Older patients with advanced hematologic malignancies, such as leukemia and lymphoma, who received a conditioning regimen that included minimal-intensity radiation therapy prior to allogeneic hematopoietic cell transplantation (HCT) had improved survival and progression-free survival outcomes. The finding, published in the November 2nd issue of JAMA, suggests that this treatment approach may be a viable option for older patients with these types of malignancies.
The study, conducted by Mohamed L. Sorror, M.D., M.Sc., of the Fred Hutchinson Cancer Research Center, Seattle, and colleagues analyzed the outcomes of older patients with advanced hematologic malignancies and comorbidities who received minimally toxic nonmyeloablative allogeneic HCT. The study was prompted by the fact that increasing age has been historically implicated in higher mortality after high-dose allogeneic HCT for patients with hematologic malignancies.
“Such transplants are preceded by intense, cytotoxic conditioning regimens aimed at reducing tumour burden. The risk of organ toxicities has limited the use of high-dose regimens to younger patients in good medical condition. Therefore, age cut-offs of 55 to 60 years have been in place for decades for high-dose HCT. This excluded the vast majority of patients from allogeneic HCT, given that median ages of patients at diagnoses of most hematologic malignancies range from 65 to 70
years,” Sorror and colleagues write.
To address this limitation the researchers developed a nonmyeloablative conditioning regimen for allogeneic HCT consisting of fludarabine, low dose of total-body irradiation given prior to HCT and a course of immunosuppression. “This regimen has allowed extension of allogeneic HCT to a previously unserved population of older or medically infirm patients,” Sorror and colleagues note in their article.
Sorror and colleagues evaluated data from 372 patients between 60 and 75 years of age (median age, 64 years) who were enrolled in prospective clinical HCT trials at 18 collaborating institutions from 1998 to 2008. They received conditioning with low-dose total body irradiation alone or combined with fludarabine, before related (n = 184) or unrelated (n = 188) donor transplants. They also received postgrafting immunosuppression therapy. The primary outcomes measured for the study were overall and progression-free survival.
As of June 23, 2010, 133 of the 372 patients were alive, with a median follow-up of 55 months. Overall, disease progression or relapse has been the most common cause of death (n = 135). Nonrelapse deaths occurred among 104 patients, mainly due to infections, graft-vs.-host disease (GVHD), and multi-organ failure. Five-year rates of overall survival and progression-free survival were 35 percent and 32 percent, respectively. The overall 5-year cumulative incidence of relapse was 41 percent.
Cumulative incidences for nonrelapse mortality at 5 years were comparable among the 3 age groups (27 percent for patients ages 60-64 vs. 26 percent for those ages 65-69 vs. 31 percent for those 70 or older). Five-year rates of overall survival were 38 percent for patients ages 60 through 64, 33 percent for those ages 65 through 69, and 25 percent for those 70 years or older.
Also, comorbid conditions and risks for disease relapse were associated with worse outcomes. Increasing age was not associated with worse outcomes. More than half of the older patients were never hospitalized, and two-thirds of survivors experienced eventual resolution of their chronic GVHD with return to normal or near-normal physical function.
“While there is much room for improvement, particularly with regard to relapse, these results are encouraging given the poor outcomes with nontransplantation treatments, especially for patients with high-risk acute myeloid leukemia, fludarabine-refractory chronic lymphocytic leukemia, or progressive lymphoma,” the researchers note in their article.
The y also note that the older population is increasing. “Demographic changes in the United States suggest that 20 percent of the population will be 65 years or older by 2030. Furthermore, increases of up to 77 percent in the number of newly diagnosed hematologic malignancies among the older population are expected to occur in the next 20 years. Greater age is also associated with increased medical comorbid conditions. Thus, establishing treatment options with curative outcomes and near-normal long-term physical function have become an important future goal for older patients with hematologic malignancies,” said Sorror and colleagues.