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. 2024 Dec;103(12):5387-5393.
doi: 10.1007/s00277-024-06106-y. Epub 2024 Nov 26.

Central nervous system relapse after allogeneic HCT in FLT3-mutated AML

Khouloud Kouidri #  1 , Fabian Acker #  2 , Rosa Toenges  2   3 , Saskia Pfaff  2 , Sarah Lindner  2   4 , Julia Riemann  2 , Marek Werth  2 , Salem Ajib  2 , Fabian Lang  2 , Björn Steffen  2 , Thomas Oellerich  2 , Hubert Serve  2 , Anjali Cremer  2 , Gesine Bug  2
Affiliations

Central nervous system relapse after allogeneic HCT in FLT3-mutated AML

Khouloud Kouidri et al. Ann Hematol. 2024 Dec.

Abstract

Central nervous system (CNS) relapse in acute myeloid leukemia (AML) is rare, but prognostically extremely unfavorable and associated with very high mortality rates. Aim of our single-center study was to define risk factors for CNS relapse in patients with FLT3-mutated AML after allogeneic hematopoietic cell transplantation (HCT) and to determine the impact of pre-emptive or salvage therapy with FLT3-inhibitors (FLT3i) on occurrence of CNS relapse and overall prognosis. We analyzed 39 FLT3-mutated AML patients who were treated with intensive induction therapy and consecutively underwent HCT at our institution. We observed that the remission status before HCT was strongly associated with relapse probability. Notably, FLT3-mutated AML showed a high propensity for CNS relapse with a cumulative incidence of 50% (95% confidence interval [CI], 16-77) at 2 years in non-responders pre-HCT compared to 0% in responders (cause-specific hazard ratio, 24.5, 95% CI, 2.9-206.2; p = 0.003). This was not abrogated by pre-emptive or salvage therapy with FLT3i in first relapse. Targeted therapies prior to transplant, use of intrathecal chemoprophylaxis or closer monitoring may be considered in patients with FLT3-mutated AML with active disease prior to HCT in order to prevent CNS relapse.

Keywords: AML; CNS; FLT3; HCT; Real-World Data; Relapse; Retrospective.

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Conflict of interest statement

Declarations. Ethical approval: All data obtained in this study involving human participants were collected in accordance with ethical standards of our institutional research committee (SHN-1-2022) and with the 1964 Helsinki Declaration. Consent to participate: Informed consent was obtained from all individual participants included in the study. Competing interests: KK received support for attending meetings from BeiGene (not related to this work).FA received support for attending meetings and speaker’s honoraria from AstraZeneca and consultant fees from IQVIA and AMGEN (not related to this work).FL received honoraria and consultant fees from Bristol Myers Squibb, Incyte, and Celgene and consultancy, honoraria and research funding from Novartis (not related to this work).GB received honoraria from BMS, Gilead, Jazz, Novartis and Otsuka and travel support from Gilead and Jazz (not related to this work).

Figures

Fig. 1
Fig. 1
Baseline characteristics and swimmer plot
Fig. 2
Fig. 2
Competing risk analysis and survival outcomes. Panels A and B show the cumulative incidence of CNS relapse (panel A) considering all-cause mortality a competing risk (panel B). Panels C and D illustrate progression-free (C) and overall survival (D). CI denotes confidence interval, CR/CRi complete response with/without recovery, Cum. Cumulative, HCT hematopoietic stem cell transplantation, and HR hazard ratio
See this image and copyright information in PMC

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