Professor Jane Apperley, MD, is chair of the Centre for Haematology at Imperial College London, Department of Medicine.
She is considered one of the most distinguished global hematology experts. Her key achievements include her involvement in transplant in chronic myelogenous leukemia (CML), the identification of the immune system’s role in controlling disease after transplant, and the publication of several highly cited articles. She has been elected to positions in national and international transplant societies, supporting international collaboration for the treatment of CML.
She was an invited expert for the United Kingdom’s National Institute for Health and Clinical Excellence, appraisal and re-appraisals of the use of second-generation tyrosine kinase inhibitors (TKIs) in managing patients with imatinib-resistant CML.
Dr Apperley has led an international study on the efficacy of dasatinib in patients with accelerated phase CML. She was also awarded the Good Clinical Practice Journal Clinical Academic Researcher of the Year award.
In this question-and-answer session, Isabel Cunningham, MD, editorial advisory board member for Cancer Therapy Advisor, asks Dr Apperley about the best time to begin looking for transplant candidates and how to treat patients that cause specialists particular concern.
Dr Cunningham: Dr Apperley, the world is well aware that most patients with CML will achieve significant disease control with TKI therapy. Nonetheless, there are always patients who will not achieve the desired response. Your perspective as director of a large CML research program would provide practitioners with valuable insight about how to focus on who is a potential transplant candidate, and which types of patients merit particular concern.
It would be useful to know at which point you test whether a patient has a potential family donor and in which patients preliminary search for a volunteer donor should be undertaken.
Dr Apperley: For patients who present in chronic phase, I think most physicians would agree that all should start treatment with a TKI and that the next decision point will be 3 months later when the result of the early molecular response becomes available.
If the TKI was imatinib, approximately 20% to 30% of patients will not have a real-time qualitative polymerase chain reaction (RQ-PCR) level < 10% (IS) and be eligible for a change of treatment, and probably about two-thirds will respond well. For this group, I would investigate the availability of a sibling donor at this time point.
For those lacking a sibling donor, I would of course be following their molecular response monthly and if the RQ-PCR was not clearly falling, I would initiate an unrelated donor search with the aim of being able to proceed to transplant as soon as possible if the 6-month result was unsatisfactory.
If a second-generation TKI was used from diagnosis, then about 10% will be considered for a change of drug at 3 months. At the present time, it is unclear what proportion of these patients will eventually respond to a TKI, but I suspect that this is a group with a considerably poorer prognosis and I would try to find a donor (sibling or unrelated) at this point.
Of course, any patient who loses an established response to a TKI is also at risk of disease progression, so I would begin a donor search if the loss of response cannot be explained by lack of compliance.
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For patients presenting with features of accelerated phase disease, I would start all on a TKI but check for a sibling donor immediately and an unrelated donor if the RQ-PCR was > 10% (IS) at 3 months.
Allogeneic transplant is the only therapy that offers a chance of long-term survival to patients presenting in blast crisis, so a suitable donor should be sought immediately.