Post-transplantation cyclophosphamide and antithymocyte globulin in 8/10 HLA-mismatched unrelated donor transplantation: the analysis on behalf of the transplant complications working party of the EBMT.

Allogeneic hematopoietic cell transplantation (alloHCT) from 8/10 HLA-matched unrelated donor is performed in a minority of patients. There is little data on its outcomes and consequently, guidelines on optimal transplantation procedures are lacking. The Transplant complications working party of the EBMT performed a registry study comparing approaches to graft-versus-host disease (GVHD) prophylaxis in recipients of alloHCT from 8/10 HLA-mismatched unrelated donors (8/10 MMUD).

Selection of unrelated donors for allogeneic transplantation using post-transplant cyclophosphamide in acute lymphoblastic leukemia: An analysis by the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation.

Conflicting data exist on the impact of mismatched unrelated donor (MMUD) compared to matched unrelated donor (MUD) in hematopoietic cell transplantation (HCT) with post-transplant cyclophosphamide (PTCy), highlighting the need for disease-specific research. We conducted a retrospective analysis of donor characteristics in 350 patients with acute lymphoblastic leukemia (ALL) in complete remission (CR) who received 8/8 human leukocyte antigen (HLA)-matched MUD and 7/8 HLA-matched MMUD. The primary endpoint was leukemia-free survival (LFS).

Graft-versus-host disease is not associated with reduced incidence of relapse following haploidentical stem cell transplantation with post-transplant cyclophosphamide for acute lymphoblastic leukaemia: A study on behalf of the Acute Leukaemia Working Party of European Society for Blood and Marrow Transplantation.

The graft-versus-leukaemia effect (GVL) is closely associated with graft-versus-host disease (GVHD) after human leucocyte antigen (HLA)-matched allogeneic stem-cell transplantation (SCT) in acute lymphoblastic leukaemia (ALL). However, there are no data on this association following haploidentical SCT (haploSCT) with post-transplant cyclophosphamide (PTCy). We assessed the impact of acute and chronic GVHD on haploSCT outcomes in 516 adult ALL patients.

Impact of the addition of antithymocyte globulin to post-transplantation cyclophosphamide in haploidentical transplantation with peripheral blood compared to post-transplantation cyclophosphamide alone: A retrospective study on behalf of the Cellular Therapy and Immunobiology Working Party of the European Society for Blood and Marrow Transplantation.

In the setting of haploidentical haematopoietic cell transplantation (HCT), post-transplant cyclophosphamide (PTCy) has dramatically reduced the incidence of graft-versus-host disease (GVHD) and non-relapse mortality. To further reduce GVHD incidence, the addition of antithymocyte globulin (ATG) to PTCy was evaluated in retrospective and non-comparative prospective studies showing promising results. We conducted a large retrospective analysis of the European Society for Blood and Marrow Transplantation (EBMT) registry to evaluate this approach.

A peripherally inserted central catheter offers a secure and reliable method of venous access for patients newly diagnosed with acute promyelocytic leukaemia.

Introduction: Newly diagnosed acute promyelocytic leukaemia (APL) poses a significant bleeding risk. Current treatment guidelines advise against invasive procedures, such as central venous catheter placement. However, ensuring safe intravenous administration of both anti-leukaemic and supportive therapies is critical.

TGF-β Decreases NK Cell Mobility and Cytotoxic Efficacy in Complex in vitro Models of the Leukemia Microenvironment.

Background: Natural killer (NK) cell-based therapies represent a promising approach for acute myeloid leukemia (AML) relapse, yet their efficacy is hindered by immunosuppressive factors such as transforming growth factor beta (TGF-β) in the tumor microenvironment. This study investigated the effects of TGF-β on NK cell cytotoxicity and migration using 2D and 3D co-culture models that mimic the leukemic microenvironment.

Methods: TGF-β production was evaluated in AML-derived leukemic cell lines and mesenchymal stromal cells (hTERT-MSCs) using ELISA.

Donor impact on allogeneic transplant outcomes with PTCy for severe aplastic anemia: a study of the SAAWP EBMT.

