Assessment of safety and immunogenicity of MHC homozygous iPSC-derived CD34+ hematopoietic progenitors in an NHP model
In this study, D’Souza and colleagues examined the effects of infusion of nonhuman primate (NHP)–induced pluripotent stem cell (iPSC)–derived hematopoietic progenitors (iHPs) with known myeloid potential in an NHP model system of myeloablative transplant with autologous stem cell rescue. The goal was to assess the safety and efficacy of the addition of these iPSC-derived hematopoietic progenitors on the kinetics of hematopoietic reconstitution as well as potential for immune mediated alloantibody production in major histocompatibility complex (MHC)–matched or mismatched immunocompetent primates. The primary conclusions are that the iHP infusions were safe and well tolerated and were hypoimmunogenic for alloantibody production despite MHC mismatch conditions and upregulation of HLA with IFNg.
Bendamustine or high-dose cytarabine-based induction with rituximab in transplant-eligible mantle cell lymphoma
Villa et al compared the clinical outcomes of patients with a diagnosis of mantle cell lymphoma (MCL) who received rituximab plus bendamustine (R-B) for induction treatment to those who received RCHOP/RDHAP for induction. The authors showed that outcomes were comparable between the 2 cohorts. R-B is an attractive regimen for physicians and patients and is commonly used in the first-line setting for MCL. Therefore, this study serves as supportive evidence for this approach. With the introduction of novel treatments options for MCL in the relapse setting, utilization of less toxic regimens is reasonable as long as efficacy is not compromised.
Respiratory viruses in hematopoietic cell transplant candidates: impact of preexisting lower tract disease on outcomes
Waghmare et al describe the impact of respiratory virus positivity in adult patients prior to transplant. Although human rhinovirus (HRV) has been increasingly recognized as a potential pathogen for lower respiratory disease (LRD), which can lead to poor outcome in patient's undergoing hematopoietic stem cell transplantation, this study helps clarify the potential risk for early transplant related mortality in the setting of HRV-related LRD prior to allogeneic stem cell transplantation.
Desmopressin response depends on the presence and type of genetic variants in patients with type 1 and type 2 von Willebrand disease
In this study, Atiq et al report on the response to desmopressin in a patient population with von Willebrand disease (VWD) enrolled in the Win study. Seventy-two type 1 patients without a VWF gene variant, 108 with a VWF variant, and 70 with type 2 VWD were enrolled. All patients with type 1 VWD without a variant achieved a complete response. In contrast, complete responses were only observed in 64% patients with type 1 VWD and a variant and in 31 % with type 2 VWD. The authors therefore concluded that the desmopressin response highly depends on the VWF gene variants.
Loss of METTL3 attenuates blastic plasmacytoid dendritic cell neoplasm response to PRMT5 inhibition via IFN signaling
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematologic malignancy with poor clinical outcomes. Protein arginine methyltransferase 5 (PRMT5) dependency is a recurrent feature of BPDCN, but specific roles for PRMT5 in the evolution of the disease is unresolved. Here, Rethnam and coworkers found a link between the inhibition of PRMT5 and intron retention of the key RNA methylation gene METTL3. The authors also showed that depletion of METTL3 in a BPDCN cell line induced a significant increase in interferon signaling, which was enhanced further by PRMT5 inhibition. Identification and characterization of this novel pathway suggests that inhibition of PRMT5 may be a viable therapeutic for the treatment of BPDCN.
In vivo genome-wide CRISPR screening in murine acute myeloid leukemia uncovers microenvironmental dependencies
Mercier and co-authors present a CRISPR screening that extensively tests the necessity of genes for in vitro vs in vivo growth of 2 acute myeloid leukemia (AML) types, using murine models that resemble human disease. The group uncovers significant differences and overlaps in the molecular dependencies. Particularly interestingly, they identify in vivo genes that are important for cell-cell and cell-matrix interactions as well as metabolic dependencies that cannot be identified with in vitro only studies. This dataset has the potential to become a significant reference screen for in vivo dependencies of AML cells.
