Optimized GVHD Prevention in HLA-Mismatched Unrelated Allogeneic HCT Using a PTCY-Based Approach.

Although post-transplant cyclophosphamide (PTCY)-based prophylaxis has become a widely adopted strategy for preventing graft-versus-host disease (GVHD) in 9 out of 10 HLA-mismatched unrelated donors (MMUDs), allogeneic hematopoietic cell transplants (allo-HCTs), data on the safety and efficacy of PTCY in this setting remain limited. This single-center study investigates the outcomes of 94 adults with hematological malignancies undergoing MMUD allo-HCT with PTCY and tacrolimus (Tac) (PTCY-Tac) between 2014 and 2023. The median age was 53 years, and 60.

Discovery of 6,7-Dihydropyrazolo[1,5-]pyrazin-4(5)-one Derivatives as mGluR Negative Allosteric Modulators with Activity in a Rodent's Model of Cognition.

Allosteric modulators of the metabotropic group II receptors, mGluR and mGluR, have been widely explored due to their ability to modulate cognitive and neurological functions in mood disorders, although none have been approved yet. In our search for new and selective mGluR negative allosteric modulators (NAMs), series of 6,7-dihydropyrazolo[1,5-]pyrazin-4(5)-one derivatives were identified from our published series of 1,3,5-trisubstituted pyrazoles. SAR evolution of the initial hit resulted in 100-fold improvement in the mGluR NAM potency and subsequent selection of compound based on its overall profile, including selectivity and ADMET properties.

Outcomes of older adults undergoing allogeneic hematopoietic cell transplantation with post-transplant cyclophosphamide based prophylaxis.

This study evaluates the feasibility of using post-transplant cyclophosphamide (PTCY) prophylaxis in allo-hematopoietic cell transplantation (HCT) for adults aged 65 and older. PTCY is increasingly used to prevent graft-versus-host disease (GVHD) across all donor types, but concerns remain about potential risks, especially in older patients. Fifty-seven adults aged 65 or older with hematological malignancies, undergoing their first allo-HCT with PTCY prophylaxis between January 2011 and January 2023 were included.

Safety and efficacy of G-CSF after allogeneic hematopoietic cell transplantation using post-transplant cyclophosphamide: clinical and in vitro examination of endothelial activation.

Since 2021 the use of G-CSF was implemented in allo-HCT with PTCY-based prophylaxis with the aim of shortening the aplastic phase and reducing infectious complications. This study investigates the effectiveness of this change in protocol performed at our institution. One-hundred forty-six adults undergoing allo-HCT with PTCY-based prophylaxis were included, and among them, 58 (40%) received G-CSF.