A conditioning regimen using minimal-intensity radiation therapy before bone marrow or stem cell transplantation (hematopoietic cell transplantation [HCT]) may be a viable option for older patients with advanced hematologic malignancies, such as leukemia or lymphoma, who cannot tolerate stronger pretransplant treatment.
HCT is usually preceded by intense cytotoxic conditioning regimens aimed at reducing tumor burden. Due to the risk of organ toxicities, however, these high-dose regimens have been limited to people younger than 55 or 60 years. Given that most hematologic malignancies are diagnosed at median ages of 65 to 70 years, the vast majority of patients who might benefit from allogeneic HCT have been excluded from the treatment.
To address this limitation, researchers developed a minimally toxic, nonmyeloablative regimen for allogeneic HCT for patients with advanced hematologic malignancies who are older or have comorbid conditions. From 1998 to 2008, 372 patients, aged 60 to 75 years (median 64 years), at 18 institutions participated in prospective clinical HCT trials employing conditioning with low-dose total body irradiation alone or combined with fludarabine. The patients then underwent bone marrow or stem cell transplantation from related (n=184) or unrelated (n=188) donors and postgrafting immunosuppression therapy.
As of June 23, 2010 (median follow-up 55 months), 133 of the patients were alive. Five-year rates of overall survival and progression-free survival were 35% and 32%, respectively. The overall 5-year cumulative incidence of relapse was 41%. Within age groups, 5-year rates of overall survival were 38% for patients aged 60 to 64 years, 33% for those 65 to 69 years, and 25% for those 70 years or older.
The most common cause of death has been disease progression or relapse (135 patients). Infections, graft-vs-host disease, and multiorgan failure accounted for the other 104 deaths. The investigators found that comorbid conditions and risks for disease relapse, but not increasing age, were associated with worse outcomes (JAMA. 2011;306:1874-1883).