Post-transplant day +100 MRD detection rather than mixed chimerism predicts relapses after allo-SCT for intermediate risk AML patients transplanted in CR.

Klyuchnikov, Evgeny; Badbaran, Anita; Massoud, Radwan; Fritsche-Friedland, Ulrike; Freiberger, Petra; Ayuk, Francis; Wolschke, Christine; Bacher, Ulrike; Kröger, Nicolaus (2022). Post-transplant day +100 MRD detection rather than mixed chimerism predicts relapses after allo-SCT for intermediate risk AML patients transplanted in CR. Transplantation and cellular therapy, 28(7), 374.e1-374.e9. Elsevier 10.1016/j.jtct.2022.04.009

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BACKGROUND

Chimerism and minimal residual disease (MRD) are suggested to be prognostic for post-transplant relapses in AML patients. Nevertheless, the predictive values of both approaches in homogeneous population remain underinvestigated. Here, we suggest that MRD may have a higher predictive value for relapses than mixed chimerism (MC) in intermediate risk AML patients.

PATIENTS AND METHODS

79 patients with intermediate risk AML (male, n=40, median age, 57 (19-77)) were included. MRD detection on day +100 was performed in bone marrow (multiparameter flow cytometry and quantitative real-time PCR for NPM1-mutated patients). Chimerism analysis was measured in peripheral blood. MC was defined as persistence of <99.9% of donor alleles.

RESULTS

The area under the ROC curve was highest for qPCR-MRD (0.93) followed by MFC-MRD (0.80) and MC (0.65). The highest relapses at 3 years were observed in day +100 qPCR-MRD positive patients (100%) followed by MFC-MRD positive patients (55%, p<0.001). No patients with MC and without detectable MRD developed relapses. The 3-year OS and LFS for patients with MC without detectable MRD were both 86% (61-96%) compared with day +100 MFC-MRD positive (OS: 61%, 36-84%; LFS: 30%, 11-59%) and with day +100 qPCR-MRD positive patients (OS: 17%, 3-56%, p=0.001; LFS: 0%, p<0.001).

CONCLUSIONS

In intermediate-risk AML, the qPCR-MRD on day +100 is highly predictive for relapse and long-term survival after allo-SCT, closely followed by MFC-MRD. In contrast, the chimerism status has limited predictive potential. Thus, molecular and flow-cytometric MRD monitoring in the first months post-transplant rather than MC is able to identify patients with an increased relapse risk who may benefit from early post-transplant pre-emptive intervention.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Haematology and Central Haematological Laboratory

UniBE Contributor:

Bacher, Vera Ulrike

Subjects:

600 Technology > 610 Medicine & health

ISSN:

2666-6367

Publisher:

Elsevier

Language:

English

Submitter:

Pubmed Import

Date Deposited:

19 Apr 2022 17:15

Last Modified:

15 Apr 2023 00:25

Publisher DOI:

10.1016/j.jtct.2022.04.009

PubMed ID:

35429661

Uncontrolled Keywords:

acute myeloid leukemia (AML) allogeneic hematopoietic stem cell transplantation (allo-SCT) minimal/measurable residual disease (MRD) mixed chimerism multiparameter flow cytometry (MFC) quantitative real-time PCR (qPCR)

BORIS DOI:

10.48350/169364

URI:

https://boris.unibe.ch/id/eprint/169364

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