Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2023 Apr 1;9(4):519-526.
doi: 10.1001/jamaoncol.2022.7605.

Allogeneic Hematopoietic Cell Transplantation vs Standard Consolidation Chemotherapy in Patients With Intermediate-Risk Acute Myeloid Leukemia: A Randomized Clinical Trial

Martin Bornhäuser  1   2 , Christoph Schliemann  3 , Johannes Schetelig  1 , Christoph Röllig  1 , Michael Kramer  1 , Bertram Glass  4 , Uwe Platzbecker  5 , Andreas Burchert  6 , Mathias Hänel  7 , Lutz P Müller  8 , Stefan Klein  9 , Gesine Bug  10 , Dietrich Beelen  11 , Wolf Rösler  12 , Kerstin Schäfer-Eckart  13 , Christoph Schmid  14 , Edgar Jost  15 , Georg Lenz  3 , Johanna Tischer  16 , Karsten Spiekermann  16 , Markus Pfirrmann  17 , Hubert Serve  10 , Friedrich Stölzel  1 , Nael Alakel  1 , Jan Moritz Middeke  1 , Christian Thiede  1 , Gerhard Ehninger  1 , Wolfgang E Berdel  3 , Matthias Stelljes  3
Affiliations
Clinical Trial

Allogeneic Hematopoietic Cell Transplantation vs Standard Consolidation Chemotherapy in Patients With Intermediate-Risk Acute Myeloid Leukemia: A Randomized Clinical Trial

Martin Bornhäuser et al. JAMA Oncol. .

Abstract

Importance: The ideal postremission strategy in intermediate-risk acute myeloid leukemia (AML) in first complete remission (CR) has been a matter of debate.

Objective: To explore the optimal therapy for patients with intermediate-risk AML after first complete remission.

Design, settings, and participants: This investigator-initiated, open-label, 2-armed, phase 3 randomized clinical trial assessed patients at 16 hospitals in Germany from February 2, 2011, until July 1, 2018. Key eligibility criteria included cytogenetically defined intermediate-risk AML according to Medical Research Council classification, first CR or CR with incomplete blood cell count recovery after conventional induction therapy, age of 18 to 60 years, and availability of a human leukocyte antigen (HLA)-matched sibling or unrelated donor. A detailed statistical analysis plan was written and finalized on July 7, 2020. Data were exported for analysis on April 13, 2021.

Interventions: Patients were randomized 1:1 to receive allogeneic hematopoietic cell transplantation (HCT) or high-dose cytarabine for consolidation and salvage HCT only in case of relapse. Strata for randomization included age (18-40 vs 41-60 years), NPM1 and CEBPA variation status, and donor type (unrelated vs related).

Main outcomes and measures: End points included overall-survival as the primary outcome and disease-free survival, cumulative incidence of relapse, treatment-related mortality, and quality of life measured according to the Medical Outcomes Study 36-Item Short-Form Health Survey as secondary outcomes.

Results: A total of 143 patients (mean [SD] age, 48.2 [9.8] years; 81 [57%] male) with AML who fulfilled the eligibility criteria were randomized. In the intention-to-treat analysis, the probability of survival at 2 years was 74% (95% CI, 62%-83%) after primary allogeneic HCT and 84% (95% CI, 73%-92%) after consolidation chemotherapy (P = .22). Disease-free survival after HCT at 2 years was 69% (95% CI, 57%-80%) compared with 40% (95% CI, 28%-53%) after consolidation chemotherapy (P = .001). Allogeneic HCT during the first CR was associated with a cumulative incidence of relapse at 2 years of 20% (95% CI, 13%-31%) compared with 58% (95% CI, 47%-71%; P < .001). Nonrelapse mortality at 2 years after primary allogeneic HCT was 9% (95% CI, 5%-19%) and 2% (95% CI, 0%-11%) after consolidation chemotherapy (P = .005). Similar outcomes were observed when analyses were confined to the 96 patients at intermediate risk according to the European Leukemia Network classification. Most importantly, all 41 patients relapsing after consolidation chemotherapy (36 hematologic, 4 molecular, and 1 extramedullary) proceeded to allogeneic HCT. No significant differences in health-related quality of life measures were observed between groups.

Conclusions and relevance: Primary allogeneic HCT during first CR was not associated with superior overall survival compared with consolidation chemotherapy in patients 60 years or younger with intermediate-risk AML during the first CR and an available donor.

