Pre-Transplant Chromosome Genomic Array Testing Improves Prognosis for Myelofibrosis Patients Undergoing Transplantation.

Background: Despite its known superior diagnostic yield for chromosomal anomalies compared to karyotype and FISH studies, Chromosome Genomic Array Testing (CGAT) is not used as a routine clinical test for myelofibrosis. Meanwhile, although many prognostic systems exist that risk stratify patients at diagnosis, limited tools are available to prognosticate transplant outcome.

Objective: The current study aimed at testing if CGAT results obtained before transplantation improves prognosis of post-transplant outcome in myelofibrosis patients compared with current risk categorization systems namely DIPSS plus.

An ultra-short-period super-Earth with an extremely high density and an outer companion.

We present the discovery and characterization of a new multi-planetary system around the Sun-like star K2-360 (EPIC 201595106). K2-360 was first identified in K2 photometry as the host of an ultra-short-period (USP) planet candidate with a period of 0.88 d.

Long-term survival after unrelated donor marrow transplantation for aplastic anaemia after optimized conditioning regimen: a retrospective multicentre cohort study.

Background: Almost all acquired severe aplastic anaemia is immune mediated and characterised by hypocellular bone marrow and ≥2 affected haematopoietic lineages. The optimal preparartive regimen for unrelated donor transplantation remains to be established. We aimed to study long-term outcomes after unrelated donor transplantation for severe aplastic anaemia with de-escalation of cyclophosphamide (Cy) dose in steps of 50 mg/kg (150, 100, 50, 0 mg/kg) in combination with total body irradiation (TBI) 2 Gy, anti-thymocyte globulin (ATG) and fludarabine.

Risk prediction for clonal cytopenia: multicenter real-world evidence.

Clonal cytopenia of undetermined significance (CCUS) represents a distinct disease entity characterized by myeloid-related somatic mutations with a variant allele fraction of ≥2% in individuals with unexplained cytopenia(s) but without a myeloid neoplasm (MN). Notably, CCUS carries a risk of progressing to MN, particularly in cases featuring high-risk mutations. Understanding CCUS requires dedicated studies to elucidate its risk factors and natural history.

How I reduce and treat posttransplant relapse of MDS.

Allogeneic hematopoietic stem cell transplantation (HSCT) is the only potentially curative option for patients with high-risk myelodysplastic syndromes (MDS). Advances in conditioning regimens and supportive measures have reduced treatment-related mortality and increased the role of transplantation, leading to more patients undergoing HSCT. However, posttransplant relapse of MDS remains a leading cause of morbidity and mortality for this procedure, necessitating expert management and ongoing results analysis.

Discovery of U2AF1 neoantigens in myeloid neoplasms.

Background: Myelodysplastic syndromes (MDS) arise from somatic mutations acquired in hematopoietic stem and progenitor cells, causing cytopenias and predisposing to transformation into secondary acute myeloid leukemia (sAML). Recurrent mutations in spliceosome genes, including , are attractive therapeutic targets as they are prevalent in MDS and sAML, arise early in neoplastic cells, and are generally absent from normal cells, including normal hematopoietic cells. MDS and sAML are susceptible to T cell-mediated killing, and thus engineered T-cell immunotherapies hold promise for their treatment.

A resonant sextuplet of sub-Neptunes transiting the bright star HD 110067.

Planets with radii between that of the Earth and Neptune (hereafter referred to as 'sub-Neptunes') are found in close-in orbits around more than half of all Sun-like stars. However, their composition, formation and evolution remain poorly understood. The study of multiplanetary systems offers an opportunity to investigate the outcomes of planet formation and evolution while controlling for initial conditions and environment.

JAK2 V617F mutation and associated chromosomal alterations in primary and secondary myelofibrosis and post-HCT outcomes.

JAK2 V617F is the most common driver mutation in primary or secondary myelofibrosis for which allogeneic hematopoietic cell transplantation (HCT) is the only curative treatment. Knowledge of the prognostic utility of JAK2 alterations in the HCT setting is limited. We identified all patients with MF who received HCT between 2000 and 2016 and had a pre-HCT blood sample (N = 973) available at the Center of International Blood and Marrow Transplant Research biorepository.

R-Loop Accumulation in Spliceosome Mutant Leukemias Confers Sensitivity to PARP1 Inhibition by Triggering Transcription-Replication Conflicts.

Unlabelled: RNA splicing factor (SF) gene mutations are commonly observed in patients with myeloid malignancies. Here we showed that SRSF2- and U2AF1-mutant leukemias are preferentially sensitive to PARP inhibitors (PARPi), despite being proficient in homologous recombination repair. Instead, SF-mutant leukemias exhibited R-loop accumulation that elicited an R-loop-associated PARP1 response, rendering cells dependent on PARP1 activity for survival.

Whole-genome sequencing identifies novel predictors for hematopoietic cell transplant outcomes for patients with myelodysplastic syndrome: a CIBMTR study.

Recurrent mutations in TP53, RAS pathway and JAK2 genes were shown to be highly prognostic of allogeneic hematopoietic cell transplant (alloHCT) outcomes in myelodysplastic syndromes (MDS). However, a significant proportion of MDS patients has no such mutations. Whole-genome sequencing (WGS) empowers the discovery of novel prognostic genetic alterations.

Prognostic landscape of mitochondrial genome in myelodysplastic syndrome after stem-cell transplantation.