The use of post-transplant cyclophosphamide (PTCy) for graft-versus-host disease (GVHD) prophylaxis in severe aplastic anemia (SAA) remains understudied, particularly beyond haploidentical transplants. We analyzed outcomes of SAA patients who underwent stem cell transplantation (SCT) with PTCy from haploidentical donors (n = 209), HLA-matched sibling donors (MSD, n = 70), and unrelated donors (UD, n = 69) using EBMT data from 2010 to 2022. Median age was 22 years, and median time to transplantation was 8.

Addition of mycophenolate mofetil to a calcineurin inhibitor and post-transplant cyclophosphamide results in lower incidence of extensive chronic graft-versus-host disease in HLA-matched allogeneic hematopoietic stem cell transplantation for acute myeloid leukemia in complete remission: a matched-pair analysis on behalf of the Acute Leukemia Working Party of the EBMT.

Whether one or two agents added to post-transplant cyclophosphamide (PTCy) are needed in HLA-matched allogeneic hematopoietic stem cell transplantation (allo-HSCT) with peripheral blood stem cells (PBSC) is debated. We retrospectively compared PTCy in association with a calcineurin inhibitor (PTCy+CNI) or with a CNI plus mycophenolate mofetil (PTCy+CNI+MMF) in adult patients transplanted for acute myeloid leukemia in first complete remission and receiving PBSC in the period from 2010 to 2020. Propensity score matching was performed using exact matching for donor type (related or unrelated) and the nearest neighbor for other variables (i.

Use of machine learning techniques to predict poor survival after hematopoietic cell transplantation for myelofibrosis.

With the incorporation of effective therapies for myelofibrosis (MF), accurately predicting outcomes after allogeneic hematopoietic cell transplantation (allo-HCT) is crucial for determining the optimal timing for this procedure. Using data from 5183 patients with MF who underwent first allo-HCT between 2005 and 2020 at European Society for Blood and Marrow Transplantation centers, we examined different machine learning (ML) models to predict overall survival after transplant. The cohort was divided into a training set (75%) and a test set (25%) for model validation.

Absence of pre-transplant T cell response against LAA is associated with Flt3-ITD mutation and increased relapse-risk in AML patients with HSCT.

Aims: This study aimed to examine changes in the repertoire of functional T-cells specific for six leukemia-associated antigens (LAA), including WT1, PRAME, MUC1, CCNA1, NPM1, and NPM1c, during immune reconstitution following allogeneic transplantation of hematopoietic stem cells (HSCT) in patients with acute myeloid leukemia.

Patients & Methods: LAA-specific T cell response was measured by ELISPOT- IFNγ and intracellular cytokine staining in 47 patients before starting conditioning therapy (baseline) and 7 months after HSCT.

Results: The positive cumulative LAA-specific T cell response before HSCT was associated with a decreased risk of relapse after HSCT.

The landscape of immune monitoring in CAR-T cell therapy: A comprehensive review and survey study by the Cellular Therapy and Immunobiology Working Party of the EBMT.

Immune monitoring of cell therapies is a complex and evolving topic, particularly in the rapid expanding field of chimeric antigen receptor T (CAR-T) cell applications. Defining essential, recommended, and optional immune monitoring data post-CAR-T cell infusion is crucial to improve patient outcomes and inform post-treatment decisions. To address this gap, we conducted a survey-based study across centers affiliated with the European Society for Blood and Marrow Transplantation (EBMT), focusing on patients treated with European Medicines Agency (EMA)-approved CAR-T products.

Cytogenetic and molecular risk-driven conditioning intensity in acute myeloid leukemia patients undergoing stem cell transplantation with post-transplant cyclophosphamide: a study from the acute leukemia working party of the EBMT.

We retrospectively analyzed the impact of conditioning intensity on transplant outcomes according to their cytogenetic/molecular risk in a cohort of 1823 patients with acute myeloid leukemia (AML) and intermediate- or adverse-risk cytogenetics in first complete remission (CR1). These patients received their first hematopoietic stem cell transplantation (HSCT) using post-transplant cyclophosphamide (PTCy). The intermediate-risk cytogenetic group included 1386 (76%) patients, and 608 (34%) had mutated FLT3-ITD.

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.

