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Bone Marrow Transplantation Research Group

Clinical Haematology and Bone Marrow Transplantation

Laboratory members
Head: Associate Professor Anthony Schwarer

Gerri Bollard
Mirek Kapuscinski
Ann Stewart
Mingus Rose
Kate Ward, PhD student
Tamara Etto, PhD student
Oanh Nguyen, Honours student
Christina Ioannidis, Honours student

Bone Marrow Transplantation

The bone marrow transplant program has had a busy year with activity in clinical research and translational research. The primary goal of our translational, laboratory-based research is the understanding of the graft-versus-leukaemia phenomenon and the development of laboratory techniques that attempt to harness this phenomenon to increase the chance of curing patients with leukaemia and, at the same time, potentially decreasing the side‑effects and risks of transplantation. Our clinical research activity includes involvement in national and international trials of new treatments for malignant diseases such as leukaemia, lymphoma and myeloma as well conducting trials that we have designed ourselves.

The bone marrow transplant laboratory has three senior scientists (Gerri Bollard, Mirek Kapuscinski and Ann Stewart), one research scientist (Mingus Rose), two PhD students (Kate Ward and Tamara Etto) and two BSc Honours students (Oanh Nguyen and Christina Ioannidis). The laboratory is headed by Associate Professor Anthony Schwarer. Gerri Bollard runs the stem cell processing and cryopreservation section of the laboratory, manipulating the peripheral blood stem cells and bone marrow stem cells from patients and donors. Mirek Kapuscinski assists Gerri Bollard on the clinical side as well as conducting his own research into chimerism post transplant. He also supervised Christina Ioannidis. Christina investigated the association of vitamin D receptor polymorphisms with post transplant complications such as graft-versus-host disease.

Ann Stewart has been collaborating with Joanna Paddle-Ledinek of the Burns Unit to generate large numbers of keratinocytes that may help develop techniques that will allow us to remove immune cells from the donor stem cells that are capable of causing graft-versus-host disease while retaining those immune cells that are important for the graft-versus-leukaemia phenomenon. In addition, Dr Stewart supervised Oanh Nguyen who developed a technique using insect cells to produce large amounts of a viral protein (CMV pp65) which can be used to generate immune cells that can prevent infection with CMV post transplant. This technique can be adapted to allow us to develop specific immune cells against many infectious organisms.

Mingus Rose has been working with natural killer (NK) cells. Recent work by others suggested that NK cells play a crucial role in generating a graft-versus-leukaemia effect in a special transplant scenario termed haploidentical transplantation where the donor and patient are only half-matched for the tissue typing antigens (HLA). This is an exciting new transplant technique that has the potential to change the way transplantation is performed throughout the world.

Christina Ioannides and Oanh Nguyen, the BSc Honours students in the lab, both obtained first class (H1) honours for their work in 2004.

The clinical team of the bone marrow transplant program consists of Associate Professor Anthony P. Schwarer, Associate Professor Andrew Spencer and Dr Sharon Avery. Associate Professor Spencer runs the myeloma research program which is described in a separate section of this report. The clinical team is involved in many clinical trials conducted by international groups (eg European Organisation for the Research and Treatment of Cancer, Centre for International Blood and Marrow Transplantation and Research), and by national groups (eg Australasian Leukaemia and Lymphoma Group, Australian Bone Marrow Transplant Recipient Registry).

These cooperative trials have focused on new treatment of chronic myeloid leukaemia, non-Hodgkin’s lymphoma, acute myeloid leukaemia, Burkitt’s leukaemia/lymphoma and multiple myeloma. Such trials are important in helping set a new standard of care for these diseases.

The bone marrow transplant program has also conducted a number of in-house trials including a technique for reactivating the thymus to help improve immune recovery after transplantation as well as a trial pioneering haploidentical transplantation in Australia. This latter trial is based on the work of a group of Italian researchers who have developed a technique that has the promise to find donors for patients who need transplantation but do not have tissue-type matched donors. This new technique uses family member donors who are only half matched to generate a graft with a very potent graft-versus-leukaemia effect. Preliminary results from the Italian researchers show a cure rate five times that of standard transplantation. We are the first group in Australia to set up such a program.

Our clinical trials would not be possible without Jenny Muirhead and Rosemary McGinnes, our two tireless data managers.

Laboratory research projects

  • Evaluation of peripheral blood stem cell engraftment in non-myeloablative transplant recipients
  • Development of sensitive molecular detection methods for haemopoietic chimerism measurement
  • Vitamin D receptor gene polymorphisms as a predictive marker in non‑myeloablative allogeneic stem cell transplantation
  • Epigenetic regulation of alkylating drug sensitivity in malignant lymphoid cells
  • Decreasing graft-versus-host disease: The use of dendritic cells and keratinocytes to stimulate  potential GVHD-causing T cells to allow depletion of these cells while preserving the T cells responsible for the graft-versus-leukaemia phenomenon and immune recovery after haematopoietic stem cell transplantation
  • Characterisation of CD34+ derived dendritic cells for the use in the generation of CMV specific T cells
  • Generation of the polymorphic minor histocompatibility antigen, HA-1, for use in immunotherapy
  • Production and purification of human cytomegalovirus (HCMV) recombinant protein IE1.pp65 using the baculovirus system to generate a multiple anti-HCMV T cell response
  • Database contributions
  • Prospective study of allogeneic and autologous bone marrow transplant recipients (Australian Bone Marrow Transplant Recipient Registry)
  • Prospective study of allogeneic and autologous bone marrow transplant for patients with life threatening haematological disorders (Centre for International Blood and Marrow Transplant Research)
  • Prospective study of matched unrelated donor transplants (Australian Bone Marrow Donor Registry)