0000000000342441
AUTHOR
Wolfgang Bethge
Predicted Indirectly reCognizable HLA epitopes (PIRCHE) are associated with poorer outcome after single mismatch unrelated donor stem cell transplantation: a study of the Cooperative Transplant Study Group (KTS) of the German Group for Bone Marrow and Stem Cell Transplantation (DAG-KBT)
There is no established standard for selection of mismatched unrelated donors. Indirect recognition of HLA mismatches can be predicted using the model of “Predicted Indirectly ReCognizable HLA Epitopes” (PIRCHE). We performed a multicenter retrospective study evaluating the impact PIRCHE on outcome after allogeneic stem cell transplantation (allo-HSCT) from single mismatched (HLA 9/10 matched) unrelated donors. The study cohort included 424 adult recipients of HLA 9/10 matched unrelated donor transplants (9/10 MUD), treated for AML or MDS at 6 transplant centers across Germany. Detection of PIRCHE was associated with lower overall survival (OS) (47 vs. 57%, <i>p</i> = 0.04), hig…
GVHD prophylaxis plus ATLG after myeloablative allogeneic haemopoietic peripheral blood stem-cell transplantation from HLA-identical siblings in patients with acute leukaemia in remission: final results of quality of life and long-term outcome analysis of a phase 3 randomised study
Summary Background We previously showed that human anti-T-lymphocyte globulin (ATLG) plus ciclosporin and methotrexate given to patients with acute leukaemia in remission, having allogeneic haemopoietic stem-cell transplantation with peripheral blood stem cells from an HLA-identical sibling donor after myeloablative conditioning, significantly reduced 2-year chronic graft-versus-host disease (cGVHD) incidence and severity, without increasing disease relapse and infections, and improves cGVHD-free and relapse-free survival (cGRFS). The aim of an extended follow-up study was the assessment of long-term outcomes, which are, in this context, scarcely reported in the literature. We report unpubl…
Late Non-Relapse Mortality (NRM) after Standard-of-Care (SOC) CAR-T Cell Therapy for Large B-Cell Lymphoma (LBCL): Frequency, Causes, and Risk Factors.a GLA/DRST Real World Analysis
Abstract Introduction Although the labeled CD19 targeting CAR-T cell constructs axi-cel and tisa-cel are generally associated with an acceptable safety profile, non-relapse deaths can occur. Little is known about timing, causes and predictors of NRM following SOC CAR-T cell therapy for LBCL. Here, we analyzed frequency, causes, and risk factors of non-relapse deaths with focus on late NRM (beyond 4 weeks after dosing) using registry data provided by the DRST, the national partner of the EBMT. Methods Patients were selected from 356 consecutive patients who received SOC CAR-T treatment of LBCL between November 2018 and April 2021 at 21 German centers and were registered with the DRST/EBMT. B…
Relevance of the Hematopoietic Cell Transplantation-Specific Comorbidity Index (HCT-CI) On Non-Relapse Related Mortality (NRM) in Patients with Acute Lymphoblastic Leukemia (ALL) Receiving Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) in First Complete Remission: Results From the GMALL Study Group.
