At-Home Care Program for Acute Myeloid Leukemia Induction Phase in Patients Treated with Venetoclax-Based Low-Intensity Regimens.

Even though venetoclax in combination with azacitidine (VenAza) is considered a low-intensity regimen, its patients present a high incidence of cytopenia and infections during the first courses, making the initial management a challenging phase. This difficulty in our center led to the establishment of an At-Home (AH) program for ramp-up and follow-up patients during the VenAza combination induction phase focused on therapy administration, patient and caregiver education, and management of adverse events (AEs). A total of 70 patients with newly diagnosed acute myeloid leukemia (ND-AML) or relapsed/refractory AML (R/R AML) were treated with VenAza from March 2019 to May 2022.

Neurological manifestations of MGUS.

Monoclonal gammopathy of undetermined significance (MGUS) is a highly prevalent disorder characterized by a small bone marrow plasma cell or lymphoplasmacytic clone (less than 10%) that produces a small amount of monoclonal paraprotein without associated organ damage. Most patients with MGUS display benign behavior indefinitely, but some progress to an overt malignancy, and others develop organ damage despite no increase in monoclonal protein, resulting in the so-called MG of clinical significance (MGCS). This concept includes different disorders depending on the organ involved, and among them, MG of neurological significance (MGNS) constitutes a real challenge from both a diagnostic and therapeutic point of view.

Genetic Disruption of Blimp-1 Drastically Augments the Antitumor Efficacy of BCMA-Targeting CAR-T Cells.

Chimeric antigen receptor-T (CAR-T) cells directed against B-cell maturation antigen (BCMA) are an effective treatment for multiple myeloma (MM), but short persistence and frequent relapses are challenges for this immunotherapy. This lack of durability has been attributed to the premature terminal differentiation of CAR-T cells which prevents the formation of long-lived memory cells that maintain anti-tumour responses. To improve long-term efficacy, we used CRISPR/Cas9-mediated gene editing to ablate the expression of the transcription factor Blimp-1.

Clinical impact of [18F]FDG-PET/CT in ARI0002h treatment, a CAR-T against BCMA for relapsed/refractory multiple myeloma.

Multiple myeloma (MM) remains incurable, with poor outcomes in heavily pre-treated patients with plasmacytomas. Chimeric antigen receptor (CAR) T-cell therapy has emerged as a promising treatment option; however, outcomes after such therapy in patients with soft-tissue plasmacytomas and other bone lesions remain poorly understood. Data regarding these parameters is scarce within the specific context of CAR T-cell treatment.

Reduced Dose of Post-Transplant Cyclophosphamide with Tacrolimus for the Prevention of Graft-versus-Host Disease in HLA-Matched Donor Peripheral Blood Stem Cell Transplants: A Prospective Pilot Study.

PTCY 50 mg/kg/day on days +3/+4 is an excellent strategy to prevent GVHD. However, its use is associated with adverse outcomes such as delayed engraftment, increased risk of infection, and cardiac complications. This pilot study evaluates the efficacy and toxicity of a reduced dose of PTCY (40 mg/kg/day) combined with tacrolimus in 22 peripheral blood HLA-matched alloHSCT patients.

The evolving pattern of the monoclonal protein improves the IMWG 2/20/20 classification for patients with smoldering multiple myeloma.

The 2/20/20 International Myeloma Working Group (IMWG) score is the most employed risk score in clinical practice to evaluate the risk of progression from smoldering multiple myeloma (SMM) to symptomatic multiple myeloma. However, it faces a serious limitation: The risk score is applied at diagnosis and cannot be reapplied. Since a dynamic accurate patient risk assessment for progression is necessary, we aimed to investigate whether the detection of an evolving pattern in serum M-protein (SMP) improves the identification of high-risk patients.

EASIX and cardiac adverse events after allogeneic hematopoietic cell transplantation.

This study investigates the interaction between endothelial activation, indirectly measured using EASIX, and the probability of presenting cardiac adverse events (CAE) during the first year after allo-HCT. The 437 consecutive adults undergoing PB allo-HCT from 2012 and 2021 were included. EASIX was retrospectively calculated before and during the first 6 months after allo-HCT and transformed to log2-base to conduct the statistical analysis.

