- P-selectin deficiency promotes liver senescence in sickle cell disease mice
- Infusion of selected leukemia-specific donor T cells promotes GVL without GVHD
- Inflammatory signaling and increased T-cell exhaustion contribute to CAR T-cell failure
- Autologous vs allogeneic transplantation of poor-risk peripheral T-cell NHL
- ABO-incompatible platelet transfusion worsens outcomes after intracerebral hemorrhage
- Spotlight: emerging therapies for inv(16)AML
- Blood Podcast, Season 2, Episode 19
In this week’s episode, we will review a randomized phase 3 study of patients with high-risk peripheral T-cell lymphoma that compares results from autologous versus allogeneic stem cell transplant during consolidation, look at a report that examines the significance of ABO-incompatible platelet transfusion on outcomes after intracerebral hemorrhage, and learn about how immune dysregulation mediated by tumor interferon signaling and myeloid-derived suppressor cells is associated with CAR-T-cell resistance in large B-cell lymphoma.
Clinical effects of administering leukemia-specific donor T cells to patients with AML/MDS after allogeneic transplant
Separating graft-versus-leukemia (GVL) from graft-versus-host disease (GVHD) has been the holy grail for preventing leukemic relapse following hematopoietic cell transplant (HCT). Lulla et al report successful expansion of donor T cells selected for leukemia-specific antigens and infusion into 25 patients with high-risk or relapsed acute myeloid leukemia (AML) following HCT. Infusions did not increase GVHD and had in vivo anti-leukemic activity. These early results raise hope for successfully separating GVL and GVHD.
Tumor interferon signaling and suppressive myeloid cells are associated with CAR T-cell failure in large B-cell lymphoma
Over half of patients who respond to chimeric antigen receptor (CAR) T-cell therapy relapse, and although some relapses are associated with target antigen loss, there is strong evidence that immune dysregulation plays an important role in CAR T-cell failure. Jain and colleagues examined the impact of inflammatory signaling in lymphoma cells and tumor-associated macrophages and myeloid-derived suppressor cells (MDSCs) on CAR-T success. They demonstrate that high levels of interferon signaling are associated with increased macrophages, MDSCs, and increased PD-L1 expression and predict for therapy failure.
A randomized phase 3 trial of autologous vs allogeneic transplantation as part of first-line therapy in poor-risk peripheral T-NHL
Schmitz and colleagues report results of a phase 3 trial investigating whether consolidative allogeneic transplantation (alloSCT) is superior to autologous transplantation (autoSCT) for management of patients with peripheral T-cell lymphoma. No patients proceeding to alloSCT relapsed, compared with 36% of patients undergoing autoSCT. However, disease control is offset by nonrelapse mortality, with overall survival favoring autoSCT. The authors conclude that treatment of choice remains chemotherapy followed by autoSCT, with alloSCT reserved for patients relapsing after autoSCT.
P-selectin inhibition prevents sickle cell disease (SCD)–associated vaso-occlusion, and the P-selectin inhibitor crizanlizumab has been approved by the US Food and Drug Administration to treat patients with SCD. Vats et al examined the impact of P-selectin knockout in SCD mice and demonstrated that although vaso-occlusion is reduced, hepatobiliary injury and fibrosis are increased. They emphasize the necessity of investigating the long-term impact of crizanlizumab on liver pathophysiology.
Impacts of ABO-incompatible platelet transfusions on platelet recovery and outcomes after intracerebral hemorrhage
Platelet transfusions are generally not type specific, and ABO-incompatible platelet transfusions are the norm. Magid-Bernstein and colleagues investigated the impact of ABO-incompatible platelet transfusion on outcomes after intracerebral hemorrhage. Despite no significant difference in hemorrhage extension, the transfusion of ABO-incompatible platelets is associated with markedly poorer platelet recovery and significantly worse neurologic recovery and survival.