Bisantrene in combination with fludarabine and clofarabine as salvage therapy for adult patients with refractory or relapsed acute myeloid leukaemia (AML)-An open-label, phase I/II study.

Bisantrene (Bis), an anthracene derivative with topoisomerase-II inhibitory activity and low cardiotoxicity, may enhance its efficacy when combined with nucleoside analogues such as clofarabine (Clo) and fludarabine (Flu) in preclinical acute myeloid leukaemia (AML) studies. We conducted a phase I/II open-label study (NCT04989335) to evaluate the safety and efficacy of Bis/Clo/Flu in relapsed/refractory AML. Twenty-one patients (median age: 47 years, 55% female) received Flu (10 mg/m), Clo (30 mg/m) and Bis (250 mg/m) intravenously for 4 days.

Efficacy and safety of Glofitamab in patients with R/R DLBCL in real life setting- a retrospective study.

Glofitamab, a CD20-directed CD3 T-cell engager, was recently FDA-approved after demonstrating a 52% overall response rate (ORR) and a 39% complete response (CR) rate in heavily pretreated diffuse large B-cell lymphoma (DLBCL) patients. However, real-world data on its efficacy and safety remain limited. This study evaluated glofitamab's performance in clinical practice.

An inflammatory biomarker signature of response to CAR-T cell therapy in non-Hodgkin lymphoma.

Disease progression is a substantial challenge in patients with non-Hodgkin lymphoma (NHL) undergoing chimeric antigen receptor T cell (CAR-T) therapy. Here we present InflaMix (INFLAmmation MIXture Model), an unsupervised quantitative model integrating 14 pre-CAR-T infusion laboratory and cytokine measures capturing inflammation and end-organ function. Developed using a cohort of 149 patients with NHL, InflaMix revealed an inflammatory signature associated with a high risk of CAR-T treatment failure, including increased hazard of death or relapse (hazard ratio, 2.

Pretreatment pulmonary function testing has limited utility in B-cell lymphoma treated with CD19 CAR T cells.

Pulmonary function tests (PFTs) are recommended for hematopoietic cell transplantation (HCT) evaluation. However, their prognostic value in chimeric antigen receptor T-cell (CAR-T) therapy remains unclear. We assessed the predictive significance of PFTs and pulmonary comorbidity classifications, per the Hematopoietic Cell Transplantation-Comorbidity Index (HCT-CI), in patients with B-cell lymphoma undergoing autologous CD19 CAR-T therapy.

Point-of-care anti-CD19 chimeric antigen receptor T-cell therapy for relapsed/refractory follicular lymphoma.

Patients with relapsed/refractory follicular lymphoma (R/R-FL) often require multiple treatment lines. We performed a phase 1b/2 single-center clinical trial of autologous point-of-care anti-CD19 chimeric antigen receptor (CAR) T-cells in R/R-FL patients treated patients with ≥ 2 treatment lines. All 26 patients enrolled received CAR T-cell infusion at a median of 11 days after leukapheresis.

IGHV allele similarity clustering improves genotype inference from adaptive immune receptor repertoire sequencing data.

In adaptive immune receptor repertoire analysis, determining the germline variable (V) allele associated with each T- and B-cell receptor sequence is a crucial step. This process is highly impacted by allele annotations. Aligning sequences, assigning them to specific germline alleles, and inferring individual genotypes are challenging when the repertoire is highly mutated, or sequence reads do not cover the whole V region.

B cell M-CLL clones retain selection against replacement mutations in their immunoglobulin gene framework regions.

Introduction: Chronic lymphocytic leukemia (CLL) is the most common adult leukemia, accounting for 30-40% of all adult leukemias. The dynamics of B-lymphocyte CLL clones with mutated immunoglobulin heavy chain variable region (IgHV) genes in their tumor (M-CLL) can be studied using mutational lineage trees.

Methods: Here, we used lineage tree-based analyses of somatic hypermutation (SHM) and selection in M-CLL clones, comparing the dominant (presumably malignant) clones of 15 CLL patients to their non-dominant (presumably normal) B cell clones, and to those of healthy control repertoires.

IgTreeZ, A Toolkit for Immunoglobulin Gene Lineage Tree-Based Analysis, Reveals CDR3s Are Crucial for Selection Analysis.

Somatic hypermutation (SHM) is an important diversification mechanism that plays a part in the creation of immune memory. Immunoglobulin (Ig) variable region gene lineage trees were used over the last four decades to model SHM and the selection mechanisms operating on B cell clones. We hereby present IgTreeZ (Immunoglobulin Tree analyZer), a python-based tool that analyses many aspects of Ig gene lineage trees and their repertoires.

Allogeneic Hematopoietic Cell Transplantation after Chimeric Antigen Receptor T Cell Therapy in Large B Cell Lymphoma.

Anti-CD19 chimeric antigen receptor T cell (CAR-T) therapy has transformed the care of patients with relapsed/refractory large B cell lymphoma (LBCL). However, approximately 60% of CAR-T recipients ultimately will experience disease recurrence or progression. Salvage therapies after CAR-T treatment failures are of limited efficacy and have a short duration of response.

Outcomes of first therapy after CD19-CAR-T treatment failure in large B-cell lymphoma.

Persistence or recurrence of large B-cell lymphoma after CD19-CAR-T is common, yet data guiding management are limited. We describe outcomes and features following CAR-T treatment failure. Of 305 adults who received CD19-CAR-T, 182 experienced disease recurrence or progression (1-year cumulative incidence 63% [95%CI: 57-69]).

