Editorial Note: In recent years, advancements in Hematopoietic Cell Transplantation (HCT) technology have significantly improved long-term survival rates, with about 80% of patients achieving disease-free survival for more than two years post-transplant. However, as time progresses, long-term survivors of transplantation still face the risk of chronic complications, which directly impact their quality of life and outcomes post-transplant. The 50th European Society for Blood and Marrow Transplantation (EBMT) annual meeting took place from April 14 to 17, 2024, in Glasgow, UK. At the meeting, Professor Rachel Phelan from the Children's Hospital of Wisconsin, a specialist in blood and marrow transplantation, introduced the recently updated "International Guidelines for Screening and Prevention Measures for Long-Term Survivors of Transplant and Cell Therapy" (Bone Marrow Transplant. 2024 Feb 27. Epub ahead of print). Hematology News invited Professor Phelan to share and interpret the key updates of the guidelines with a broad readership.
“Oncology Frontier – Hematology Frontier”: Could you share with us the main contents of this guideline update?
Professor Phelan: As the indications for Hematopoietic Cell Transplantation (HCT) and cellular therapies expand and the transplantation techniques improve, the number of HCTs performed each year continues to rise. Advances in HCT technology and supportive care have enabled more patients to achieve long-term survival. However, long-term survivors still face the risk of chronic complications, influenced by factors before, during, and after transplantation, and each patient has unique triggers and complications post-transplant. The “International Guidelines for Screening and Prevention Measures for Long-Term Survivors of Transplant and Cell Therapy” were first issued in 2006 and updated in 2012. Considering the evolving practices in HCT and cell therapies, the American Society for Transplantation and Cellular Therapy (ASTCT) convened an international panel of experts to revise the guidelines, aimed at further improving long-term outcomes for transplant patients.
Compared to the previous guidelines, the new version includes many content updates. In summary, the new guidelines have added sections on hematopoietic complications; recommendations for psychological adjustment, cognitive dysfunction, and quality of life; updated vaccination guidelines; assessments for post-transplant cancer screening; and guidelines for special populations, including autoimmune diseases, hemoglobinopathies, bone marrow failure, congenital immune disorders/metabolic dysregulation, myeloma/amyloidosis, adolescents and young patients, and elderly patients. It will take a considerable amount of time to fully comprehend all aspects, but it is hoped that particular attention will be paid to the sections on hematologic complications and long-term monitoring. There are significant updates on how to monitor for malignancies, particularly complications such as colorectal cancer and head and neck squamous cell carcinoma, which readers should especially note. Additionally, assessments of long-term cognitive function and quality of life are crucial for patients’ post-transplant quality of life and also deserve attention.
The Guideline is very extensive, and is open access and now available for everybody to use in their standard clinical practice. You are correct – we continue to perform more and more transplants every year, and we also continue to do a lot better at transplanting patients, in terms of improvements in overall survival. We anticipate larger and larger numbers of long-term survivors, so it is really important that all of us are aware of the specific long-term side effects or late effects that they may be at risk for. Every patient has a unique set of predisposing factors and complications post-transplant that puts them at risk for those late effects, as well as what they receive for treatment. There were a number of different updates in this Guideline compared to the prior one. It will take a really long time for me to go through all of them, but a few of the things that I updated in the talk at EBMT were the addition of a number of sections to the Guideline, including a focus on hematologic complications and how those should be monitored long term. There were also a number of updates on how surveillance for subsequent malignant neoplasms should be approached, specifically with the development of complications such as colorectal cancer or squamous cell carcinoma of the head and neck. I would like the reader to pay particular attention to those. We also substantially updated our sections on cognitive function and quality of life assessments in the long term. We have come to recognize more and more that what is important to the patient’s quality of life as they are living for decades post-transplant really becomes critical. So we provide some recommendations for assessments of quality of life, patient reported outcomes, caregiver and spousal support, as well as cognitive function post-transplant. We really want to make sure that attention is paid to those sections as well.
“Oncology Frontier – Hematology Frontier”: To further optimize the long-term prognosis after transplantation, could you discuss aspects of the entire HCT process that could be optimized?
Professor Phelan: In the transplant process, many methods that can be optimized to improve patients’ long-term survival rates actually depend on the patient’s age and the underlying indications for their transplant. Therefore, there are numerous points for optimization, but I believe that over the years, we have made significant efforts, particularly in pediatric patients, to reduce the use of radiation therapy. The ultimate goal for patients is cure, but we also must acknowledge that if we cannot eliminate some treatments due to their high toxicity, we can manage these patients with long-term monitoring to detect the long-term side effects of treatment as early as possible, allowing for proactive intervention and treatment.
Additionally, the advent of gene therapy may also change our approach to long-term survival for patients undergoing transplantation for non-malignant diseases. Overall, I believe we are seeing exciting progress in transplantation and other treatments, which promises to lower the risks associated with long-term survival in both children and adult patients.
A lot of what can be optimized during the transplant process to improve long-term outcomes for survivorship is really dependent on the age of the patient, and what their underlying indication for transplantation is. So it is really varied, but I would say, over the years, we have accomplished things like using less radiation, specifically in pediatric patients (which is something we are striving for), and there are a number of different clinical trials trying to decide whether or not we need to use radiation in pediatric and adult patients. Sometimes we still do though. The ultimate goal is to achieve that cure, but then we also need to know that if we can’t take away some of the more toxic therapies, that we need to monitor those patients perhaps a little differently long term in order to identify long-term side effects early in order to facilitate the diagnosis and treatment of those long-term side effects. The advent of gene therapy I think will also change our long-term outlook for some patients who are transplanted for non-malignant diseases. I think there are a lot of exciting changes in transplant and other therapeutic approaches that hopefully will decrease the risk of late effects in pediatric and adult patients. There is more to be seen, but it is really important that we continue to study this area, and hopefully we will see improvements over time.