Despite mitochondrial DNA (mtDNA) mutations are common events in cancer, their global frequency and clinical impact have not been comprehensively characterized in patients with myelodysplastic neoplasia (also known as myelodysplastic syndromes, MDS). Here we performed whole-genome sequencing (WGS) on samples obtained before allogenic hematopoietic cell transplantation (allo-HCT) from 494 patients with MDS who were enrolled in the Center for International Blood and Marrow Transplant Research. We evaluated the impact of mtDNA mutations on transplantation outcomes, including overall survival (OS), relapse, relapse-free survival (RFS), and transplant-related mortality (TRM).

Association between Prior Cytotoxic Therapy, Antecedent Hematologic Disorder, and Outcome after Allogeneic Hematopoietic Cell Transplantation in Adult Acute Myeloid Leukemia.

(1) Background: Secondary acute myeloid leukemia (AML), i.e., AML arising from prior therapy (therapy-related) and/or an antecedent hematologic disorder (AHD) is generally associated with worse outcomes compared to de novo AML.

Splenomegaly in patients with primary or secondary myelofibrosis who are candidates for allogeneic hematopoietic cell transplantation: a Position Paper on behalf of the Chronic Malignancies Working Party of the EBMT.

Splenomegaly is a hallmark of myelofibrosis, a debilitating haematological malignancy for which the only curative option is allogeneic haematopoietic cell transplantation (HCT). Considerable splenic enlargement might be associated with a higher risk of delayed engraftment and graft failure, increased non-relapse mortality, and worse overall survival after HCT as compared with patients without significantly enlarged splenomegaly. Currently, there are no standardised guidelines to assist transplantation physicians in deciding optimal management of splenomegaly before HCT.

Prediction of Busulfan Clearance by Predose Plasma Metabolomic Profiling.

Intravenous busulfan doses are often personalized to a target plasma exposure (targeted busulfan) using an individual's busulfan clearance (BuCL). We evaluated whether BuCL could be predicted by a predose plasma panel of 841 endogenous metabolomic compounds (EMCs). In this prospective cohort of 132 hematopoietic cell transplantation (HCT) patients, all had samples collected immediately before busulfan administration (preBU) and 96 had samples collected 2 weeks before busulfan (2-week-preBU).

Transplantation for myeloid neoplasms with antecedent solid tumor.

Background: Definitive treatment of acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), and myeloproliferative neoplasm (MPN) involves allogeneic hematopoietic stem cell transplantation (allo-HSCT), either with myeloablative (MAC) or reduced-intensity conditioning (RIC). These diseases may arise in patients with a prior solid tumor. The impact of antecedent solid tumor on transplantation decision-making and outcomes is not well defined.

Germline-somatic JAK2 interactions are associated with clonal expansion in myelofibrosis.

Myelofibrosis is a rare myeloproliferative neoplasm (MPN) with high risk for progression to acute myeloid leukemia. Our integrated genomic analysis of up to 933 myelofibrosis cases identifies 6 germline susceptibility loci, 4 of which overlap with previously identified MPN loci. Virtual karyotyping identifies high frequencies of mosaic chromosomal alterations (mCAs), with enrichment at myelofibrosis GWAS susceptibility loci and recurrently somatically mutated MPN genes (e.

Haploidentical bone marrow transplantation in patients with relapsed or refractory severe aplastic anaemia in the USA (BMT CTN 1502): a multicentre, single-arm, phase 2 trial.

Background: Relapsed severe aplastic anaemia is a marrow failure disorder with high morbidity and mortality. It is often treated with bone marrow transplantation at relapse post-immunosuppressive therapy, but under-represented minorities often cannot find a suitably matched donor. This study aimed to understand the 1-year overall survival in patients with relapsed or refractory severe aplastic anaemia after haploidentical bone marrow transplantation.

Eprenetapopt Plus Azacitidine After Allogeneic Hematopoietic Stem-Cell Transplantation for -Mutant Acute Myeloid Leukemia and Myelodysplastic Syndromes.

Purpose: Outcomes are poor in -mutant (m) acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), even after allogeneic hematopoietic stem-cell transplant (HCT). Eprenetapopt (APR-246) is a first-in-class, small-molecule p53 reactivator.

Patients And Methods: We conducted a phase II, multicenter, open-label trial to assess efficacy and safety of eprenetapopt combined with azacitidine as maintenance therapy after HCT (ClinicalTrials.

Utility of the Treatment-Related Mortality (TRM) score to predict outcomes of adults with acute myeloid leukemia undergoing allogeneic hematopoietic cell transplantation.

There is long-standing interest in estimating non-relapse mortality (NRM) after allogeneic hematopoietic cell transplantation (HCT) for AML, but existing tools have limited discriminative capacity. Using single-institution data from 861 adults with AML, we retrospectively examined the Treatment-Related Mortality (TRM) score, originally developed to predict early mortality following induction chemotherapy, as a predictor of post-HCT outcome. NRM risks increased stepwise across the four TRM score quartiles (at 3 years: 9% [95% confidence interval: 5-13%] in Q1 vs.

NCCN Guidelines® Insights: Myelodysplastic Syndromes, Version 3.2022.

The NCCN Guidelines for Myelodysplastic Syndromes (MDS) provide recommendations for the evaluation, diagnosis, and management of patients with MDS based on a review of clinical evidence that has led to important advances in treatment or has yielded new information on biologic factors that may have prognostic significance in MDS. The multidisciplinary panel of MDS experts meets on an annual basis to update the recommendations. These NCCN Guidelines Insights focus on some of the updates for the 2022 version of the NCCN Guidelines, which include treatment recommendations both for lower-risk and higher-risk MDS, emerging therapies, supportive care recommendations, and genetic familial high-risk assessment for hereditary myeloid malignancy predisposition syndromes.