate unrelated donor search immediately during re-induction, as time to transplant affects outcomes 1, 2
• Do not attribute findings to post-transplant effects—42% CBFB rearrangement represents frank relapse, not minimal residual disease 5, 2