General AML

Prognostic significance of MRD status in high-risk AML patients– oral abstract in AML at SOHO 2017

The fifth Annual Meeting of the Society of Hematologic Oncology (SOHO) took place at the Westin Galleria in Houston, Texas, between 13th–16th September 2017 and the AML Global Portal is delighted to give an overview on the key abstracts in Acute Myeloid Leukemia (AML).

There was a session dedicated to AML on 15th September 2017, and it was co-chaired by Daniel DeAngelo from the Dana-Farber Cancer Institute, Boston, and a member of our North America Steering Committee, Jeffrey Lancet from Moffitt Cancer Center.

Abstract AML-075 titled “MRD Status and its Prognostic Significance in High-Risk AML Patients: A Single Center Experience” was presented by Matteo Piccini from Università degli Studi di Firenze, Firenze, Italy, during this session.

The speaker presented results from their retrospective study which analyzed the MRD status using a Leukemia Imunophenotype (LAIP)-based strategy in 134 AML patients who were diagnosed and treated at Università degli Studi di Firenze between 2008–2013.

  • One-hundred and five patients achieved Complete Remission (CR)
  • In high-risk AML patients (n = 30), post-induction MRD status exhibited strong prognostic significance
  • MRD-negative high-risk AML patients had a significantly better Overall Survival (OS [P = 0.024]) and Disease Free Survival (DFS [P = 0.017]) compared to MRD-positive high-risk patients

The speaker concluded by highlighting that the results of their study shows the “importance of post-induction MRD status” particularly in high-risk AML patients. Additionally, MRD status could possibly guide the “clinical decision making regarding the time of transplantation or the choice of stem source”.

Abstract:
Introduction

Minimal residual disease plays a pivotal role in clinical decision-making and treatment tailoring in acute lymphoblastic leukemia . Conversely, the prognostic significance of MRD and its clinical usefulness in the management of acute myeloid leukemia patients is still debated. While MRD status seems to add clinically useful information in favorable and intermediate-risk patients , its role in high cytogenetic risk patients is much less defined.

Methods

We set out to analyze the MRD status at different time-points in a cohort of 134 AML patients diagnosed and treated at our Institution between 2008 and 2013. Cytogenetic and molecular characterization was carried out according to ELN guidelines. All patients received induction chemotherapy with ICE regimen (idarubicin, standard-dose cytarabine, etoposide) and consolidated with similar schedules of intermediate and high-dose cytarabine. MRD status was determined by 8-colours flow-cytometry using a leukemia-associated immunophenotype-based strategy. We identified up to 4 different LAIPs for each patient at diagnosis; each LAIP was systematically monitored at subsequent MRD time-points. MRD positivity was defined as the presence of a cluster of LAIP+ cells accounting for at least 0.01% of bone marrow cellularity.

Results

All the patients had at least one identifiable LAIP at diagnosis. Most patients (90%) had at least 2 identifiable LAIPs. One hundred and five patients achieved CR and were evaluable for MRD status. Overall, MRD status exhibited strong prognostic significance in terms of OS and DFS both in the post-induction and post-consolidation setting while considering the whole population. When restricting the analysis to the high cytogenetic risk population (n=30), post-induction MRD status maintained its prognostic significance both in terms of DFS and OS: specifically, post-induction MRD-negative patients fared considerably better with median DFS and OS not being reached (p=0.017; 0.024). Most patients received an allogeneic HSCT shortly upon achievement of CR; therefore, observation was not censored for HSCT.

Conclusions

Overall these data highlight the importance of post-induction MRD status even in high-risk patients, possibly guiding clinical decision-making regarding the timing of HSCT or the choice of stem cells source (eg: matched unrelated donor vs haploidentical donor).

References
  1. Piccini M. & Fani A. MRD Status and its Prognostic Significance in High-Risk AML Patients: A Single Center Experience. Clinical Lymphoma, Myeloma, and Leukemia. 2017 Sep; 17(suppl 2):S278–S279. DOI: http://dx.doi.org/10.1016/j.clml.2017.07.058.