Old Pathogens-New Patient Types: Infections in a CAR T-Cell Recipient. Could It Get Any More Complicated?

The case discussed involves a 41-year-old Italian man who was a candidate for chimeric antigen receptor T-cell therapy (CAR-T) for mediastinal diffuse large B-cell lymphoma. His CAR-T treatment was postponed several times due to prolonged relapsing COVID-19 and new onset of pulmonary Mycobacterium tuberculosis diseases. After 11 weeks of antimycobacterial treatment, CAR T-cell therapy was performed, but complicated by cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS).

Superior GVHD-Free, Relapse-Free Survival for Haploidentical Transplant With PTCy Than Matched Unrelated Donor for AML Patients Transplanted in Second Complete Remission: A Study From the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation.

Donor preference for acute myeloid leukemia (AML) patients transplanted in second complete remission (CR2) remains unclear, and hematopoietic cell transplantation (HCT) with post-transplant cyclophosphamide (PTCy) from a haploidentical donor (HAPLO) merits attention. Data of 3878 adult AML patients receiving a first allo-HCT in CR2 from the European Society of Blood and Marrow Transplantation registry between 2010 and 2022 were analyzed. Univariate analyses and Cox regression models were used.

Hemoadsorption as a Supportive Strategy for Severe Toxicity Associated With Chimeric Antigen Receptor T-Cell Therapy: A Case Series.

Rationale & Objective: To describe the use and effects of extracorporeal blood purification with hemoadsorption in managing severe complications after treatment with chimeric antigen receptor T-cells (CAR-T).

Study Design: Retrospective analysis of a case series.

Setting & Participants: Hematological department and intensive care unit from a single institution.

The Human Bone Marrow May Offer an IL-15-Dependent Survival Niche for EOMES Tr1-Like Cells.

Maintenance of memory T-cells in the bone marrow and systemically depends on the homeostatic cytokines IL-7 and IL-15. An immunological memory may also exist for regulatory T-cells. EOMEStype-1 regulatory (Tr1)-like cells have a rapid in vivo turnover, but whether they are short-lived effector cells or are maintained long-term has not been investigated.

Posttransplant cyclophosphamide as GVHD prophylaxis in patients receiving mismatched unrelated HCT: the PHYLOS trial.

Posttransplant high-dose cyclophosphamide (PTCy) is effective in overcoming the negative impact of HLA disparity in the haploidentical setting. In light of these results, we investigated the efficacy of PTCy, in improving clinical outcomes of hematopoietic stem cell transplantation (HSCT) from a mismatched unrelated donor (MMUD) in patients with acute myeloid malignancies by reducing the incidence and severity of acute graft-versus-host disease (aGVHD). A prospective, single-arm, phase 2 study (PHYLOS) was conducted by the Gruppo Italiano Trapianto di Midollo Osseo.

The impact of individual comorbidities in transplant recipients receiving post-transplant cyclophosphamide.

Post-transplant cyclophosphamide (PTCY) is increasingly used as effective graft-versus-host disease (GvHD) prophylaxis in allogeneic hematopoietic-cell transplantation (allo-HCT). However, PTCY is associated with toxicities. Whether patients with specific comorbidities are more vulnerable to cyclophosphamide-induced toxicity is unclear.

Pre-engraftment bloodstream infection after allogeneic haematopoietic cell transplant: 18-year trends in aetiology, resistance and mortality.

Bloodstream infections (BSI) are frequent complications after allogeneic hematopoietic cell transplant (HCT). This study reports data on pre-engraftment BSI in years 2016-2021 and analyses changes in incidence, aetiology, resistance and mortality compared with two previous periods (2004-2009 and 2010-2015). In years 2004-2021, 1364 patients received HCT.

Acute kidney injury in hematological patients treated with CAR-T cells: risk factors, clinical presentation and impact on outcomes.

Chimeric antigen receptor T-cell (CAR-T) therapy has revolutionized the treatment of hematologic malignancies, yet it carries significant risks, including acute kidney injury (AKI). In this study, we investigated the risk factors and clinical impact of AKI in patients undergoing CAR-T cell therapy. This retrospective study involved hematologic patients treated with CAR-T therapy.

Mycoplasma hominis as Cause of Extragenital Infection in Patients with Hypogammaglobulinemia: Report of 2 Cases and Literature Review.

Mycoplasma hominis can be a part of human urogenital tract microbiome, and it is a frequent cause of urogenital infections. In rare cases, it can also cause extragenital infections, especially in immunocompromised patients. In this case series, we report two cases and provide a literature review of extragenital infections caused by M.

Tacrolimus versus cyclosporine a combined with post-transplantation cyclophosphamide for AML In first complete remission: a study from the acute leukemia working party (EBMT).

Choice of calcineurin inhibitor may impact the outcome of patients undergoing T-cell replete hematopoietic cell transplantation (HCT) with post-transplant cyclophosphamide (PT-Cy) and mycophenolate mofetil (MMF) for prophylaxis of graft-versus-host disease (GVHD). We retrospectively analyzed 2427 patients with acute myeloid leukemia (AML) in first remission transplanted from a haploidentical (n = 1844) or unrelated donor (UD, n = 583) using cyclosporine A (CSA, 63%) or tacrolimus (TAC, 37%) and PT-Cy/MMF. In univariate analysis, CSA and TAC groups did not differ in 2-year leukemia-free or overall survival, cumulative incidence (CI) of relapse or non-relapse mortality.

Peripheral blood stem cell versus bone marrow graft for patients ≥60 years undergoing reduced intensity conditioning haploidentical transplantation for acute myeloid leukemia in complete remission: An analysis of the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation.