Trial registration: ClinicalTrials.gov Identifier: NCT01246752.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest Disclosures: Dr Bornhäuser reported receiving personal fees from Jazz Pharmaceuticals and Gilead outside the submitted work. Dr Schetelig reported receiving grants from the German Ministry for Education and Research (Bundesministerium für Bildung und Forschung) during the conduct of the study, personal fees from the AstraZeneca and BeiGene advisory boards, and lecture fees and personal fees from the Janssen, Bristol Myers Squibb (BMS), and AbbVie advisory boards outside the submitted work. Dr Röllig reported receiving grants from AbbVie, Novartis, and Pfizer and personal fees from Amgen, BMS, Jazz Pharmaceuticals, and Servier outside the submitted work. Dr Burchert reported receiving personal fees from Gilead, AOP Health, Incyte, and from Pfizer outside the submitted work. Dr Hänel reported receiving personal fees from Amgen, Bayer Vital, Celgene, Gilead, GlaxoSmithKline, Jazz Pharmaceuticals, Novartis, Roche, and Takeda outside the submitted work. Dr Müller reported receiving grants from Amgen Inc and personal fees from Celgene, Pfizer, and Neovii outside the submitted work. Dr Bug reported receiving personal fees from Novartis, Jazz Pharmaceuticals, Celgene/BMS, Pfizer, Gilead, and Novartis outside the submitted work. Dr Lenz reported receiving grants from Roche, Janssen, Agios, Aquinox, AstraZeneca, Gilead, Morphosys, and Bayer and personal fees from Roche, Janssen, AstraZeneca, BMS, Gilead, Sobi, ADC Therapeutics, AbbVie, Genmab, Morphosys, Incyte, Bayer, Karyopharm, Miltenyi, PentixaPharm, Novartis, Takeda, NanoString, and Constellation outside the submitted work. Dr Middeke reported receiving grants from Janssen, Novartis, and Jazz Pharmaceuticals and personal fees from AbbVie, AstraZeneca, Roche, Astellas, Jazz Pharmaceuticals, Janssen, and Novartis outside the submitted work. Dr Thiede reported part ownership in AgenDix GmbH during the conduct of the study and receiving personal fees from Novartis, Jazz Pharmaceuticals, Bayer, and Janssen outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. CONSORT Flow Diagram
Allo-HCT indicates allogeneic hematopoietic stem cell transplant; CR, complete remission; and CRi, complete remission with incomplete blood cell count recovery.
Figure 2.
Figure 2.. Kaplan-Meier Estimates of Overall and Disease-Free Survival According to the Intention-to-Treat Analysis
Allo-HCT indicates allogeneic hematopoietic stem cell transplant.
Figure 3.
Figure 3.. Analyses of Overall and Disease-Free Survival According to Prognostic Baseline Factors
Hazard ratios (HRs) for age of 40 years or younger could not be estimated because of the small number of events. Allo-HCT indicates allogeneic hematopoietic stem cell transplant; ELN, European Leukemia Network; HLA, human leukocyte antigen; UD, unrelated donor.
Figure 4.
Figure 4.. Cumulative Incidence of Nonrelapse Mortality and Incidence of Relapse
Allo-HCT indicates allogeneic hematopoietic cell transplant.
See this image and copyright information in PMC

References

    1. Estey EH. Acute myeloid leukemia: 2021 update on risk-stratification and management. Am J Hematol. 2020;95(11):1368-1398. doi:10.1002/ajh.25975 - DOI - PubMed
    1. Cancer Stat Facts . Leukemia—acute myeloid leukemia (AML). Accessed January 15, 2022. https://seer.cancer.gov/statfacts/html/amyl.html
    1. Döhner H, Estey E, Grimwade D, et al. . Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. Blood. 2017;129(4):424-447. doi:10.1182/blood-2016-08-733196 - DOI - PMC - PubMed
    1. Sorror ML, Storer BE, Fathi AT, et al. . Development and validation of a novel acute myeloid leukemia-composite model to estimate risks of mortality. JAMA Oncol. 2017;3(12):1675-1682. doi:10.1001/jamaoncol.2017.2714 - DOI - PMC - PubMed
    1. Dombret H, Gardin C. An update of current treatments for adult acute myeloid leukemia. Blood. 2016;127(1):53-61. doi:10.1182/blood-2015-08-604520 - DOI - PMC - PubMed

Publication types

Associated data