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3588 Long-Term Follow-up of AML Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation after Primary Induction Failure

Program: Oral and Poster Abstracts
Session: 723. Allogeneic Transplantation: Long-term Follow-up and Disease Recurrence: Poster II
Hematology Disease Topics & Pathways:
Research, Acute Myeloid Malignancies, AML, Biological therapies, adult, Clinical Research, health outcomes research, Diseases, Therapies, survivorship, Myeloid Malignancies, Study Population, Human, Transplantation
Sunday, December 10, 2023, 6:00 PM-8:00 PM

Miriam Mozaffari Jovein, MD1*, Gabriele Ihorst, Ph.D2*, Jesus Duque Afonso, MD1, Ralph Wäsch, MD3, Claudia Wehr, MD3*, Hartmut Bertz, MD3*, Justus Duyster, MD3*, Robert Zeiser, MD4, Jürgen Finke, MD3 and Florian Scherer, MD3

1Department of Hematology, Oncology and Stem Cell Transplantation, Faculty of Medicine, University of Freiburg, Freiburg im Breisgau, Germany
2Clinical Trials Unit, University Medical Center Freiburg, Freiburg, Germany
3Department of Hematology, Oncology and Stem Cell Transplantation, Faculty of Medicine, University of Freiburg, Freiburg, Germany
4Department of Internal Medicine I, Hematology, Oncology and Stem Cell Transplantation, Medical Center - University of Freiburg, Faculty of Medicine, Freiburg, Germany


Allogeneic hematopoietic stem cell transplantation (HCT) is the standard consolidation treatment for most patients with adverse-risk acute myeloid leukemia (AML). Achieving complete remission (CR) before HCT has been associated with improved clinical outcomes. Thus, AML patients with primary induction failure (PIF) are often not considered for immediate allogeneic HCT, despite being the only curative option. Most recently, Stelljes et al. reported similar survival rates after a median follow-up of 37 months for relapsed/refractory AML patients who either proceeded directly to allogeneic HCT or underwent intensive remission induction prior to HCT within the ASAP trial (Stelljes et al., ASH Annual Meeting 2022). Yet, the effect of immediate allogeneic HCT in this clinical setting for long-term prognosis is still largely unclear. Thus, we explored long-term clinical outcomes of AML patients with PIF undergoing allogeneic HCT with active disease at our institution over a period of 30 years between 1989 and 2019, and investigated associations with molecular and clinical features.


We retrospectively analyzed AML patients undergoing allogeneic HCT after PIF at the University Medical Center Freiburg (Germany) between 1989 and 2019. PIF was defined as never achieving CR during induction or re-induction, assessed either by cytomorphology or molecular measurable residual disease as defined by the NCI (Version 23.06d, Code C70622). All clinical examinations and laboratory analyses were performed as part of standard clinical care. Statistical analyses were performed considering the entire cohort as well as distinct transplant periods: i) 1989-2000, ii) 2001-2010, and iii) 2011-2019. Primary endpoints were disease-free survival (DFS) and overall survival (OS). Other endpoints were time to relapse and time to non-relapse mortality (NRM).


We included 220 patients in this retrospective single-center study, with a median follow-up of 8.5 years (range: 0.06-25.4). Median age of patients was 55 years (range: 20-75), increasing over time as reduced toxicity conditioning became more established (1989-2000: 13.9%; 2011-2019: 61.8%). Patients received in median two lines of treatment before HCT (range: 1-6). Blast count in bone marrow before initiation of allogeneic HCT was in median 36% (range: 0-95%). Molecular risk was assessed in 63.2% of patients, while genetic information was missing in 36.8% of AML cases. 39.8% of AML patients were disease-free after 1 year, 25.2% after 5 and 18.7% after 10 years from allogeneic HCT (Fig. 1A). 206 patients (93.6%) were alive at day 30 after HCT and 59 patients (26.8%) were alive at the time of the analysis. Median OS was 1.05 years, with 1-year, 5-year, and 10-year OS rates being 50.4%, 29.8%, and 21.6%, respectively (Fig. 1A). Survival rates were largely stable over time. 5-year OS in patients treated between 1989-2000 was 28.7%, in those receiving HCT between 2001 and 2010 28.7%, and 30.3% in patients transplanted between 2011 and 2019 (Fig. 1A). NRM was 29.3% after 5 years and 32.5% after 10 years (Fig. 1A). Over time, relapse rates decreased, with 5-year relapse rates of 45.7% between 1989 and 2000 and 33.3% between 2011 and 2019 (Fig. 1A). The main cause of death after HCT was AML progression/relapse (57.8%), while infections (19.3%), GvHD (11.2%), and treatment-related toxicity (8.4%) were leading causes of NRM. In Cox regression analyses incorporating known molecular and clinical risk factors, poor performance status (ECOG > 1 vs. 0-1; DFS: p=0.001, HR 2.26, 95% CI 1.37-3.73; OS: p=8*10-5, HR 2.76, 95% CI 1.66-4.58,), adverse genetic risk at AML diagnosis (vs. intermediate/favorable risk; DFS: p=0.03, HR 1.6, 95% CI 1.1-2.4; OS: p=0.01, HR 1.7, 95% CI 1.1-2.6), and long diagnosis-to-HCT interval (DFS: p=0.01, HR 2.7, 95% CI 1.2-6.1; OS: p=0.005, HR 3.1, 95% CI 1.4-6.8) were strongly and independently associated with unfavorable DFS and OS (Fig. 1B).


We here demonstrated that immediate allogeneic HCT in AML patients with active disease represents a valid alternative to intensive remission induction prior to HCT and provides long-term survival and cure in a significant proportion of patients, suggesting to proceed with allogeneic HCT in patients with refractory disease as soon as a donor is available. The benefit of hypomethylating agents and venetoclax therapy prior to allogeneic HCT remains to be elucidated.

Disclosures: Duque Afonso: NovoNordisk: Honoraria; AstraZeneca: Honoraria; SOBI: Honoraria, Other: Travel Support; Lilly: Other: Travel Support; Roche: Other: Travel Support; IPSEN: Honoraria; Amgen: Honoraria; Roche: Consultancy, Honoraria, Other: Travel Support; Riemser: Honoraria. Wäsch: Sanofi: Honoraria; BMS: Other: Travel support; Pfizer: Other: Travel support; Kite/Gilead: Other: Travel support; Janssen: Other: Travel support; Takeda: Honoraria; Pfizer: Honoraria; Kite/Gilead: Honoraria; Janssen: Honoraria; BMS/Celgene: Honoraria; Amgen: Honoraria; Abbvie: Honoraria; Sanofi: Research Funding; Janssen: Research Funding; Takeda: Consultancy; Sanofi: Consultancy; Pfizer: Consultancy; Kite/Gilead: Consultancy; Novartis: Consultancy; Janssen: Consultancy; BMS/Celgene: Consultancy; Amgen: Consultancy. Zeiser: novartis: Consultancy, Honoraria, Research Funding; incyte: Consultancy, Honoraria; MNK: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; Medac: Honoraria; VectivBio: Consultancy. Finke: Neovii: Honoraria, Research Funding, Speakers Bureau; Riemser: Honoraria, Research Funding, Speakers Bureau; Gilead Sciences: Current holder of stock options in a privately-held company; AbbVie: Current holder of stock options in a privately-held company; Roche: Current holder of stock options in a privately-held company; Medac: Honoraria, Research Funding. Scherer: Gilead Sciences: Research Funding; Takeda: Research Funding; Roche Sequencing Solutions: Research Funding.

*signifies non-member of ASH