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The AETHERA trial demonstrated that brentuximab vedotin (BV) consolidation after autologous stem cell transplantation (ASCT) in patients with Hodgkin lymphoma (HL) at high risk of relapse/progression increases progression-free survival (PFS). Patients previously exposed to BV were excluded from that trial. However, BV alone or in combination with chemotherapy is frequently used as front-line treatment and/or pre-ASCT salvage therapy. We analyzed data from 156 patients with high-risk HL who underwent ASCT with (BV-CON, n = 62) or without (non-BV, n = 94) BV consolidation. Fifty-seven patients received BV-based salvage regimens before ASCT. The 3-year overall survival and PFS for all patients were 91.6% and 70.0%, respectively. Multivariate analysis showed that BV-CON was associated with better PFS (HR 0.39, p = 0.01), whereas positive PET at transplant leaded to worse PFS (HR 2.71, p = 0.001). BV-CON improved PFS in PET-positive patients (72.2% vs. 43.0%, p = 0.05), with a beneficial trend observed in PET negative (88.8% vs. 75.2%, p = 0.09). BV-CON patients with or without BV exposure pre-ASCT had a significantly better PFS than non-BV with or without BV pretransplant treatment (HR 0.36, p = 0.004). The efficacy of real-life BV consolidation therapy was similar to that in the AETHERA trial. This therapeutic strategy improves survival independently of BV exposure prior to ASCT. [ABSTRACT FROM AUTHOR]

Background: Allogeneic stem cell transplantation is the treatment of choice for acute myeloid leukemia (AML) patients. Unmanipulated haploidentical transplantation (Haplo‐HSCT) is commonly used for those AML patients who need a timely transplant and do not have a suitable matched donor, but relapse rates are still high, and improvements are needed. Adoptive immunotherapy using natural killer cells (NK cells) could be a promising tool to improved Haplo‐HSCT but, to date, no optimal infusion and manufacturing protocols have been developed. Study Design and Methods: In this study, we describe a quick and reproducible protocol for clinical‐grade production of haploidentical donor NK cells using double immunomagnetic depletion and enrichment protocol and overnight IL‐15 stimulation. Results: Thus, we have obtained 8 viable and functional NK cell products that have been safely infused to five AML patients undergoing unmanipulated Haplo‐HSCT. Discussion: Our results demonstrate the safety and feasibility of manufactured NK IL15 cells obtained from an adult allogeneic donor in the setting of haploidentical transplantation for AML patients. [ABSTRACT FROM AUTHOR]

Alloreactivity triggered by interaction between killer cell immunoglobulin-like receptors ( KIRs) and natural killer ( NK) cells plays a role in the graft-versus-tumor effect after hematopoietic stem cell transplantation ( SCT). Our aim in this study was to evaluate this role in the setting of T-cell-repleted haploidentical SCT with postinfusion high-dose cyclophosphamide ( PT-Cy). We included 33 patients. Among patient-donor pairs with at least 1 inhibitory KIR ( iKIR) gene mismatch, event-free survival ( EFS) and cumulative incidence of relapse 1 year after transplant were significantly better (85% vs. 37% [ P = 0.008] and 18% vs. 46% [ P = 0.041], respectively). A subanalysis in 12 patients with Hodgkin's lymphoma ( HL) showed an improvement in EFS 1 year after transplant in those patients with KIR ligand mismatch (100% vs. 25%, P = 0.012), although overall survival ( OS) was not affected (85% vs. 80%, P = 0.2). Eight of 12 patient-donors pairs presented iKIR mismatches. Of note, this outcome was better in the small subgroup, both for EFS (100% vs. 25%, P = 0.012) and for OS (100% vs. 37%, P = 0.004). Our data suggest that in the setting of T-cell-repleted haploidentical SCT with PT-Cy, iKIR mismatch is associated with improved survival, with particularly good results for both iKIR and KIR ligand mismatches in patients with HL. [ABSTRACT FROM AUTHOR]

Allogeneic stem cell transplantation (allo- SCT) has become the treatment of choice in patients with intermediate-risk and high-risk acute myeloid leukemia ( AML). The quality of response to treatment, assessed in terms of detection of minimal residual disease ( MRD), has been consistently associated with prognosis and clinical outcome in patients with AML. The aim of the present study was to evaluate the prognostic impact of analyzing MRD in bone marrow using 4-color multiparametric flow cytometry ( MFC) in 29 patients with AML before and after allo- SCT. Eighteen patients who were shown to be MRD-negative [≤0.1% leukemia-associated immunophenotypes ( LAIPs)] by MFC at transplantation and underwent allo- SCT had lower rates of relapse (15% vs. 66%, P = 0.045), better overall 1-yr survival (83% vs. 52%, P = 0.021) and a lower cumulative incidence of relapse ( P = 0.032) than patients who were MRD-positive (>0.1%). All post-transplant MRD-positive patients underwent a therapeutic intervention after transplant (tapering of immunosuppression, donor lymphocyte infusion, or re-transplant) with the intention of preventing relapse. Disease was controlled and MRD disappeared in five of these patients. Disease recurred in the other seven patients. We can conclude that follow-up with MFC for the detection of MRD in AML before and after SCT is useful for predicting relapse. In the post-transplant setting, monitoring of MRD by MFC could be a key preemptive intervention. [ABSTRACT FROM AUTHOR]