In patients older than 55 years with AML in first CR, should we search for a matched unrelated donor when an old sibling donor is available?

Abstract

on behalf of the Acute Leukemia Working Party of EBMT Allogeneic hematopoietic transplantation is increasingly used in patients aged 55 years or more with AML. The question of whether outcomes can be improved with an allele-level 8/8 HLA-matched unrelated donor (MUD) rather than an older HLA-matched sibling (MSD, more than 55 years) is still unanswered. We thus analyzed outcomes in 714 patients aged 55 years and older with AML in first CR (CR1) who received PBSCs after a reduced-intensity conditioning hematopoietic cell transplant from a MUD (n = 310) or a MSD (n = 404) in a recent period (2005)(2006)(2007)(2008)(2009)(2010). The 3-year cumulative incidences (CIs) of non-relapse mortality were 17% and 23% with MSD and MUD, respectively (P = 0.17). The 3-year CIs of relapse were 37% and 30%, respectively (P = 0.12), resulting in a 3-year CI of leukemia-free survival of 46% and 47%, respectively (P = 0.51). The 3-year overall survival was 49% with both MSD and MUD.In conclusion, HLA-identical sibling donors aged 55 years or more should not be excluded because of age for patients aged 55 years and older with AML in CR1.

MYC protein expression is an important prognostic factor in acute myeloid leukemia

“…These patients are known to be at higher risk for relapse [30–34]. Patients with AML who are ≥55-years old have generally been considered “older” in the literature [33,35–39] and because ≥55-years is an established age group associated with more adverse cytogenetics and higher risk for relapse, that was the cutoff selected to denote “older” for this analysis [30–34]. Furthermore, many molecular biomarkers either lose their prognostic value or have not been assessed in this age group because patients ≥55-years were historically excluded from clinical trials [40–43]; thus, the impact of MYC-immunopositivity warrants further exploration in these patients.…”

“…Patients with AML who are ≥55-years-old have generally been considered “older”[33,35–39] and have historically been excluded from many clinical trials [34,35]. Thus, we focused on AML patients ≥55 years of age, as they have higher rates of relapse[30–34], early death [32–34], unfavorable cytogenetics [36,44,45], and given that the clinical significance of commonly assessed molecular biomarkers are already well-established in younger AML patients [40–43], particularly <55-years-old [46].…”

Comparison of transplant outcomes from matched sibling bone marrow or peripheral blood stem cell and unrelated cord blood in patients 50 years or older

“…However, it is unclear whether older MSDs or alternative donors provide better outcomes for older patients, although MSDs are generally a first-line donor source in younger patients. Several studies investigated whether older MSDs or younger MUDs provides better outcomes for older patients [22,23,[39][40][41][42]. Although these data were controversial, MUD is an alternative donor source for older patients.…”

Allogeneic Hematopoietic Cell Transplantation for Older Adults with Acute Myeloid Leukemia

“…The difference in outcomes may be due to the decreased allo-reactivity of older donor T cells that lead to a decrease in anti-leukemia effects [ 49 ]. In a second retrospective study using the EBMT registry that included 714 adults with AML (median age at transplant 61.4 years, range 55–74), outcomes such as relapse, non-relapse mortality, leukemia-free survival, and overall survival were similar in patients who received allo-HSCT from a matched-unrelated donor or a matched-related donor [ 50 ]. Taken together, matched-related donors and matched-unrelated donors are still the preferred donor sources, and the choice for one versus another depends on other factors related to the donor (age, smoking status, and comorbidity) and to patient-donor compatibility (7/8 or 8/8 HLA-matched, gender, ABO compatibility, and CMV status) [ 51 ].…”