Abstract Abstract 3352 Poster Board III-240 Allogeneic HSCT is established as a potent curative therapy in adult patients with high risk ALL. However, due to transplant-related morbidity and lethality the gains in relapse prevention do not necessarily translate into survival advantages in the overall patient population. Defining the role of allogeneic HSCT in ALL patients in first complete remission (CR1) according to leukemia related risk factors, to transplant related risk factors (e.g. HLA matching, conditioning therapy and immunosuppressive treatment), and to comorbidity related risks, remains a major task for upcoming clinical trials. Several retrospective studies suggest that the HCT-…
Impact of Donor-Recipient Histocompatibility and CMV-Mismatch on Outcome of Allogeneic Stem Cell Transplantation for AML and MDS: A Retrospective Registry Study of the German Stem Cell Transplant Registry (DRST) of the German Working Group for Blood and Marrow Transplantation (DAG-KBT)
Abstract Introduction Allogeneic stem cell transplantation (allo-SCT) is a curative treatment for several hematological diseases. Donor-recipient histo-incompatibility is associated with poorer outcome. Transplant outcome of CMV positive patients is reported to be poorer, if the unrelated donor is CMV negative (CMV-mismatch). Recent developments in transplant strategies including high resolution HLA-typing, toxicity-reduced conditioning regimens, CMV-monitoring, and improved supportive care have made transplants from HLA- as well as CMV- mismatched unrelated donors more feasible. We present a retrospective registry analysis from a large, and recent cohort of patients transplanted under thes…
Relative Impact of HLA Matching and Non-HLA Donor Characteristics on Outcomes of Allogeneic Stem Cell Transplantation for Acute Myeloid Leukemia and Myelodysplastic Syndrome
Increasing donor-recipient HLA disparity is associated with negative outcomes of allogeneic hematopoietic stem cell transplantation (HSCT), but its comparative relevance amid non-HLA donor characteristics is not well established. We addressed this question in 3215 HSCTs performed between 2005 and 2013 in Germany for acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). Donors were HLA-matched related (MRD; n = 872) or unrelated (10/10 MUD, n = 1553) or HLA-mismatched unrelated (10/10 MMUD, n = 790). Overall survival (OS) was similar after MRD compared with 10/10 MUD HSCT, reflecting opposing hazards of relapse (hazard ratio [HR], 1.32; P.002) and nonrelapse mortality (HR, .63; P.0…
Treosulfan or busulfan plus fludarabine as conditioning treatment before allogeneic haemopoietic stem cell transplantation for older patients with acute myeloid leukaemia or myelodysplastic syndrome (MC-FludT.14/L): a randomised, non-inferiority, phase 3 trial
Background: Further improvement of preparative regimens before allogeneic haemopoietic stem cell transplantation (HSCT) is an unmet medical need for the growing number of older or comorbid patients with acute myeloid leukaemia or myelodysplastic syndrome. We aimed to evaluate the efficacy and safety of conditioning with treosulfan plus fludarabine compared with reduced-intensity busulfan plus fludarabine in this population. Methods: We did an open-label, randomised, non-inferiority, phase 3 trial in 31 transplantation centres in France, Germany, Hungary, Italy, and Poland. Eligible patients were 18–70 years, had acute myeloid leukaemia in first or consecutive complete haematological remissi…
Sorafenib maintenance after allogeneic hematopoietic stem cell transplantation for acute myeloid leukemia with FLT3-internal tandem duplication mutation (SORMAIN).
PURPOSE Despite undergoing allogeneic hematopoietic stem cell transplantation (HCT), patients with acute myeloid leukemia (AML) with internal tandem duplication mutation in the FMS-like tyrosine kinase 3 gene ( FLT3-ITD) have a poor prognosis, frequently relapse, and die as a result of AML. It is currently unknown whether a maintenance therapy using FLT3 inhibitors, such as the multitargeted tyrosine kinase inhibitor sorafenib, improves outcome after HCT. PATIENTS AND METHODS In a randomized, placebo-controlled, double-blind phase II trial (SORMAIN; German Clinical Trials Register: DRKS00000591), 83 adult patients with FLT3-ITD–positive AML in complete hematologic remission after HCT were r…
Evaluation of six different types of sequential conditioning regimens for allogeneic stem cell transplantation in relapsed/refractory acute myelogenous leukemia – a study of the Acute Leukemia Working Party of the EBMT
The Acute Leukemia Working Party (ALWP) of the EBMT assessed the outcome of allogeneic stem cell transplantation (alloSCT) in patients with relapsed/refractory AML (r/rAML) evaluating six sequential conditioning regimens (SR) groups. A total of 2132 patients were included. LFS at 2 years was 28.9%, 33.6%, 35.3%, 20.6%, 24.4%, and 27% for the FLAMSA-TBI4, FLAMSA-Chemo, Mel-Flu-TBI8, Mel-Treo-Flu, Thio-ETO-Cy-Bu2-Flu, and Clo-ARAC-(Bu2/TBI4)-Cy groups, respectively. In patients55 years of age Mel-Flu-TBI8 had the best LFS, which was statistically significant only in comparison to the Mel-Treo-Flu group, while in patients ≥55 years LFS was best with FLAMSA-Chemo without significant differences…
Chronic graft-versus-host disease: long-term results from a randomized trial on graft-versus-host disease prophylaxis with or without anti-T-cell globulin ATG-Fresenius.
