Standardised surveillance of measurable residual disease (MRD) after allogeneic haematopoietic stem cell transplantation (allo-HCT) may enable timely therapeutic intervention in patients with acute myeloid leukaemia (AML) before overt morphological relapse. This conclusion was drawn from a retrospective review including all adult AML patients who underwent allo-HCT at the Mayo Clinic, MN, USA, between 2018 and 2025.

AML remains associated with high relapse rates despite achievement of initial morphologic remission. MRD has emerged as an established prognostic tool, playing a pivotal role in detecting residual leukaemic cells beyond the limits of conventional morphologic assessment. However, it remains unclear whether relapse detected at the MRD level confers a different prognosis compared with overt morphological relapse.

To address this question, Dr Hassan Alkhateeb (Mayo Clinic, MN, USA) and colleagues evaluated treatment patterns and outcomes associated with morphological versus MRD relapse following allo-HCT [1]. The study cohort comprised 272 consecutive AML patients who underwent allo-HCT. After a median follow-up of 128 days (range 28–741), relapse occurred in 77 patients (28%): 50 patients (65%) experienced morphological relapse, while 27 patients (35%) had MRD relapse.

ELN-adverse risk disease was significantly more common among patients with morphological relapse compared with MRD relapse (77.5% vs 22.4%; P=0.006). Overall survival (OS) following morphological relapse was markedly inferior, likely reflecting a more aggressive disease biology. One- and 2-year OS rates after morphological relapse versus MRD relapse were 21% versus 44.5% and 12.6% versus 30.5%, respectively (P=0.0014). Adverse cytogenetic abnormalities were also more frequently observed in patients with morphological relapse (58% vs 14.8%; P<0.001).

Among the 50 patients with morphological relapse, 18 patients (36%) achieved remission, with a median time to response of 73 days (range 14–296). The median duration of response was 146 days, after which 10 patients (20%) experienced a subsequent relapse.

Of the 27 patients with MRD relapse, 18 patients (67%) progressed to morphological relapse during follow-up, with a median follow-up duration of 447 days. Among the 9 patients who remained free from morphological relapse, 8 achieved MRD negativity, with a median time to MRD clearance of 69.5 days.

MRD relapse detected by digital droplet polymerase chain reaction (MRDM) was associated with a numerically superior 1-year morphological relapse-free survival and OS compared with MRD relapse defined by multiparametric flow cytometry (MRDF) or cytogenetic abnormalities (MRDC).

  1. Alkhateeb HB, et al. Outcomes of morphological versus minimal residual disease (MRD) relapse after allogeneic transplantation (allo-HCT) for acute myeloid leukemia (AML). B300, EBMT congress 2026, 22-25 March, Madrid, Spain.

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Findings from a retrospective, multicentre study underscore the importance of intensified molecular monitoring in patients with acute myeloid leukaemia (AML) early after allogeneic hematopoietic stem cell transplantation (allo-HCT). Early relapse emerged as the strongest predictor of poor prognosis, while increased mutational complexity was associated with a higher risk of early relapse [1].

Relapse following allo-HCT remains a major clinical challenge in AML and is associated with poor outcomes. To better characterise the mutational and clonal dynamics underlying relapse, 57 adult AML patients from 3 centres in Germany, Greece, and Canada who relapsed after allo-HCT were analysed. Study presenter, researcher Dr Kristina Maas-Bauer (University of Freiburg, Germany), explained that the molecular analyses performed may improve the prediction of early relapse (<6 months post-HCT) and help guide therapeutic decision-making.

Dr Maas-Bauer and colleagues performed paired next-generation sequencing (NGS) myeloid panels analyses (38–84 genes) at diagnosis/pre-HCT and again at relapse. The median patient age was 52.5 years (range 18-71). More than half of patients (54%) had adverse-risk AML according to ELN classification, while 25% had refractory disease prior to transplantation.

AML relapse following allo-HCT demonstrated substantial genetic and clonal instability. Overall, 68% of patients showed acquisition or loss of mutations, predominantly involving FLT3-ITD, NRAS, and KRAS, highlighting recurrent activation of proliferative and survival signalling pathways. In contrast, founder mutations in DNMT3A and TP53 were frequently retained. Distinct relapse evolution patterns, including constant, linear, branching, and parallel evolution, were not predictive of relapse risk and did not influence overall survival  (OS) or progression-free survival (PFS).

