Chronic graft-versus-host disease (cGVHD) remains the leading cause of nonrelapse morbidity and mortality after allogeneic hematopoietic cell transplantation (HCT). Effective therapeutic agents targeting dysregulated cytokines including interleukin-17 (IL-17) and colony-stimulating factor 1 (CSF-1) have been defined in preclinical models of cGVHD, and efficacy in subsequent clinical trials has led to their recent US Food and Drug Administration approval. Despite this, these agents are effective in only a subset of patients, expensive, difficult to access outside the United States, and used in a trial-and-error fashion. The ability to readily discern druggable, dysregulated immunity in these patients is desperately needed to facilitate the selection of appropriate treatment and to potentially identify high-risk individuals for preemptive therapy. We used single-cell sequencing-based approaches in our informative preclinical cGVHD models to "reverse engineer" temporal IL-17 and CSF-1 signatures in mouse blood that could be used to interrogate patients. We defined distinct, nonintuitive IL-17 and CSF-1 signatures in mouse blood monocytes that could be identified in relevant monocyte populations within 70% of patients at diagnosis of cGVHD and in half of patients at day +100 after HCT who subsequently developed cGVHD. These signatures can now be evaluated prospectively in clinical studies to help delineate potential responder and nonresponders to relevant therapeutics targeting these pathways.

Patients with thrombocytopenia requiring ongoing platelet transfusion support may develop inadequate platelet count increments, referred to as platelet refractoriness (PR), which further complicates their care. The underlying etiologies of PR can be broadly divided into immune and nonimmune causes. A high index of suspicion is required to initiate testing for alloimmunization, and the leading culprit in immune PR is the development of class I HLA antibodies. The approach to diagnosis of immune PR has changed over recent years with new technologies, but questions regarding the clinical significance and interpretation of these methods have not been conclusively answered. The provision of HLA-matched platelets requires close and timely coordination between transfusion services and clinical teams; however, the true impact of their provision on clinical outcomes is not clear. This paper reviews diagnostic and management challenges, appraises the existing data available to support treatment options, and identifies research gaps.

Immune cell functionality is highly dependent on the actin cytoskeleton. The actin cytoskeleton is regulated by a complex molecular machinery that involves multiple genes. Mutations in these genes can cause inborn errors of immunity, also termed immunoactinopathies, of which Wiskott-Aldrich syndrome is the best-characterized entity. Currently, mutations in 23 genes can be considered causative of immunoactinopathies. Immunoactinopathies are rare disease entities with complex combinations of clinical manifestations, including immunodeficiency, immune dysregulation, malignancies, atopy, thrombocytopenia and bleeding, skin involvement, or congenital defects. Prompt diagnosis is crucial, because hematopoietic stem cell transplantation in an early phase can offer cure and prevent further complications. This review provides a detailed summary of the clinical experience with immunoactinopathies so far, elaborates on the most distinguishing features of immunoactinopathies by providing a clinical categorization, and links this information to the underlying biological pathways. This information may be of help to clinicians in the diagnosis of patients and to eventually improve patient care.

For patients with myelodysplastic neoplasm/syndrome (MDS), allogeneic hematopoietic cell transplantation (allo-HCT) represents the only potentially curative treatment, capable of eradicating disease-related mutant hematopoietic cells and establishing normal donor hematopoiesis. Biologic-assignment clinical trials have indicated that in eligible patients, allo-HCT is associated with superior clinical outcomes compared with nontransplant therapy. However, this therapeutic option is only available to a subset of patients, and the outcome is influenced by multiple factors inherent to the patient, the MDS subtype, and the allo-HCT procedure itself. In 2017, the European Society for Blood and Marrow Transplantation (EBMT) published recommendations for allo-HCT in MDS to guide practical decision making. In the contemporary era, genomic profiling has become routine clinical practice in many centers, and the most recent classification systems include MDS entities that are defined by genetic abnormalities. In particular, the molecular International Prognostic Scoring System offers more precise prognostication across all clinical end points and currently represents the standard tool for estimating patient survival in the absence of disease-modifying treatment. Evidence from multiple sources increasingly indicates that allo-HCT should be considered at the time of diagnosis in all eligible patients with MDS. Therefore, genomic profiling for somatic mutations and testing for germ line predisposition variants are integral to determining a patient's eligibility for transplantation. Although all patients with higher-risk MDS are potential candidates for immediate transplantation, a subset of those with lower-risk MDS may also derive benefit from this procedure at an earlier disease stage. Comprehensive recommendations on behalf of an expert international panel for clinical practice and future clinical studies of relevance are presented.

Novel CD3×CD20 bispecific antibody (BsAb) immunotherapies have entered the armamentarium for follicular lymphoma and diffuse large B-cell lymphoma based on accelerated approvals. The primary challenge in utilizing BsAbs lies in patient selection due to variable responses, unique toxicity, and health economics. To date, no validated biomarkers of therapy response exist, however data demonstrating potential clinical, imaging, and biological markers relating to BsAbs are growing. This review examines current prognostic and potentially predictive biomarkers and explores future directions for nuanced patient selection.