Purpose: Relapsed acute myeloid leukemia (AML) post allogeneic hematopoietic cell transplantation (allo-HCT) has a dismal prognosis. Experimental Design: To assess prognosis of patients with recurrent AML post allo-HCT over time, we analyzed European Society for Blood and Marrow Transplantation registry data of 8,162 adult patients with AML who relapsed between 2000 and 2018 after allo-HCT performed in first complete remission from matched sibling, unrelated, or haploidentical donors. Results: The 2-year overall survival (OS) rate from relapse was 17%. For 3,630 patients, <50 years of age, the 2-year OS continuously increased from 16% between 2000 and 2004 to 18% for 2005–2009, to 21% for 2010–2014, and to 26% for 2015–2018 (P = 0.001). Improvement over time was noted both after relapse within and beyond 6 months from allo-HCT. On multivariate analysis among patients <50 years of age, OS was positively affected by a later year of relapse (baseline: 2000–2004; HR, 0.82; P < 0.02 for 2010–2014 and HR, 0.72; P = 0.0002 for 2015–2018), good performance status, favorable cytogenetics, and longer time from transplant to relapse, but negatively affected by increasing age. In contrast, among 4,532 patients, >50 years of age, the year of relapse had no influence on OS (16% for 2000–2004 and 14% for 2015–2018; P = 0.56). Regarding treatment, encouraging results were observed after second allo-HCT, which was performed within 2 years after relapse in 17% of the entire cohort, resulting in a 2-year OS of 30.7%. Conclusions: Outcome after posttransplant relapse among younger patients has improved significantly in recent years, likely reflecting, among other factors, the efficacy of posttransplant salvage including second allo-HCT.

Purpose: We evaluated outcomes of unrelated transplantation for primary refractory/relapsed (ref/rel) acute myeloid leukemia (AML), comparing two cohorts according to the year of transplant, 2000–2009 and 2010–2019. Patients and Methods: Multivariable analyses were performed using the Cox proportional-hazards regression model. Results: 3,430 patients were included; 876 underwent a transplant between 2000–2009 and 2554 in 2010–2019. Median follow-up was 8.7 (95% CI, 7.8–9.4) and 3.4 (95% CI, 3.1–3.6) years (P < 0.001). Median age was 52 (18–77) and 56 (18–79) years (P > 0.0001); 45.5% and 55.5% had refractory AML while 54.5% and 44.5% had relapsed AML. Conditioning was myeloablative in 60% and 52%, respectively. Neutrophil recovery and day 100 incidence of acute and 2-year incidence of chronic graft-versus-host disease (GvHD) were similar between the two periods. Two-year relapse incidence was higher for patients undergoing transplant in the 2000–2009 period versus those undergoing transplant in 2010–2019: 50.2% versus 45.1% (HR, 0.85; 95% CI, 0.74–0.97; P = 0. 002). Leukemia-free survival; overall survival; and GvHD-free, relapse-free survival were lower for the 2000–2009 period: 26% versus 32.1% (HR, 0.87; 95% CI, 0.78–0.97; P = 0.01), 32.1% versus 38.1% (HR, 0.86; 95% CI, 0.77–0.96; P = 0.01), and 21.5% versus 25.3% (HR, 0.89; 95% CI, 0.81–0.99; P = 0.03), respectively. Two-year nonrelapse mortality was not significantly different (23.8% vs. 23.7%; HR, 0.91; 95% CI, 0.76–1.11; P = 0.34). Conclusions: Outcome of unrelated transplantation for patients with ref/rel AML has improved in the last two decades, rescuing about one third of the patients. See related commentary by Adrianzen-Herrera and Shastri, p. 4167

The intensity of the conditioning regimen given before allogeneic hematopoietic cell transplantation (allo-HCT) can vary substantially. To confirm the ability of the recently developed transplant conditioning intensity (TCI) score to stratify the preparative regimens of allo-HCT, we used an independent and contemporary patient cohort of 4060 transplant recipients with acute myeloid leukemia meeting inclusion criteria from the discovery study (allo-HCT in first complete remission, matched donor), but who were allografted in a more recent period (2018–2021) and were one decade older (55–75 years, median 63.4 years), we assigned them to a TCI category (low n = 1934, 48%; intermediate n = 1948, 48%, high n = 178, 4%) according to the calculated TCI score ([1–2], [2.5–3.5], [4–6], respectively), and examined the validity of the TCI category in predicting early non-relapse mortality (NRM), 2-year NRM and relapse (REL). In the unadjusted comparison, the TCI index provided a significant risk stratification for d100 and d180 NRM, NRM and REL risk. In the multivariate analysis adjusted for significant variables, there was an independent association of TCI with early NRM, NRM and REL. In summary, we confirm in contemporary treated patients that TCI reflects the conditioning regimen related morbidity and anti-leukemic efficacy satisfactorily and across other established prognostic factors.