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1530 Allogeneic Transplant Can Abrogate the Relapse Risk in the Patients with Detectable Measureable Residual Disease By Multicolor Flow-Cytometry at the Time of Assessment of Acute Myeloid Leukemia Patients in First Remission

Program: Oral and Poster Abstracts
Session: 732. Clinical Allogeneic Transplantation: Results: Poster I
Hematology Disease Topics & Pathways:
Biological, AML, Diseases, bone marrow, Therapies, Myeloid Malignancies
Saturday, December 5, 2020, 7:00 AM-3:30 PM

Muhned Alhumaid, MD1,2, Georgina S. Daher-Reyes, MD3*, Arjun Law, MD1*, Auro Viswabandya, MD1, Armin Gerbitz, MD1*, Fotios Michelis, MD, PhD1*, Igor Nicolas Novitzky-Basso, MD, PhD, MRCP, FRCPath1, Jeffrey H. Lipton, MD, PhD1, Jonas Mattson, MD, PhD1*, Ivan Pasic, MD, PhD1*, Rajat Kumar, MD1, Wilson Lam, MD1, Zeyad Al-Shaibani, MD1, Hassan Sibai, MBBS4* and Dennis Dong Hwan Kim, MD1

1Hans Messner Allogeneic Transplant Program, Division of Medical Oncology and Haematology, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, ON, Canada
2King Saud Medical City, Riyadh, Saudi Arabia
3Leukemia Program, Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada
4Leukemia Program, Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada


Acute myeloid leukemia (AML) is a highly heterogeneous group of diseases with variable response to therapy. Several factors have a prognostic impact for an outcome. Despite intensive chemotherapy and hematopoietic stem cell transplant (HCT), a significant proportion of patients eventually relapse, indicating that morphological assessment is not adequate due to limitations in sensitivity, requiring a better tool for assessment of remission.


A retrospective analysis was performed in AML patients who achieved first complete remission (CR1) and the outcomes compared according to the performance of HCT, and multi-color flow cytometry (MFC)-based measurable residual disease (MRD) status (defined as negative if patients achieved 0.1% or less) assessed at the time of CR1.

In order to take account of the time interval from the MFC-MRD assessment to HCT, we applied a Mantel-Byar test for overall (OS) and relapse-free survival (RFS), considering time-to-HCT as a time-dependent covariate, while Simon and Makuch plot was used. Time-dependent Cox proportional hazard models were applied for multivariate analysis. Cumulative incidence of relapse (CIR) and non-relapse mortality (NRM) where evaluated using Fine-Gray model.


A total of 435 patients diagnosed with AML and treated with induction chemotherapy between 2015 and 2018, of whom 380 patients (87%) achieved remission, were included. MFC-MRD was assessed in 336 patients in CR1 (77%), out of 380 patients who achieved CR1, and 200 patients (53%) proceeded to HCT.

We evaluated OS, RFS, CIR and NRM according to MFC-MRD status in those patients who had negative MRD (MRDneg; n=218, 65%) vs. those with MRD (MRDpos; n=118, 35%). The OS at 2 years was 67.0% vs.40.7% (p≤0.001), RFS at 2 years was 8.7% vs. 40.6% (p≤0.001), CIR 26.9% vs.21.1% but with borderline significance (p=0.08), and NRM 32.5% vs. 20.2% with borderline significance (p=0.057).

In patients who achieved CR, we compared OS, CIR, NRM and RFS between the HCT group (n=200) vs. those who did not undergo HCT (no-HCT; n=235). Between the 2 groups, the OS at 2 years was 55.7% vs. 47.2% (p=0.004); CIR 9.7% vs. 34.6% (p≤0.001); NRM 40.9% vs. 12.6% (p≤0.001). There was no difference in RFS: 49.4% vs. 52.8% (p=0.505).

There was no difference in the time interval from the MFC-MRD assessment to HCT between the groups (MRDpos vs MRDneg) with a median of 96 days in overall patients who received HCT (p=0.31).

In the overall population, when HCT was accounted as a time-dependent covariate, we failed to observe any difference of OS (HR 1.23; p=0.19) or RFS (HR 1.09; p=0.60) between the HCT vs. no-HCT groups.

Then, we compared the OS, RFS, CIR, and NRM between the HCT vs no-HCT groups confined to the subgroups of patients with MFC-MRDneg vs MFC-MRDpos, separately. In the MFC-MRDpos subgroup, patients who underwent HCT did better: OS 54.8% in HCT vs. 25.5% in no-HCT (HR 0.52; p≤0.001) and RFS 48.7% vs. 24.1% (HR 0.45; p≤0.001). However, in the MFC-MRDneg subgroup, similar outcomes were noted between the HCT vs no-HCT groups in terms of OS 60.8% vs. 70.7% (HR 1.27, p=0.32), RFS 51.6% vs. 62.4% (HR 1.25; p=0.46) (Fig 1).

With respect to the cause of treatment failure according to treatment modality (HCT vs no-HCT) and MFC-MRD status, Fig 2 revealed different patterns of relapse vs NRM between the HCT and the no-HCT groups. In the MFC-MRDneg subgroup, HCT group showed a higher NRM over the no-HCT group (38.0% vs 8.7%; HR 2.08; p≤0.001), while relapse risk was lower in the HCT group (10.4% vs 29.3%; p≤0.001). In the MFC-MRDpos subgroup, relapse incidence was strikingly different in favor of HCT (9.5% vs 50.0%; HR, p≤0.001).

Conclusion: These findings suggest that in AML patients HCT could abrogate the relapse risk in patients who are MFC-MRDpos at the time of remission assessment, while the benefit from HCT was minimal in the subgroup that are MFC-MRDneg. Further study is strongly warranted to reach a clearer conclusion with a larger number of cohorts.

Disclosures: Lipton: Bristol-Myers Squibb: Honoraria; Takeda: Consultancy, Honoraria, Research Funding; BMS: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Pfizer: Consultancy, Honoraria, Research Funding; Ariad: Consultancy, Research Funding.

*signifies non-member of ASH