Moore, S. Breanndan

A 59‐year‐old female developed symptoms of graft‐versus‐host disease 3½ weeks after liver transplantation for primary biliary cirrhosis. Symptoms of graft‐versus‐host disease included fever, erythroderma with bullae formation, and mucosal surface ulceration. Donor lymphocytes were present in the peripheral blood. Despite treatment with equine antilymphoblast globulin, steroids and, eventually, cyclosporine withdrawal, she developed neutropenia and succumbed to sepsis. At autopsy, she had marked lymphocyte depletion involving the bone marrow and both native and donor origin lymph nodes. As expected, the liver was normal. The clinical and pathological features were remarkably similar to those of the few other reported cases of graft‐versus‐host disease after liver transplantation and transfusion‐associated graft‐versus‐host disease; therapy is usually ineffective, and progression of disease leads to pancytopenia and death from sepsis.

Abstract Anti-AnWj (Anton) has been associated with clinically significant hemolytic transfusion reactions. More than 99 percent of studied populations have RBCs that express the antigen. Reported here is a patient with anti-AnWj who was transfused with antigen-positive RBCs without adverse reaction. Immunohematology 2007; 23:55–58.

Abstract Peripheral blood infused total autograft absolute lymphocyte count (A-ALC) correlates with day 15 absolute lymphocyte count and is an independent prognostic factor for survival after autologous stem cell transplantation (ASCT) for non-Hodgkin lymphoma (NHL). Factors to enhance A-ALC collections are not well defined. We hypothesize that the number of peripheral blood apheresis collections (PBAC) directly correlates with A-ALC. 190 consecutive NHL patients who underwent ASCT at the Mayo Clinic between 1993 and 2001 were analyzed. The primary end point of the study was to assess the correlation between the number of PBAC and A-ALC. The secondary end point was to determine if the number of PBAC affected survival post-ASCT. Of the 190 patients, 18 patients underwent 1 PBAC, 23 patients 2 PBAC, 50 patients 3 PBAC, 37 patients 4 PBAC, 50 patients 5 PBAC, and 12 patients had ≥ 6 PBAC. There was no association between the number of PBAC and the number of CD34+ stem cells collected (p= 0.25). A strong association between number of PBAC and A-ALC (Kruskall Wallis test, p <0.0001)(Figure 1) was identified. Using a cut-off of 4 PBAC, superior overall survival (OS) and progression-free survival (PFS) were observed for patients that underwent 4 PBAC or more compared to patients that underwent less than 4 PBAC (86 months vs 18 months, p <0.0001; 76 months vs 10 months, p <0.0001, respectively). Multivariate analysis demonstrated PBAC ≥ 4 is an independent prognostic factor for OS (RR = 0.654, 95%CI: 0.529–0.804, p< 0.0001) and for PFS (RR = 0.682, 95%CI: 0.561–0.826, p< 0.0001) when compared with other significant factors including performance status, lactate dehydrogenase and extra nodal disease. These data suggest that increasing the number of PBAC beyond the minimum number required to meet CD34+ collection targets may result in improved overall and progression-free survival mediated by an increase in autograft absolute lymphocyte count.

Abstract Acute lung injury (ALI) is an infrequently recognized complication of transfusion therapy. Although the role of passive transfer of leukoagglutinating antibodies has been acknowledged, there is little documentation of the relationship of these antibodies in transfused blood to the human leukocyte antigen (HLA) phenotype of the recipient. Recently, we observed 5 cases of transfusion-related ALI, and in all cases leukoagglutinating and lymphocytotoxic antibodies were found in serums of the transfused blood products. In 3 cases, the antibodies corresponded to the HLA antigens of the recipient. Multiparous blood donors whose plasma contains these antibodies represent a potential transfusion hazard. It is recommended that blood component usage from donors implicated in these reactions be restricted to frozen or washed red blood cells. The incidence of leukoagglutinin-associated ALI may be more frequent than previously appreciated. Current concepts of the mechanism of microvascular pulmonary injury are discussed in relation to these cases.