By contrast, relapse occurring within the first 6 months after allo-HCT was identified as a strong independent predictor of poor OS (P=0.049). Furthermore, increased mutational burden at diagnosis independently predicted early relapse (OR 1.84; 95% CI 1.02–3.33; P=0.04), potentially reflecting rapid expansion of pre-existing dominant clones.

Dr Maas-Bauer noted that the unfavourable baseline characteristics of the study population may also have contributed to the poor survival outcomes, independent of clonal evolution or mutational patterns. Overall, these findings emphasise the importance of repeated molecular profiling, particularly during the first 6 months after transplantation. For measurable residual disease assessment, persistent mutations may represent the preferred molecular targets.

  1. Maas-Bauer C, et al. Mutational landscape changes of AML in patients relapsing after allogeneic hematopoietic cell transplantation. A342, EBMT congress 2026, 22-25 March, Madrid, Spain.

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Combining multiparameter flow cytometry (FACS) and error-corrected next-generation sequencing (NGS) for measurable residual disease (MRD) assessment improved relapse prediction in patients with acute myeloid leukaemia (AML). This dual-assessment strategy may also help identify appropriate candidates for early intervention following allogeneic hematopoietic stem cell transplantation (allo-HCT).

Accurate MRD assessment is critical in AML management to guide treatment decisions before and after allo-HCT. FACS-MRD and NGS-MRD are considered complementary modalities. Study presenter Dr Evgeny Klyuchnikov (University Medical Centre Hamburg-Eppendorf, Germany) and colleagues aimed to find possible advantages of combining them in an observational, single-centre study [1].

The analysis included 107 adult patients with AML undergoing their first allo-HCT. FACS-MRD assessment was performed with a sensitivity of 10-4 to 10-5, and an MRD positivity cut-off of 0.1%. In parallel, error-free NGS-MRD analysis was conducted using the Oncomine Myeloid MRD (RUO) Assay, with a limit of detection of approximately 0.1 % variant allele frequency.

The results demonstrated that the combined FACS and NGS was approximately 10% more accurate at predicting relapse. Before transplant, MRD was detected by FACS in 37% of patients and by NGS in 45%, with moderate-to-substantial concordance between both methods (Cohen’s kappa 0.60). Notably, among patients classified as MRD-negative by FACS, error-corrected NGS identified additional subclonal variants, including FLT3-ITD mutations, in 26% of cases, indicating discordant findings between the 2 methods and suggesting that NGS may detect residual molecular disease missed by FACS alone.

MRD positivity by either FACS-MRD or NGS-MRD was significantly associated with an increased 5-year relapse risk and lower overall survival (OS). Using FACS, the 5-year OS was 39% (95% CI, 25–55%) in MRD-positive patients versus 79% (95% CI, 68–87%) in MRD-negative patients (P<0.001). Using NGS-MRD, the corresponding 5-year OS rates were 49% (95% CI, 39–63%) versus 76% (95% CI, 64–85%; P=0.006). Patients with discordant MRD findings demonstrated an intermediate-risk profile, whereas patients who were MRD-positive by both FACS and NGS had significantly higher relapse risk and lower OS (P<0.001). In multivariate analysis, dual MRD positivity remained the strongest independent predictor of relapse (HR 6.8; 95% CI 3.0–15.0; P<0.001) and inferior OS (HR 3.2; 95% CI 1.6–6.1; P=0.001).

Dr Klyuchnikov concluded that combined MRD assessment using FACS and NGS reduces the frequency of false positives and improves relapse prediction, although it does not significantly improve OS prediction.

  1. Klyuchnikov E, et al. Combined pre-transplant MRD detection by FACS and NGS may enhance relapse prediction in AML patients receiving allo-SCT in complete remission. B293, EBMT congress 2026, 22-25 March, Madrid, Spain.

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Patients with acute myeloid leukaemia (AML) undergoing first-time umbilical cord blood transplantation (UCBT) demonstrated more favourable outcomes when harbouring FLT3 mutations compared with FLT3–wild-type AML, including longer progression-free survival (PFS) and lower relapse rates. In addition, post-transplant FLT3 inhibitor (FLT3i) maintenance therapy showed potential clinical benefit.

