Young unrelated donors confer a survival advantage for patients with myeloid malignancies compared to older siblings.

Donor age is one factor to optimize allogeneic hematopoietic cell transplantation (alloHCT). Therefore, we investigated whether young unrelated donors (UD) provide a benefit for older patients with myeloid malignancies compared to HLA-identical sibling donors (MSD). We performed a retrospective registry study on patients ≥50 years who received a first alloHCT between 2010 and 2020.

Outcomes following different upfront stem cell transplantation strategies for multiple myeloma: a statistical perspective on behalf of the Chronic Malignancies Working Party of the EBMT.

Multiple myeloma (MM) is a heterogenous malignant disease. Novel agents including bispecific antibodies and chimeric antigen receptor (CAR) T cells have improved response rates and patient outcome, but the majority of patients ultimately still relapse. High dose chemotherapy followed by autologous hematopoietic stem cell transplantation (auto-HCT) remains standard care of treatment for transplant-eligible patients.

Disease risk but not remission status determines transplant outcomes in AML: long-term outcomes of the ASAP trial.

Attempting to induce a complete remission (CR) prior to allogeneic hematopoietic cell transplantation (alloHCT) is current practice in patients with AML. A benefit of remission induction prior to alloHCT, however, has never been proven in a prospective trial. Potent conditioning regimens exist which allow for successful alloHCT in patients with active AML.

Impact of transplant conditioning, NPM1 mutations, and measurable residual disease in FLT3-ITD acute myeloid leukemia.

We conducted a post-hoc analysis of data from BMT CTN 1506 (MORPHO), a randomized trial of gilteritinib versus placebo as post-transplantation maintenance for patients with FLT3-ITD-mutated acute myeloid leukemia (AML) undergoing allogeneic hematopoietic cell transplantation (HCT), focusing the interactions between conditioning regimen intensity, measurable residual disease (MRD), and NPM1 co-mutation status reported from diagnosis. Comparing FLT3-ITD MRD before and after conditioning, there was no difference between myeloablative conditioning (MAC) and reduced intensity conditioning (RIC) in eradication or reduction of FLT3-ITD MRD. For participants who were FLT3-ITD MRD-negative pre-HCT, there was no difference in the cumulative incidence of relapse during follow-up between those receiving MAC versus RIC.

The CXCL16/CXCR6 axis is linked to immune effector cell-associated neurotoxicity in chimeric antigen receptor (CAR) T cell therapy.

Background: Immune effector cell-associated neurotoxicity syndrome (ICANS) is a common and potentially life-threatening complication of chimeric antigen receptor (CAR) T cell therapy. The underlying mechanisms of ICANS remain incompletely understood and are unlikely to be explained by cytokine excess alone.

Methods: We analyzed paired peripheral blood and cerebrospinal fluid (CSF) samples from CAR T cell-treated patients who developed ICANS (n = 11) within 5-21 days post-infusion.

High-Dose Melphalan Followed by Busulfan and Fludarabine Conditioning Prior to Allogeneic Stem Cell Transplantation in Elderly Patients with Active Acute Myeloid Leukemia-A Retrospective Single-Center Study.

In patients with relapsed or refractory (r/r) acute myeloid leukemia (AML), long-term survival in most cases can only be achieved with allogeneic hematopoietic stem cell transplantation. The introduction of sequential conditioning regimens has contributed to the steadily improving prognosis of r/r AML patients. As most studies mainly included younger patients, feasibility of sequential conditioning in elderly or comorbid patients remains subject of debate.

Prognostic significance of cytogenetic risk score in patients with secondary acute myeloid leukemia undergoing allogeneic stem cell transplantation from HLA-matched unrelated donors: a study from the ALWP /EBMT.

The cytogenetic risk category retains a pivotal role in the prediction of prognosis in acute myeloid leukemia (AML) patients undergoing hematopoietic stem cell transplantation (HSCT), however, its impact on secondary AML (sAML) is less established. We assessed whether the ELN 2022 cytogenetic risk score predicts outcomes in sAML patients in remission undergoing HSCT from HLA-matched donors performed between 2010 and 2022. Among 1119 patients, 829 had intermediate and 284 had adverse cytogenetics (6 with favorable risk were excluded).

Efficacy and safety of CAR T-cell therapy in patients with primary or secondary CNS lymphoma: A study on behalf of the EBMT and the GoCART coalition.

Patients with relapsed or refractory (r/r) primary central nervous system (CNS) lymphoma (PCNSL) or secondary central nervous system (CNS) lymphoma (SCNSL) face a dismal prognosis. They have been excluded from most clinical CAR T-cell trials as investigators feared an increased risk for severe immune effector cell-associated neurotoxicity (ICANS). To investigate the potential of anti-CD19 CAR T-cell therapy (CART) in such patients, we analyzed data of 100 patients with CNS manifestation treated with CART between January 2018 and July 2023 and reported to European Society for Blood and Marrow Transplantation.

Allogeneic stem cell transplantation in de novo core-binding factor acute myeloid leukemia in active disease: a study from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation.

Core-binding factor acute myeloid leukemia (CBF-AML) generally has a favorable prognosis, with allogeneic hematopoietic stem cell transplantation (allo-SCT) recommended for relapsed/ refractory (R/R) cases achieving second complete remission (CR). However, clinical outcomes remain suboptimal for patients who relapse or fail to achieve CR following induction chemotherapy. Allo-SCT in non-CR is a potential strategy for such patients, though supporting evidence in CBF-AML is limited.

