Issue Archive

Pure red cell aplasia (PRCA) is a rare immune-mediated cytopenia with a heterogeneous pathophysiology that dictates differential therapeutic responses. Using 4 illustrative cases, Gurnari and Maciejewski present their approach to the management of adult PRCA, including a useful algorithm for evalution and treatment of this rare disorder.

Pittman and colleagues used electronic patient reporting, actigraph device tracking, and in-home blood draws to evaluate longitudinal data on vaso-occlusive crises (VOC), sleep and activity, and biological markers in 35 patients with sickle cell disease. Reported crises over 6 months suggest an annualized VOC rate of 8, of which 75% to 80% are treated at home; VOC crisis correlates with biochemical and functional changes in cell adhesion and elevation of C-reactive protein and interleukin-6.

Mu et al used patient-derived induced pluripotent stem cells (iPSCs) to elucidate the pathophysiology of ADH5/ALDH2 deficiency, a recently described syndrome associated with Fanconi anemia–like bone marrow failure. They demonstrate that ADH5/ALDH2 is critical for protecting progenitors from formaldehyde generated by progenitor cell expansion. Failure of this pathway leads to DNA damage and increased sister chromatid exchange similar to the phenotype of DNA repair pathway mutations in Fanconi anemia.

Hemophagocytic lymphohistiocytosis (HLH) is caused by heterogeneous abnormalities that impair cytotoxic lymphocyte killing of infected and malignant cells, leading to a hyperinflammatory syndrome. Kalinichenko and colleagues describe RhoG deficiency as a novel cause of HLH. The authors demonstrate that RhoG interacts with Munc13-4 (the absence of which also causes HLH) and anchors it to the plasma membrane to facilitate cytotoxic granule release.

Chronic lymphocytic leukemia (CLL) is associated with a high rate of familial risk. In this month’s CME article, Slager et al report the incidence of monoclonal B-cell lymphocytosis (MBL), a precursor of CLL, and its rate of progression to CLL in 310 CLL families. The prevalence of MBL was 22% at baseline, with a cumulative yearly incidence of 1.8%. Progression to CLL occurred in 1% of individuals per year. These data confirm the increased rate of MBL and CLL in families of patients with CLL.

More than 80% of patients with systemic mastocytosis (SM) carry the KIT D816V mutation. Nevertheless, its clinical presentation is heterogeneous, with a wide range of prognoses likely related to secondary accompanying mutations. By creating a panel of patient-specific induced pluripotent stem cells (iPSCs), Toledo and colleagues have provided a powerful tool to investigate patient-specific SM phenotypes and to test for targeted therapies, identifying nintedanib, an angiokinase inhibitor that targets VEGFR, PDGFR, and FGFR, as a novel KIT D816V inhibitor.

The factors leading to cancer-associated thrombosis (CAT) are still not fully understood. Dunbar and colleagues analyzed the association of tumor-associated somatic mutations and clonal hematopoiesis with thrombotic risk, using more than 14 000 tumor samples. They demonstrate that while clonal hematopoiesis does not increase thrombosis risk, certain tumor-specific mutations increase the risk of CAT independently of tumor type.

Anti-CD44 antibodies have been demonstrated to have anti-inflammatory activity and ameliorate immune thrombocytopenia in murine models. Norris et al have elucidated the mechanism for this effect, demonstrating that the Fc portion of anti-CD44 antibodies inhibits macrophage phagocytosis by blocking Fc receptor–binding sites and thereby blocking phagocytosis of opsonized platelets.