Biomarkers of Efficacy and Safety of the Academic BCMA-CART ARI0002h for the Treatment of Refractory Multiple Myeloma.

Purpose: B-cell maturation antigen (BCMA)-chimeric antigen receptor T-cells (CART) improve results obtained with conventional therapy in the treatment of relapsed/refractory multiple myeloma. However, the high demand and expensive costs associated with CART therapy might prove unsustainable for health systems. Academic CARTs could potentially overcome these issues.

At-Home Foscarnet Administration in Patients with Cytomegalovirus Infection Post-Allogeneic Stem Cell Transplantation: A Unicentric, Safe, and Feasible Program.

Cytomegalovirus (CMV) infection is a relevant cause of morbimortality in patients receiving allogeneic stem cell transplantation (allo-HCT). Foscarnet (FCN) is an effective drug against CMV administered intravenously and usually on an inpatient basis. The Home Care Unit (HCU) for hematologic patients at our hospital designed an at-home FCN administration model to avoid the hospitalization of patients requiring FCN treatment.

Post-Transplantation Cyclophosphamide and Tacrolimus for Graft-versus-Host Disease Prevention after Allogeneic Hematopoietic Cell Transplantation from HLA-Matched Donors Has More Advantages Than Limitations.

This study compared the efficacy of graft-versus-host disease (GVHD) prophylaxis with post-transplantation cyclophosphamide (PTCy) and tacrolimus (Tac) versus other regimens in 272 adults undergoing peripheral blood (PB) allogeneic hematopoietic cell transplantation (allo-HCT) from HLA-matched donors. Of these 272 patients, 95 (34.9%) received PTCy/Tac.

Easix Score Correlates With Endothelial Dysfunction Biomarkers and Predicts Risk of Acute Graft-Versus-Host Disease After Allogeneic Transplantation.

Plasma biomarkers of endothelial dysfunction have been postulated for the diagnosis and prognosis of acute graft-versus-host disease (aGVHD). However, their use is not validated in clinical practice yet. The endothelial activation and stress index (EASIX), a simple score based on routine laboratory parameters, is considered to be an indirect marker of endothelial damage.

Outcomes of Patients with Newly Diagnosed Transplant-Ineligible Multiple Myeloma According to Clinical Trials Enrollment: Experience of a Single Institution.

The proportion of non-transplant-eligible (NTE) newly diagnosed multiple myeloma (NDMM) patients excluded from clinical trials (CTs) and their prognosis is unknown. CT results may not be generalizable to real-world practice due to strict recruitment criteria. We analyzed causes of NTE-NDMM patient exclusion form CTs and their outcomes.

Endothelial Activation and Stress Index in adults undergoing allogeneic hematopoietic cell transplantation with post-transplant cyclophosphamide-based prophylaxis.

Background Aims: Post-transplant cyclophosphamide (PTCY)-based prophylaxis is becoming widespread for allogeneic hematopoietic cell transplantation (allo-HCT) performed independently of the selected donor source. In parallel, use of the Endothelial Activation and Stress Index (EASIX)-considered a surrogate parameter of endothelial activation-for predicting patient outcomes and clinical complications is gaining popularity in the allo-HCT setting.

Methods: We first investigated whether the dynamics of EASIX after allo-HCT differ between patients receiving PTCY and patients receiving other prophylaxis.

The academic point-of-care anti-CD19 chimeric antigen receptor T-cell product varnimcabtagene autoleucel (ARI-0001 cells) shows efficacy and safety in the treatment of relapsed/refractory B-cell non-Hodgkin lymphoma.

Varnimcabtagene autoleucel (var-cel) is an academic anti-CD19 chimeric antigen receptor (CAR) product used for the treatment of non-Hodgkin lymphoma (NHL) in the CART19-BE-01 trial. Here we report updated outcomes of patients with NHL treated with var-cel. B-cell recovery was compared with patients with acute lymphoblastic leukaemia (ALL).

Applicability and validation of different prognostic scores in allogeneic hematopoietic cell transplant (HCT) in the post-transplant cyclophosphamide era.

