Donors with KIR-Bx Haplotypes Improve Outcome of Unrelated Hematopoietic Stem Cell Transplantation for Recipients with a Myeloid Malignant Disease and a C1 Ligand Phenotype

relapse, or transplant related mortality (TRM) (p1⁄40.2, p1⁄40.1, p1⁄40.08, respectively). To investigate why higher CPSS scores were associated with higher mortality, we performed analysis restricted to patients with relapse following HCT. Those with intermediate-2/high riskhadnearly two-fold increase in riskof death after relapse compared to thosewith low/intermediate1 CPSS scores. Corresponding rates for low/intermediate-1 risk groups,OSat1year, 3years, and5yearswere61%,48%, and44% respectivelyand for intermediate-2/high riskgroupswere 38%, 32%, and19%respectively.OSofpatientswho receivedpre-HCT treatment with hypomethylating agents, chemotherapy, or both was not different compared to th…

P043 HLA-DPB matching and donor cytomegalovirus positive (CMV+) status: An “unconventional alliance” associated with a decreased relapse incidence in unrelated hematopoietic stem cell transplantation (UHSCT)

Aim While the role of HLA-DPB1 (DP) compatibility in uHSCT regarding graft versus host disease (GVHD)- and graft versus leukaemia (GVL)-effects has been extensively discussed, its interaction with donor CMV status (dCMV), remains elusive. The aim of this study was, to investigate the impact of dCMV status in DP matched (DPM) and mismatched (DPMM) uHSCT. Methods 1749 HSCT transplant (Tx) pairs were DP genotyped with an exon 2 amplicon based NGS approach in order to assess their DP matching status. CMV sero-status as well as clinical data were retrieved from the German Stem Cell Registry. Overall survival (OS), relapse incidence (RI) and chronic GvHD (cGvHD) were defined as endpoints, while s…

Anti-CD20 immunotherapy as a bridge to tolerance, after allogeneic stem cell transplantation for patients with chronic lymphocytic leukaemia: results of the CLLX4 trial

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…

Comparison of Allogeneic Stem Cell Transplantation for Transformed Acute Myeloid Leukemia Derived from MDS, CMML or MPN. a Report of the Chronic Malignancies Working Party of EBMT

Abstract Introduction Myelodysplastic syndromes (MDS), myeloproliferative neoplasms (MPN) and chronic myelomonocytic leukemia (CMML) can progress to acute myeloid leukemia (transformed AML). The aim of this EBMT registry study was to compare 3 year outcome in patients with transformed AMLwho received allogeneic stem cell transplantation according to the primary disease. Patients and Methods Within the European Society of Blood and Marrow Transplantation (EBMT) registry, we found 4214 patients (female: 39%, male: 61%) with transformed acute myeloid leukemia, who received allogeneic stem cell transplantation between 2000 and 2014. The primary disease was MDS (n=3541), CMML (n=251) or MPN (n=4…

Impact of Donor Activating KIR Genes on HSCT Outcome in C1-Ligand Negative Myeloid Disease Patients Transplanted with Unrelated Donors-A Retrospective Study.

Natural Killer cells (NK) are lymphocytes with the potential to recognize and lyse cells which escaped T-cell mediated lysis due to their aberrant HLA expression profiles. Killer cell immunoglobulin-like receptors (KIR) influence NK-cell activity by mediation of activating or inhibitory signals upon interaction with HLA-C (C1, C2) ligands. Therefore, absence of ligands for donor inhibitory KIRs following hematopoietic stem cell transplantation (HSCT) may have an influence on its outcome. Previous studies showed that C1 negative patients have a decreased HSCT outcome. Our study, based on a cohort of 200 C1-negative patients, confirmed these findings for the endpoints: overall survival (OS: H…

Matching for the MICA-129 polymorphism is beneficial in unrelated hematopoietic stem cell transplantation.

Major histocompatibility complex class I polypeptide-related sequence A (MICA) is a highly polymorphic ligand of the activating NKG2D receptor on natural killer (NK) cells, γδ-T cells, and NKT cells. MICA incompatibilities have been associated with an increased graft-versus-host disease (GVHD) incidence, and the MICA-129 (met/val) dimorphism has been shown to influence NKG2D signaling in unrelated hematopoietic stem cell transplantation (uHSCT). We investigated the effect of MICA matching on survival after uHSCT. We sequenced 2172 patients and their respective donors for MICA. All patients and donors were high-resolution HLA-typed and matched for 10/10 (n = 1379), 9/10 (n = 636), or 8/10 (n…