Acute myeloid leukemia (AML) is a rare hematologic malignancy characterized by the clonal expansion and accumulation of immature myeloid cells (blasts) in the bone marrow, leading to impaired normal hematopoiesis [1,2]. In 2021, the global age-standardized incidence rate was 1.7 cases per 100,000. This represents an 82% increase since 1990 [3]. AML is noted for its acute and rapidly progressing nature, necessitating immediate medical intervention [2,4]. Current treatment modalities include chemotherapy, targeted therapies, immunotherapies, and hematopoietic stem cell transplantation (HSCT) [5–7]. The disease and its treatments result in severe side effects, including severe fatigue and cognitive impairment, significantly impacting patients' quality of life [8,9]. Updates to the International Consensus Classification (ICC) and World Health Organization 5^th edition (WHO5) classifications have refined AML subtypes based on genetic and molecular features, improving diagnostic accuracy and guiding treatment decisions [1,10,11].

AML's heterogeneous nature, with a diverse mutational landscape, leads to considerable variability in overall survival (OS), ranging from less than 12 months to more than five years [12,13]. Given the severe nature of refractory and relapsed AML, with a 5-year survival rate of only 10% [14,15], there is a substantial unmet medical need. Many patients still lack appropriate treatment options, underscoring the necessity for developing effective new therapies [4,16].

Currently, OS is the 'gold standard' endpoint for oncology treatment approvals and oncology clinical trials, but its use in AML presents significant challenges:

• AML Heterogeneity: Genomic diversity within AML subtypes presents various risk prognoses leading to variable OS, complicating trial design.
• Urgency of Treatment: The necessity of immediate therapeutic intervention often limits clinical trial participation.
• Use of allogeneic stem cell transplantation (alloSCT): AlloSCT, used in over 50% of younger patients, is a key component of curative-intent treatment and significantly impacts long-term outcomes [7,13,17–19]. The role of alloSCT must be carefully considered in trial design and survival analysis to accurately assess treatment effects.
• Delayed Drug Approvals: While OS provides the most definitive measure of treatment benefit, trials using OS as the primary endpoint can require long follow-up periods, delaying routine patient access to novel therapies while OS trial data is collected.

These challenges lead to additional complexity in enrollment of clinical trials and longer trial read-outs, which delay approval of novel therapies in AML. The adoption of alternative endpoints, such as measurable residual disease (MRD), could accelerate drug development by providing an earlier indication of treatment response while using OS collected as a dual, or secondary endpoint. Event-free survival (EFS) has been supported by regulators and health technology assessment (HTA) bodies as a valid endpoint in AML [20–24]. However, despite the potential for this endpoint to speed up approvals, authorities might not always view it as reliable. Indeed, the definition of negative events and the timing of its evaluation can differ greatly across clinical trials [25,26].

In the context of AML, complete remission (CR) is traditionally defined by the presence of less than 5% blasts in the bone marrow, recovery of peripheral blood counts, and absence of extramedullary disease, serving as a clinical endpoint in both trials and practice [27]. MRD, previously termed minimal residual disease, refers to the post-treatment presence of a small number of detectable cancer cells that conventional pathological and clinical exams cannot identify [28]. The nomenclature shift from ‘minimal residual disease’ to ‘measurable residual disease’ has been advocated due to advancements in detection technologies, enabling the identification of residual disease at significantly lower thresholds than previously possible [29]. Whether the term is ‘Measurable’ or ‘Minimal’, the key factor is establishing scientifically validated thresholds that can be applied consistently across technologies and clinical trials for its intended application. From a regulatory perspective, it is critical to determine the appropriate threshold and align scientific advances with regulatory frameworks, such as a surrogate endpoint. An MRD-negative result indicates no detectable cancer cells. While not guaranteed, patients with MRD-negative status have been observed to have improved OS and reduced relapse rates [30–34]. Monitoring MRD in AML therefore informs treatment efficacy and serves as a robust prognostic marker [28,35–38].

