Megadose CD34(+) cell grafts improve recovery of T cell engraftment but not B cell immunity in patients with severe combined immunodeficiency disease undergoing haplocompatible nonmyeloablative transplantation.

Abstract

To determine whether T cell engraftment and recovery of B cell immunity could be improved, we prospectively treated 15 children with severe combined immunodeficiency disease (SCID) with megadoses of haplocompatible CD34(+) cells and a fixed number of CD3(+) cells without previous myeloablative chemotherapy. Evidence of T cell engraftment was seen in 73% of patients (95% confidence interval [CI] = 48%-90%). Engraftment was more likely in patients with X-linked SCID and in those with evidence of maternal engraftment at the time of diagnosis. In patients with T cell engraftment, the median time to development of a CD4 count > 200 cells/mm(3) and a phytohemagglutinin response > 50% of control was 1.2 and 4.9 months, respectively. Clearance of preexisting infections occurred after a median of 2.8 months. B cell function developed in 33% of engrafted patients (95% CI = 14%-61%). The 1-year event-free survival (EFS) rate was 60% (95% CI = 36%-80%), and the overall survival (OS) rate was 87% (95% CI = 61%-98%), with a median follow-up of 39 months. The use of megadoses of CD34(+) cells with a fixed number of CD3(+) cells in nonmyeloablative hematopoietic stem cell transplantation (HSCT) in patients with SCID is associated with excellent engraftment, T cell recovery, and OS; however, B cell function does not recover in most patients.

• Authors: Christopher C Dvorak, Giun-Yi Hung, Biljana Horn, Elizabeth Dunn, Ching-Ying Oon, Morton J Cowan
• Journal: Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation (Biol Blood Marrow Transplant) Vol. 14 Issue 10 Pg. 1125-1133 (Oct 2008) ISSN: 1523-6536 [Electronic] United States
• PMID: 18804042 (Publication Type: Clinical Trial, Journal Article)

Chemical References

• Antigens, CD34

Topics

• Antigens, CD34
• B-Lymphocytes (physiology)
• Child
• Female
• Haplotypes
• Hematopoietic Stem Cell Transplantation (methods, mortality)
• Humans
• Immune System (physiology)
• Kinetics
• Lymphocyte Count
• Male
• Regeneration
• Remission Induction
• Severe Combined Immunodeficiency (mortality, therapy)
• Survival Rate
• T-Lymphocytes (physiology)
• Transplantation Conditioning (methods)