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Acute myeloid leukemia (AML)

Transplant advances and outcomes

Allogeneic stem cell transplantation is an important treatment option in the management of adult acute myeloid leukemia (AML). [1] Worldwide, physicians perform more than 7,000 allogeneic transplants for AML, making it the most common and fastest growing indication for allogeneic HCT. [2]

Recent advances informing clinical decision-making include increasing identification of prognostic genetic markers in AML used to determine the disease risk status and a composite comorbidity/age score for treatment risk stratification. [1-8]

Because of these advances, more is known about which patients are eligible for hematopoietic cell transplantation (HCT) and which are not. In addition, large-scale studies have determined the optimal timing for HCT. Patients with AML transplanted while in first or second complete remission have significantly better outcomes than patients transplanted with advanced disease. This is true whether the patient is undergoing matched related or matched unrelated HCT.

Recent research shows an upper age limit may not be a barrier to allogeneic HCT for patients with AML. A CIBMTR® study published in Bone Marrow Transplantation showed differences in outcomes among patient groups were better associated with covariates, such as comorbidities and immunosuppression regimen, than age. Research suggests that patient age alone should not be considered exclusion criteria for a transplant consultation. [9]

For patients with intermediate- and poor-risk cytogenetics, a meta-analysis demonstrated a survival benefit of allogeneic HCT in first complete remission over chemotherapy. [10] Early referral for HCT evaluation for these at-risk patients at an early disease stage can significantly improve survival. [11,12]

Recommended timing for transplant consultation

High-resolution HLA typing is recommended at diagnosis for all patients.

HCT consultation should take place early after initial diagnosis for patients with AML, including:

  • Primary induction failure
  • Measurable (also known as minimal) residual disease after initial therapy
  • CR1 – except favorable risk AML [defined as: t(8;21)(q22;q22.1); RUNX1-RUNX1T1, inv(16)(p13.1q22) or t(16;16)(p13.1;q22); CBFB-MYH11, mutated NPM1 without FLT3-ITD, biallelic mutated]. Transplant consultation may be reasonable for favorable-risk AML patients with unusual or adverse co-mutations or cytogenetic alterations. Early referral for allogeneic HCT should also be considered for any patients in CR1 who are 60 years old or older; regardless of cytogenetic or genomic information.
  • Antecedent hematological disease (e.g., myelodysplastic syndrome [MDS]), either based on prior clinical diagnosis or suggested by the presence of secondary-type somatic mutations on molecular testing
  • Treatment-related leukemia
  • First relapse
  • CR2 and beyond, if not previously evaluated

References

  1. Vyas P, Appelbaum FR, Craddock C. Allogeneic hematopoietic cell transplantation for acute myeloid leukemia. Biol Blood Marrow Transplant. 2015; 21(1): 8-15. Access
  2. Gratwohl A, Baldomero H, Aljurf M, et al. Hematopoietic stem cell transplantation: A global perspective. JAMA. 2010; 303(16): 1617-1624. Access
  3. Patel JP, Gönen M, Figueroa ME, et al. Prognostic relevance of integrated genetic profiling in acute myeloid leukemia. N Engl J Med. 2012; 366(12): 1079-1089. Access
  4. Röllig C, Bornhäuser M, Kramer M. et al. Allogeneic stem-cell transplantation in patients with NPM1-mutated acute myeloid leukemia: Results from a prospective donor versus no-donor analysis of patients after upfront HLA typing within the SAL-AML 2003 trial. J Clin Oncol. 2015; 33(5): 403-410. Access
  5. Ofran Y, Rowe JM. Genetic profiling in acute myeloid leukaemia – where are we and what is its role in patient management. Br J Haematol. 2013; 160(3): 302-320. Access
  6. Döhner H, Estey E, Grimwade D, et al. Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. Blood. 2017; 129(4): 424-447. Access
  7. Schlenk RF, Kayser S, Bullinger L, et al. Differential impact of allelic ratio and insertion site in FLT3-ITD-positive AML with respect to allogeneic transplantation. Blood. 2014; 124(23): 3441-3449. Access
  8. Sorror ML, Storb RF, Sandmaier BM, et al. Comorbidity-age index: A clinical measure of biologic age before allogeneic hematopoietic cell transplantation. J Clin Oncol. 2014; 32(29): 3249-3256. Access
  9. Maakaron, J.E., Zhang, MJ., Chen, K. et al. Age is no barrier for adults undergoing HCT for AML in CR1: contemporary CIBMTR analysis. Bone Marrow Transplant. 2022:57: 911–917. Access
  10. Koreth J, Schlenk R, Kopecky KJ, et al. Allogeneic stem cell transplantation for acute myeloid leukemia in first complete remission: Systematic review and meta-analysis of prospective clinical trials. JAMA. 2009; 301(22): 2349-2361. Access
  11. Pidala J, Lee SJ, Ahn KW, et al. Nonpermissive HLA-DPB1 mismatch increases mortality after myeloablative unrelated allogeneic hematopoietic cell transplantation. Blood. 2014; 124(16): 2596-2606. Access
  12. Lee SJ, Klein J, Haagenson M, et al. High-resolution donor-recipient HLA matching contributes to the success of unrelated donor marrow transplantation. Blood. 2007; 110(13): 4576-4583. Access
  13. NMDP and ASTCT Recommended Timing for Transplant Consultation. Download PDF 
  14. National Comprehensive Cancer Network. Acute Myeloid Leukemia. (Version 2.2022). Access