For patients with AML, achieving early MRD-negative results and maintaining a durable response is crucial due to the relapse risk. MRD measurement methods include multiparameter flow cytometry (MFC), real-time quantitative polymerase chain reaction (RQ-PCR), and next-generation sequencing (NGS) [36]. Ongoing technological advancements, such as integrating machine learning to enhance interpretation, are improving MRD detection capabilities [39].

Several factors highlight MRD's recognized potential:

• Prognostic Utility: MRD is widely acknowledged for its prognostic significance in AML due to its reliability in indicating disease presence [40,41]. MRD has a strong prognostic value in some settings, which varies based on AML subgroups (e.g., TP53 and FLT-3 mutations) and treatment modalities such as eligibility for hematopoietic stem cell transplantation or patient fitness [38,42,43].
• Differentiation of Treatment Modalities: MRD status informs treatment regime decisions in AML and other hematological malignancies to enhance outcomes [44].
• Advancements in Molecular Diagnostics: Refinements of next-generation sequencing for deeper MRD resolution and novel techniques, such as circulating tumor DNA (ctDNA) analysis, enhance MRD relevance through more specific and sensitive measurements and standardization [45,46].

In multiple myeloma (MM), the U.S. Food and Drug Administration (FDA)’s Oncologic Drugs Advisory Committee (ODAC) have endorsed MRD-negativity as a surrogate endpoint for progression-free survival (PFS)/OS for accelerated approvals, based on meta-analyses showing a strong correlation between MRD negativity and PFS/OS. On this basis, the FDA ODAC unanimously endorsed (12-0) using MRD-negativity as a surrogate endpoint for accelerated approvals [47,48]. The European Medicines Agency (EMA) also recognizes MRD-negativity as a valid endpoint in MM studies and as an intermediate endpoint in chronic lymphocytic leukemia (CLL) studies [49–51]. These endorsements were based on comprehensive evidence, together with significant input from expert clinicians and patient groups. The generation of similar, robust evidence levels are anticipated for MRD in AML.

Despite growing clinical and patient support for MRD as a meaningful prognostic marker in AML, its acceptance as a surrogate endpoint for OS in clinical trials remains limited among health authorities and payers. MPAACT is an industry-led research consortium established in 2021. Comprised of multiple industry partners, MPAACT primary objective is to investigate the potential utility of MRD as a surrogate endpoint for OS in patients with AML and to improve patients’ lives by bringing novel therapies to patients faster. To support this goal, MPAACT collaborates with experts in the field to facilitate knowledge exchange and to compile a robust data set for evaluation [52].

Meta-analyses that have been conducted to date demonstrate MRD prognostic impact and correlation with OS [42,43,53–56]. Building on previous research, MPAACT, in collaboration with health authorities, is now using trial-level and individual patient-level data from clinical trials meta-analyses to analyze the correlation between MRD and OS in AML. MPAACT is conducting a preparatory analysis to define the MRD threshold and timepoint as well as an appropriate window (e.g., +/- 7 days, +/- 15 days) for MRD assessment to align data across trials. The next stage will assess the application of this identified MRD-negativity timepoint as an early endpoint in clinical trials and will also evaluate MRD's surrogacy for OS through trial-level data. In the relapse/refractory settings, it will need to account to the use of targeted therapies in molecularly defined subgroups (targetable mutation such as FLT3, NPM1, IDH1/2, KMT2a mutations are present in approximately 45% of the relapses) for which the detection of the residual mutation levels by polymerase chain reaction (PCR) tests may also inform the evaluation of the residual disease burden [57,58]. MPAACT's ongoing work together with regulatory and HTA discussions aim to provide robust evaluation of MRD-negativity as a surrogate endpoint for OS in AML.

