According to an investigation in the November 2 issue of JAMA, older individuals who received a conditioning regimen that consisted of minimal-intensity radiation therapy for advanced hematologic malignancies, such as lymphoma and leukemia, before receiving allogeneic (genetically different) hematopoietic cell transplantation (HCT; recipe of stem cells or bone marrow transplant) had progression-free and survival outcomes indicating that this treatment method might be a suitable option for older individuals with these cancers.

Background information in the study suggests:

“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.”

In order to address this limitation, scientists developed a nonmyeloablative conditioning regimen for allogeneic HCT, which is a procedure that uses lower doses of chemotherapy and/or radiation without causing eradication of all bone marrow cells before stem cell transplant. The procedure relies on graft-vs.-tumor effects to treat cancer and involves fludarabine, a chemotherapy drug, together with a low dose of total-body irradiation prior to HCT and a course of immunosuppression.

The researchers explain:

“This regimen has allowed extension of allogeneic HCT to a previously unserved population of older or medically infirm patients.”

Mohamed L. Sorror, M.D., M.Sc., of the Fred Hutchinson Cancer Research Center, Seattle, and his team conducted a study in order to evaluate the outcomes of older individuals who suffer from advanced hematologic malignancies who received minimally toxic nonmyeloablative allogeneic HCT.

From 1998 to 2008 the study enrolled 372 patients aged between 60 to 75 years (median age, 64 years), in prospective clinical HCT trials at 18 participating institutions using conditioning with low-dose total body irradiation alone or together with fludarabine, before related (n = 184) or unrelated (n = 188) donor transplants. In addition participants received post-grafting immunosuppressive therapy. The main outcomes measured for the investigation were overall and progression-free survival.

133 of the 372 patients were alive as of June 23, 2010, with a median follow-up of 55 months. The team discovered that overall, progression of the disease or relapse has been the most prevalent cause of death (n=135). Deaths that were no related to relapse occurred among 104 patients, primarily due to infections, multi-organ failure and graft-vs.-host disease (GVHD). Overall 5 year progression-free and survival rates were 35% and 32% respectively. In addition the overall five year cumulative prevalence of relapse was 41%.

The prevalence of non-relapse mortality at five years was similar among the three age groups – 27% for individuals aged between 60 to 64, 26% for patients aged 65 to 69, and 31% for those aged 70+. For individuals 60-64 the five-year overall survival rate was 38%, for patients 65-69 33%, and for those aged 70+ 25%.

Furthermore, worse outcomes were connected with comorbid conditions and risks for relapse, but not increasing age. Over half of participants were never hospitalized, and two-thirds of those who survived eventually experienced resolution of their chronic GVHD with physical function returning to normal or near-normal.

The researchers explain:

“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 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.”

In an Associated Report in the same journal, Shin Mineishi, M.D., of the University of Michigan, Ann Arbor, Mich., comments on the discoveries of this investigation:

“Development and refinement of reduced-intensity, nonmyeloablative allogeneic hematopoietic stem cell transplantation (HSCT) has been an important accomplishment in HSCT over the last 15 years. As reported by Sorror et al, even among patients aged 60 through 75 years overall survival, progression-free survival, and other outcomes now appear almost comparable to those in younger patients. Although age alone should no longer be considered a limiting factor for allogeneic HSCT, more questions have been raised, and more problems need to be resolved for achieving optimal outcomes for older patients receiving allogeneic HSCT.”

Written by: Grace Rattue