What is the mortality rate for Acute Myeloid Leukemia (AML) recurrence, specifically after a stem cell transplant?

Mortality Rate for AML Recurrence After Stem Cell Transplant

For a third total recurrence of AML (first recurrence after stem cell transplant), mortality is extremely high, with expected survival measured in months rather than years, and the vast majority of patients will not survive beyond 1-2 years.

Prognosis Based on Timing of Post-Transplant Relapse

The timing of relapse after stem cell transplantation is the single most critical prognostic factor:

• Relapse within 6 months post-transplant: 3-year survival probability of only 4% 1, 2
• Relapse 6-24 months post-transplant: 3-year survival probability of 12% 1, 2
• Relapse 2-3 years post-transplant: 3-year survival probability of 26% 1, 2
• Relapse >3 years post-transplant: 3-year survival probability of 38% 1, 2

The median overall survival for patients relapsing after allogeneic stem cell transplantation is approximately 6 months 3.

Context of Third Recurrence

By the third recurrence, patients face compounding adverse factors:

• Exhausted salvage options: Standard chemotherapy regimens have already failed multiple times 1
• Resistant disease biology: The leukemia has demonstrated progressive resistance to treatment 1
• Treatment-related organ damage: Cumulative toxicity from prior intensive therapies 1
• Accumulated comorbidities: Multiple prior treatment courses increase comorbidity burden 4

The 30-day mortality with intensive salvage chemotherapy in heavily pretreated patients can reach 14% or higher, making aggressive treatment questionable without extraordinary circumstances 1.

Treatment Options and Expected Outcomes

Second Allogeneic Transplant

Second allogeneic stem cell transplantation is only considered for highly selected patients who relapse >5 months after first transplant 1:

• Overall 2-year survival after second transplant: 36% 4
• 5-year survival for patients with low disease burden (<5% bone marrow blasts): 25% 5
• 5-year survival for patients with high disease burden: 12% 5
• Non-relapse mortality remains substantial at 18% at 2 years 4

Favorable prognostic factors for second transplant include:

• Absence of chronic GVHD after first transplant 4
• HCT comorbidity index <2 at time of second transplant 4
• Low disease burden (<5% bone marrow blasts) 5, 3
• Longer time to relapse (>6 months) 3

Donor Lymphocyte Infusion (DLI)

• DLI combined with chemotherapy or FLT3 inhibitors is rarely effective in the long term 6
• May be considered for patients with low disease burden and longer time since first transplant 3
• 2-year overall survival after second cellular therapy (DLI or second transplant): 44.9% (95% CI: 28.5%-61.4%) in selected patients with <5% bone marrow blasts 3

Targeted Therapy for FLT3-Mutated AML

For patients with FLT3-mutated AML:

• Gilteritinib monotherapy provides median overall survival of 9.3 months in first relapse 1
• Expect significantly worse outcomes in third recurrence 1
• Sorafenib may achieve long-lasting responses in a small proportion of patients 6

Clinical Trial Enrollment

Clinical trial enrollment should be the first priority for patients with third recurrence, if available 1.

Best Supportive Care Approach

For patients not candidates for active therapy, focus on:

• Transfusion support for symptomatic anemia and thrombocytopenia 1
• Cytoreductive therapy (hydroxyurea) for symptom control 1
• Early palliative care consultation 1
• Quality of life optimization 1

Critical Prognostic Factors

Disease-Related Factors

• Adverse cytogenetics: Associated with worse outcomes after relapse 7, 3
• FLT3-ITD mutation: Predicts early relapse (within 3-6 months post-transplant) 7
• NPM1 mutation: Associated with adverse outcomes after relapse 3
• TP53 abnormality: Associated with poor survival 3

Transplant-Related Factors

• Time to relapse: Most powerful predictor of post-relapse survival 7, 3
• Relapse type: Measurable residual disease relapse has better outcomes than morphologic relapse 3
• Chronic GVHD after first transplant: Associated with worse outcomes if second transplant attempted 4

Summary of Expected Mortality

For a patient experiencing their first relapse after stem cell transplant (third total recurrence):

• If relapse occurs <6 months post-transplant: 96% mortality at 3 years 1, 2
• If relapse occurs 6-24 months post-transplant: 88% mortality at 3 years 1, 2
• Median survival across all post-transplant relapses: 6 months 3
• Disease recurrence is the cause of death in 73% of patients who die after second transplant 4

The prognosis is grave, and aggressive treatment should be carefully weighed against quality of life considerations, with strong consideration for palliative care involvement early in the disease course 1.