This multi-stakeholder research study was conducted to explore the perspectives of key opinion leaders (KOLs), payers, and patient advocates on the role of MRD in AML. The objective was to assess the perceived value, challenges, and future potential of MRD as a clinical trial and policy-relevant endpoint, particularly in the context of patient access to innovative treatments.

MPAACT, an industry-led research consortium, conducted a research to gather multi-stakeholder perspectives. This research ensured coverage of predefined topics. The approach included an initial semi-structured individual interview and two advisory boards with a patient advocate representing a leukemia patient advocacy network, healthcare professionals, payers and HTA experts. The initial interview allowed to raise the key topics and gather individual perspective. The first advisory board allowed to discuss these topics with all stakeholders and raise the main problematics. The second advisory board allowed to set what is needed to ensure changes. All advisory board outcomes and the manuscript were shared with the stakeholders to ensure the reporting was complete and correctly reflected. To safeguard independence, external facilitators conducted all sessions, and authors/sponsors primarily acted as silent listeners. Contributors were purposively selected from six countries: United States, United Kingdom, Germany, France, Italy, and Spain, based on their expertise, AML working group members or guideline contributions in AML as well as familiarity with clinical trial endpoints. All contributors provided informed consent to this research, and the study was conducted in accordance with applicable ethical guidelines. This research was not designed to achieve thematic saturation or to support formal qualitative coding.

Data collection

Stakeholder interviews

From a total of 11 stakeholders, 10 in-depth, semi-structured individual interviews were conducted between August and September 2024 with:

• Key Opinion Leaders from France (n=1), the United States of America (USA) (n=2), and Spain (n=1)
• Payers and HTA Experts (n=5) (i.e., hospital pharmacist, insurance professionals, and/or HTA consultants) from the USA, United Kingdom (UK), Germany, France, and Italy
• Patient Advocate (n=1) representing an international leukemia advocacy network

Each interview followed a standardized guide with predefined questions tailored to the stakeholder group and covered five thematic domains: (i) major unmet needs in AML, (ii) challenges beyond unmet needs, (iii) key future innovations, (iv) patient-centered perspectives, and (v) MRD as a clinical measure. Interviews were recorded, transcribed, and summarized in structured capture sheets.

Advisory boards

Two multi-stakeholder advisory boards were convened in October and November 2024, respectively. Contributors included the previously interviewed stakeholders, an additional KOL from France, and additional representatives from industry and academia. The boards aimed to:

• Validate and expand upon interview findings
• Align on key challenges to MRD acceptance
• Prioritize actionable strategies for policy advancement

Outputs included consensus statements, prioritized solution strategies, and a call to action.

Data analysis

Interview transcripts, capture sheets, and advisory board reports were thematically analyzed using a framework approach. Data were ultimately categorized for each interview group into five predefined domains (see section “Validation and Triangulation”). Within each domain, stakeholder perspectives were synthesized and compared to identify:

• Converging themes (shared across stakeholder groups)
• Diverging or nuanced perspectives (unique to specific groups)

Validation and triangulation

Findings were triangulated across three data sources:

• Detailed individual interview transcripts
• Structured capture sheets organized by topic, and captured by the facilitator during the interviews
• Advisory board discussions

This multi-source evaluation ensured the consistency and robustness of the synthesized insights. The most critical issues were then prioritized anonymously by the advisory board members using a virtual Mentimeter® poll function in the first advisory board.

The findings were subsequently organized into categories according to the subjects discussed: i. Major unmet needs in AML, ii. Challenges beyond unmet needs, iii. Future directions in AML, iv. Patient-centered perspectives, v. MRD as a clinical trial measure (refer to Table 1).

Table 1 presents the perspectives gathered through stakeholder semi-structured individual interviews, systematically organized according to the predefined thematic categories outlined in the methods section. These categories include major unmet needs, challenges beyond unmet needs, future directions in AML, patient-centered perspectives, and the role of MRD as a clinical measure. The table includes the three stakeholder groups: KOLs, Payers and HTA Experts, and Patient Advocate.

