Volume 130, Issue 10

Cover Figure: NUDT15 variants underlying thiopurine intolerance in children with ALL. See the article by Moriyama et al.

WASHINGTON, September 7, 2017 – Welcome to “This Week in Blood,” a weekly snapshot of the hottest studies from each week’s issue of Blood, the official journal of the American Society of Hematology (ASH), hand-picked by Blood Editor-in-Chief Bob Löwenberg, MD, PhD, and Deputy Editor Nancy Berliner, MD.

Pembrolizumab, pomalidomide, and low-dose dexamethasone for relapsed/refractory multiple myeloma
Badros and colleagues report the results of immune checkpoint inhibition combined with proteasome inhibition in relapsed multiple myeloma, demonstrating 60% response rates, some durable, with acceptable toxicity; myeloma cell PD-L1 expression may predict response.

Role of ADP receptors on platelets in the growth of ovarian cancer
Platelets have been shown to enhance tumor cell growth and metastasis. Cho et al further elucidate this pathway with studies of significant potential clinical import, demonstrating that treatment with the P2Y12 ADP receptor inhibitor ticagrelor strongly inhibits growth of ovarian tumor cells in tumor-bearing mice, a response that is platelet dependent and mimicked by P2Y12 knockout.

Circulating dsDNA, endothelial injury, and complement activation in thrombotic microangiopathy and GVHD
Gloude et al provide significant insight into the pathophysiology of transplant-associated thrombotic microangiopathy (TMA) by measurement of circulating dsDNA. They propose that TMA reflects NET-induced complement activation associated with interleukin-8–stimulated neutrophil recovery, and their studies link endothelial injury to the development of both TMA and graft-versus-host disease (GVHD).

Laboratory predictors of bleeding and the effect of platelet and RBC transfusions on bleeding outcomes in the PLADO trial
Uhl et al report on predictors of bleeding in a secondary analysis of 16,320 patient-days in the Platelet Dose (PLADO) trial, suggesting that, in addition to platelet counts of ≤5000/μl and elevated international normalized ratio (INR) and activated partial thromboplastin time (aPTT), anemia (hematocrit ≤25) may be a marker of increased hemorrhagic risk.

A new tool for rapid and reliable diagnosis of HLA loss relapses after HSCT
Haploidentical transplantation has increased hematopoietic stem cell transplantation (HSCT) options for patients with leukemia, but relapse remains an important cause of death. About one-third of relapsed patients have leukemia-specific loss of the mismatched HLA, preventing graft-versus-leukemia effects. Ahci and colleagues describe a simple polymerase chain reaction–based assay to detect HLA loss, facilitating identification of patients for whom donor lymphocyte infusion may not be optimal therapy.

Analysis of the recovery of CD247 expression in a PID patient: insights into the spontaneous repair of defective genes
In a Brief Report, Blázquez-Moreno and colleagues analyze spontaneous reversion of primary immunodeficiency (PID), demonstrating that compensatory mutations arise in some PID syndromes but not others, reflecting the intrinsic mutability of their cognate disease-causing genes.

Pathophysiology of thrombotic thrombocytopenic purpura
Sadler presents an erudite review of the state of our understanding of the pathophysiology of thrombotic thrombocytopenic purpura, with a discussion of how these concepts may direct decisions about therapy and prognosis.


This week's complete table of contents

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