Interferon gamma release assay has potential in the prediction of chronic graft-versus-host disease in recipients of myeloablative allogeneic hematopoietic stem cell transplantation with post-transplantation cyclophosphamide-based graft-versus-host disease prophylaxis.

Background: The rate of immune reconstitution after allogeneic hematopoietic stem cell transplantation (allo-HSCT) plays the principal role in the development of serious post-transplant complications. However, the post-transplantation course has a significant impact on shaping the immune system of the recipient, per se, thus representing risk factors for subsequent unfavorable outcomes. The predictive power of an interferon gamma (IFNγ) release assay (IGRA) on graft-versus-host disease (GVHD) or hematological relapse in recipients of allo-HSCT treated with post-transplantation cyclophosphamide and the impact of these complications on the restoration of cellular immune responsiveness was evaluated.

Corrigendum: Good manufacturing practice-grade generation of CD19 and CD123-specific CAR-T cells using piggyBac transposon and allogeneic feeder cells in patients diagnosed with B-cell non-Hodgkin lymphoma and acute myeloid leukemia.

[This corrects the article DOI: 10.3389/fimmu.2024.

Several factors that predict the outcome of large B-cell lymphoma patients who relapse/progress after chimeric antigen receptor (CAR) T-cell therapy can be identified before cell administration.

Aim: The aim of this study was to analyse the outcomes of patients with large B-cell lymphoma (LBCL) treated with chimeric antigen receptor T-cell therapy (CAR-Tx), with a focus on outcomes after CAR T-cell failure, and to define the risk factors for rapid progression and further treatment.

Methods: We analysed 107 patients with LBCL from the Czech Republic and Slovakia who were treated in ≥3rd-line with tisagenlecleucel or axicabtagene ciloleucel between 2019 and 2022.

Results: The overall response rate (ORR) was 60%, with a 50% complete response (CR) rate.

Higher survival following transplantation with a mismatched unrelated donor with posttransplant cyclophosphamide-based graft-versus-host disease prophylaxis than with double unit umbilical cord blood in patients with acute myeloid leukemia in first complete remission: A study from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation.

The best donor option for acute myeloid leukemia (AML) patients lacking an HLA-matched donor has remained intensively debated. We herein report the results of a large retrospective registry study comparing hematopoietic cell transplantation (HCT) outcomes between double-unit umbilical cord blood transplantation (dCBT, n = 209) versus 9/10 HLA-matched unrelated donor (UD) with posttransplant cyclophosphamide (PTCy)-based graft-versus-host disease (GVHD) prophylaxis (UD 9/10, n = 270) in patients with AML in first complete remission (CR1). Inclusion criteria consisted of adult patient, AML in CR1 at transplantation, either peripheral blood stem cells (PBSC) from UD 9/10 with PTCy as GVHD prophylaxis or dCBT without PTCy, transplantation between 2013 and 2021, and no in vivo T-cell depletion.

Good manufacturing practice-grade generation of CD19 and CD123-specific CAR-T cells using piggyBac transposon and allogeneic feeder cells in patients diagnosed with B-cell non-Hodgkin lymphoma and acute myeloid leukemia.

Background: The non-viral production of CAR-T cells through electroporation of transposon DNA plasmids is an alternative approach to lentiviral/retroviral methods. This method is particularly suitable for early-phase clinical trials involving novel types of CAR-T cells. The primary disadvantage of non-viral methods is the lower production efficiency compared to viral-based methods, which becomes a limiting factor for CAR-T production, especially in chemotherapy-pretreated lymphopenic patients.

Young (<35 years) haploidentical versus old (≥35 years) mismatched unrelated donors and vice versa for allogeneic stem cell transplantation with post-transplant cyclophosphamide in patients with acute myeloid leukemia in first remission: a study on behalf of the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation.

We compared transplantation (HSCT) outcomes in AML patients undergoing HSCT with post-transplant cyclophosphamide (PTCy) in first complete remission from 1065 young (<35 years) haploidentical (Haplo) donors (yHaplo) vs. 147 old (≥35 years) mismatched unrelated donors (oMMUD) (first comparison) and from 271 young (<35 years) MMUD (yMMUD) vs. 1315 old (≥35 years) Haplo donors (oHaplo) (second comparison).

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.