Key opinion leaders

KOLs echoed the multifaceted challenges in AML treatment. Despite therapeutic advancements, frontline regimens often fail to achieve durable remission, particularly in older adults, and continued reliance on stem cell transplantation although sometimes curative, remains constrained by relapse and toxicity. Diagnostic inconsistencies further complicate treatment planning across centers. Future innovations, harnessing molecular monitoring, MRD, and novel therapies, hold the promise to drastically change AML care.

KOLs emphasize the potential of MRD monitoring to refine risk stratification, although standardization remains a barrier. Optimism surrounds emerging targeted therapies, including CAR-T cells and Menin inhibitors, alongside the transformative role of venetoclax, which requires further optimization to balance efficacy and tolerability. Emphasizing a patient-centered approach that prioritizes reducing toxicity and improving quality of life will also remain critical to achieving transformative changes in AML management. Refer to Table 1.

Payers and HTA experts

From the payer and HTA expert perspective, the AML treatment landscape is at a pivotal juncture. While innovations such as MRD monitoring and targeted therapies offer promise, vital challenges remain. There is a consistent emphasis on the urgent need for therapies that improve OS, especially in relapsed, refractory and unfit patients. Equally important is the demand for treatments with fewer grade 3/4 adverse events, particularly in transplant-ineligible populations.

Reimbursement decisions are often hindered by the lack of mature OS data, especially in cost-effectiveness-driven systems such as National Institute for Health and Care Excellence (NICE). Payers also highlight the challenge of balancing high treatment costs with demonstrable clinical and patient-centered benefit. AML’s inherent heterogeneity requires personalized treatment approaches, yet the cost of genetic testing remains a barrier to widespread implementation of MRD testing.

While early diagnosis is not a primary focus of HTA, it is acknowledged as beneficial. Broader systemic issues persist: diagnostic test pricing and the lack of standardization in MRD testing within a fragmented treatment landscape, as well as high drug prices although increasing market competition, all contribute to payer hesitancy. The variability in MRD methodologies across institutions undermines confidence in its reliability, and AML’s low prevalence limits statistical power in clinical trials, complicating the demonstration of treatment benefit. Despite cautious openness to MRD as a surrogate endpoint, particularly if it correlates with OS, relapse prevention, or quality of life, payers and HTA experts stress the need for robust, standardized evidence. Collaborative efforts among clinicians, HTA bodies, manufacturers, and patients will be crucial in reshaping AML care toward sustainable and meaningful long-term outcomes. Refer to Table 1.

Patient advocate

Acute leukemia patients, including AML patients, face specific challenges, from the aggressive nature of the disease to the long-term physical and psychological toll of treatments like bone marrow transplants. Fatigue is one of the most debilitating and under-recognized symptoms in AML, affecting both younger and older patients. It significantly impairs daily functioning and emotional well-being, yet is not enough considered in clinical conversations. Post-transplant complications, especially chronic graft-versus-host disease (GvHD), are a major source of long-term burden. MRD, as a monitoring and potential surrogate tool, represents a significant opportunity to enhance patient care and clinical outcomes. Moreover, patients often require repeated explanations and clearer communication at treatment initiation to fully grasp the implications of clinical terms like MRD or CR. Without this support, confusion, anxiety, and misinterpretation of test results, especially when MRD is positive, can occur. Realizing its full potential will depend on clear communication, and a sustained focus on reducing treatment burdens, improving quality of life, and meeting the diverse needs of AML patients at different stages of life. MRD should inform regulatory and reimbursement decisions only once its clinical relevance has been validated. It must complement, rather than replace OS data.

