Issue Archive

The C5 inhibitor eculizumab has opened the door to therapeutic blockade of the terminal complement pathway in practice and raised questions about its regulation. In a Plenary Paper, Mannes and colleagues describe potentially paradigm-shifting research related to the complement cascade with important translational implications for complement-driven diseases such as paroxysmal nocturnal hemoglobinuria, atypical hemolytic-uremic syndrome, and antiphospholipid syndromes.

Goodman et al provide a provocative Perspective on whether the evidence base is sufficient for widespread treatment of patients with multiple myeloma that is not yet causing end-organ damage.

Cook and Phillips provide their expert views on how to treat patients with adult T-cell leukemia/lymphoma (ATL), an uncommon complication of long-term infection with human T-lymphotropic virus type 1. Using 4 cases to orient clinicians to the diversity of presentation and management strategies of ATL, they highlight current treatment outcomes and potential areas for future progress.

Zhao and colleagues report detailed genomic analyses of 44 adult patients with relapsed CD19-positive B-cell acute lymphoblastic leukemia (B-ALL) treated with blinatumomab. They reveal that while specific leukemogenic genetic mutations do not predict response, a tumor-intrinsic transcriptomic signature of heightened immune signaling is associated with response; furthermore, pretreatment identification of a specific CD19 alternative splicing variant is associated with subsequent blinatumomab treatment resistance or failure.

Fenwarth et al tackled the challenge of how to choose which patients should be selected for allogeneic hematopoietic stem cell transplant in first remission. By incorporating genomic data via the the “knowledge bank” of Gerstung et al, minimal residual disease data, and the existing standard recommendations (European LeukemiaNet 2017), they demonstrate enhanced predictive power for benefit and for harm in a cohort of 656 patients prospectively enrolled in a French national trial.

Hao et al describe how the known natural mutations of the enzyme γ-glutamyl carboxylase (GGCX) affect the differential γ-carboxylation of 3 major vitamin K–dependent proteins with widely different functions in coagulation and noncoagulation functions such as vascular calcification and bone metabolism. Their data explain why vitamin K administration is beneficial for correcting phenotypes of GGCX mutations associated with bleeding but has minimal impact when mutations are present with nonbleeding phenotypes.

This retrospective analysis of data on cohorts of pediatric patients receiving hematopoietic stem cell transplantation is an important step towards understanding the interactions between social determinants of health, insurance coverage, and outcomes of high-complexity therapy for hematological disease. Using postal codes as a surrogate for economic disadvantage and insurance data, Bona and colleagues found that neighborhood poverty is associated with higher transplant-related mortality (TRM) for patients with malignant disease but not those with nonmalignant disease and that survival and TRM appear worse for those with Medicaid rather than private insurance.