Evaluation of the Impact of the Disease Risk Index and Pre-Transplant Measurable Residual Disease By Flow Cytometry As Prognostic Factors in Allogeneic Hematopoietic Cell Transplantation in Patients with Acute Myeloid Leukemia
Authors: Marques Carolina Perrone , Silveira Ana Carolina de Almeida , Zezzi Jade , Chaves Felipe Galvão Batista , da Rocha Juliana Dall'Agnol , Stanzione Renata Leati , Kerbauy Mariana Nassif , Hamerschlak Nelson , Santos Fabio P. S. , Arcuri Leonardo Javier , Ribeiro Andreza Feitosa 
Published: December 2023

Introduction: Allogeneic hematopoietic cell transplantation (HCT) is the therapy with the best curative potential for patients with intermediate/high-risk acute myeloid leukemia (AML). Although many factors may influence the outcomes of allogeneic HSCT, risk stratification and disease status at the time of transplant are two of the strongest prognostic factors of post-transplant survival². In this context, the Disease Risk Index (DRI) was developed and validated in a cohort of more than 13.000 patients and stratifies patients into 4 groups with different overall survivals (OS)². Measurable residual disease (MRD) is also an important and consolidated biomarker for the prognosis, monitoring, and treatment effectiveness evaluation³.

Objective: To compare the impact of the pre-transplant DRI and MRD in patients with AML in OS and leukemia-free survival of patients treated with allogeneic HSCT in a private institution in Brazil from January 2017 to May 2023.

Methods: This is a retrospective, unicentric study. MRD was evaluated immediately before transplantation by 10-color flow cytometry and was considered positive if ≥0.1%. DRI was grouped into two groups: low/intermediate risk and high/very high risk. Statistical analyzes were performed using the Cox regression model.

Results: With a median follow-up of 18 months, a total of 57 patients were included, 34 of whom had negative MRD and 23, positive. The mean ages in these groups were 55 and 60 years, respectively. HCT-CI was 0-2 in 91% of the patients in the MRD-negative group, and in 78% of the MRD-positive group. The type of donors was similar in both group (MRD positive or negative): 20-30% of related donors, 25-40% of haploidentical and 40-45% unrelated donors. The reduced-intensity conditioning regimen (RIC) was the used in 70% of the patients. In the MDR + group, peripheral stem cell source was more used than in the MDR negative group. In univariate analysis, DRI had an impact on overall survival (OS) with an HR=3.52 (95%CI 1.46 - 8.5) and p=0.075 for low/intermediate risk compared with high/very high risk, while in the multivariate analysis this impact was not maintained with HR=2.31 (95%CI 0.92 - 5.82) and p=0.075. A pre-transplant positive MRD was a risk factor for death in univariate analysis, with an HR=5.99 (95%CI 2.93- 26.82) and p&lt;0.001. The impact of MRD HR 8.87 (2.93 - 26.83) and p &lt; 0.001, age HR 1.09 (1.04 - 1.15) with p = 0.001 and bone marrow source HR 0.29 (0.08 - 1.06) are prognostic factors even when controlled for age, cell source and type of transplant. One-year overall survival in the MRD-negative group was 90% (79-100%), and 53% (36-80%) in the MRD-positive group. Additionally, one-year leukemia-free survival in the MRD-negative group was 70% (55-89%) and 45% (28-72%) in MRD-positive.

Conclusion: Our results show that both DRI and pre-transplant MRD may have an impact on OS and LFS, although pre-transplant MRD seemed to perform better than DRI in multivariable analysis in patients with acute myeloid leukemia undergoing hematopoietic cell transplantation.