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 (genetically different) hematopoietic cell transplantation (HCT; receipt of bone marrow or stem cells transplant) had survival and progression-free survival outcomes suggesting that this treatment approach may be a viable option for older patients with these malignancies, according to a scientific study.
“Increasing age has been historically implicated in higher mortality after high-dose allogeneic HCT for patients with hematologic malignancies [cancers of the blood or bone marrow]. Such transplants are preceded by intense, cytotoxic [toxic to cells] conditioning regimens aimed at reducing tumor burden. The risk of organ toxicities has limited the use of high-dose regimens to younger patients in good medical condition. Therefore, age cutoffs 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 [midpoint] ages of patients at diagnoses of most hematologic malignancies range from 65 to 70 years,” according to background information provided in the research.
To address this limitation, a nonmyeloablative (an approach using lower doses of chemotherapy and/or radiation that does not lead to eradication of all bone marrow cells prior to stem cell transplant) conditioning regimen for allogeneic HCT was developed. The regimen relies on graft-vs.-tumor effects to cure cancer and consists of the chemotherapy drug fludarabine and a low dose of total-body irradiation before 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,” the authors write.
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 who received minimally toxic nonmyeloablative allogeneic HCT. From 1998 to 2008, 372 patients ages 60 to 75 years (median age, 64 years) were enrolled in prospective clinical HCT trials at 18 collaborating institutions using 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 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, but not increasing age, were 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.