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Autoantibodies to the von Willebrand factor–cleaving protease ADAMTS13 cause recurring, life-threatening episodes of thrombotic microangiopathy in immune thrombotic thrombocytopenic purpura (iTTP). Alongside plasma exchange and recently caplacizumab, rituximab and steroids are mainstays of guideline-recommended treatment. In this Plenary Paper, a retrospective analysis of a large United States iTTP registry, Chaturvedi et al identify racial differences in clinical outcomes, with less benefit from rituximab in Black patients than in White patients, especially in relapsed disease. Their findings have implications for current care and require further investigations into the mechanisms underlying these differences.


In this article, Döhner and international colleagues provide a major update to the European Leukemia Network (ELN) recommendations, a key guideline for physicians caring for patients with acute myeloid leukemia (AML) and a benchmark for clinical trial design and reporting. Aligning with the newly proposed consensus classification of AML published last week in Blood for reporting diagnosis, the authors outline revised response criteria and guidance on the use of measurable residual disease testing. The revised ELN genetic risk classification highlights the utility of molecular testing. Treatment recommendations incorporate recently approved targeted therapies into advice on intensive versus nonintensive induction therapies, the use of maintenance therapy, and the timing of allogeneic stem cell transplantation.


Ferrero and colleagues present a longitudinal analysis of molecular measurable residual disease (MRD) assessments in patients with mantle cell lymphoma (MCL) treated on a prospective clinical trial with chemoimmunotherapy, autologous stem cell transplant, and either maintenance lenalidomide or observation. The authors report on the prognostic and predictive utility of serial peripheral blood allele–specific testing and identify its suitability for future MRD-guided treatment regimens.

MEF2D fusions, a recurrent feature in B-cell precursor acute lymphoblastic leukemia (BCP-ALL), are associated with poor prognosis. Zhang and colleagues dissect the molecular mechanisms underlying the pathogenic function of the MEF2D-HNRNPUL1 fusion, revealing that it impairs B-cell development. The authors also show that the HDAC inhibitor panobinostat in combination with chemotherapy improves overall survival in a murine model, suggesting a potential targeted intervention for BCP-ALL bearing MEF2D fusions.


In this month’s CME article, Robin and colleagues report on the role of allogeneic stem cell transplant in patients with chronic myelomonocytic leukemia (CMML) using 2 major international registry data sets with 1114 patients and statistical modeling that accounts for the risk of transformation to acute myeloid leukemia (AML). They found that allografting before transformation decreases life expectancy in patients with lower risk CMML but improves 5-year overall survival in patients with higher risk disease. These data aid decision-making around the timing of allografting for fit, younger patients with CMML.


The formation of large von Willebrand factor (VWF) tubules is a critical step in formation and maturation of high-molecular-weight multimers that are required for proper hemostasis. Anderson et al describe the structure of the central tubulation, revealing novel findings about how tubule formation and concatemerization occur. These findings provide clues as to how several von Willebrand disease mutations result in abnormal bleeding.


Using murine models, Zhu and colleagues identify vasoactive intestinal peptide (VIP) production by plasmacytoid dendritic cells (pDCs) as an important mechanism that regulates the alloreactivity of allogeneic T cells. Expression and release of VIP by donor pDCs mitigate the severity of acute graft-versus-host disease (GVHD), especially gut GVHD, but do not compromise graft-versus-leukemia effects. These data argue for clinical trials to investigate whether donor pDCs or treatment with VIP could protect patients from acute gut GVHD.




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