Editor’s Note: As the population continues to age, the incidence of hematologic malignancies in the elderly has been rising, presenting new challenges for clinical treatment. From April 14 to 17, 2024, the 50th European Society for Blood and Marrow Transplantation (EBMT) Annual Meeting was held in Glasgow, UK. The conference focused on the latest advancements in stem cell transplantation and cellular therapies, pushing forward improved clinical outcomes for patients with blood diseases. “Oncology Frontier – Hematology Frontier” invited Professor Peiyan Kong from The Second Affiliated Hospital of Army Medical University (Xinqiao Hospital) to share her insights on the challenges in diagnosing and treating hematologic malignancies in elderly patients, the selection of transplant donors, and the prevention of infections and GVHD post-transplant.

Oncology Frontier – Hematology Frontier: With society facing an aging population, many hematologic malignancies are prevalent among the elderly. Can you discuss the challenges this presents in clinical practice?

Professor Peiyan Kong: The content of this EBMT meeting was very innovative, focusing on particularly relevant issues such as hematopoietic stem cell transplantation for elderly patients with hematologic malignancies. Common malignancies such as leukemia, especially acute myeloid leukemia (AML), multiple myeloma, and non-Hodgkin lymphoma, have seen an increased incidence in the elderly as the aging process accelerates. The transplantation of older patients has become a growing focus as the population ages. Data from the EBMT meeting also show that the proportion of elderly transplants is increasing annually, with surprising specifics revealed: for example, the percentage of allogeneic hematopoietic stem cell transplant recipients over the age of 65 was just 1% in 2000, but rose to 6.7% by 2014. The change in the proportion of autologous hematopoietic stem cell transplant recipients is even more significant, from 3.4% in 2000 to 9.8% in 2014. It has been ten years since the last data point, and the numbers have likely increased further; we look forward to the upcoming data release.

In our country, the issue of transplantation in elderly patients is also of great concern. For instance, at our center (Second Affiliated Hospital of Army Medical University [Xinqiao Hospital]), we have completed many cases of transplantation in patients over the age of 65 in recent years. The oldest patient I have managed was 68, and we are currently preparing for a transplant for a 72-year-old patient who is very eager and meets all the necessary criteria, so we believe that age is not an issue. As more cases involving elderly patients accumulate, everyone is most concerned about the survival data. However, the data from this EBMT meeting regarding elderly transplant recipients are not optimistic. While the three-year survival rate for younger transplant patients is 70%, it is only 40% for elderly patients. Facing an aging society and an increasing number of elderly transplant recipients, improving patient outcomes and benefits remains a significant challenge for the future.

Oncology Frontier – Hematology Frontier: The EBMT conference focused heavily on cellular therapies and bone marrow transplantation for hematologic malignancies. Historically, transplantation was only deemed suitable for cancer patients under 60 years of age. With advancements in transplantation technology and supportive care, is transplantation feasible for elderly patients? Please share your perspective.

Professor Peiyan Kong: Regarding transplantation in elderly patients, our primary concern is the indications for transplantation to determine if it is necessary for the patient. Next, we focus on whether the patient can tolerate the entire transplantation process. Taking myeloid leukemia as an example, high-risk genetic and chromosomal abnormalities are very common in patients over 65, and these elderly patients often have several high-risk mutations. The more genetic mutations present, the poorer the prognosis may be. The need for transplantation in elderly patients is evident, as chemotherapy alone cannot guarantee long-term survival outcomes. Before proceeding with a transplant, an assessment is necessary, which includes three main aspects.

First, an evaluation of the patient’s vital organ functions, especially cardiac, pulmonary, hepatic, and renal functions. If any organ dysfunction is present, such as chronic obstructive pulmonary disease (COPD) leading to poor lung function, chronic coronary artery disease, hypertension, poor cardiac function, or cirrhosis, these conditions may pose relative contraindications to transplantation. It’s unclear whether coronary artery disease patients with stents have absolute contraindications; in such cases, transplantation may significantly decrease quality of life. I have encountered patients who have had stents implanted and then underwent transplantation, some of whom had a history of embolism in cerebral vessels, leading to very complex complications post-transplant.

Second, the assessment of comorbidity indexes is crucial. There are populations that, despite not having organ failure, may have poor self-care abilities; we refer to these as “frail populations.” Evaluating this group is also vital.