In the context of T-cell replete haploidentical stem cell transplantation (Haplo-SCT) using post-transplantation cyclophosphamide (PT-Cy), it is still unknown whether peripheral blood (PB) or bone marrow (BM) is the best graft source. While PB is associated with a higher incidence of graft-versus-host disease (GVHD), it may induce a stronger graft-versus-leukemia effect compared to BM, notably in acute myeloid leukemia (AML). From the EBMT registry database, we compared T-cell replete PB (n = 595) versus BM (n = 209) grafts in a large cohort of 804 patients over the age of 60 years who underwent Haplo-SCT with PT-Cy for an AML in first or second complete remission.

Early CAR CD4 T-lymphocytes recovery following CAR-T cell infusion: A worse outcome in diffuse large B cell lymphoma.

CAR CD4 T cell lymphopenia is an emerging issue following CAR-T cell therapy. We analyzed the determinants of CD4 T cell recovery and a possible association with survival in 31 consecutive patients treated with commercial CAR-T for diffuse large B-cell (DLBCL) or mantle cell lymphoma. Circulating immune subpopulations were characterized through multiparametric-flow cytometry.

Haploidentical transplantation in primary refractory/relapsed secondary vs de novo AML: from the ALWP/EBMT.

We compared the outcomes of haploidentical stem cell transplantation (haplo-HSCT) with posttransplant cyclophosphamide (PTCy) in 719 patients with primary refractory (PR) or first relapse (Rel) secondary acute myeloid leukemia (sAML; n = 129) vs those with de novo AML (n = 590), who received HSCT between 2010 and 2022. A higher percentage of patients with sAML vs de novo AML had PR disease (73.6% vs 58.

Lower blood levels of isavuconazole in critically ill patients compared with other populations: possible need for therapeutic drug monitoring.

Background: Isavuconazole is first-line treatment of invasive aspergillosis. Therapeutic drug monitoring (TDM) is deemed not necessary, since most patients reached therapeutic levels (>1 mg/L) in large studies. Low levels were reported in some critically ill patients admitted to the ICU.

Acute graft versus host disease 1976-2020: reduced incidence and predictive factors.

We studied the incidence of acute graft versus host disease (GvHD) and its outcome in three consecutive time frames (year <2000; 2000-2010; >2010), in 3,120 patients allografted in two transplant Centers between 1976 and 2020. The median age increased over the three periods from 32 to 42 to 54 years ( < 0.00001).

Adenovirus infection in adult patients undergoing allogeneic hematopoietic stem cell transplant: Incidence, clinical management, and outcome.

Background: Adenovirus infection (ADVi) is an emergent complication in adult patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) and is associated with poor outcome. Available data on risk factors and optimal management of ADVi in adult allo-HSCT recipients are limited, and recommendations on monitoring and pre-emptive therapy are mainly based on pediatric data.

Methods: In this single-center, retrospective study, we reported all cases of positive ADV-DNA from adult patients undergoing allo-HSCT in the period 2014-2019.

An aggressive form of MOGAD treated with aHSCT: A case report.

Background: Although myelin-oligodendrocyte-glycoprotein (MOG)-antibody-associated disease (MOGAD) has been considered a more favorable demyelinating central nervous system disorder, recent data evidence that some patients might experience severe relapses and high disability. Actual treatment-options are acquired mostly from anti-aquaporin-4-antibody-positive neuromyelitis optica spectrum disorder and rely on clinical experience. Therefore, treatment of aggressive forms of MOGAD can be challenging.

Cord blood transplantation for AML: Comparable LFS in patients with de novo versus secondary AML in CR1, an ALWP/EBMT study.

We investigated whether secondary versus de novo acute myeloid leukaemia (AML) would be associated with poor outcomes in adult acute AML patients in first complete remission (CR1) receiving unrelated cord blood transplantation (CBT). This is a retrospective study from the acute leukaemia working party of the European Society for Blood and Marrow Transplantation. Inclusion criteria included adult at first allogeneic haematopoietic cell transplantation between 2000 and 2021, unrelated single or double unit CBT, AML in CR1, no ex vivo T-cell depletion and no post-transplant cyclophosphamide.

Graft-versus-Host Disease Prophylaxis with Post- Transplantation Cyclophosphamide in Chronic Myeloid Leukemia Patients Undergoing Allogeneic Hematopoietic Cell Transplantation from an Unrelated or Mismatched Related Donor: A Comparative Study from the Chronic Malignancies Working Party of the EBMT (CMWP-EBMT).

Outcomes following allogeneic hematopoietic cell transplantation (allo-HCT) for chronic myeloid leukemia (CML) with post-transplantation cyclophosphamide (PTCy) using an unrelated donor (UD) or a mismatched related donor (MMRD) remain unknown. We report a retrospective comparison of PTCy-based allo-HCT from a UD, non-PTCy allo-HCT from a UD, and PTCy allo-HCT from an MMRD. Inclusion criteria were adult patients with CML undergoing first allo-HCT between 2012 and 2019 from a UD with either PTCy or non-PTCy graft-versus-host disease (GVHD) prophylaxis or from an MMRD using PTCy.

Brain FDG-PET findings in chimeric antigen receptor T-cell therapy neurotoxicity for diffuse large B-cell lymphoma.

Background And Purpose: Chimeric antigen receptor (CAR) T-cell therapy is potentially associated with treatment-related toxicities mainly consisting of cytokine release syndrome (CRS) and immune-effector cell-associated neurotoxicity syndrome (ICANS). We evaluated brain metabolic correlates of CRS with and without ICANS in diffuse large B-cell lymphoma patients treated with CAR-T.

Methods: Twenty-one refractory DLCBLs underwent whole-body and brain [ F]-fluorodeoxyglucose (FDG) PET before and 30 days after treatment with CAR-T.