TEST:

TruSight Myeloid Sequencing Panel

Although the number of patients was limited in current study, combination therapy with HMA and venetoclax resulted in improved treatment responses and a higher rate of successful bridging to HSCT. These findings underscore the need for further large-scale studies to investigate the impact of combination treatment on MDS patients undergoing transplantation.

However, the survival differences between patients with or without cytogenetic abnormalities or gene mutations within the same category of IPSS-R or IPSS-M suggest that these two scoring systems may not fully capture the prognostic implications of cytogenetics change or gene mutations. Further studies examining immune dysregulation, or the microenvironment may be warranted to enhance current risk stratification tools and improve our understanding of the pathophysiology of MDS.

Six weeks later, while receiving the CD20-directed immunotherapies glofitamab and obinutuzumab, another bone marrow biopsy revealed eradication of the B-ALL and new involvement by pure erythroid leukemia (PEL). This patient's B-ALL lacked an IGH::BCL2 fusion resulting from t(14; 18), suggesting it did not arise through transformation of his prior FL/DLBCL. Instead, the B-ALL was likely caused by his extensive exposure to genotoxic chemotherapy drugs – including alkylating agents – for his preceding lymphomas. The shared cytogenetic and molecular features between this patient's B-ALL and PEL imply they are clonally related.

Only two patients in the MRD negative group received the FLT3 inhibitor midostaurin combined with chemotherapy...NGS-MRD was not prognostic in this cohort of FLT3-TKD mutated AML patients. Shared first authors : Isabell Arnhardt, Christian M Vonk Shared senior authorship : Michael Heuser, Peter J.M. Valk

Such information will be invaluable for making treatment decisions in this grave prognostic disease otherwise. Ongoing work will dissect the exact treatment modalities and their influence on the TP53MT configurational switch.

Ongoing work would further dissect the exact impact of resistant/relapse signature and a weighted impact on survival and outcomes. Ongoing analysis in other disease groups will be presented at the ASH conference.

Here, we report a comprehensive analysis of baseline MCH mutational landscape in pts enrolled in the Fondazione Italiana Linfomi (FIL) MCL0208 phase 3 trial (NCT 02354313), evaluating lenalidomide maintenance vs observation after chemoimmunotherapy and ASCT in untreated MCL pts ≤ 65 years...In conclusion, we provided the M-CH mutational landscape at baseline in younger MCL pts and we showed for the first time the unfavorable clinical impact of large CH clones on MCL progression. Figure 1.

Aims: Here, we report a comprehensive analysis of baseline M-CHIP mutational landscape in pts enrolled in theFondazione Italiana Linfomi (FIL) MCL0208 phase 3 trial (NCT 02354313), evaluating lenalidomide (LEN)maintenance vs observation after chemoimmunotherapy and ASCT in untreated MCL pts ≤ 65 years... In conclusion, we provided the M-CHIP mutational landscape at baseline in younger MCL pts from aprospective clinical trial and we showed for the first time the unfavorable clinical impact of large CH clones onMCL progression. Further studies are ongoing on CH mutations detected during follow-up.

Highly heterogeneous molecular genetic profile is present in patients from adverse risk group. Mutations ingenes that activate intracellular signaling pathways are most common in high-risk AML. The presence of morethan 6 mutations and ASXL1mut+ and SRSF2mut+ status negatively affect the survival of patients.

NPM1 mutations were identified in 21. 7% of 1,520 patients. Patients with NPM1mut were older and had higherWBC counts and LDH levels, and more often had a normal karyotype, but less adverse cytogenetic features,including monosomal karyotype and MR cytogenetic abnormalities at diagnosis compared to NPM1wtpatients.

Notably, none of the patients received oral azacitidine as maintenance therapy... The results indicated that NPM1-/FLT3-ITD- and NPM1+/FLT3-ITD- subgroups in DNMT3A mutated AML benefit from allo-HSCT in CR1. Larger cohorts are warranted to validate these findings.

Notably, none of the patients received oral azacitidine as maintenance therapy... The results indicated that NPM1-/FLT3-ITD- and NPM1+/FLT3-ITD- subgroups in DNMT3A mutated AML benefit from allo-HSCT in CR1. Larger cohorts are warranted to validate these findings.