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There are currently no effective anti-viral treatments for coronavirus disease 2019 (COVID-19)–hospitalized patients with hypoxemia. Lymphopenia is a biomarker of disease severity usually present in patients who are hospitalized. Approaches to increasing lymphocytes exerting an anti-viral effect must be considered to treat these patients. Following our phase 1 study, we performed a phase 2 randomized multicenter clinical trial in which we evaluated the efficacy of the infusion of allogeneic off-the-shelf CD45RA− memory T cells containing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific T cells from convalescent donors plus the standard of care (SoC) versus just the SoC treatment. Eighty-four patients were enrolled in three Spanish centers. The patients were randomized into the infusion of 1 × 106/kg CD45RA− memory T cells or the SoC. We selected four unvaccinated donors based on the expression of interferon gamma SARS-CoV-2–specific response within the CD45RA− memory T cells and the most frequent human leukocyte antigen typing in the Spanish population. We analyzed data from 81 patients. The primary outcome for recovery, defined as the proportion of participants in each group with normalization of fever, oxygen saturation sustained for at least 24 hours and lymphopenia recovery through day 14 or at discharge, was met for the experimental arm. We also observed faster lymphocyte recovery in the experimental group. We did not observe any treatment-related adverse events. Adoptive cell therapy with off-the-shelf CD45RA− memory T cells containing SAR-CoV-2–specific T cells is safe, effective and accelerates lymphocyte recovery of patients with COVID-19 pneumonia and/or lymphopenia. NCT04578210 [ABSTRACT FROM AUTHOR]

In this report, we describe a case of somatic mutations in the two HLA‐B genes in a patient with acute myelogenous leukemia. The HLA‐B*15:01 allele showed an insertion of two nucleotides within exon 2 leading to a premature stop codon. HLA‐B*40:01 showed one nucleotide substitution within exon 3, identical to that described for B*15:258N. The restriction of these mutations in leukemic cells was confirmed in patient's samples from buccal epithelial cells and hematopoietic cells obtained when the patient was in remission. The clinical significance of somatic HLA mutations in cancer seems to be associated with escape from immune surveillance and clonal evolution. The analysis of possible mutations in HLA genes of tumor cells would be valuable information for the outcome of the disease and stem cell donor selection. [ABSTRACT FROM AUTHOR]

Background aims. Despite the efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT), the procedure is still associated with high toxicity in patients with refractory graft-versus-host disease (GvHD). Mesenchymal stromal cells (MSCs) are a new mode of therapy in the context of allo-HSCT. The objective of this study was to evaluate the safety and feasibility of the use of adipose tissue-derived MSCs (AT-MSCs) in patients with chronic GvHD. Methods. Fourteen patients with moderate (n = 7) or severe (n = 7) chronic GvHD received 1 x 106/kg (group A, n = 9) or 3 x 106/kg (group B, n = 5) AT-MSCs with cyclosporine and prednisone as first-line therapy. Results. Ten of the 14 patients were able to continue under the protocol: 80% were in complete remission, and 100% were off of steroids at week 56. The remaining 4 patients either worsened from chronic GvHD (n = 3) or abandoned the study (n = 1). At the end of the study, 11 of 14 patients are alive (overall survival 71.4%, median survival of 45.3 weeks). No suspected unexpected serious adverse reactions occurred during the trial. Neither relapse of underlying disease nor mortality due to infection was observed in this cohort. Biological studies showed increased CD 19, CD4 and tumor necrosis factor-α with a temporary decrease in natural killer cells. Discussion. AT-MSCs, in combination with immunosuppressive therapy, may be considered feasible and safe and likely would have an impact on the course of chronic GvHD. More studies are warranted to understand the potential benefits of AT-MSCs in these patients. [ABSTRACT FROM AUTHOR]

High-dose chemotherapy supported by autologous stem cell transplant (ASCT) remains the treatment of choice for patients with lymphoma failing first-line chemotherapy. Recent evidence suggests a relationship between the genetic variations in genes involved in DNA repair and the outcome of patients with a number of malignancies. In this work, we retrospectively evaluated the influence of an XRCC1 polymorphism (rs25487) on the treatment results in a series of 73 patients with lymphoma subjected to ASCT. The factors correlated to overall survival were the disease status at transplant and XRCC1 genotype. Carriers of a mutant A allele had a two-fold higher risk of death than those with the wild-type genotype. In addition, patients harboring one or two copies of the A allele (GA/AA) were 4.5-fold more likely to develop therapy-related acute myeloid (t-AML). Thus, the cumulative probability of t-AML at 10 years was 37 ±± 13%% in patients with the mutant A allele as compared to 8.5 ±± 6%% in the remaining cases ( p == 0.04). Our findings suggest that genetic variation in the DNA repair gene XRCC1 may play a role in the results of transplant in patients with lymphoma. [ABSTRACT FROM AUTHOR]

Abstract: Background: Between 30% and 60% of patients with thrombotic thrombocytopenic purpura (TTP) relapse and mortality remains at 15–20%. Limited clinical data suggest that the administration of anti-CD20 antibody (rituximab) may be useful in preventing acute refractory and chronic relapsing TTP. Design and methods: We studied the clinical response to rituximab in 24 adult patients (median age 42years, range 24–72years) from 15 Spanish centers with an acute refractory (14 patients) or acute relapsing (10 patients) episode of idiopathic TTP. On admission, every patient received daily plasma exchange (PE). Rituximab was administered at a dose of 375mg/m2 weekly for a median of 13days (range 0–57days) after starting PE for a median of 4 doses (range 1–8 doses). Results: No severe acute or delayed toxicity was observed in the patients treated with rituximab. Three (12.5%) patients died because of TTP-related causes. The remaining 21 (87.5%) patients achieved complete remission in a median of 21days (range 2–35days) after initiating rituximab. After a median follow-up of 30months (range 7.5–74months), 18 patients are in remission and 3 patients have relapsed at 7, 29, and 29months. Conclusions: Rituximab appears to be a safe, effective therapy and has a high response rate for the treatment of acute refractory or relapsing idiopathic TTP in adult patients. [ABSTRACT FROM AUTHOR]

Patients with postransplant lymphoproliferative disease (PTLD) who are refractory to rituximab-based regimens have extremely poor prognosis. Data is lacking in the setting of solid organ transplantation (SOT)-related PTLD treated with chimeric antigen receptor T-cell (CAR-T) therapy. Moreover, limited information is available on the influence of concomitant immunosuppressive drugs on CAR-T function. Here, we describe the clinical outcome in one PTLD patient and propose a strategy for tailoring immunosuppressive treatment and organ monitoring in patients with kidney allografts after CAR-T infusion. This report also reviews the limited published data in the setting of SOT-related PTLD treated with CAR-T, which appears to be a feasible treatment in this clinical scenario, without severe toxicity and capable of inducing sustained responses. A noteworthy finding is that in most reported cases patients underwent complete or partial discontinuation of immunosuppressive drugs, with only one documented case of allograft rejection. [ABSTRACT FROM AUTHOR]