We investigated the predictive capacity of six prognostic indices [Karnofsky Performance Status (KPS), Hematopoietic Cell Transplant-Specific Comorbidity Index (HCT-CI), Disease Risk Index (DRI), European Bone Marrow Transplantation (EBMT) and Revised Pre-Transplantation Assessment of Mortality (rPAM) Scores and Endothelial Activation and Stress Index (EASIX)] in 205 adults undergoing post-transplant cyclophosphamide (PTCy)-based allo-HCT. KPS, HCT-CI, DRI and EASIX grouped patients into higher and lower risk strata. KPS and EASIX maintained appropriate discrimination for OS prediction across the first 2 years after allo-HCT [receiver operating characteristic curve (area under the curve (AUC) > 55 %)].

Fractionated initial infusion and booster dose of ARI0002h, a humanised, BCMA-directed CAR T-cell therapy, for patients with relapsed or refractory multiple myeloma (CARTBCMA-HCB-01): a single-arm, multicentre, academic pilot study.

Background: Chimeric antigen receptor (CAR) T-cell therapy is a promising option for patients with heavily treated multiple myeloma. Point-of-care manufacturing can increase the availability of these treatments worldwide. We aimed to assess the safety and activity of ARI0002h, a BCMA-targeted CAR T-cell therapy developed by academia, in patients with relapsed or refractory multiple myeloma.

All-trans retinoic acid works synergistically with the γ-secretase inhibitor crenigacestat to augment BCMA on multiple myeloma and the efficacy of BCMA-CAR T cells.

B-cell maturation antigen (BCMA) is the lead antigen for chimeric antigen receptor (CAR) T-cell therapy in multiple myeloma (MM). A challenge is inter- and intra-patient heterogeneity in BCMA expression on MM cells and BCMA downmodulation under therapeutic pressure. Accordingly, there is a desire to augment and sustain BCMA expression on MM cells in patients that receive BCMA-CAR T-cell therapy.

Effect of CD34 Cell Dose on the Outcomes of Allogeneic Stem Cell Transplantation with Post-Transplantation Cyclophosphamide.

The impact of infused CD34 cell dose on outcomes after allogeneic hematopoietic stem cell transplantation (alloHSCT) using standard graft-versus-host disease (GVHD) prophylaxis remains controversial. Information on this subject is scarce for alloHSCT using high-dose post-transplantation cyclophosphamide (PTCy). We aimed to assess the effect of CD34 cell dose in peripheral blood stem cell (PBSC) grafts on the outcome of alloHSCT using PTCy-based GVHD prophylaxis.

Incidence, risk factors, and impact of early cardiac toxicity after allogeneic hematopoietic cell transplant.

This study investigates early cardiac events (ECEs) occurring during the first 180 days after allogeneic hematopoietic cell transplant (allo-HCT) in 416 adults receiving posttransplant cyclophosphamide (PTCY) (n = 258) or not receiving PTCY (n = 158). Total body irradiation (TBI) was given to 133 (31.9%) patients, of whom 111 (83.

Prognostic impact of MYD88 and CXCR4 mutations assessed by droplet digital polymerase chain reaction in IgM monoclonal gammopathy of undetermined significance and smouldering Waldenström macroglobulinaemia.

Waldenström macroglobulinaemia (WM) is characterized by recurrent somatic mutations in MYD88 and CXCR4 genes. However, limitations arise when analysing these mutations in IgM monoclonal gammopathy of undetermined significance (MGUS) or smouldering WM (SWM) given the lower tumour load. Here, we used droplet digital polymerase chain reaction (ddPCR) to analyse MYD88 L265P and CXCR4 S338* mutations (C1013G and C1013A) in unsorted bone marrow (BM) or cell-free DNA (cfDNA) samples from 101 IgM MGUS and 69 SWM patients.

Paraskeletal and extramedullary plasmacytomas in multiple myeloma at diagnosis and at first relapse: 50-years of experience from an academic institution.

From January 1970 to December 2018, 1304 patients were diagnosed with multiple myeloma (MM) at our institution and 256 (19.6%) had plasmacytomas (Ps) (paraskeletal -PPs- 17.6%, extramedullary -EMPs-1.

Long-Term Responders After Autologous Stem Cell Transplantation in Multiple Myeloma.

Introduction: Multiple myeloma (MM) is considered an incurable hematological neoplasm. For transplant-eligible patients, initial treatment includes an induction phase followed by an autologous stem cell transplantation (ASCT). Despite the introduction of several drugs in the past years, relapses still occur.