Multipotent lineage potential in B cell acute lymphoblastic leukemia is associated with distinct cellular origins and clinical features.

Developmental origins and their associations with lineage plasticity and treatment response in B-cell progenitor acute lymphoblastic leukemia (B-ALL) are mostly unexplored. Here, we integrated single-cell transcriptome sequencing (scRNA-seq) of 89 B-ALL samples with a single-cell atlas of normal human B cell development incorporating functional and molecular assays. We observed subtype- and sample-dependent correlation with normal developmental stage, with intra-subtype and intra-patient heterogeneity.

Patients with AML and an IDH2-R172 mutation exhibit a unique initial response to intensive chemotherapy induction.

The utility of a midcycle bone marrow biopsy (BMB) for early assessment of response in patients with acute myeloid leukemia (AML) after intensive chemotherapy (IC) induction is contested. Even when challenged, there is little consideration as to the possibility of different response dynamics among genetically defined subgroups. Clinical observations led to the hypothesis that patients with AML and mutations in IDH2-R172 (R172-m) exhibit particularly slow blast reduction after IC induction.

CPX-351 +/- gemtuzumab ozogamicin as induction therapy for adult patients with newly diagnosed, favourable-intermediate risk, FLT3-ITD negative, AML: A pilot study.

This pilot study evaluated CPX-351 in adults with newly diagnosed, favourable-intermediate risk, FLT3-ITD-negative AML. Twenty patients received CPX-351 for induction, with six also receiving gemtuzumab ozogamicin (GO). The complete response rate was 95%, with 42% achieving flow-based minimal residual disease (MRD) negativity post-induction.

Blinatumomab for MRD-Negative Acute Lymphoblastic Leukemia in Adults.

Background: Many older adults with B-cell precursor acute lymphoblastic leukemia (BCP-ALL) have a relapse despite having a measurable residual disease (MRD)-negative complete remission with combination chemotherapy. The addition of blinatumomab, a bispecific T-cell engager molecule that is approved for the treatment of relapsed, refractory, and MRD-positive BCP-ALL, may have efficacy in patients with MRD-negative remission.

Methods: In a phase 3 trial, we randomly assigned patients 30 to 70 years of age with -negative BCP-ALL (with :: indicating fusion) who had MRD-negative remission (defined as <0.

SINGLE CELL DISSECTION OF DEVELOPMENTAL ORIGINS AND TRANSCRIPTIONAL HETEROGENEITY IN B-CELL ACUTE LYMPHOBLASTIC LEUKEMIA.

Sequencing of bulk tumor populations has improved genetic classification and risk assessment of B-ALL, but does not directly examine intratumor heterogeneity or infer leukemia cellular origins. We profiled 89 B-ALL samples by single-cell RNA-seq (scRNA-seq) and compared them to a reference map of normal human B-cell development established using both functional and molecular assays. Intra-sample heterogeneity was driven by cell cycle, metabolism, differentiation, and inflammation transcriptional programs.

Biologic and clinical features of childhood gamma delta T-ALL: identification of STAG2/LMO2 γδ T-ALL as an extremely high risk leukemia in the very young.

Purpose: Gamma delta T-cell receptor-positive acute lymphoblastic leukemia (γδ T-ALL) is a high-risk but poorly characterized disease.

Methods: We studied clinical features of 200 pediatric γδ T-ALL, and compared the prognosis of 93 cases to 1,067 protocol-matched non-γδ T-ALL. Genomic features were defined by transcriptome and genome sequencing.

What Influences the Decision to Proceed to Transplant for Patients With AML in First Remission?

Although allogeneic hematopoietic cell transplantation (allo-HCT) remains the backbone of curative treatment for the majority of fit adults diagnosed with AML, there is indeed a subset of patients for whom long-term remission may be achieved without transplantation. Remarkable changes in our knowledge of AML biology in recent years has transformed the landscape of diagnosis, management, and treatment of AML. Specifically, markedly increased understanding of molecular characteristics of AML, the expanded application of minimal/measurable residual diseases testing, and an increased armamentarium of leukemia-directed therapeutic agents have created a new paradigm for the medical care of patients with AML.

