Measurable residual disease quantification in adult patients with KMT2A-rearranged acute lymphoblastic leukemia

Le résumé fourni par la source

In adult ALL, 5–10% of patients show KMT2A translocations ( KMT2A rearrangements) with only a few secondary alterations, implicating it as a leukemia-initiating factor [ 1 , 2 ]. Approximately 95% of all fusions in adult ALL are KMT2A :: AFF1 or KMT2A :: MLLT1 [ 3 ]. KMT2A -rearranged adult ALL patients are generally considered high-risk and are treated with intensified therapy, including allogeneic hematopoietic stem cell transplantation (SCT) [ 4 ]. Current ALL treatment protocols are often guided by measurable residual disease (MRD)-based risk stratification [ 4 , 5 , 6 , 7 , 8 ], however, limited data are available regarding the prognostic value of MRD in adult ALL with KMT2A rearrangement. In infant KMT2A -rearranged ALL, more reliable MRD data were obtained using the individual KMT2A breakpoints as molecular MRD target as compared to IG / TR [ 6 , 9 , 10 , 11 ], but no such comparisons have been made in adult ALL. We evaluated the impact of MRD on disease-free survival (DFS) and overall survival (OS) in a cohort of 156 KMT2A -rearranged adult patients and compared IG / TR - and KMT2A -based MRD levels in 46 patients. In total, 769 bone marrow and/or peripheral blood samples from 193 adult ALL patients with KMT2A rearrangement (175 KMT2A :: AFF1 , 13 KMT2A :: MLLT1 , 1 KMT2A :: MLLT3 , 4 KMT2A+ unspecified) obtained between 2001 and 2021 were available for longitudinal MRD measurements. All patients were treated according to different protocols of the German Multicenter ALL (GMALL) study group and gave their informed consent to further scientific investigations on residual material. Patients with KMT2A :: AFF1 aged up to 55 years were assigned to the high-risk group and were candidates for SCT in first CR after consolidation I. Immunophenotyping and MRD measurement with real-time PCR based on KMT2A fusion genes and clonal IG / TR gene rearrangements were performed in central laboratories as previously described [ 10 , 11 ]. MRD measurements were interpreted according to EuroMRD guidelines [ 12 ]. MRD results were considered discordant if positivity/negativity discordance in the same sample was evidenced. For the evaluation of DFS and OS, MRD levels were compared at three different time points: end of induction I, after induction II/ pre-consolidation I, post-consolidation I/pre SCT (around week 16) (Fig. S 2 ) [ 11 ]. MRD levels were classified as molecular response (MRD < 10 –4 or negative), molecular failure with low MRD (≥10 –4 and <10 –2 ), and high MRD (≥10 –2 ). Further statistical details are provided in the online supplement to this letter.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.