Primary endpoints were disease-free survival (DFS) and overall survival (OS). Throughout the manuscript, analyses were performed considering the entire cohort as well as distinct transplant periods: (i) 1989–2000, (ii) 2001–2010, and (iii) 2011–2019 (Table 1).ĭata was collected prospectively and analyzed in a retrospective fashion. Molecular risk at diagnosis and response was categorized according to the respective guidelines and criteria applicable at the time the patient was treated. Patients were treated at the discretion of the treating physician and according to institutional standards and national/international guidelines. All analyses were performed in accordance with the Declaration of Helsinki.Ĭlinical and molecular examinations as well as laboratory analyses were performed as part of standard clinical care. Patients provided written informed consent for the use of their data for clinical research after approval by the local Ethics Committee (22-1490-S1-retro). We evaluated clinical and molecular data from 220 patients receiving allogeneic HCT after PIF at the University Medical Center Freiburg (Germany) between 19, with PIF being defined as never achieving CR during induction or re-induction, assessed either by cytomorphology or molecular measurable residual disease (MRD), as defined by the NCI (Version 23.06d, Code C70622). In this single-center retrospective analysis, we explored long-term outcomes of 220 AML patients with PIF undergoing allogeneic HCT with active disease at our institution over a period of 30 years between 19, and investigated molecular and clinical features associated with clinical prognosis. Yet, median follow-up of this study was 37 months and the value of immediate allogeneic HCT in this clinical setting for induction of long-term response and durable remission is largely unclear. reported that patients with relapsed/refractory AML had similar survival rates regardless of whether they proceeded directly to allogeneic HCT or underwent intensive remission induction prior to HCT within the ASAP trial. Thus, AML patients with primary induction failure (PIF) who never achieve CR are often not considered for immediate allogeneic HCT and receive various other re-induction strategies, although allogeneic HCT represents the only curative option for these patients. Achieving complete remission (CR) before allogeneic HCT has been associated with improved clinical outcomes. Furthermore, the introduction of reduced toxicity conditioning (RTC) regimens has made allogeneic HCT accessible for less fit and elderly patients. Outcomes of patients with AML undergoing allogeneic HCT have significantly improved over the last decades, mostly due to advances in stem cell harvesting modalities, supportive care, and infection management. Similar content being viewed by othersĪllogeneic hematopoietic stem cell transplantation (HCT) is the standard consolidation treatment for most patients with adverse-risk acute myeloid leukemia (AML). Collectively, our data suggests that immediate allogeneic HCT after PIF offers long-term survival and cure in a substantial subset of cases and that high-risk AML patients who never achieved complete response during induction might benefit from early donor search. Adverse molecular risk features determined at initial diagnosis, poor performance status at the time of allogeneic HCT, and long diagnosis-to-HCT intervals were associated with unfavorable prognosis. 10-year non-relapse mortality was 32.5%, and 48.8% of patients showed disease relapse within 10 years after allogeneic HCT. In this high-risk population, disease-free survival was 25.2% after 5 years and 18.7% after 10 years, while overall survival rates were 29.8% and 21.6% after 5 and 10 years of HCT, respectively. Here, we retrospectively evaluated long-term outcomes of 220 AML patients undergoing allogeneic HCT after PIF who never achieved remission, and identified clinical and molecular risk factors associated with treatment response and ultimate prognosis. Primary induction failure (PIF) in acute myeloid leukemia (AML) patients is associated with poor outcome, with allogeneic hematopoietic stem cell transplantation (HCT) being the sole curative therapeutic option.
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