Placental expanded mesenchymal-like cells (PLX-R18) for poor graft function after hematopoietic cell transplantation: A phase I study.

Persistent cytopenia in the post-hematopoietic cell transplantation (HCT) setting can occur despite adequate engraftment of donor cells. PLX-R18, a placental-derived mesenchymal-like cell product, is expanded ex vivo in a 3-dimensional environment. PLX-R18 cells secrete a large array of hematopoietic factors, which promote regeneration, maturation, and differentiation of hematopoietic cells and stimulate their migration to peripheral blood.

Obesity in adult acute myeloid leukemia is not associated with inferior response or survival even when dose capping anthracyclines: An ECOG-ACRIN analysis.

Background: Obesity (body mass index [BMI] ≥30 kg/m ) is an important epidemiological risk factor for developing acute myeloid leukemia (AML). Therefore, the authors studied the association of obesity with clinical and genetic phenotype and its impact on outcome in adults with AML.

Methods: The authors analyzed BMI in 1088 adults who were receiving intensive remission induction and consolidation therapy in two prospective, randomized therapeutic clinical trials of the Eastern Cooperative Oncology Group-American College of Radiology Imaging Network: E1900 (ClinicalTrials.

The increasingly blurred line between induction, consolidation and maintenance in acute myeloid leukaemia.

Since the early 1970s, the treatment of acute myeloid leukaemia (AML) has undergone a major transformation. Initially based on only two drugs, an anthracycline and cytosine arabinoside, the aim of therapy was to achieve a haematological response allowing patients to recover and go home. Back in those early days, cure was not a realistic expectation.

Measurable residual disease by flow cytometry in acute myeloid leukemia is prognostic, independent of genomic profiling.

Measurable residual disease (MRD) assessment provides a potent indicator of the efficacy of anti-leukemic therapy. It is unknown, however, whether integrating MRD with molecular profiling better identifies patients at risk of relapse. To investigate the clinical relevance of MRD in relation to a molecular-based prognostic schema, we measured MRD by flow cytometry in 189 AML patients enrolled in ECOG-ACRIN E1900 trial (NCT00049517) in morphologic complete remission (CR) (28.

Enhancer retargeting of CDX2 and UBTF::ATXN7L3 define a subtype of high-risk B-progenitor acute lymphoblastic leukemia.

Transcriptome sequencing has identified multiple subtypes of B-progenitor acute lymphoblastic leukemia (B-ALL) of prognostic significance, but a minority of cases lack a known genetic driver. Here, we used integrated whole-genome (WGS) and -transcriptome sequencing (RNA-seq), enhancer mapping, and chromatin topology analysis to identify previously unrecognized genomic drivers in B-ALL. Newly diagnosed (n = 3221) and relapsed (n = 177) B-ALL cases with tumor RNA-seq were studied.

Anti-CD20 monoclonal antibodies inhibit seropositive response to Covid-19 vaccination in non-Hodgkin lymphoma patients within 6 months after treatment.

The Covid-19 pandemic has caused millions of deaths worldwide. Although vaccines have been developed, patients on immunosuppressive therapy are less likely to respond. This study was aimed at investigating the efficacy of a Covid-19 vaccine (Pfizer-BioNTech) in patients with non-Hodgkin lymphoma treated with anti-CD20 monoclonal antibodies.

Changing trends in the therapy of acute myeloid leukemia.

There has been remarkable progress in the treatment of acute myeloid leukemia (AML) which has spanned 5 decades. The changing trends have led to new approaches and significant improvement in outcomes. This review has summarized the historical insights that have shaped the current treatment paradigms of AML.

Risk of Cancer in Paediatric onset Inflammatory Bowel Diseases: A Nation-wide Study From the epi-IIRN.

Background: Paediatric onset IBD [PIBD] is characterised by a more extensive phenotype than adult-onset IBD and a higher utilisation of immunosuppressive medications; both may be associated with malignancy. We aimed to assess the risk of cancer in a nationwide cohort of PIBD and to explore the risks associated with medical treatments.

Methods: PIBD patients [<18 years old] were included from the epi-IIRN cohort, covering 98% of the Israeli population from 2005, linked to the national cancer registry.