Issue Archive

In this Blood Spotlight, Hume et al address what we can learn about macrophage biology through single-cell RNA sequencing (scRNA-seq) analyses. The authors highlight important caveats relating to tissue disaggregation, including the fragmentation of macrophages that can lead to underrepresentation in scRNA-seq datasets and that the attachment of fragments to unrelated cells may lead to misassignment of transcripts. These concerns demand orthogonal confirmation of single-cell findings, wherever possible.

In a phase 1b trial of the addition of the anti-CD19 antibody tafasitamab to R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone), Belada et al randomly assigned patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL) with a poor prognosis (International Prognostic Index score of 2-5) to also receive lenalidomide. The authors’ data from 66 patients suggest acceptable safety and encouraging efficacy with 2-year progression-free survival exceeding 74%, thereby forming the basis for a phase 3 trial in high-risk patients with DLBCL.

Classical Hodgkin lymphoma (cHL) is highly sensitive to treatment with inhibitors of programmed cell death protein 1 (PD-1), but a significant proportion of patients have resistant disease. Mei and colleagues report on the results of combining the histone deacetylase inhibitor vorinostat, which can increase major histocompatibility complex class 1 expression, with the PD-1 inhibitor pembrolizumab, demonstrating an impressive response rate of 78% in 32 patients with relapsed cHL. Responses in 56% of patients with disease refractory prior to PD-1 therapy suggest this combination warrants further exploration in this difficult-to-treat population.

In this month’s CME article, Brocklebank et al present detailed clinical characteristics and complete genetic analyses of a large United Kingdom cohort of patients with suspected complement-associated atypical hemolytic uremic syndrome (CaHUS) treated with eculizumab. The authors demonstrate superiority over historical therapies in genotype-matched patients with CaHUS, document that outcome after eculizumab cessation is genotype-dependent, and show that relapse is very unlikely if no pathogenic gene variant is present. The data also reveal a new causative genetic lesion for eculizumab-refractory CaHUS and provide a benchmark that should prove useful as additional options for CaHUS treatment emerge.

Masetti and colleagues report on a multicenter observational study of 90 children that investigated the role of the microbiome in pediatric allogeneic hematopoietic stem cell transplantation (allo-HSCT). The authors’ results indicate that patients with high fecal microbial diversity prior to allo-HSCT have longer overall survival and lower incidence of acute graft-versus-host disease compared with patients with low microbial diversity. Higher pretransplant diversity is associated with higher abundance of short-chain fatty acid–producing organisms, suggesting a potentially causative relationship, as has also been observed in adult allo-HSCT recipients.