Cellular and humoral response to the fourth BNT162b2 mRNA COVID-19 vaccine dose in patients with CLL.

We assessed the humoral and cellular response to the fourth BNT162b2 mRNA COVID-19 vaccine dose in patients with CLL. A total of 67 patients with CLL and 85 age matched controls tested for serologic response and pseudo-neutralization assay. We also tested the functional T-cell response by interferon gamma (IFNγ) to spike protein in 26 patients.

Point-of-care CAR T-cell therapy as salvage strategy for out-of-specification tisagenlecleucel.

Tisagenlecleucel (tisa-cel) is an anti-CD19 chimeric antigen receptor (CAR) T-cell therapy approved for patients with relapsed/refractory large B-cell lymphoma. Outcomes of patients with out-of-commercial specification (OOS) CAR T products are not well characterized. We therefore assessed 37 adult patients who underwent leukapheresis for tisa-cel therapy in a single center.

Point-of-care anti-CD19 CAR T-cells for treatment of relapsed and refractory aggressive B-cell lymphoma.

Anti CD19 chimeric antigen receptor (CAR) T-cell therapy has transformed the care of relapsed and refractory aggressive B-cell lymphoma. However, financial toxicity and manufacturing time represent barriers to its widespread implementation. Study applicability, toxicity, and efficacy of a locally produced autologous CD19-directed CAR T-cell product were studied.

Imaging of Hematological Patients in the Era of COVID-19.

The COVID-19 pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), resulted in changes in management and imaging routines for patients with hematological malignancies. Treating physicians had to familiarize themselves with a new disease, with distinct imaging manifestations, sometimes overlapping with other infections prevalent in this patient population. In some aspects, infected hematological patients might exhibit a different disease course, and routine imaging in asymptomatic hematological patients may result in unexpected COVID-19 findings, implying covert infection, that should be further explored.

Targeting the actin nucleation promoting factor WASp provides a therapeutic approach for hematopoietic malignancies.

Cancer cells depend on actin cytoskeleton rearrangement to carry out hallmark malignant functions including activation, proliferation, migration and invasiveness. Wiskott-Aldrich Syndrome protein (WASp) is an actin nucleation-promoting factor and is a key regulator of actin polymerization in hematopoietic cells. The involvement of WASp in malignancies is incompletely understood.

Outcomes Related to FDG-PET-CT Response in Patients With Hodgkin Lymphoma Treated With Brentuximab-Vedotin at Relapse or Consolidation.

Background: Brentuximab-vedotin (BV) monotherapy has shown high efficacy in heavily pre-treated patients with relapsed or refractory Hodgkin lymphoma (HL) after high-dose chemotherapy or autologous stem cell transplantation (ASCT). We retrospectively analyzed the outcomes of treatment with BV of HL patients and examined the predictive ability of PET-CT for response in this setting.

Patients And Methods: Records of 49 HL patients (median age, 39 years, 55% male) treated with BV for relapse (71.

Progression of disease within 24 months of initial therapy (POD24) detected incidentally in imaging does not necessarily indicate worse outcome.

Progression of disease within 24 months of initial therapy (POD24) has previously been identified as a predictor of reduced overall survival (OS) for patients with follicular lymphoma (FL). Here we attempt to validate this finding in a retrospective cohort and understand whether the method by which progression is determined, clinically or radiographically, influences POD24 robustness. We reviewed records of 635 patients with FL and included 317 patients in our analysis.

Recognizing severe fatigue and decline in quality of life in Hodgkin lymphoma survivors.

Hodgkin lymphoma (HL) is common in young adults and considered curable in most patients. Young HL survivors (HLS) are at risk of long-term adverse effects. Our study aimed to assess various fatigue and quality of life (QoL) complaints, and their correlations with treatment.

Efficacy of Gemcitabine as Salvage Therapy for Relapsed and Refractory Aggressive Non-Hodgkin Lymphoma.

Gemcitabine-based salvage therapy is considered an effective treatment for relapsed and refractory Non-Hodgkin's lymphoma (NHL). We analyzed the outcome of 41 consecutive NHL patients treated with gemcitabine-based regimens between January 2007 and October 2015. Twenty-eight males and 13 females (median age 66.

FDG PET-CT evaluation in neurolymphomatosis: imaging characteristics and clinical outcomes.

Neurolymphomatosis (NL) often represents unidentified non-Hodgkin lymphoma relapses. Considering its severity, early detection and treatment are crucial. We outline one hospital's F-FDG-PET-CT imaging findings of NL, along with the patients' clinical characteristics.

Extrafollicular PD1 and Intrafollicular CD3 Expression Are Associated With Survival in Follicular Lymphoma.

Introduction: Both microenvironment and tumor biomarkers impact outcome in follicular lymphoma (FL). We aimed to study the effect of Ki-67, CD3, CD68, and PD1 expression on outcome of FL.

Materials And Methods: Forty-eight patients were included.

Ethnic variation in medical and lifestyle risk factors for B cell non-Hodgkin lymphoma: A case-control study among Israelis and Palestinians.

Background: Risk factors for B-cell non-Hodgkin lymphoma (B-NHL) have not been assessed among Palestinian Arabs (PA) and Israeli Jews (IJ).

Methods: In a case-control study we investigated self-reported medical and lifestyle exposures, reporting odds ratios (ORs) and 95% confidence intervals [CIs], by ethnicity, for overall B-NHL and subtypes.

Results: We recruited 823 cases and 808 healthy controls.