Issue Archive

Using 3 illustrative cases, Chaer et al discuss the options for the prevention and therapy of COVID-19 infection in patients with hematologic malignancies and recipients of cellular therapies. The authors provide useful practical recommendations and algorithms for current treatment.

In this month’s CME article, Cuvelier and colleagues report on outcomes over a 35-year period for patients with adenosine deaminase (ADA)-deficient severe combined immune deficiency who were enrolled in the Primary Immune Deficiency Treatment Consortium (PIDTC). Event-free survival prior to 2020 favored gene therapy (GT) over hematopoietic cell transplant (HCT); however, for patients treated after the year 2000 without infection, there was no difference between HCT and GT. This finding suggests that patients undergoing definitive therapy early in life before infectious complications may be considered for HCT, especially when GT is not available.

XIAP deficiency causes hyperinflammatory disease (X-linked lymphoproliferative disease) and hemophagocytic lymphohistiocytosis related to dysregulated TNF-receptor signaling and increased NFRP3 inflammasome activity. Chiang et al demonstrated that downregulation of inflammasome activity with quercetin reduces cytokine levels in XIAP mice, supporting a trial of the agent for the treatment of XIAP deficiency.

DDX41 germline mutations define the most common genetic syndrome predisposing to myeloid neoplasms (MN). Two papers highlight the genetic landscape and prognostic implications of germline DDX41-related MN. Li et al analyzed DDX41 variants and demonstrated that germline causal variants identify a population with a distinct AML subtype. The group, characterized by male predominance, late onset, and favorable prognosis, develop concurrent somatic DDX41 variants but rarely show the usual MN-associated somatic mutations. This contrasts to patients with variants of uncertain significance who develop MN with canonical MN-associated mutations, suggesting they define distinct entities. In the second article, Duployez et al confirmed the prognostic significance in 191 patients with DDX41 germline mutation, reporting higher remission rates and longer overall survival than patients without DDX41 germline mutation. Transplantation in first remission prolonged relapse-free survival but not overall survival.

DDX41 germline mutations define the most common genetic syndrome predisposing to myeloid neoplasms (MN). Two papers highlight the genetic landscape and prognostic implications of germline DDX41-related MN. Li et al analyzed DDX41 variants and demonstrated that germline causal variants identify a population with a distinct AML subtype. The group, characterized by male predominance, late onset, and favorable prognosis, develop concurrent somatic DDX41 variants but rarely show the usual MN-associated somatic mutations. This contrasts to patients with variants of uncertain significance who develop MN with canonical MN-associated mutations, suggesting they define distinct entities. In the second article, Duployez et al confirmed the prognostic significance in 191 patients with DDX41 germline mutation, reporting higher remission rates and longer overall survival than patients without DDX41 germline mutation. Transplantation in first remission prolonged relapse-free survival but not overall survival.

Nyffenegger and colleagues report that blocking ferriportin with vamifeport reduces hemolysis in a murine model of sickle cell disease (SCD). Vamifeport reduces intracellular iron and induces iron-limited hematopoiesis. Since a small decrease in the intracellular sickle hemoglobin concentration has a marked impact on the delay time for sickling, reducing sickle hemoglobin decreases sickling and hemolysis. In addition, vamifeport also reduces adhesion molecule expression, decreasing inflammation. This supports further development of vamifeport as a novel therapy for SCD.

In this article, Borogovac et al emphasized the burden of stroke and neuropsychiatric symptoms in patients with hereditary thrombotic thrombocytopenic purpura (hTTP) based on an analysis of the International hTTP Registry. Given the rarity of hTTP, patient numbers were small; nevertheless, the prevalence of stroke reached 100% in patients over the age of 50. Nearly all patients also had evidence of neuropsychiatric symptoms. These data confirm the need to diagnose hTTP as early as possible and support the use of prophylaxis to prevent future events.