Journal - Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation (United States )

Journal - Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation (United States )

Abstract :

Patients undergoing autologous hematopoietic stem cell transplantation (autoHCT) are at increased risk for infection with Streptococcus pneumoniae and have impaired antibody responses to pneumococcal polysaccharide vaccines. We performed this study to examine the ability of autoHCT patients to respond to a heptavalent pneumococcal conjugate vaccine (PCV7) given after transplantation and to determine whether there was a potential benefit of immunizing these patients before stem cell collection. Sixty-one patients scheduled for autoHCT were randomized to receive either PCV7 or no vaccine before stem cell collection. After stem cell reinfusion, all study patients were immunized with PCV7 at 3, 6, and 12 months. Pneumococcal immunoglobulin G antibody concentrations were measured at the time of each immunization and 1 month after the 12-month dose. Serotype-specific pneumococcal antibody concentrations were significantly higher in patients immunized with PCV7 before stem cell collection compared with patients not immunized before their stem cells were collected for 6 of 7 serotypes at 3 months, 6 of 7 serotypes at 6 months, 4 of 7 serotypes at 12 months, and 3 of 7 serotypes at 13 months. After the 3-dose series of PCV7 after autoHCT, >60% of study patients had protective concentrations of antibody to all 7 vaccine serotypes regardless of immunization before stem cell collection. Pneumococcal conjugate vaccine is immunogenic in autoHCT patients and may be an effective strategy to prevent invasive disease after transplantation.

Journal - Pediatric transplantation (Denmark )

Abstract :

Graft-vs-host disease (GVHD) is one of the most difficult problems in stem cell transplantation. It is best considered in the context of the normal immune response. The role of the immune system is to identify and eliminate foreign antigens. In the case of GVHD, the antigens are minor histocompatibility antigens (mHA) recognized in an inflammatory milieu. The immune system cannot reasonably be expected to selectively recognize microbial antigens and ignore mHA. This approach would require the generation of selective tolerance--something that clearly occurs but which we have frustratingly little control over. While we can often treat and remit even life-threatening GVHD, the consequence has been the development of fatal opportunistic infections. The challenge is to change our style of thinking about GVHD to allow a transition from a 'nuclear winter' approach that controls GVHD at the price of infection, to a more selective patient approach that recognizes the limitations of immunosuppressive therapy.

Journal - Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation (United States )

Journal - Bone marrow transplantation (England )

Abstract :

Interleukin-11 (IL-11) decreases cytokine release and increases survival in murine BMT models. In these systems, it reduces gut permeability, partially polarizes T cells to a Th2 phenotype, down-regulates IL-12, prevents mucositis, and accelerates recovery of oral and bowel mucosa. We conducted a randomized double-blind pilot study of rhIL-11 administered with cyclosporine/MTX prophylaxis after cytoxan/TBI conditioning and allogeneic stem cell transplantation for hematologic malignancies. Patients received rhIL-11, 50 microg/kg subcutaneously daily or placebo in a 3:1 ratio. Treatment was administered prior to the start of conditioning and continued up to 21 days. The study was designed to assess safety with stopping rules for cardiac arrhythmias and mortality. Although projected to accrue 20 patients, only 13 patients (10 IL-11, three placebo) were enrolled because the early stopping rule for mortality was triggered. Of 10 evaluable patients who received IL-11, four died by day 40 and one died on day 85. Deaths were attributable to transplant-related toxicity. One of three placebo recipients died of suicide, the other two are alive. Patients receiving IL-11 had severe fluid retention and early mortality, making it impossible to determine whether IL-11 given in this schedule can reduce the rate of GVHD. Grade B-D acute GVHD occurred in two of eight evaluable patients on IL-11 and one of three patients on placebo. The primary adverse events of the study were severe fluid retention resistant to diuresis (average weight gain 9 +/- 4%) and multiorgan failure in five of 10 evaluable patients. The use of IL-11 as GVHD prophylaxis in allogeneic transplantation cannot be recommended as administered in this trial.

Journal - The New England journal of medicine (United States )