Allogeneic transplantation therapy for the treatment of leukaemia

Abstract

The leukaemias are a diverse group of disseminated malignancies arising from haematopoietic cells. These cells reside primarily in the blood and bone marrow, where they form nodules and interact with stromal cells. The disseminated nature of these malignancies means they cannot be removed surgically, and arise in a state similar to metastases. A wide variety of leukaemias have been described in the literature. This dissertation describes the biology of the four most common human leukaemias: chronic lymphocytic leukaemia, chronic myeloid leukaemia, acute lymphoblastic leukaemia, and acute myeloid leukaemia.

Allogeneic cell transplantation in the form of bone marrow transplantation, haematopoietic stem cell transplantation, or umbilical cord blood transplantation, represents one of the front line treatment options for the eradication of leukaemia.

Although effective, this approach has frequent and serious complications, including the development of acute and/or chronic graft versus host disease, and serious post transplantation infections, which result in a high rate of treatment related mortality amongst recipients.

In this review current protocols for allogeneic cell transplantation are discussed, including matching of the patient with a suitable donor, and the mechanistic detail of acute and chronic graft versus host disease. The generation and efficacy of donor lymphocyte infusions of T cells, including the traditional use of CD4+ and CD8+ _T cells, T regulatory cells, and the efficacy and mechanisms of innate immunity generated against leukaemia by _T cells and NKT cells are detailed, as are the implications of using dendritic cells to generate antigen specific adaptive immune responses towards leukaemia.

The clinical utilisation of ex vivo expanded dendritic cells, NK cells, NKT cells, _T cells, and T regulatory cells, in addition to the use of stem cell or bone marrow transplantation, and _T cells has great potential to reduce treatment related mortality, the incidence and severity of graft versus host disease, and relapse rates.

In the concluding chapter suggestions for potential new allogeneic cell transplantation protocols taking advantage of recent research into the anti-leukaemic and anti-pathogen functions of these cells, to be evaluated for the treatment of each of the four discussed leukaemias are detailed.