Early allogeneic stem cell transplantation after melphalan-induced aplasia leads to long-term survival in patients with primary refractory AML

The prognosis of patients with AML, who fail to achieve complete remission after induction therapy (= primary refractory disease) has been dismal for many years. Allo-HSCT is the only curative approach and standard of care for eligible patients in this group. The need for inducing a remission before transplantation in primary refractory patients has not been finally clarified. The objective of this retrospective single-center evaluation is to analyze the outcomes of primary refractory patients who underwent immediate allogeneic HSCT after chemotherapy induced aplasia in the context of the conditioning regimen in a real-life setting. We started a program of immediate transplantation policy for eligible patients with refractory AML after induction chemotherapy in our center in 2010. All patients with a diagnosis of primary refractory AML who underwent their first allogeneic hematopoietic stem cell transplantation in active disease between 03/2010 and 07/2023 at the department of Hematology at Klinikum Nuremberg, Germany, were included and analyzed. 50 patients were included in this analysis. Mean time from start of induction treatment to transplantation was 3 months (range 1.4-7.8 months). Melphalan (100-140 mg/m²) for induction of aplasia was used in 45/50 pts (90%) prior to conditioning. After a median follow-up of 9.97 (range: 0.03-143.8) months 18/50 (36%) patients were alive without relapse. Median and mean relapse free survival were 9.97 (range: 0.03-143.8) and 28.13 (range: 0.03-143.8) months respectively. The median and mean OS were 9.97 (range: 0.03-143.8) and 28.64 (range: 0.03-143.8) months. The 100-day, 1-year and 2-year survival rates were 66%, 48% and 42% respectively. Cumulative incidence of relapse at 2-years after transplantation was 18.5% (95% C.I., 10.3% - 33.1%) with a median time from HSCT to relapse of 4.85 (Range: 0.67-18,3) months. Cumulative incidence of non-relapse mortality at 100 days, 1- year and 2-years was 26% (95% C.I., 16.3% - 41.5%), 36.3% (C.I., 25.1% - 52.5%) and 38.4% (95% C.I., 26.9% - 54.7%) respectively. Main cause of overall mortality was TRM (58.1%) with Sepsis (41.9%) being the biggest single contributor. The only significant independent factor associated with decreased overall and 100-day survival was a positive patient CMV-status (independent of donor CMV-serostatus). The observed survival-rates in our study compare favorably to those published for established salvage-therapy regimens as well as other retrospective studies analyzing HSCT in active disease. We demonstrate that allogeneic hematopoietic stem cell transplantation in active disease is a reasonable approach for patients with primary refractory AML offering the chance for long-term survival for about one third of patients. The effect is compromised by the high incidence of non-relapse mortality.