Outcome of Patients With IDH-Mutated AML Following Allogeneic Stem Cell Transplantation-A Retrospective Analysis on Behalf of the German Registry for Hematopoietic Stem Cell Transplantation and Cell Therapy, DRST.

Mutations in isocitrate dehydrogenase 1 and 2 genes (IDH1 and IDH2) are found in 15% to 20% of patients with acute myeloid leukemia (AML). IDH inhibitors have been introduced as targeted treatment and are currently under investigation as maintenance therapy after allogeneic transplantation (allo-SCT). Since reports about the outcome of IDH1- and IDH2-mutated (IDHmut) AML after allo-SCT are limited, we retrospectively analyzed 356 IDH-mutated AML patients (IDH1 40%, IDH2 60%).

Inotuzumab Ozogamicin as First-Line Therapy in Acute Lymphoblastic Leukemia.

The long-term outcome of older patients with acute lymphoblastic leukemia (ALL) is poor due to a reduced ability to tolerate intensive chemotherapy, a more aggressive disease biology, and the presence of comorbidities. Older adults with Philadelphia chromosome-negative (Ph-) B-cell ALL have the highest rates of treatment failure and complications, and the pediatric-inspired regimens that are effective in younger adults are severely limited by their toxicity in older patients. Targeted therapies, including inotuzumab ozogamicin (InO) and blinatumomab, have potent activity in B-cell ALL and are used today as single agents, and in combination with chemotherapy in both salvage and frontline ALL therapy.

Common hereditary variants of the APOE gene and posttransplant outcome in acute myeloid leukemia.

Apolipoprotein E (APOE) has multiple functions in metabolism and immunoregulation. Its common germ line variants APOE2, APOE3, and APOE4 give rise to 3 functionally distinct gene products. Previous studies reported yin-yang roles of APOE2 and APOE4 in immunological processes, but their effects in hematopoietic stem cell transplantation (HSCT) have never been studied.

Characterizing the ideal patient for treatment with inotuzumab ozogamicin for relapsed/refractory acute lymphoblastic leukemia: a systematic literature review.

Introduction: Inotuzumab ozogamicin (InO) is indicated for the treatment of adults with relapsed or refractory (R/R) acute lymphoblastic leukemia (ALL). This systematic literature review (CRD42022330496) assessed outcomes by baseline characteristics for patients with R/R ALL treated with InO to identify which patients may benefit most.

Methods: In adherence with PRISMA guidelines, searches were run in Embase and MEDLINE.

Measurable residual disease and posttransplantation gilteritinib maintenance for patients with FLT3-ITD-mutated AML.

BMT CTN (Blood and Marrow Transplant Clinical Trials Network) 1506 ("MORPHO") was a randomized study of gilteritinib compared with placebo as maintenance therapy after hematopoietic cell transplantation (HCT) for patients with FLT3-ITD-mutated acute myeloid leukemia (AML). A key secondary end point was to determine the impact on survival of before and/or after HCT measurable residual disease (MRD), as determined using a highly sensitive assay for FLT3-ITD mutations. Generally, gilteritinib maintenance therapy was associated with improved relapse-free survival (RFS) for participants with detectable peri-HCT MRD, whereas no benefit was evident for those lacking detectable MRD.

Comparison of fludarabine/melphalan (FM140) with fludarabine/melphalan/BCNU (FBM110) in patients with relapsed/refractory AML undergoing allogeneic hematopoietic cell transplantation - a registry study on behalf of the EBMT Acute Leukemia Working Party.

The treatment of relapsed/refractory acute myeloid leukemia (AML) is associated with a dismal prognosis. The allogeneic hematopoietic cell transplantation (allo-HCT) is frequently performed as salvage therapy. Reduced intensity conditioning protocols have been developed with the aim of reducing the leukemia burden without increasing their toxicity.

Ph- ALL: immunotherapy in upfront treatment.

Antibody-based and cell-based novel immunotherapies, such as bispecific T-cell engagers (BiTE), antibody-drug conjugates, or chimeric antigen receptor (CAR) T cells are currently standard treatment options for patients with relapsed or refractory (R/R) B-cell precursor acute lymphoblastic leukemia (ALL). To date, CD20-targeting monoclonal antibodies and the CD19-targeting BiTE's blinatumomab have been established elements of frontline therapy, either in patients with CD20+ ALL or in patients with measurable disease (MRD) following conventional chemotherapy. Recently, blinatumomab has also demonstrated a survival benefit in patients with MRD-negative ALL.

Does size matter? Center-specific characteristics and survival after allogeneic hematopoietic cell transplantation for acute myeloid leukemia: an analysis of the German Registry for Stem Cell Transplantation and Cell Therapy.

We investigated the effect of center-specific variables on overall survival (OS) after allogeneic hematopoietic cell transplantation (alloHCT) in acute myeloid leukemia (AML). Eligible for the study were adult patients reported to the German Registry for Hematopoietic Stem Cell Transplantation and Cell Therapy (DRST) receiving first alloHCT for AML from a related or matched (>9/10 HLA-match) unrelated donor in the period 2015-2021. Primary endpoint was OS at 12 months from alloHCT.