Abstract Rationale Acute lung injury (ALI) that develops 6 hours after transfusion (TRALI) is the leading cause of transfusion-related mortality. Several transfusion characteristics have been postulated as risk factors for TRALI, but the evidence is limited to retrospective studies. Objectives To compare patient and transfusion risk factors between patients who do and do not develop ALI. Methods In this prospective cohort study, consecutive transfused critically ill patients were closely observed for development of ALI. Donor samples were collected from the transfusion bags. Risk factors were compared between patients who developed ALI after transfusion and transfused control patients, matched by age, sex, and admission diagnosis. Measurements and Main Results Seventy-four of 901 transfused patients developed ALI within 6 hours of transfusion (8%). Compared with transfused control subjects, patients with ALI were more likely to have sepsis (37 vs. 22%, P = 0.016) and a history of chronic alcohol abuse (37 vs. 18%, P = 0.006). When adjusted for patient characteristics, transfusion of plasma from female donors (odds ratio [OR], 5.09; 95% confidence interval [95% CI], 1.37–18.85) rather than male donors (OR, 1.60; 95% CI, 0.76 to 3.37), number of pregnancies among the donors (OR, 1.19; 95% CI, 1.05 to 1.34), number of donor units positive for anti-granulocyte antibodies (OR, 4.85; 95% CI, 1.32–17.86) and anti–HLA class II antibodies (OR, 3.08; 95% CI, 1.15–8.25), and concentration of lysophosphatidylcholine in the donor product (OR, 1.69; 95% CI, 1.10 to 2.59) were associated with the development of ALI. Conclusions Both patient and transfusion risk factors determine the probability of ALI after transfusion. Transfusion factors represent attractive targets for the prevention of ALI.

Controversy exists regarding the pathogenic or predictive role of anti-myelin oligodendrocyte glycoprotein (MOG) antibodies in patients with multiple sclerosis (MS). Four immunopathological patterns (IP) have been recognized in early active MS lesions, suggesting heterogeneous pathogenic mechanisms. Whether MOG antibodies contribute to this pathological heterogeneity and potentially serve as biomarkers to identify specific pathological patterns is unknown. Here we report the frequencies of antibodies to human recombinant MOG (identified by Western blot and enzymelinked immunoabsorbent assay (ELISA)) in patients with pathologically proven demyelinating disease, and investigate whether antibody status is associated with clinical course, HLA-DR2 genotype, IP or treatment response to plasmapheresis. The biopsy cohort consisted of 72 patients: 12 pattern I, 43 pattern II and 17 pattern III. No association was found between MOG antibody status and conversion to clinically definite MS, DR-2 status, IP or response to plasmapheresis. There was poor agreement between Western blot and ELISA (kappa=0.07 for MOG IgM). Fluctuations in antibody seropositivity were seen for 3/4 patients tested serially by Western blot. This study does not support a pathologic pattern-specific role for MOG-antibodies. Variable MOG-antibody status on serial measurements, coupled with the lack of Western blot and ELISA correlations, raises concern regarding the use of MOG-antibody as an MS biomarker and underscores the need for methodological consensus.

Using chromosome heteromorphisms and blood cell types as genetic markers, we demonstrated chimerism in a chi46,XX/46,XY true hermaphrodite. The pattern of inheritance of the chromosome heteromorphisms indicates that this individual was probably conceived by the fertilization, by two different spermatozoa, of an ovum and the second meiotic division polar body derived from the ovum and subsequent fusion of the two zygotes. This conclusion is based on the identification of the same maternal chromosomes 13, 16, and 21 in both the 46,XX and 46,XY cells of the patient. In the two cell lines of the chimera, chromosomal markers showed different paternal No. 9 chromosomes and sex chromosomes, as well as the same paternal chromosome 22.