Issue Archive

Although inv(16) AML is considered a low-risk AML, more than two-thirds of older patients relapse, especially those who cannot tolerate high-dose consolidation therapies that are critical to disease control. In a Blood Spotlight, Surapally et al highlight the current understanding of the molecular pathophysiology of the fusion oncogene CBFβ-SMMHC in driving inv(16) AML and discuss how that understanding informs potential novel therapies to improve disease prognosis.

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.

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.

Hamadani et al report results of a phase 1 study of loncastuximab tesirine, a CD19 antibody–drug conjugate, in the treatment of relapsed/refractory non-Hodgkin lymphoma. They establish a phase 2 dosing schedule with acceptable toxicity. They report an overall response rate of 45.6% with 26.7% complete responses, encouraging further study of this agent for treatment of relapsed lymphoma.

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.

Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is caused by autoantibodies to ADAMTS13, most of which target the spacer domain of ADAMTS13. Using bioinformatic modeling, Ercig et al designed a series of N-glycan insertions to interfere with antibody binding and identified a variant that binds without reducing ADAMTS13 proteolytic activity. They propose this variant as a possible novel therapeutic option for iTTP treatment.

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.