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Current Issue
Volume 140,
Issue 12,
September 22 2022

Issue Highlights

Latest in Blood
Free Articles
Plenary Papers
Shruti Chaturvedi; Ana G. Antun; Andrew M. Farland; Ryan Woods; Ara Metjian; Yara A. Park; Gustaaf de Ridder; Briana Gibson; Raj S. Kasthuri; Darla K. Liles; Frank Akwaa; Todd Clover; Lisa Baumann Kreuziger; J. Evan Sadler; Meera Sridharan; Ronald S. Go; Keith R. McCrae; Harsh Vardhan Upreti; Angela Liu; Ming Y. Lim; Radhika Gangaraju; X. Long Zheng; Jay S. Raval; Camila Masias; Spero R. Cataland; Andrew Johnson; Elizabeth Davis; Michael D. Evans; Marshall A. Mazepa; for the United States Thrombotic Microangiopathies Consortium
DOI: 10.1182/blood.2022016640
First Edition
Koji Izutsu; Shinichi Makita; Kisato Nosaka; Makoto Yoshimitsu; Atae Utsunomiya; Shigeru Kusumoto; Satoko Morishima; Kunihiro Tsukasaki; Toyotaka Kawamata; Takaaki Ono; Shinya Rai; Hiroo Katsuya; Jun Ishikawa; Hironori Yamada; Kazunobu Kato; Masaya Tachibana; Yasuyuki Kakurai; Nobuaki Adachi; Kensei Tobinai; Kentaro Yonekura; Kenji Ishitsuka
DOI: 10.1182/blood.2022016862
Clinical Trials and Observations
Koji Izutsu; Shinichi Makita; Kisato Nosaka; Makoto Yoshimitsu; Atae Utsunomiya; Shigeru Kusumoto; Satoko Morishima; Kunihiro Tsukasaki; Toyotaka Kawamata; Takaaki Ono; Shinya Rai; Hiroo Katsuya; Jun Ishikawa; Hironori Yamada; Kazunobu Kato; Masaya Tachibana; Yasuyuki Kakurai; Nobuaki Adachi; Kensei Tobinai; Kentaro Yonekura; Kenji Ishitsuka
DOI: 10.1182/blood.2022016862

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Featured Content

Race affects treatment outcomes in iTTP, 2022 ELN AML recommendations, and a comprehensive MRD assessment in MCL

In this week’s episode we’ll take a quick look at the latest European Leukemia Net recommendations for the diagnosis and management of acute myeloid leukemia. We’ll also describe a comprehensive analysis of a phase 3 trial indicating that MRD is a strong outcome predictor over the entire natural history of mantle cell lymphoma, setting the stage for potential risk stratification tools that may be suitable for MRD-guided treatment. We'll also look at a large US registry study demonstrating that black patients with idiopathic thrombotic thrombocytopenic purpura had a shorter time to relapse and less response to rituximab compared to white patients. These findings suggest a potential need for closer monitoring, early retreatment, and alternative treatments.

Race, rituximab, and relapse in TTP

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.

Punctual and kinetic MRD analysis from the Fondazione Italiana Linfomi MCL0208 phase 3 trial in mantle cell lymphoma

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.

Functional, structural, and molecular characterizations of the leukemogenic driver MEF2D-HNRNPUL1 fusion

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.

Role of allogeneic transplantation in chronic myelomonocytic leukemia: an international collaborative analysis

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.

Structures of VWF tubules before and after concatemerization reveal a mechanism of disulfide bond exchange

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.

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