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Measurable residual disease (MRD) in adults with acute myeloid leukemia (AML) in complete remission is an important prognostic marker, but detection methodology requires optimization. Persistence of mutated NPM1or FLT3-ITD in the blood of adult patients with AML in first complete remission (CR1) prior to allogeneic hematopoietic cell transplant (alloHCT) associates with increased relapse and death after transplant. The prognostic implications of persistence of other common AML-associated mutations, such as IDH1, at this treatment landmark however remain incompletely defined. We performed testing for residual IDH1variants (IDH1m) in pre-transplant CR1 blood of 148 adult patients undergoing alloHCT for IDH1-mutated AML at a CIBMTR reporting site between 2013 and 2019. No statistically significant post-transplant differences were observed between those testing IDH1m positive (n= 53, 36%) and negative pre-transplant (overall survival (OS): p= 0.4; relapse: p= 0.5). For patients with IDH1mutated AML co-mutated with NPM1and/or FLT3-ITD, only detection of persistent mutated NPM1and/or FLT3-ITD was associated with significantly higher rates of relapse (p= 0.01). These data, from the largest study to date, do not support the detection of IDH1mutation in CR1 blood prior to alloHCT as evidence of AML MRD for increased post-transplant relapse risk.

AimsCongenital sideroblastic anaemias (CSAs) are a group of rare disorders with the presence of ring sideroblasts in the bone marrow. Pathogenic variants are inherited in an autosomal recessive/X-linked fashion. The study was aimed at characterising the spectrum of mutations in SLC25A38and ALAS2genes in sideroblastic anaemia patients, exploring the genotype-phenotype correlation and identifying the haplotype associated with any recurrent mutation.Patients and methodsTwenty probable CSA patients were retrospectively analysed for genetic variants in ALAS2and SLC25A38genes by direct bidirectional sequencing. Real-time PCR was used to quantify gene expression in a case with promoter region variant in ALAS2. Three single nucleotide polymorphisms were used to establish the haplotype associated with a recurrent variant in the SLC25A38gene.ResultsSix patients had causative variants in ALAS2(30%) and 11 had variants in SLC25A38(55%). The ALAS2mutated cases presented at a significantly later age than the SLC25A38cases. A frameshift variant in SLC25A38(c.409dupG) was identified in six unrelated patients and was a common variant in our population exhibiting ‘founder effect’.ConclusionThis is the largest series of sideroblastic anaemia cases with molecular characterisation from the Indian subcontinent.

Introduction:Next-generation sequencing (NGS) represents a promising modality for measurable residual disease (MRD) testing in patients with acute myeloid leukemia (AML), but systematic efforts are required to define the appropriate targets, test characteristics, and clinical implications. We recently reported that detection of persistent NPM1or FLT3internal tandem duplication (ITD) mutations in adults with AML in first complete remission (CR1) prior to allogeneic hematopoietic cell transplantation (alloHCT) is associated with increased relapse and death compared with those testing negative (JAMA 2023, PMID: 36881031). FLT3tyrosine kinase domain (TKD) variants are present in 7-10% of adult patients with AML but the utility of this target for AML MRD testing in CR1 prior to alloHCT was previously unknown.

Background:In the past year, multiple studies have demonstrated the drastically increased risk of relapse and death in patients with Acute Myeloid Leukemia (AML) who have persistent FLT3internal tandem duplication (ITD) mutations detectable in clinical remission by next generation sequencing (NGS). Translating this evidence into a change in clinical practice requires both widely available testing and a clear understanding of the clinical implications of FLT3-ITD detection at defined threshold levels. In the largest of the recent studies (Pre-MEASURE, PMID: 36881031), we performed FLT3-ITD MRD detection in blood DNA collected from 608 patients at the time of first remission (CR1) prior to allogeneic hematopoietic cell transplant (alloHCT). To evaluate cross-assay comparability and the impact of residual disease burden levels, we performed analysis on this cohort using a commercially available FLT3-ITD MRD NGS assay.

Introduction: Detection of measurable residual disease (MRD) prior to allogeneic hematopoietic cell transplant (alloHCT) in patients with acute myeloid leukemia (AML) in remission is associated with increased relapse and inferior survival after transplant. We recently reported that next-generation sequencing (NGS) detection of mutated NPM1or FLT3-ITD in first complete remission (CR1) blood prior to alloHCT is strongly associated with increased relapse and death (PMID: 36881031). However, the prognostic implications of detecting persistence of other common AML-associated mutations at this treatment landmark remain incompletely defined. Around 20% of patients diagnosed with AML have variants in isocitrate dehydrogenase ( IDH) genes (~7% for IDH1) and clinical outcomes are known to differ due to co-occurrence of other mutations, IDHsubtypes, treatment strategies, and patient factors. Studies have examined the relationship between residual IDH1variants ( IDH1m) in CR and subsequent clinical outcomes, but definitive standardized evidence to inform decision-making for the clinical utility of IDH1mas a target for AML MRD testing was not previously available.