Issue Archive

In this Blood Spotlight, Rasche and colleagues present the state of the art of immunotherapy for multiple myeloma. They discuss the role of monoclonal antibodies that are part of the new backbone of myeloma therapy and the promise of future T-cell therapies, looking toward a future for a potential cure of the disease with chemotherapy-free regimens.

Kraft and Godley review the approach to diagnosing germline cancer disposition, through historical clues and through interpretation of next-generation sequencing that may indicate germline mutations. They further discuss the impact on germline predisposition syndromes on treatment and hematopoietic stem cell transplant.

Cortes reviews considerations for tyrosine kinase inhibitor choice for patients with underlying secondary morbidities, including cardiovascular disease, renal dysfunction, pleural effusion, and glucose intolerance.

The authors present a multicenter phase 2 trial of carfilzomib, lendalidomide, and dexamethasone (KRd), followed by autologous stem cell transplant and maintenance KRd in previously untreated patients with multiple myeloma. They report excellent long-term outcomes with high rates of complete remission that deepen with time.

Rosen and colleagues compared factor VIII level determination by one-step assay versus chromogenic assay and demonstrated that the 2 assays are discrepant, especially when measuring transgenic factor VIII following gene therapy. While both recombinant subcutaneous factor VIII and recombinant factor VIII yield similar results by chromogenic assay, the 1-step assay tends to show higher activity when measuring transgenic factor VIII.

Neuronal signals have been implicated in hematopoietic stem cell (HSC) proliferation. Grey and colleagues demonstrated that HSCs are enriched for expression of RET, a receptor tyrosine kinase activated by glial-derived neurotrophic factor, and that activation of RET improves HSC expansion and transplant potential. This pathway holds promise for promoting ex vivo HSC expansion for stem cell transplantation.

Extranodal natural killer (NK) T-cell lymphoma is a rare Epstein-Barr virus–positive non-Hodgkin lymphoma. Central nervous system (CNS) relapse is rare but has a terrible prognosis, leading to efforts to identify predictive factors for CNS recurrence. The authors demonstrate that CNS relapse can be predicted by a modification of the prognostic index of natural killer lymphoma score based on the number of extranodal sites. Prophylaxis with intermediate-dose methotrexate may decrease CNS relapse.

Danek et al demonstrated a role for the canonical Wnt signaling pathway in regulating steady-state and emergency granulopoiesis. The signaling pathway is mediated by interaction between β-catenin and the TCF/LEF transcription factors; mice with a dominant negative form of TCF4 that abrogates this interaction are neutropenic and have reduced neutrophil maturation. The authors confirmed that this is mediated through downregulation of neutrophil-specific gene expression, notably the G-CSF receptor.

Perreault and colleagues examined antibody titers in sequential samples from serum donors recovering from COVID-19 and demonstrated that antibody titers fall over 3-4 months. These results have important implications for convalescent serum collection and seroprevalence studies.