Abstract
Treatment options for older patients with intermediate or high-risk acute myeloid leukemia (AML) remain unsatisfactory. Allogeneic stem cell transplantation, the treatment of choice for the majority of younger AML patients, has been hampered in elderly patients by higher treatment related mortality, comorbidities and lack of a suitable donor. With the higher availability of suitable donors as well as of reduced intensity conditioning regimens, novel low intensity treatments prior to transplantation and optimized supportive care, the number of older AML patients being successfully transplanted is steadily increasing. Against this background, we review current treatment strategies for older AML patients planned for allogeneic stem cell transplantation based on clinical trial data, discussing differences between approaches with advantages and pitfalls of each. We summarize pre-treatment considerations that need to be taken into account in this highly heterogeneous older population. Finally, we offer an outlook on areas of ongoing clinical research, including novel immunotherapeutic approaches that may improve access to curative therapies for a larger number of older AML patients.
Highlights
Acute myeloid leukemia (AML) occurs in children and adults at any age, but it is primarily a disease of the elderly, most frequently diagnosed at a median age of 72 years [1]
During the entire lifetime acquisition of somatic mutations leads to clonal hematopoiesis and pre-leukemic lesions, which continuously increase the risk for acute leukemia with age [2,3,4]
Beside the difficulties in treatment of elderly AML patients due to comorbidities and reduced performance status, poor outcome is caused by a different disease biology with more frequent aberrant cytogenetics and often emerging secondary to myelodysplastic syndromes (MDS) or myeloproliferative neoplasms (MPN) [6,7]
Summary
Acute myeloid leukemia (AML) occurs in children and adults at any age, but it is primarily a disease of the elderly, most frequently diagnosed at a median age of 72 years [1]. There has never been a prospective study comparing RIC allogeneic HSCT to consolidation with chemotherapy alone, but a retrospective comparison of RIC allo-HSCT with chemotherapy in patients aged 60–70 years with AML in first complete remission (CR) showed that allo-HSCT was associated with a significantly lower risk of relapse (32% vs 81% at 3 years, p < 0.001), higher non-relapse mortality (NRM) (36% vs 4% at three years, p < 0.001), and longer disease free survival (DFS) An ongoing prospective randomized phase III study comparing conventional chemotherapy to allogeneic HSCT for older AML patients in first CR will hopefully bring clarity to the dilemma of decision-making whether or not to transplant elderly AML patients This data should help to prevent an undertreated population which is not offered curative intent treatment
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