Synthesis from the advisory boards and differences in the points of view

All stakeholders agree that AML remains an area of high unmet need, especially for R/R and transplant-ineligible patients. While KOLs and payers focus on survival and efficacy, the patient advocate emphasizes quality of life and challenges of survivorship. Indeed, there was clear recognition across stakeholder groups that the toxicity burden of existing AML regimens remains a major concern. Stakeholders converge on the issue of inconsistency whether in diagnostics, clinical trial design, or engagement in policy processes. There is a strong call for standardization and methodological rigor, alongside a clear need to embed patient voices meaningfully into trial design and policy frameworks. These insights point to the need for more inclusive, standardized, and transparent processes across the clinical and policy landscape.

MRD is viewed as both a unifying and polarizing endpoint. While all stakeholders recognize its potential, perspectives differ regarding its readiness for adoption. Its future as a surrogate endpoint for OS in AML depends on demonstrating robust, correlations with long-term outcomes including sensitivity analysis for specific subgroups of patients, and on integrating patient perspectives into its interpretation. Despite broad recognition of MRD’s potential as a meaningful prognostic marker, stakeholders identify critical barriers that must be addressed to enable its acceptance as a surrogate endpoint for OS in AML clinical trials by regulatory and HTA bodies. Payers and KOLs emphasize methodological and economic barriers, while the patient advocate highlights the limited inclusion of patient voices in clinical trial design.

Prioritization of the key issues

The use of MRD-negativity by regulatory and HTA bodies as a valid surrogate for OS in AML clinical trials necessitates addressing three key issues: (1) AML heterogeneity, (2) lack of standardized MRD definitions, and (3) the need for robust clinical validation evidence.

AML heterogeneity

AML's genetic drivers and treatment complexity result in diverse treatment modalities that impact MRD data interpretation and comparability. An MRD framework that works across all AML subgroups and treatment modalities is essential to overcome these challenges.

Standardization of definitions, timepoints and testing methods

The widespread adoption of MRD in AML is hindered by the lack of a unique MRD test valid for all AML subtypes (i.e. unlike MM) which results in:

• Inconsistent definitions: MRD cut-off thresholds and how residual disease is characterized, varies across institutions, complicating inter-study comparisons [59,60].
• Divergent timepoints for testing: Standardization of MRD measurement at specific timepoints is necessary to ensure data reliability [61].
• Heterogeneity in testing methods: Mmultiparameter flow cytometry, quantitative polymerase chain reaction, and next-generation sequencing-based MRD detection methodologies must be harmonized to be recognized by Regulatory bodies.

A globally accepted MRD definition and consistent thresholds for MRD negativity are vital. The FDA has accepted a bone marrow MRD threshold of less than 0.01% as supporting evidence of efficacy for drugs demonstrating durable complete responses (CR) in relapsed or refractory AML [20]. Whilst this limit may evolve with technological advancements, it serves as a useful starting point for the standardization of an efficacy threshold. Consistent MRD assessment timepoints and methodologies, including multiparameter flow cytometry, quantitative polymerase chain reaction, digital polymerase chain reaction, and next-generation sequencing, require alignment.

Need for robust clinical evidence

A robust correlation between treatment effects on MRD and OS is necessary to validate MRD as a surrogate endpoint for OS. However, the heterogeneity of OS in AML complicates this relationship. Good prognosis subgroups can achieve prolonged survival, leading to longer timeframes to reach OS, while poor prognosis subgroups require urgent treatment, making it challenging to investigate new treatments and recruit patients for new trials [16,62]. Supporting initiatives to integrate the use of MRD as an outcome in clinical trials and meaningful collaboration with healthcare providers, clinicians and patients is needed to ensure robust evidence generation in this complex disease.

The potential of MRD as an early clinical endpoint for approvals in AML offers a promising pathway to enhance patient care and, ultimately, quality of life. This paper is based on the participation of international key stakeholders with extensive backgrounds in AML and different HTA perspectives. Our research highlights how critical it is to have clinicians, patient advocacy groups, and payers working together. The findings should be interpreted as expert stakeholder insights to inform clinical development and HTA processes. The objective of this perspective is to frame where we stand in the diagnosis, treatment and drug approvals in AML and to outline safeguards that should be considered for MRD to become an established endpoint in AML.

