Non-Myeloablative Stem Cell Transplantation for Congenital Immunodeficiencies

Abstract

Allogeneic haematopoietic stem cell transplantation (HSCT) can be a highly successful treatment option for individuals with congenital im- munodeficiency states. The strategy for HSCT is varied but in cases where there is preservation of residual T cell function, conditioning regimes have been used and have been based around a combination of busulphan and cyclophosphamide with or without serotherapy. In patients with coexisting organ damage this has resulted in significant morbidity and mortality. We have therefore used a low-intensity conditioning regime for transplantation in this group of immunodeficiency patients. Twenty-one patients with a variety of different immunodeficiencies were treated using the following conditioning regimes: (I) fludarabine/melphalan/ATG or Campath IH (n = 16), (2) fludarabine/cyclophosphamide/Campath IH (n = 1), (3) TBI/CyA/MMF n = l), (4) fludarabine/melphalan/busulphan/ATG n = 3). In 13 cases matched (n = 9) and 1 Ag mismatched (n = 4) unrelated donors were used and in eight cases transplants from matched sibhngs (K = 4), 1 Ag mismatched sibling (n = 1), matched parent (n = 1) and haploidentical parents (n=3) were performed. At a median follow-up of 13 months, 19 of 21 (90%) patients were still alive following the transplant procedure. Despite a T cell replete graft and the use of un- related donor grafts in the majority of patients studied there was no evidence of significant organ disease. Immune reconstitution in terms of CD3⁺ and CD4⁺ T cell recovery and function was equivalent in comparison with a historical cohort. We believe that this low-intensity approach has significant implications for transplantation of indi- viduals with immunodeficiency states with established organ disease.