Defective anticarbohydrate antibody responses to naturally occurring bacteria following bone marrow transplantation

AbstractThe long-term recipients of allogeneic bone marrow transplantation (BMT) are at an increased risk of death due to bacterial infections. We evaluated the anticarbohydrate antibody responses of BMT recipients to a naturally occurring bacterial carbohydrate, polyribose phosphate (PRP). The recipients of autologous BMT achieved protective anti-PRP levels (>100 ng/mL) by 3 years after transplantation, with a pattern consistent with a recapitulation of the ontogeny of anticarbohydrate antibody responses. None of the six recipients of unrelated BMT who were off immunosuppressive therapy had protective anti-PRP levels, though their response to a protein antigen (tetanus toxoid) was normal. Of 48 recipients of histocompatible BMT, 22 (46%) had protective anti-PRP antibody levels, whereas 13 (27%) recipients who were >3 years post-BMT did not have protective levels. Therefore, all unrelated recipients and a significant proportion of histocompatible recipients without clinical graft-vs.-host disease had persistent and prolonged defects in their capacity to produce antibodies to naturally occurring bacterial carbohydrate antigens. These results suggest that allogeneic BMT recipients should be longitudinally evaluated for their anticarbohydrate antibody responses and that patients with defective antibody responses should receive prophylactic antibiotics or replacement immunoglobulin therapy or both to reduce their risk of late bacterial infections.Biol Blood Marrow Transplant 1999;5(1):46-50

The Biology of Chronic Graft-versus-Host Disease: A Task Force Report from the National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease

Chronic graft-versus-host disease (GVHD) is the leading cause of late, nonrelapse mortality and disability in allogeneic hematopoietic cell transplantation recipients and a major obstacle to improving outcomes. The biology of chronic GVHD remains enigmatic, but understanding the underpinnings of the immunologic mechanisms responsible for the initiation and progression of disease is fundamental to developing effective prevention and treatment strategies. The goals of this task force review are as follows: • Summarize the current state of the science regarding pathogenic mechanisms of chronic GVHD and critical knowledge gaps. • Develop working hypotheses/overriding concepts for chronic GVHD development. • Define the usefulness of current preclinical models to test working hypotheses and ultimately discover and develop new therapeutic strategies. • Identify shortcomings of preclinical models, and define criteria for the creation of additional models to address these limitations. This document is intended as a review of our understanding of chronic GVHD biology and therapies resulting from preclinical studies, and as a platform for developing innovative clinical strategies to prevent and treat chronic GVHD

Long-term neurocognitive function of pediatric patients with severe combined immune deficiency (SCID): pre- and post-hematopoietic stem cell transplant (HSCT).

BACKGROUND:Hematopoietic stem cell transplantation (HSCT) is the only cure for patients with severe combined immunodeficiency (SCID). The purpose of this study was to evaluate long-term neurodevelopment of patients with SCID following myeloablative chemotherapy and HSCT. MATERIALS AND METHODS:Sixteen pediatric patients diagnosed with SCID were tested using the Bayley Scales of Infant Development and the validated Vineland Adaptive Behavior Scales (VABS) pre- and 1-year post-HSCT. Three years post-HSCT, there were 11 patients available for testing and four patients available 5 years post-HSCT. Patients greater than 3 years of age were administered the Wechsler Preschool and Primary Scale of Intelligence. Both raw scores and scaled scores were analyzed. RESULTS:There was a significant decrease 1 year post-HSCT in the Bayley Mental Developmental Index (MDI) [92.5 (pre) vs. 70.81 (1 year post), p < 0.0001] and the VABS [99.73 (pre) vs. 79.87 (1 year post), p = <0.0001]. There was a significant decrease over time in the MDI [95.00 (pre) vs. 72.64 (1 year post) vs. 71.82 (3 years post), p < 0.0001], but no significant change between 1 and 3 years post-HSCT. There was no change in the Bayley Psychomotor Development Scale (PDI) [82.4 (pre) vs. 84.8 (1 year post), p = 0.68]. The PDI scores decreased over time [86.29 (pre) vs. 86 (1 year post) vs. 74.14 (3 years post), p = 0.045]. Although there was a decrease in scaled scores, there was not a loss of skills. Analysis of raw scores showed that there was an increase in the raw test scores, which indicated that these children acquired developmental skills, but at a slower rate than normal infants and toddlers. Younger children had a more significant decrease in adaptive scores compared with older children. CONCLUSIONS:These findings may reflect the effects of the isolation and prolonged hospitalization that characterizes the immediate post-transplant period. Patients miss out on social interactions and learning opportunities that normally occur at their respective stages of development. These restrictions keep patients from acquiring developmentally appropriate cognitive skills as well as gross and fine motor developmental milestones. Longitudinal follow-up will be important to quantify acquisition of skills