Issue Archive

Plasma exchange and immunosuppression have been the standard treatment for acquired immune thrombotic thrombocytopenic purpura (TTP) for the last 3 decades. In a Plenary Paper, Coppo and colleagues provide evidence that translates clinical trial data into everyday clinical practice for the potential addition of the anti–von Willebrand factor nanobody caplacizumab to that standard.

Burkitt lymphoma (BL) is an uncommon but distinctive, highly aggressive lymphoma. Crombie and LaCasce review its clinical, pathologic, and genomic features and discuss standard and emerging treatment options for adult patients with BL.

Uy and colleagues report the results of a multicenter phase 1/2 study of flotetuzumab, a dual-affinity (CD3ε and CD123) retargeting (DART) protein, in patients with relapsed or refractory acute myeloid leukemia (AML). The drug brings together effector T cells and target cells (CD123-expressing AML blasts). Preliminary efficacy data indicate an 18% complete response rate at the recommended phase 2 dose; higher rates are seen in less heavily pretreated patients and in AMLs with high immune infiltration.

γ-Aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the central nervous system, but its receptor is also expressed by hematopoietic progenitors. In genetic and pharmacological experiments, Shao et al show that GABA and its receptor can regulate murine and human stem cell function, including function in transplant models. These data suggest that the GABA receptor is an attractive new molecular target for intervention to enhance human stem cell engraftment.

Fontan and colleagues report a functional genomics screen that identifies genes and pathways that augment or interfere with the efficacy of a MALT1 inhibitor. Building on these insights, they demonstrate that simultaneous MALT1 and MTORC1 inhibition triggers synergistic killing in both in vitro and in vivo models of diffuse large B-cell lymphoma (DLBCL). These data should inform interpretation of observations in ongoing early-phase trials of MALT1 inhibitors.

In these two short reports, the authors approach the issue of whether hydroxyurea (HU) use in young males has major irreversible effects on sperm production. Joseph et al analyzed and compared sperm parameters in male patients with sickle cell disease (SCD) who were exposed or not exposed to HU before puberty. They report semen abnormalities in all patients but no differences between groups. Independently, Gille et al provide evidence for the lack of in vivo HU-related decreases in the spermatogonial pool in biopsy specimens from young males with SCD but evidence for a negative effect of SCD itself. Together, these reports suggest that the use of HU in young males does not adversely affect fertility.

Agkisacucetin is a novel venom-derived antithrombotic drug candidate currently in phase 2 clinical trials. To understand its mechanism of action, Wang and colleagues solved the crystal structure of the glycoprotein Ib α chain (GPIbα) N-terminal domain in complex with agkisacucetin, revealing that the drug can sterically block the interaction of GPIb receptor with both von Willebrand factor and thrombin proteins, thereby inhibiting platelet function.

In these two short reports, the authors approach the issue of whether hydroxyurea (HU) use in young males has major irreversible effects on sperm production. Joseph et al analyzed and compared sperm parameters in male patients with sickle cell disease (SCD) who were exposed or not exposed to HU before puberty. They report semen abnormalities in all patients but no differences between groups. Independently, Gille et al provide evidence for the lack of in vivo HU-related decreases in the spermatogonial pool in biopsy specimens from young males with SCD but evidence for a negative effect of SCD itself. Together, these reports suggest that the use of HU in young males does not adversely affect fertility.