Treatment for Acute Myelogenous Leukemia by Low Dose Irradiation Based Conditioning and Hematopoietic Cell Transplantation from Related and Unrelated Donors.

Conventional allogeneic hematopoietic cell transplantation (HCT) is effective treatment for AML, but its use has been restricted to younger patients in good medical condition. However, AML is increasingly common with advancing age, and older patients have more adverse prognostic features than younger patients. The vast majority of older patients who reach a CR with chemotherapy relapse within two years from diagnosis and die within three years. The situation is similar in patients with secondary AML or with AML in CR2, more advanced remission status or in partial remission, where median duration of disease-free survival (DFS) is generally <12 months. The use of low-dose irradiation-based preparative regimens has allowed extending allografting to, and exploring graft-versus-tumor effects in, older and medically infirm patients.

The present study included 122 patients with AML ineligible for conventional transplants. Their disease stages ranged from CR1 to resistant disease, and their median age was 57.5 (range 17–74) years. The patients were given 2 Gy total body irradiation (TBI) on day 0 with and without preceding fludarabine (30 mg/m2/d from days -4 to -2). After HCT, cyclosporine, 6.25 mg/kg, was given twice daily from day -3, and mycophenolate mofetil, 15 mg/kg, twice daily from day 0. HLA-matched related donors were used in 58, and HLA-matched/partially matched unrelated donors in 64 patients. Among 121 (one died to early after transplant) evaluable patients, 116 (95.8%) had durable engraftment. Cumulative incidences of acute GvHD grade II-IV were 33 % after related and 42% after unrelated HCT. With a median observation time of 17 (range 4–57) months, 58 patients were alive, 53 of whom were in complete remissions. Cumulative non-relapse mortalities (NRM) were 12% and 27%, and the cumulative relapse mortalities were 47% and 34% at 2 years for related and unrelated recipients, respectively. Two-year overall survival (OS) was 41%, and DFS was 35%, with stages of the disease and cytogenetic risks being major determinants for outcomes. Patients transplanted in CR1 had a 2-year OS of 40% after related and 57% after unrelated HCT. We concluded that HCT from related and unrelated donors after low-dose TBI is promising therapy for elderly patients and medically infirm younger patients with AML not eligible for conventional HCT. Due to the lower relapse rates, results in patients with unrelated donors were better than results in patients with related donors. Results have encouraged studies of the role of low-dose irradiation-based conditioning and allogeneic HCT in the primary treatment of patients with AML ≥60 years.