Transplantation for myelofibrosis patients in the ruxolitinib era: a registry study from the Société Francophone de Greffe de Moelle et de Thérapie Cellulaire.

In this SFGM-TC registry study, we report the results after stem cell transplantation (HSCT) in 305 myelofibrosis patients, in order to determine potential risk factors associated with outcomes, especially regarding previous treatment with ruxolitinib. A total of 102 patients were transplanted from an HLA-matched-sibling donor (MSD), and 143 patients received ruxolitinib. In contrast with previous studies, our results showed significantly worse outcomes for ruxolitinib patients regarding overall survival (OS) and non-relapse mortality (NRM), especially in the context of unrelated donors (URD).

Optimization of universal allogeneic CAR-T cells combining CRISPR and transposon-based technologies for treatment of acute myeloid leukemia.

Despite the potential of CAR-T therapies for hematological malignancies, their efficacy in patients with relapse and refractory Acute Myeloid Leukemia has been limited. The aim of our study has been to develop and manufacture a CAR-T cell product that addresses some of the current limitations. We initially compared the phenotype of T cells from AML patients and healthy young and elderly controls.

The transcriptomic landscape of elderly acute myeloid leukemia identifies and as a favorable signature in high-risk patients.

Acute myeloid leukemia (AML) in the elderly remains a clinical challenge, with a five-year overall survival rate below 10%. The current ELN 2017 genetic risk classification considers cytogenetic and mutational characteristics to stratify fit AML patients into different prognostic groups. However, this classification is not validated for elderly patients treated with a non-intensive approach, and its performance may be suboptimal in this context.

Biallelic TET2 mutations confer sensitivity to 5'-azacitidine in acute myeloid leukemia.

Precision medicine can significantly improve outcomes for patients with cancer, but implementation requires comprehensive characterization of tumor cells to identify therapeutically exploitable vulnerabilities. Here, we describe somatic biallelic TET2 mutations in an elderly patient with acute myeloid leukemia (AML) that was chemoresistant to anthracycline and cytarabine but acutely sensitive to 5'-azacitidine (5'-Aza) hypomethylating monotherapy, resulting in long-term morphological remission. Given the role of TET2 as a regulator of genomic methylation, we hypothesized that mutant TET2 allele dosage affects response to 5'-Aza.

Low Rate of Infectious Enterocolitis in Allogeneic Stem Cell Transplant Recipients with Acute Diarrhea: A Prospective Study by the GETH-TC.

Acute diarrhea is a common and debilitating complication in recipients of allogeneic hematopoietic stem cell transplantation (HCT). In this prospective, observational, and multicenter study we examined all episodes occurring in the first 6 months of 142 consecutive adult patients who underwent a reduced-intensity conditioning HCT in 10 Spanish tertiary university hospitals. Fifty-four patients (38%) developed a total of 75 acute diarrhea episodes.

Integrated flow cytometry and sequencing to reconstruct evolutionary patterns from dysplasia to acute myeloid leukemia.

Clonal evolution in acute myeloid leukemia (AML) originates long before diagnosis and is a dynamic process that may affect survival. However, it remains uninvestigated during routine diagnostic workups. We hypothesized that the mutational status of bone marrow dysplastic cells and leukemic blasts, analyzed at the onset of AML using integrated multidimensional flow cytometry (MFC) immunophenotyping and fluorescence-activated cell sorting (FACS) with next-generation sequencing (NGS), could reconstruct leukemogenesis.

Updates on the Management of Acute Myeloid Leukemia.

Acute myeloid leukemia is a heterogeneous disease defined by a large spectrum of genetic aberrations that are potential therapeutic targets. New targeted therapies have changed the landscape for a disease with poor outcomes. They are more effective than standard chemotherapy with a good safety profile.

Humoral/Cellular Immune Discordance in Stem Cell Donors: Impact on Cytomegalovirus-Specific Immune Reconstitution after Related Hematopoietic Transplantation.

Cytomegalovirus (CMV) reactivation is an important cause of complications after hematopoietic stem cell transplantation (HSCT). Discrepancies between serologic and cellular CMV-specific immune response have been reported. This study evaluated the impact of lack of CMV-specific CD8 T cell response in seropositive donors (ie, discordant donors) on the reconstitution of CMV-specific cell-mediated immunity (CMI) after related HSCT in seropositive recipients.

Measurable residual disease in elderly acute myeloid leukemia: results from the PETHEMA-FLUGAZA phase 3 clinical trial.

The value of measurable residual disease (MRD) in elderly patients with acute myeloid leukemia (AML) is inconsistent between those treated with intensive vs hypomethylating drugs, and unknown after semi-intensive therapy. We investigated the role of MRD in refining complete remission (CR) and treatment duration in the phase 3 FLUGAZA clinical trial, which randomized 283 elderly AML patients to induction and consolidation with fludarabine plus cytarabine (FLUGA) vs 5-azacitidine. After consolidation, patients continued treatment if MRD was ≥0.

Simplification to dual antiretroviral therapy including a ritonavir-boosted protease inhibitor in treatment-experienced HIV-1-infected patients.

Objectives: To assess the effectiveness of simplification to a dual antiretroviral regimen containing a ritonavir-boosted protease inhibitor (PI/r) in treatment-experienced HIV-1-infected patients.

Methods: Retrospective analysis of 131 HIV-1-infected patients on suppressive antiretroviral treatment (HIV-RNA <50 copies/mL) who switched to a maintenance dual antiretroviral regimen, containing a PI/r, in three hospitals in Spain. Virological failure was defined as confirmed HIV-RNA >50 copies/mL.

Dual therapy based on a ritonavir-boosted protease inhibitor as a novel salvage strategy for HIV-1-infected patients on a failing antiretroviral regimen.

Objectives: To assess the efficacy and safety of dual-antiretroviral therapy containing a ritonavir-boosted protease inhibitor (PI/r) in treatment-experienced patients failing a current antiretroviral regimen.

Methods: Retrospective analysis of 60 consecutive HIV-1-infected patients who started a dual-antiretroviral rescue regimen containing a PI/r, in three hospitals in Spain. Virological failure was defined as confirmed HIV RNA >50 copies/mL at treatment week 24 or later.