Our research in Birmingham is tailoring therapies for hard to treat chronic lymphoblastic leukaemia (CLL), and finding new treatments for non-Hodgkin lymphoma (NHL), acute myeloid leukaemia (AML) and myeloma. We are also conducting research and clinical trials that are looking for ways to improve the success of stem cell transplants and want to prevent complications, such as Graft versus Host Disease (GvHD). And we have a trial which is refining treatment for children who have acute lymphoblastic leukaemia (ALL) or a type of NHL called lymphoblastic lymphoma (LBL), so that there are less side effects.
Our Trials Acceleration Programme (TAP) hub and centre is based at The Queen Elizabeth Hospital in Birmingham. A number of TAP trials are being led from here that are looking for new ways to treat people with AML and myelodysplastic syndromes (MDS), with a focus on finding treatments that are suitable for people that are unable to tolerate current treatments, and for those who have relapsed.
Professor Tatjana Stankovic and her team want to improve the outcome of people with hard to treat CLL, by tailoring therapies for this group of people. People with CLL are usually treated with chemotherapy and monoclonal antibodies, such as rituximab. While most people do well on these types of treatments, some unfortunately do not respond, or eventually relapse. One way CLL becomes resistant to chemotherapy is through changes in the ATM and TP53 genes. In healthy cells, these genes produce proteins that check for DNA damage in the cell before it divides. In CLL cells that carry these gene changes, the proteins that check for DNA damage proteins are missing. People with these gene changes are also more likely to see their CLL return, and generally have a poorer outcome. Professor Tatjana Stankovic is analysing samples from people enrolled in clinical trials, so they can look at behaviour of blood cancers with defective ATM and TP53 cells. Researchers will also test in the laboratory individual patients’ CLL cells to determine which currently available treatment is most efficient in killing these cells.
Diffuse large B cell lymphoma (DLBCL) the common lymphoma, and is highly aggressive. This type of lymphoma is usually treated with chemotherapy together with an antibody therapy called rituximab. However, this approach does not work well for everyone, as many people do not respond, or only have a partial response. DLBCL appears to avoid immune responses directed against it, although the exact mechanisms are still unclear, so Dr Graham Taylor and his team want to find out how. Researchers hope that improving our understanding of these fundamental processes may lead to improved immune-based treatments for DLBCL that work by restoring or enhancing immune responses against the tumour.
Another lymphoma project is being led by Professor Paul Murray. The team want to find new ways to treat people with Hodgkin lymphoma, so they can improve outcomes for those who do not respond well to, or who are to tolerate conventional therapies. There is also a need to reduce the long-term side-effects of chemotherapy and radiotherapy, which can be harsh especially in children and young adults. Professor Murray and his team want to investigate how two naturally occurring small molecules called lipids can cause Hodgkin lymphoma when they are over-produced. Researchers will be testing if new drugs designed to inhibit lipids are effective in animal models of these lymphomas, and will determine if measuring lipid levels in tissues and blood helps researchers identify people who might benefit from these new therapies.
Professors Constanze Bonifer and Peter Cockerill are finding out what turns healthy blood stem cells into leukaemic stem cells. Many leukaemias are known to be sustained by transformed blood stem cells – sometimes known as ‘leukaemic stem cells’ or “cancer stem cells” - as a result of genetic changes they have acquired that permanently disrupt their normal behaviour. The team are focussing on acute myeloid leukaemia (AML) stem cells, which often have changes in important regulator genes, disrupting the blood cell production. If we can learn about the mechanisms that turn healthy blood stem cells into leukaemic cells, we may be able to reverse this process.
We are also supporting a project that wants to improve the success of stem cell transplants. Although this treatment can cure many blood cancers, it is not always effective, and some people can relapse after the procedure. Professor Paul Moss and his team want to investigate exactly how donor immune cells recognise and kill cancer cells – a process called graft-versus-leukaemia (GvL). The team want to find ways to boost the strength of GvL, and will study how the genes of transplant donors and recipients can influence clinical outcome, so that transplant treatments can be modified to the needs of individual people.
Graft versus Host Disease (GvHD) is a complication that can arise from stem cell transplants. This is where the donor immune system recognises the normal cells of the recipient as “foreign” and attacks them, leading to organ damage. People with GvHD are usually given steroids, which dampens down the immune system. But this course of treatment does not work for everyone because some people can become dependent on steroids, or the treatment stops working. Dr Ram Malladi is leading the AZTEC trial that wants to see if using a chemotherapy called azacitidine can help people with GvHD who are dependent on steroid treatment, or who are no longer responding to steroids.
Dr Farhat Khanim is looking at repurposing existing drugs to treat myeloma. People with myeloma are usually treated with chemotherapy, which can be combined with steroids and biological therapies. But despite treatment being initially successful, in some people myeloma comes back. And because myeloma affects predominantly people over the age of 60, conventional treatments may not be suitable as the side effects can be harsh. Dr Khanim and his team are looking for treatments that have fewer side effects, but are still effective in older people and those with resistant or relapsed disease. The team have identified a combination of an anti-epileptic drug and an anti-tapeworm drug called ‘VaN’ that can kill myeloma cells in the laboratory. They now want to do further testing on this combination in the lab, with the ultimate aim of taking VaN therapy to clinical trials in older people with myeloma, and those whose disease has become resistant or has returned.
We have lots of clinical trials based at The University of Birmingham. The UKALL 2011 is being led by Professor Ajay Vora, and is looking at treatment for children who have acute lymphoblastic leukaemia (ALL) or a type of non-Hodgkin lymphoma (NHL) called lymphoblastic lymphoma (LBL). Researchers want to see if using standard drugs in slightly different ways can achieve the same results but with fewer side effects, and reduce the risk of the blood cancer from returning.
Professor Charlies Craddock is also leading a number of TAP trials that are looking for new ways to treat people with acute myeloid leukaemia (AML) and myelodysplastic syndromes (MDS). In particular we want to find treatments that are suitable for people that are unable to tolerate conventional treatments, such as intensive chemotherapy, and for those who have relapsed after stem cell transplants.