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Hematopoietic cell transplantation (HCT) is a potentially curative treatment for children and adults with malignant and non-malignant diseases. Despite increasing survival rates, long-term morbidity following HCT is substantial. Neurocognitive dysfunction is a serious cause of morbidity, yet little is known about neurocognitive dysfunction following HCT. To address this gap, collaborative efforts of the Center for International Blood and Marrow Transplant Research and the European Society for Blood and Marrow Transplantation undertook an expert review of neurocognitive dysfunction following HCT. In this review, we define what constitutes neurocognitive dysfunction, characterize its risk factors and sequelae, describe tools and methods to assess neurocognitive function in HCT recipients, and discuss possible interventions for HCT patients with this condition. This review aims to help clinicians understand the scope of this health-related problem, highlight its impact on well-being of survivors, and to help determine factors that may improve identification of patients at risk for declines in cognitive functioning after HCT. In particular, we review strategies for preventing and treating neurocognitive dysfunction in HCT patients. Lastly, we highlight the need for well-designed studies to develop and test interventions aimed at preventing and improving neurocognitive dysfunction and its sequelae following HCT.

Effectively treating patients with multiple myeloma is challenging. The development of therapeutic regimens over the past decade that incorporate the proteasome inhibitor bortezomib and the immunomodulatory drugs thalidomide and lenalidomide has been the cornerstone of improving the outcome of patients with myeloma. Although these treatment regimens have improved patient survival, nearly all patients eventually relapse. Our improved understanding of the biology of the disease and the importance of the microenvironment has translated into ongoing work to help overcome the challenge of relapse. Several classes of agents including next-generation proteasome inhibitors, immunomodulatory agents, selective histone-deacetylase inhibitors, antibody and antitumor immunotherapy approaches are currently undergoing preclinical and clinical evaluation. This Review provides an update on the latest advances in the treatment of multiple myeloma. In particular, we focus on novel therapies including modulating protein homeostasis, kinases inhibitors, targeting accessory cells and cytokines, and immunomodulatory agents. A discussion of the challenges associated with these therapeutic approaches is also presented.

Plasmacytomas are localized tumors of monoclonal plasma cells without evidence of significant bone marrow infiltration or systemic myeloma, comprising ∼2–10% of all plasma cell neoplasms.1 Medullary plasmacytomas classically occur in the bone of the vertebrae or skull, whereas extramedullary plasmacytomas occur in the soft tissues, most frequently in the head and neck region involving the sinuses or rhinopharynx.1 Both medullary and extramedullary plasmacytomas occur in males more often than in females with a median age at diagnosis of 54 years.1 Furthermore, plasmacytomas in general are fairly radiosensitive, such that the current treatment of choice is localized radiation therapy except in cases of neurologic compromise or bone instability that require surgical resection.2 There is no evidence thus far that adjuvant systemic chemotherapy offers additional clinical benefit.2 Despite these similarities, medullary and extramedullary plasmacytomas are considered distinct clinical entities owing to differences in their predisposition to evolve into multiple myeloma (MM). Medullary plasmacytomas are traditionally thought to have a higher risk of progression, also with a lower 5-year survival rate of 33% once they have progressed to MM (as opposed to 5-year survival rate of 100% in extramedullary plasmacytomas that progress to MM).2 Yet, very little is known regarding genetic or molecular factors that distinguish these two groups of plasmacytomas and influence their clinical outcome.