Treatment for Acute Myelogenous Leukemia by Low-Dose, Total-Body, Irradiation-Based Conditioning and Hematopoietic Cell Transplantation From Related and Unrelated Donors

Baylor University, Waco, Texas, United States
Journal of Clinical Oncology (Impact Factor: 18.43). 02/2006; 24(3):444-53. DOI: 10.1200/JCO.2005.03.1765
Source: PubMed


The use of low-dose, irradiation-based preparative regimens have allowed the extension of allografting to older and medically infirm patients. The study reported here assessed outcomes for patients with acute myeloid leukemia (AML) in different stages of their disease, who were not considered candidates for conventional hematopoietic cell transplantation (HCT) because of age and/or other known risk factors and were given minimal conditioning followed by HCT from related or unrelated donors.
The present study included 122 patients with AML, who were conditioned with 2 Gy total-body irradiation (TBI) on day 0 with or without preceding fludarabine (30 mg/m2/d from days -4 to -2), and given postgrafting cyclosporine at 6.25 mg/kg twice daily from day -3 and mycophenolate mofetil at 15 mg/kg twice daily from day 0.
Durable engraftment was observed in 95% of the patients. Cumulative incidences of acute graft-versus-host disease grades 2 to 4 at 6 months were 35% after related and 42% after unrelated HCT, respectively. With a median follow-up of 44 months (range, 26 to 79 months), 51 patients were alive, of whom 48 were in complete remission (CR). Cumulative nonrelapse mortalities were 10% and 22%, and cumulative mortalities from disease progression were 47% and 33% at 2 years for related and unrelated recipients, respectively. Overall, 2-year survival was 48%, and disease-free survival was 44%. Patients receiving transplantation in CR1 had 2-year overall survivals of 44% after related and 63% after unrelated HCT, respectively.
We conclude that HCT from related and unrelated donors after low-dose TBI is a promising treatment for elderly patients with AML.

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    • "There are a numerous of RIC regimens which vary not only with respect to dose intensity but also to the type of agents used. Since dose does matter [88, 89], most protocols are moving from the initially established “minimal dose” concept with 2 Gy TBI/fludarabin [75, 78] to more intensive, while nontoxic, regimens (reduced toxicity conditioning, RTC). In this vein, the addition of one or two alkylating agents in the conditioning seems to be more effective in controlling leukemia than truly nonmyeloablative ones [79, 84]. "
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    Journal of Oncology 06/2010; 2010(3):943823. DOI:10.1155/2010/943823
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    • "Regardless of the various conditioning regimens, the occurrence of acute GVHD (≥grade II), chronic GVHD, 2-year overall survival (OS), and NST relapse rate are about 35%, 40%, 40%, and 50%, respectively, suggesting similar outcomes to those in CST [37,38]. However, NST is superior to chemotherapy in patients older than 50 years with AML and in those in their first complete remission [39]. "
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    • "Ionizing radiation (IR) is frequently used in the treatment of solid cancers, in the conditional treatment before allotransplantation of leukemia patients and in radioisotope-conjugated therapeutic antibodies directed against AML cells [8,9]. IR and anthracyclines induce growth arrest and cell death through DNA-damage, but also involve cell membrane-related effects in regulation of apoptosis [4-7,10]. "
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