Evolving Role of Stem Cell Transplant in the Elderly

The median age at presentation for hematologic disorders such as leukemia, myelodysplasia, lymphoma, and myeloma is over 60 years.[1] Newer targeted therapeutic approaches have led to promising results in these maladies, particularly in the initial treatment approach.[2-4] Respectable remission rates have been achieved for about half of the patients treated. Despite the improved remission rates, patients with these diseases still relapse. Elderly patients (conventionally defined as those over the age of 60 years old) have a higher risk of relapse of their disease. Factors such as abnormal cytogenetics and other intrinsic genetic changes in the cells are more commonly seen in this elderly group, leading to poorer outcomes compared to their younger counterparts. The presence of these features has limited the usefulness of salvage chemotherapy once the patient has relapsed or experienced disease progression.

Transplantation has been the mainstay of therapy for patients with relapsed and/or high-risk hematologic disorders. This approach has mainly been used in patients under the age of 60. Outcomes using autologous transplant are superior to standard therapy in the treatment of relapsed aggressive lymphoma.[5] In myeloma, where advances in up-front therapies have improved overall survival, transplantation has been a useful approach in advanced disease. Early superiority was proven over traditional chemotherapeutic approaches for patients with myeloma. Despite not being curative for most of these patients, single and tandem transplant have provided long-term disease-free and overall survival in a small group of patients. Allogeneic transplant is the only therapy with a chance of cure for relapsed acute myeloid leukemia and for patients with high-risk (International Prognostic Scoring System intermediate-2 and high) myelodysplasia.

Challenges in Older Patients

The biggest obstacle to overcome has been the overwhelming bias against transplantation in this "elderly" group of patients. Concerns about regimens that are too toxic immediately posttransplant or that could lead to later sequelae have limited referrals of these patients to transplant centers. Furthermore, multiple regimens of chemotherapy prior to a transplant referral can lead to a self-fulfilling prophecy of poorer outcomes, from inadequate collection of hematopoietic stem cells to poorer-risk patients being transplanted.

Bringing the patient to transplant earlier allows for the appropriate use of dose-intense strategies when there is a better chance of cure. Advances in the pretransplant conditioning regimens and supportive care posttransplantation have reduced treatment-related mortality to acceptable levels. Based on improvements in the procedure, including the efficient procurement of hematopoietic stem cells, the use of growth factors, and the improved antibiotic and antifungal armamentarium, most transplant centers have increased their upper age limit from 40 to 70–80 years old.

Improving Trends

In "Hematopoietic Stem Cell Transplantation in the Elderly," Ballester et al have summarized past and more current experiences and outcomes using transplantation in elderly patients. The lack of randomized trials have made it more difficult to draw firm conclusions, but improved trends noted in treatment-related mortality, progression-free survival, and overall survival prove the promise of this approach in the elderly cohort.

Moreover, adjustments in dose intensity—whether it be from a nonmyeloablative, reduced-intensity, or fully ablative approach—allow for therapy to fit the risk profile of the patient and the disease. Targeting levels of the conditioning regimes allows for precise doses of therapy to be delivered when it counts the most.[6] The "one-size-fits-all" approach that was used previously in the transplant setting is no longer appropriate. Improvements in the posttransplant care of complications such as infections and graft-vs-host disease have also led to improvements in survival.