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The rate of MRD clearance in AML with standard consolidation chemotherapy is not well defined. A multi-institution retrospective analysis was performed on 107 consecutively treated AML patients in morphologic complete remission with detectable MRD post-induction therapy who received standard chemotherapy consolidation. In response to standard intermediate/high-dose cytarabine consolidation therapy, 26 of 60 patients (43.3%) with MRD threshold of detection of at least 0.1% converted to MRD-negative status (undetectable with assay used), and 6 of 47 patients (12.8%) with MRD threshold of detection > 0.1% converted to MRD-negative status. Multivariable logistic regression for patients with MRD threshold of detection of at least 0.1% showed that, when controlling for age, ELN risk category, dose of cytarabine, and use of a combination agent, treatment with 1 cycle of consolidation cytarabine versus ≥2 cycles decreased the odds of conversion of AML to MRD-negative (OR = 0.24, 95% CI 0.07–0.85, p = 0.03). [ABSTRACT FROM AUTHOR]

We conducted a retrospective analysis of WT1-mutated acute myeloid leukemia (AML) patients who underwent allogeneic stem cell transplant. Thirty-seven patients with WT1-mutated AML were identified. Primary induction failure (40%) and early relapse rate (18%) after idarubicin/cytarabine (7 + 3) chemotherapy were observed. All patients with induction failure subsequently achieved CR with additional chemotherapy. There was no significant difference between outcomes after myeloablative vs. reduced intensity (Fludarabine/Melphalan [Flu/Mel]) conditioning regimens. RFS but not OS was significantly better in patients who received FLAG-IDA prior to transplant and/or a fludarabine-containing conditioning. In an independent ex vivo study, WT1-mutated AML samples exhibited greater sensitivity to fludarabine (p = 0.026) and melphalan (p = 0.0005) than non-WT1-mutated AML samples while there was no difference between sensitivity to cytarabine. Our data favor using a fludarabine-based induction for AML with WT1 mutation instead of 7 + 3. Fludarabine conditioning regimens for alloHCT showed better RFS but not OS. [ABSTRACT FROM AUTHOR]

Habitat heterogeneity is a key driver of biodiversity of macroorganisms, yet how heterogeneity structures belowground microbial communities is not well understood. Importantly, belowground microbial communities may respond to any number of abiotic, biotic, and spatial drivers found in heterogeneous environments. Here, we examine potential drivers of prokaryotic and fungal communities in soils across the heterogenous landscape of the imperiled Florida scrub, a pyrogenic ecosystem where slight differences in elevation lead to large changes in water and nutrient availability and vegetation composition. We employ a comprehensive, large-scale sampling design to characterize the communities of prokaryotes and fungi associated with three habitat types and two soil depths (crust and subterranean) to evaluate (i) differences in microbial communities across these heterogeneous habitats, (ii) the relative roles of abiotic, biotic, and spatial drivers in shaping community structure, and (iii) the distribution of fungal guilds across these habitats. We sequenced soils from 40 complete replicates of habitat × soil depth combinations and sequenced the prokaryotic 16S and fungal internal transcribed spacer (ITS) regions using Illumina MiSeq. Habitat heterogeneity generated distinct communities of soil prokaryotes and fungi. Spatial distance played a role in structuring crust communities, whereas subterranean microbial communities were primarily structured by the shrub community, whose roots they presumably interacted with. This result helps to explain the unexpected transition we observed between arbuscular mycorrhiza–dominated soils at low-elevation habitats to ectomycorrhiza-dominated soils at high-elevation habitats. Our results challenge previous notions of environmental determinism of microbial communities and generate new hypotheses regarding symbiotic relationships across heterogeneous environments. [ABSTRACT FROM AUTHOR]

Philadelphia (Ph)-like acute lymphoblastic leukemia (ALL) is a high-risk subgroup of B cell ALL with distinct genotypes, unified by gene expression profile similar to Ph-positive ALL, but lacking the BCR::ABL1 fusion. Ph-like ALL patients respond inadequately to conventional chemotherapy with higher rates of induction failure, persistent measurable residual disease, and lower survival rates compared to other B cell ALL subtypes. Considering Ph-like ALL's chemo-refractory nature, there is an interest in pursuing innovative therapeutic approaches to treat, including the combination of tyrosine kinase inhibitors with frontline regimens, and early introduction of novel antibody-drug conjugates and immunotherapies. Accurate diagnosis and disease-risk stratification are key to increase access for high-risk patients to allogeneic hematopoietic cell transplantation in their first complete remission. In this review, we will discuss our current knowledge of pathogenesis of Ph-like ALL, diagnostic strategies, as well as emerging data on new and current treatment strategies for this disease. [ABSTRACT FROM AUTHOR]

Rearrangements of I lysine [K] methyltransferase 2 A i ( I KMT2A i ) gene, previously known as the I MLL i gene, occur in 3 to 7% of adult patients with de novo AML and are enriched in therapy-related disease, particularly after treatment with topoisomerase II inhibitors [[1]]. Response and survival of patients with KMT2A rearranged acute myeloid leukemia (AML) receiving venetoclax in combination with hypomethylating agent therapy (HMA). The inferior prognosis of KMT2A rearranged AML patients undergoing alloSCT presents an opportunity for post-transplant maintenance trials with therapies targeting KMT2A. [Extracted from the article]