Dr Nina Orfali MB PhD FRCPath
Consultant Haematologist, St. James Hospital, Dublin, Ireland and Haematology Association of Ireland Member
Despite predictions that targeted drug therapies would supersede the need for stem cell transplantation in acute myeloid leukaemia (AML), the demand for transplant across Europe continues to rise.
The last decade has brought about remarkable developments in our understanding of acute myeloid leukaemia (AML), a group of malignancies characterised by the accumulation of immature blood cells in the bone marrow and peripheral bloodstream.
In 2008, tumour DNA from a patient with AML became the first cancer genome to be fully characterised. We have since been steadily learning more about the genetic mutations that drive this condition. Today, with modern sequencing technology, almost every patient diagnosed has access to the molecular profiling of leukaemia-associated genes to guide a personalised prognosis.
However, rather than providing a shortcut to cure, the breadth of genetic data available has highlighted the extraordinary complexity of AML. A plethora of mutations occur in varying combinations from patient to patient and even within an individual patient, sub-populations of leukaemia cells carrying different mutations can co-exist. In truth, no two cases of AML are the same.
With genetic testing, the proportion of AML patients classified as having high-risk disease is increasing.
Allogeneic stem cell transplantation
While ‘good-risk’ AML may be cured with chemotherapy alone, for those with high-risk disease, allogeneic (donor) haematopoietic stem cell transplantation offers the only shot at long-term survival. Transplantation harnesses the power of a donor-derived immune system to recognise leukaemia cells as foreign and eradicate them – a so-called ‘graft versus leukaemia’ effect. The procedure carries with it inherent risks, but roughly 50% of all transplanted patients are alive five years later.
Increasing demand for transplantation
With genetic testing, the proportion of AML patients classified as having high-risk disease is increasing. We are also seeing more cases that have evolved from underlying bone marrow disorders or that arise in patients who have been exposed to chemo- or radiotherapy for prior cancer diagnoses. These cases tend to behave aggressively and are seldom cured without transplantation.
Novel therapeutic agents are helping more patients with high-risk, relapsed or refractory disease to achieve treatment responses that enable them to proceed to transplantation.
The lack of a fully immunogenetically-matched donor has traditionally proven a major obstacle to transplantation. With alternative transplant approaches, ‘haplo-identical’ (half-matched) family members or umbilical cord blood can be successfully used as a stem cell source, meaning a donor will be available for the majority in need.
Older patients have the highest incidence of AML and yet the poorest outcomes. Age has long been perceived as a barrier to transplantation but with reduced-intensity strategies and improved supportive care, curative transplants are increasingly being offered to fit older patients.