Allogeneic haematopoietic stem cell transplantation (allo-HCT) is a commonly used therapeutic strategy in FLT3-mutated AML and may contribute to prolonged overall survival (OS). When a suitable donor is unavailable, UCBT represents a potential alternative, alongside haploidentical T-cell–depleted peripheral blood stem cell transplantation. UCBT is thought to provide a stronger graft-versus-leukaemia (GvL) effect compared with other graft sources, although supporting data remain limited. In a retrospective study (jRCT1031230158), a Japanese research group compared the outcomes after UCBT in patients with FLT3-mutated versus FLT3-wild-type AML. Interim 1-year results from this single-centre analysis were presented by Dr Aya Nishida (Toranomon Hospital, Japan) [1].

Among 177 eligible patients who underwent their first UCBT at Toranomon Hospital between January 2019 and December 2023, 36 patients had FLT3-mutated AML, and 31 had FLT3-wild-type AML. All patients in the FLT3-mutated cohort harboured FLT3 internal tandem duplication (ITD) mutations. The median age was 56.4 years in both cohorts, and all but 3 participants had de novo AML.

The results demonstrated a trend toward improved 1-year PFS in the FLT3-mutated cohort compared with the FLT3-wild-type cohort: 70.6% versus 51.6% (P=0.14). A similar trend was observed for OS: 70.6% versus 54.5% (P=0.39). In univariate analysis, the relapse rate was significantly lower in patients with FLT3-mutated disease than in those with FLT3-wild-type disease: 7.0% versus 27.0% (P=0.02). By contrast, non-relapse mortality (NRM) did not differ significantly between groups: 21.0% versus 34.5% (P=0.55).

In multivariate analysis, age ≥60 years and higher transplant-related comorbidity burden (HCT-CI ≥2) were associated with inferior OS and PFS. No factors were significantly associated with relapse risk. Within the FLT3-mutated cohort, post-transplant FLT3i maintenance therapy with gilteritinib showed potential clinical benefit, although selection bias could not be excluded. Among the 19 patients who received gilteritinib maintenance, both PFS and OS were 78.6%, while the relapse rate was 5.3%, and NRM was 16.1%.

  1. Nishida A, et al. Comparison of umbilical cord blood transplantation outcomes between FLT3-mutated and -wild-type AML in a matched-pair cohort. P119, EBMT congress 2026, 22-25 March, Madrid, Spain.

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A real-world, single-centre experience confirmed that FLT3 inhibitors (FLT3i) can be safely integrated into the treatment of acute myeloid leukaemia (AML) in the context of allogeneic hematopoietic stem cell transplantation (allo-HCT). Importantly, FLT3i therapy did not impair engraftment or significantly increase the risk of graft-versus-host disease (GvHD) in this study.

The study was conducted at the San Gerardo Hospital in Monza, Italy, and presented by PhD student Francesca Duca (University of Milano-Bicocca, Italy) [1]. Ms Duca and colleagues retrospectively analysed 17 patients with FLT3-mutated AML, who underwent HCT and received FLT3i therapy before and/or after transplantation. Clinical efficacy, impact on graft function, and tolerability were assessed.

The 17 patients were divided into 4 treatment groups, with the following efficacy outcomes observed:

  1. Post-transplant maintenance with sorafenib after complete remission (n=10): median overall survival (OS) was 22.5 months (range 10–99), while median progression-free survival (PFS) was 20 months (range 3–75). Two patients relapsed during or after maintenance therapy and subsequently received gilteritinib. After a median follow-up of 23 months, 8 patients remained alive.
  2. Gilteritinib as second-line bridging therapy to transplant in refractory/relapsed (R/R) disease (n=3): all patients successfully proceeded to transplantation and maintained durable remissions when gilteritinib was continued post-HCT. Median OS was 44 months (range 11–53), and median PFS was 38 months (range 11–50). At the time of reporting, all patients remained in complete remission.
  3. Patients treated after post-transplant relapse without prior FLT3i maintenance (n=2):  outcomes were poor, with a median OS of 16.5 months (range 14–19) and a median PFS of 6.5 months (range 4–9). Neither patient survived.
  4. Complex treatment pathways with sequential FLT3i exposure (n=2): both patients received azacitidine, venetoclax, and sorafenib; 1 patient for R/R AML before HCT with continuation of sorafenib post-transplant, and the other following relapse 1 year after HCT. After 5 months, the second patient switched to gilteritinib following a second relapse and achieved a third remission. Both patients remained alive after a median follow-up of 32 months.