Third, cognitive assessment is important. Some patients with Alzheimer’s disease have very poor cognitive functions, making post-transplant cooperation very difficult. In the past decade, there has been a lot of content and complexity in assessing these elderly patients, but simplifying the assessment process might lead to incomplete evaluations. Therefore, a lot depends on the clinical experience that doctors continuously develop. In summary, we only proceed with intensified or reduced-dose chemotherapy and consider transplantation when the patient is indeed capable of tolerating it and we have achieved complete remission (CR) to ensure the best therapeutic effects.

The choice of conditioning regimen is also one of the challenges we face. Due to potential toxicities that cannot be managed with intensive conditioning, we generally opt for reduced-intensity conditioning for patients over 65, which is a consensus both domestically and globally. Under reduced-intensity conditions, we must pay special attention to monitoring post-transplant complications such as infections and graft rejection. Monitoring in elderly transplant patients needs to be particularly meticulous, and we must pay close attention to all patient complaints to prevent complications from being identified too late. For example, common symptoms like dizziness and fatigue could be indicative of encephalitis, which is difficult to treat, so heightened vigilance is essential. Another important aspect to ensure survival is maintenance therapy; early intervention in preventative treatments is crucial, as elderly patients have fewer chances of recovery after a relapse compared to younger patients, making maintenance therapy extremely important.

Oncology Frontier – Hematology Frontier: With the growing clinical demand for transplantation, this conference also featured extensive discussions on the selection of transplant donors. Based on your clinical experience, what considerations do you have when selecting donors for elderly patients?

Professor Peiyan Kong: In the selection of transplant donors for elderly patients, clinicians initially prefer fully matched donors. However, studies indicate that familial fully matched donors for elderly recipients are often older themselves, and it’s uncertain whether these are better or worse compared to younger unrelated donors from bone marrow registries. Although young unrelated donors may have an increased risk of rejection, elderly matched familial donors might have higher relapse rates. Therefore, the overall survival data for both types of donors are quite similar, and either can be chosen. However, particular attention should be paid to the focus of these study data, such as preventing relapse and treating GVHD, to ensure better survival rates. Reported survival rates are around 40%, which I believe could still be improved. If fully matched donors are not available, haploidentical donors (half-matched) can also be considered. A specific report presented during the EBMT opening ceremony discussed the data on haploidentical transplantation for patients over 60, suggesting that elderly patients might benefit from reduced-intensity conditioning combined with post-transplant cyclophosphamide (PTCy) for preventing GVHD, hence the application of haploidentical transplantation is likely to become increasingly widespread since finding a fully matched donor is relatively rare.

Oncology Frontier – Hematology Frontier: Lastly, could you discuss how to proactively prevent infections and GVHD in elderly transplant patients to improve their long-term survival?

Professor Peiyan Kong: The EBMT conference featured many sessions on the prevention of GVHD, which are very helpful to our practice. GVHD in elderly patients undergoing allogeneic hematopoietic stem cell transplantation is even more pronounced than in younger individuals. First, prevention and early monitoring are crucial. By assessing serological or circulating biomarkers within a week post-transplantation, we can predict the onset of GVHD. If the risk is high, we intensify monitoring and intervene early. Additionally, ruxolitinib is becoming increasingly important in first-line treatment for GVHD, especially since elderly patients often have conditions like hypertension and diabetes that limit the use of first-line steroid treatments. Combining steroids with ruxolitinib can help reduce or even stop steroid use early, avoiding the long-term complications associated with steroids. Regarding infection prevention, there has been increased research in recent years on post-transplant viral infections. Enhanced monitoring for viruses like COVID-19 and influenza is essential. Early detection and the prompt use of specific antiviral medications can reduce severe complications from viral infections, such as thrombotic microangiopathy (TMA). Finally, in terms of fungal prevention, especially in elderly patients with diabetes and underlying diseases, enhanced monitoring is necessary. It is advisable to use broad-spectrum antifungal medications, such as posaconazole, to ensure effectiveness.

Expert Profile Professor Peiyan Kong is a Chief Physician and Doctoral Supervisor at the Second Affiliated Hospital of Army Medical University (Xinqiao Hospital). She is a member of the Hemostasis and Thrombosis Group of the Hematology Branch of the Chinese Medical Association, a member of the Geriatrics Society of China, a member of the Southern China Lymphoma Research Group, and holds several key positions in regional cancer and hematology societies in Chongqing.