Immune response to the 23-valent polysaccharide pneumococcal vaccine after the 7-valent conjugate vaccine in allogeneic stem cell transplant recipients: results from the EBMT IDWP01 trial.

The current recommendations for active immunization after stem cell transplant (SCT) include 3 doses of 7-valent pneumococcal conjugate vaccine (PCV7) from 3 months after transplant, followed by a 23-valent polysaccharide pneumococcal vaccine (PPV23). However, until now, the immune response to PPV23 after PCV7 has not been assessed after SCT. In the EBMT IDWP01 trial, 101 patients received 1 dose of PPV23 at 12 or 18 months, both after 3 doses of PCV7. The efficacy of PPV23 was assessed 1 month later and at 24 months after transplant by the pneumococcal serotype 1 and 5 antibody levels. Serotype 1 and 5 are not included in PCV7. Although the geometric mean concentrations were significantly higher 1 month after PPV23, for both antigens, the response rates (> or =0.15 microg/mL), in the range of 68-94%, were not different between groups independent of the assessment date. One PPV23 dose after 3 PCV7 doses, already known to increase the response to PCV7, also extends the serotype coverage given 12 or 18 months after transplant.

Autologous hematopoietic stem cell transplantation for autoimmune diseases: an observational study on 12 years' experience from the European Group for Blood and Marrow Transplantation Working Party on Autoimmune Diseases.

BACKGROUND: Autologous hematopoietic stem cell transplantation has been used since 1996 for the treatment of severe autoimmune diseases refractory to approved therapies. We evaluated the long-term outcomes of these transplants and aimed to identify potential prognostic factors. DESIGN AND METHODS: In this observational study we analyzed all first autologous hematopoietic stem cell transplants for autoimmune diseases reported to the European Group for Blood and Marrow Transplantation (EBMT) registry between 1996-2007. The primary end-points for analysis were overall survival, progression-free survival and transplant-related mortality at 100 days. RESULTS: Nine hundred patients with autoimmune diseases (64% female; median age, 35 years) who underwent a first autologous hematopoietic stem cell transplant were included. The main diseases were multiple sclerosis (n=345), systemic sclerosis (n=175), systemic lupus erythematosus (n=85), rheumatoid arthritis (n=89), juvenile arthritis (n=65), and hematologic immune cytopenia (n=37). Among all patients, the 5-year survival was 85% and the progression-free survival 43%, although the rates varied widely according to the type of autoimmune disease. By multivariate analysis, the 100-day transplant-related mortality was associated with the transplant centers' experience (P=0.003) and type of autoimmune disease (P=0.03). No significant influence of transplant technique was identified. Age less than 35 years (P=0.004), transplantation after 2000 (P=0.0015) and diagnosis (P=0.0007) were associated with progression-free survival. CONCLUSIONS: This largest cohort studied worldwide shows that autologous hematopoietic stem cell transplantation can induce sustained remissions for more than 5 years in patients with severe autoimmune diseases refractory to conventional therapy. The type of autoimmune disease, rather than transplant technique, was the most relevant determinant of outcome. Results improved with time and were associated with the transplant centers' experience. These data support ongoing and planned phase III trials to evaluate the place of autologous hematopoietic stem cell transplantation in the treatment strategy for severe autoimmune diseases.

Randomized study of early versus late immunization with pneumococcal conjugate vaccine after allogeneic stem cell transplantation.

BACKGROUND: Invasive pneumococcal disease is a life-threatening complication after allogeneic stem cell transplantation, and at least 20% of cases occur within 1 year after transplantation. The 23-valent pneumococcal polysaccharide vaccine (PPV23) has limited efficacy, especially during the first year after transplantation. The immune response to the conjugated vaccines is expected to be better than that to the polysaccharide vaccine, but the optimal timing of vaccination is not defined. Our objective was to show that a 7-valent pneumococcal conjugate vaccine (PCV7; Prevnar) was not inferior when first given 3 months after transplantation, compared with when first given 9 months after transplantation. METHODS: We performed a multicenter, randomized, noninferiority study involving 158 patients from 13 European Group for Blood and Marrow Transplantation centers who were randomly allocated at approximately 100 days after myeloablative stem cell transplantation to receive a series of vaccinations (3 doses of PCV7 given 1 month apart) that was started immediately (i.e., 3 months after transplantation) or 6 months later (i.e., 9 months after transplantation). The primary evaluation criterion was the rate of response (antibody level, > or = 0.15 microg/mL for each of the 7 serotypes) at 1 month after the third dose of PCV7. The noninferiority margin was 20%. All patients were followed up for 24 months after transplantation or until death, whichever occurred first. RESULTS: We found that the response rate was not lower after early vaccination (79% [45 of 57 patients]) than after late vaccination (82% [47 of 57 patients]) (difference, -3.5%; 90% confidence interval, -15.6 to 8.6; not significant). CONCLUSIONS: We conclude that PCV7 vaccination at 3 months after stem cell transplantation is not inferior to PCV7 vaccination at 9 months after transplantation. Because invasive pneumococcal disease can occur early, we recommend starting the PCV7 vaccination series at 3 months after transplantation to ensure earlier protection against Streptococcus pneumoniae. However, the early vaccination may result in only short-lasting response and may not prime for a 23-valent pneumococcal polysaccharide vaccine boost as efficiently as the late vaccination.