Post-Transplantation Multicolored Flow Cytometry–Minimal Residual Disease Status on Day 100 Predicts Outcomes for Patients With Refractory Acute Myeloid Leukemia

Klyuchnikov, Evgeny; Badbaran, Anita; Massoud, Radwan; Fritsche-Friedland, Ulrike; Janson, Dietlinde; Ayuk, Francis; Christopeit, Maximilian; Wolschke, Christine; Bacher, Ulrike; Kröger, Nicolaus (2022). Post-Transplantation Multicolored Flow Cytometry–Minimal Residual Disease Status on Day 100 Predicts Outcomes for Patients With Refractory Acute Myeloid Leukemia. Transplantation and cellular therapy, 28(5), 267.e1-267.e7. Elsevier 10.1016/j.jtct.2022.01.014

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BACKGROUND

Patients with relapsed/refractory AML have a dismal prognosis. Allogeneic stem cell transplantation (allo-SCT) provides a curative approach, however the overall survival (OS) remains low (20-40%). In this setting, though some effective approaches have been evaluated in the recent years, the management of such patients still remains challenging.

OBJECTIVES

In this study we evaluated the predictive role of post-transplant day +100 MRD detection for post-transplant outcomes for patients with refractory AML.

STUDY DESIGN

Fifty-six adult patients with refractory AML (median age 58, 20-76; male, 61%) who underwent allo-SCT were included in this retrospective monocentric study. Twenty-nine patients (52%) received FLAMSA-based conditioning. MRD was assessed using multicolored flow cytometry (MFC) according to ELN guidelines ("different from normal" and LAIP). The sensitivity of the method was 10-4 - 10-5. The median marrow blast count at allo-SCT was 25% (range 6-91%). At day +100 post-transplant, 40 patients (71%) experienced MFC-MRD negativity, 16 patients (29%) were MRD positive. All included patients survived at least 100 days post-transplant without relapse. Uni- and multivariate analysis based on Kaplan-Meier and Cox proportional hazards method were performed.

RESULTS

The median follow-up was 16 months (range 3-66). The post-transplant day 100 MRD negative patients received rather two allografts (27% vs 6%, p=0.08). In multivariate analysis, day +100 MRD status (negative vs positive) (OS: 0.23 (0.1-0.54), p=0.001; relapses: 0.20 (0.1-0.49), p=0.0005) and FLAMSA vs other regimens (0.34 (0.1-0.83), p=0.018; relapses: 0.43 (0.17-1.1), p=0.07) independently impacted post-transplant survival.

CONCLUSIONS

We suggest that post-transplant day +100 MFC-MRD detection plays predictive role in refractory AML patients and may help to define possible candidates for early post-transplant interventions aiming to decrease the relapse risk and improve survival.

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