In the century since the discovery of the ABO blood groups, numerous associations between ABO groups and disease have been noted. However, the selection pressures defining the ABO distributions remain uncertain. We review published information on Plasmodium falciparum infection and ABO blood groups. DNA sequence information dates the emergence and development of the group O allele to a period of evolution before human migration out of Africa, concomitant with P falciparum's activity. The current geographic distribution of group O is also consistent with a selection pressure by P falciparum in favor of group O individuals in malaria-endemic regions. We critically review clinical reports of ABO and P falciparum infection, documenting a correlation between disease severity and ABO group. Finally, we review published data on the pathogenesis of P falciparum infection, and propose a biologic model to summarize the role of ABO blood groups in cytoadherence biology. Such ABO-related mechanisms also point to a new hypothesis to account for selection of the Le(a−b−) phenotype. Taken together, a broad range of available evidence suggests that the origin, distribution, and relative proportion of ABO blood groups in humans may have been directly influenced by selective genetic pressure from P falciparum infection.

Each year approximately 100 million blood donations are made worldwide.¹ Regulatory agencies use radiolabeled cell survival and in vitro markers of hemolysis rather than measures of oxygen delivery to establish the maximal duration of blood storage, which is usually 5 or 6 weeks depending on the jurisdiction. During storage, however, red blood cells (RBCs) undergo changes that might impair the capacity for tissue oxygenation by transfused RBCs.^2-7

Key Points: Fifty percent of TA-GVHD cases occur in patients who would not be predicted to be at risk for TA-GVHD by current guidelines for blood irradiation. Donor lymphocytes whose HLA antigens are all shared by the recipient dominate in TA-GVHD cases, particularly in immune-competent recipients.

Severe malaria is a leading cause of childhood mortality in Africa. However, at presentation, it is difficult to predict which children with severe malaria are at greatest risk of death. Dysregulated host inflammatory responses and endothelial activation play central roles in severe malaria pathogenesis. We hypothesized that biomarkers of these processes would accurately predict outcome among children with severe malaria. Plasma was obtained from children with uncomplicated malaria (n = 53), cerebral malaria (n = 44) and severe malarial anemia (n = 59) at time of presentation to hospital in Kampala, Uganda. Levels of angiopoietin-2, von Willebrand Factor (vWF), vWF propeptide, soluble P-selectin, soluble intercellular adhesion molecule-1 (ICAM-1), soluble endoglin, soluble FMS-like tyrosine kinase-1 (Flt-1), soluble Tie-2, C-reactive protein, procalcitonin, 10 kDa interferon gamma-induced protein (IP-10), and soluble triggering receptor expressed on myeloid cells-1 (TREM-1) were determined by ELISA. Receiver operating characteristic (ROC) curve analysis was used to assess predictive accuracy of individual biomarkers. Six biomarkers (angiopoietin-2, soluble ICAM-1, soluble Flt-1, procalcitonin, IP-10, soluble TREM-1) discriminated well between children who survived severe malaria infection and those who subsequently died (area under ROC curve>0.7). Combinational approaches were applied in an attempt to improve accuracy. A biomarker score was developed based on dichotomization and summation of the six biomarkers, resulting in 95.7% (95% CI: 78.1–99.9) sensitivity and 88.8% (79.7–94.7) specificity for predicting death. Similar predictive accuracy was achieved with models comprised of 3 biomarkers. Classification tree analysis generated a 3-marker model with 100% sensitivity and 92.5% specificity (cross-validated misclassification rate: 15.4%, standard error 4.9%). We identified novel host biomarkers of pediatric severe and fatal malaria (soluble TREM-1 and soluble Flt-1) and generated simple biomarker combinations that accurately predicted death in an African pediatric population. While requiring validation in further studies, these results suggest the utility of combinatorial biomarker strategies as prognostic tests for severe malaria.

Summary: Involvement of the central nervous system (CNS) in multiple myeloma (MM) is a rare complication, with reported survival of <6 months. This report describes 37 MM patients with leptomeningeal and/or parenchymal brain involvement treated at our institution and identifies factors associated with long‐term survival. From January 1999 to December 2010, 37 patients with CNS MM were evaluated at our institution. Clinical characteristics, treatment and survival were retrospectively collected. CNS disease was present at MM diagnosis in 24% and at relapse in 76%. Plasma cell leukemia (40%) and skull plasmacytomas (65%) were common, suggesting haematological and contiguous spread. Intrathecal (IT) chemotherapy was used in 81%, cranial and/or spinal irradiation in 78%, and various systemic therapies [immunomodulatory agents (IMiDs) (51%), cisplatin‐based (DPACE; cisplatin, doxorubicin, cyclophosphamide, etoposide) (27%), bortezomib (19%), alkylators (11%), dexamethasone alone (8%), auto‐transplant (5%)]. Median survival from CNS disease was only 4·6 months [95% confidence interval (CI): 2·8–6·7]; however, nine patients had prolonged survival (median: 17·1 months, 95% CI: 13·2–67·4). In general, these long‐term survivors were treated with radiotherapy, multi‐dosing IT chemotherapy, and IMiD‐containing therapy. CNS MM is a highly aggressive disease but in our experience, long‐term survival can be achieved with the combination of multi‐dosing IT chemotherapy, radiation and IMiD‐based therapy.