FLT3i therapy administered before transplantation did not compromise engraftment in any treatment group. The incidence of acute GvHD ranged from 20% to 50%. The most common grade 3–4 toxicities were cytopenias, which were manageable with dose modifications. One case of myopericarditis was reported in group 4. Overall, approximately half of all participants experienced infections, all of which were manageable with standard therapy.

The authors concluded that sorafenib maintenance was associated with low relapse rates and favourable survival outcomes, while gilteritinib effectively bridged refractory patients to transplantation. The unfavourable outcomes observed in group 3 further supported the early use of FLT3i therapy.

  1. Duca F, et al. Targeting FLT3: a real-life, single-center analysis of FLT3 inhibitors use in the allogeneic transplant setting. P257, EBMT congress 2026, 22-25 March, Madrid, Spain.

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The 2-year leukaemia-free survival (LFS) with prophylaxis using a FLT3 inhibitor (FLT3i) exceeded 80% after allogeneic haematopoietic stem cell transplantation (allo-HCT) in patients with acute myeloid leukaemia (AML). These findings, derived from an EBMT registry-based multicentre analysis, further support the use of FLT3i therapy, particularly sorafenib, as standard post-HCT maintenance [1].

Relapse following transplantation remains frequent and continues to represent a major challenge in AML management. This non-randomised EBMT study aimed to evaluate the relative efficacy and safety of FLT3i compared with hypomethylating agents (HMAs), as well as the impact of patient selection, treatment timing, and treatment duration. The results were presented by Dr Nour Moukalled (American University of Beirut, Lebanon) [1].

The study included 317 adult AML patients in first complete remission who underwent HCT and received a FLT3i or HMA prophylaxis within 180 days post-transplantation, Dr Moukalled explained. Of these, 171 patients received a FLT3i (58% sorafenib, 30% midostaurin, and 11% gilteritinib), while 146 patients received HMA maintenance (92% azacitidine and 8% decitabine). As the study was non-randomised, significant between-group differences were observed, most notably in mutation status, cytogenetics, and treatment exposure before or after HCT.

FLT3i therapy was initiated at a median of 74 days post-HCT and continued for a median duration of 364 days. After a median follow-up of 3 years, the 2-year overall survival (OS) from the start of prophylaxis was 87% (95% CI 81–91%), while the 2-year LFS was 82% (95% CI 75–87%). These outcomes were not significantly influenced by age, measurable residual disease (MRD) status at HCT, prior FLT3i exposure, previous graft-versus-host disease (GvHD), or the specific FLT3i used. Stratified by FLT3i agent, the 2-year OS and LFS rates were 88% and 81% for sorafenib, 91% and 87% for midostaurin, and 70% and 70% for gilteritinib (P=0.13 and P=0.28, respectively). Importantly, the 2-year cumulative incidence of relapse was significantly higher in patients who were MRD-positive at transplantation compared with MRD-negative patients (21% vs 8%; P=0.03).

HMA maintenance also demonstrated encouraging outcomes, particularly in patients with prior GVHD. HMA therapy was initiated at a median of 69 days post-HCT and continued for a median of 172 days. The 2-year OS was 77% (95% CI 69–83%), while the 2-year LFS was 72% (95% CI 64–78%). Age, AML type, cytogenetic profile, and pre-transplant MRD status did not significantly influence these outcomes. However, prior GvHD before initiation of maintenance was associated with significantly improved OS and LFS:

  • 2-year OS: 91% (95% CI 78–97%) versus 71% (95% CI 60–79%; P=0.03);
  • 2-year LFS 85% (95% CI 72–93%) versus 66% (95% CI 55–74%; P=0.02).
  1. Moukalled N, et al. Maintenance therapy post hematopoietic stem cell transplant in acute myeloid leukemia with FLT3 inhibitors and hypomethylating agents: insights from the EBMT Acute Leukemia Working Party. B289, EBMT congress 2026, 22-25 March, Madrid, Spain.

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