As of today, MRD-negativity is an established prognostic marker in AML, at the patient level, consistently associated with improved outcomes, although the strength of association may vary by assay, timing, and disease subgroup. Despite potential variations, MRD is clinically relevant for risk stratification and clinical trial design. Regulators and stakeholders have encouraged structured evidence?generation programs to evaluate its potential surrogacy at the trial level.

MPAACT is conducting preparatory analyses to define the MRD threshold, timepoints and an appropriate window (i.e. +/- 7 days, +/- 15 days) for MRD assessment to align data across trials. The next stage will assess the application of this identified MRD-negativity timepoint as an early endpoint in clinical trials and will also evaluate MRD's surrogacy for OS through trial-level data.

It is essential to take into account the complexity of the diagnosis, and the disease itself, as well as to ensure that the steps towards the acceptance of new endpoints are actionable. For instance, the difference in treatment regimens and the broader use of MRD directed therapy at the patient level in pediatric AML will have to be taken in consideration in the statistical plan and in the interpretation of results [41,63].

To advance and safeguard the acceptance of MRD as a valid endpoint in AML, the following actions are recommended:

1. Develop globally accepted MRD thresholds, timepoint and assessment guidelines: Establish comprehensive guidelines for MRD use in clinical practice to enable uniform testing methodologies and datasets.
2. Engage stakeholders: Raise awareness and educate patients, clinicians, regulators, payers, and patient advocacy groups on the potential of MRD and its significance for both clinical trials and clinical practice.
3. Systematically conduct assessments: Implement standardized MRD measurement and reporting methods and achieve consensus on clinical thresholds to generate robust data and improve MRD testing familiarity among clinicians.
4. Generate MRD & OS putcomes: Integrate MRD assessments with OS as dual or secondary endpoint in clinical trials and real-world evidence (RWE) studies to further facilitate the adoption of MRD in trial designs.

Premature adoption of MRD as a surrogate endpoint presents several risks, including the potential misestimation of clinical benefit, where treatment effects may be overestimated or underestimated, and inconsistencies arising from variability in assays and assessment timepoints, which can limit the comparability of results. Equitable access may be a concern if high?quality MRD testing varies across centers. These risks can be mitigated through standardization of MRD definitions, assay performance criteria, and fixed MRD timepoints. Additional safeguards include the use of dual or secondary endpoint strategies that integrate OS and MRD assessments, supported by post?authorization confirmatory evidence.

According to stakeholders interviewed, MRD is increasingly regarded as a more sensitive and reliable predictor for treatment response and prognosis. However, additional evidence is needed to support its broader acceptance in clinical practice. By integrating MRD into clinical trials, treatment guidelines and evaluations of treatment value in AML, we can help ensure that promising therapies reach patients faster and are made accessible through reimbursement pathways.

Achieving this goal will require close collaboration among all stakeholders - regulators, HTA bodies, industry, patient advocacy groups and healthcare professionals. Recognizing MRD-negativity as a valid surrogate for OS a meaningful indicator of treatment success can help deliver better, more personalized care to people living with AML.

Vintura: Dr. Ann-Sophie Kuschel, Vintura, Dr. Medha Kothari, Vintura, Wouter Bloem, Vintura

The content of this paper is based on interviews and roundtable discussions with key stakeholders in the field. We want to thank the following people for their participation:

(alphabetical order by surname)