Abstract Previous randomized graft-versus-host disease (GVHD)-prophylaxis trials have failed to demonstrate reduced incidence and severity of chronic GVHD (cGVHD). Here we reanalyzed and updated a randomized phase 3 trial comparing standard GVHD prophylaxis with or without pretransplantation ATG-Fresenius (ATG-F) in 201 adult patients receiving myeloablative conditioning before transplantation from unrelated donors. The cumulative incidence of extensive cGVHD after 3 years was 12.2% in the ATG-F group versus 45.0% in the control group (P < .0001). The 3-year cumulative incidence of relapse and of nonrelapse mortality was 32.6% and 19.4% in the ATG-F group and 28.2% and 33.5% in the contr…
Allogeneic stem cell transplantation after conditioning with treosulfan, etoposide and cyclophosphamide for patients with acute lymphoblastic leukemia (ALL) not eligible for TBI-containing regimens: a phase II-Study on behalf of the German ALL Study Group (GMALL) and the German Cooperative Transplant Study Group
Abstract Total-body-irradiation (TBI) based preparative regimens are considered as standard conditioning therapy for allogeneic stem cell transplantation (AHSC) in patients with acute lymphoblastic leukemia (ALL). Within a multi-center prospective phase II study we have investigated the toxicity and efficacy of a non-TBI-based regimen consisting of treosulfan, etoposide, and cyclophosphamide in patients with ALL. Inclusion criteria were complete remission, non-eligibility for TBI or patient’s wish to avoid TBI. Between July 2007 and August 2010, 50 patients with a median age of 46.5 years were enrolled at ten German centers. 74% of the patients were in 1. CR and 26% 2. or higher CR.The cond…
Antilymphocyte Globulin for Prevention of Chronic Graft-versus-Host Disease.
Clinical Trial, Phase III; Journal Article; Multicenter Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't; BACKGROUND Chronic graft-versus-host disease (GVHD) is the leading cause of later illness and death after allogeneic hematopoietic stem-cell transplantation. We hypothesized that the inclusion of antihuman T-lymphocyte immune globulin (ATG) in a myeloablative conditioning regimen for patients with acute leukemia would result in a significant reduction in chronic GVHD 2 years after allogeneic peripheral-blood stem-cell transplantation from an HLA-identical sibling. METHODS We conducted a prospective, multicenter, open-label, randomized phase 3 study of ATG as part of …
Standard of Care CAR-T Cell Therapy for Large B-Cell Lymphoma (LBCL): Does Bridging Efficacy Matter? a German GLA/DRST Real World Analysis
Abstract Introduction The CD19 targeting CAR-T cell constructs axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel) have become an accepted standard salvage treatment of LBCL beyond the second line. Patients scheduled for approved CAR-T cell therapies usually have 4-8 weeks wait time for CAR-T cell infusion, thus often requiring bridging strategies in rapidly progressing patients to achieve disease control until start of lymphodepletion. It is still unclear, however, if the adverse impact of active progressive lymphoma can be overcome by successful bridging. We have addressed this question using registry data provided by the German Registry for Stem Cell Transplantation (DRST),…
Comparison of a New Reduced Toxicity Myeloablative Treosulfan and Fludarabine Preparative Regimen with Myeloablative Busulfan or Melphalan in Combination with Fludarabine in Older Patients with Acute Myeloid Leukemia or Myelodysplastic Syndromes: A Retrospective Matched Pair Analysis of Patients from a Prospective Randomized Trial and the European Blood and Marrow Transplantation Society Registry
Background The best preparative regimen for the growing number of older acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) patients undergoing allogeneic hematopoietic cell transplantation (HCT) from matched related (MRD) or unrelated donors (MUD) remains undefined. A large randomized phase III trial (MC-FludT.14/L study: ClinicalTrials.gov Identifier: NCT00822393) recently demonstrated that myeloablative intravenous (IV) treosulfan (10 g/m² IV on days -4 to -2) in combination with fludarabine (TreoFlu) improves outcome in older and/or comorbid patients with AML in complete remission (CR) or MDS compared with the reference reduced intensity busulfan (0.8 mg/kg IV in 6-hour inte…