Prof. Pierre Fenaux           Hospital St. Louis, Paris University (France) 
Dr. Giorgia Gambarelli       HTA & Hospital expert (Italy)
Dr. Mark Litzow                  Mayo Clinic (U.S.)
Dr. Bruno Paiva                  University Hospital of Salamanca (Spain)
Ms. Anne Pierre Pickaert    Acute Leukemia Advocates Network (ALAN; global network)
Dr. Gail Roboz                    Weill Medical College of Cornell University (U.S.)
Prof. Norbert Vey                Institut Paoli-Calmettes Cancer Center (France)
Mr. Andrew Walker             HTA expert (U.K.)
Prof. Jürgen Wasem          HTA expert (Germany)
Dr. Olivier Wong                HTA expert (France)
Anonymous participant    A large US-based insurance company 
Artificial Intelligence (AI)-Assisted Technology (e.g., privacy secured company-owned solutions) was utilized to enhance the readability and language of this work, in accordance with applicable directives and procedures. The authors have reviewed and edited the output and take full responsibility for the content of this publication.

Conceptualization, M.N., MH.BZ., T.P., B.W., R.P., and D.LdM.; methodology, M.N., MH.BZ., V.H., and K.M.; validation, MH.BZ, V.H., K.M., T.P., B.C., T.J.P., C.L., BR.B., B.W., R.P., and D.LdM.; writing—original draft preparation, MH.BZ, V.H., K.M., T.P., and T.J.P.; writing—review and editing, MH.BZ, V.H., K.M., T.P., T.J.P., C.L., B.W., R.P., and D.LdM.; supervision, B.W., R.P., and D.LdM.; project administration, M.N., MH.BZ, V.H., K.M.; All authors have read and agreed to the published version of the manuscript.

The authors contributed to the funding and design of the study. The content is derived from interviews and advisory boards in which the authors acted primarily as listeners. The findings and recommendations presented in the manuscript are based solely on the insights and data gathered from these discussions, ensuring the integrity and independence of the research. Stakeholder perspectives were provided voluntarily and independently, without any influence from the authors or sponsoring organizations.

This work was funded by MPAACT, an industry-led research consortium established in 2021 and comprised of multiple industry partners. Industry partners include Genentech (a member of the Roche Group), Johnson and Johnson, Servier, Bristol Myers Squibb, AbbVie, Novartis and Kura Oncology.

AI: Artificial Intelligence; AML: Acute Myeloid Leukemia; ALL: Acute Lymphocytic/Lymphoblastic Leukemia; CBER: Center for Biologics Evaluation and Research; CDER: Center for Drug Evaluation and Research; CHMP: Committee for Medicinal Products for Human Use; CML: Chronic Myelogenous Leukemia; CLL: Chronic Lymphocytic Leukemia; CR: Complete Response; DNA: Deoxyribonucleic Acid; DOAJ: Directory of Open Access Journals; EFS: Event-Free Survival; ECOG: Eastern Cooperative Oncology Group; EMA: European Medicines Agency; FDA: Food and Drug Administration; G-BA: Gemeinsamer Bundesausschuss (German Joint Federal Committee); GvHD: Graft-versus-host disease; HAS: Haute Autorité de Santé (French National Authority for Health); HOVON: Dutch-Belgian Hemato-Oncology Cooperative Group; HSCT: Hematopoietic Stem Cell Transplantation; HTA: Health Technology Assessment; ICC: International Consensus Classification; KOL: Key Opinion Leader; LD: Linear Dichroism; MFC: Multiparameter Flow Cytometry; MPAACT: Measurable Residual Disease Partnership and Alliance in Acute Myeloid Leukemia Clinical Treatment; MRD: Measurable Residual Disease (old: Minimal Residual Disease); NCRI: National Cancer Research Institute; NGS: Next-Generation Sequencing; NICE: National Institute for Health and Care Excellence; ODAC: Oncologic Drugs Advisory Committee; OS: Overall Survival; PAG: Patient Advocacy Group; PCR: Polymerase Chain Reaction; PFS: Progression-Free Survival; RQ-PCR: Real-Time Quantitative Polymerase Chain Reaction; RWE: Real-World Evidence; SWOG: Southwest Oncology Group; TLA: Three Letter Acronym; UK: United Kingdom; USA: United States of America; WHO5: World Health Organization 5th edition.