Researchers from the Fred Hutchinson Cancer Research Center have reported that a reduced allogeneic stem cell transplant regimen consisting of 131I-anti-CD45 antibody, Fludara® (fludarabine), and low-dose total body irradiation results in a one-year survival of 41% in elderly patients with advanced acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (MDS). The details of this study appeared early online on September 28, 2009 in Blood.[1] 

There has been significant improvement in the treatment of patients with AML who are 60 years of age or younger over the past two or three decades. However, there has been little improvement in the outcomes of the majority of patients with AML who are diagnosed beyond the age of 60 years. Allogeneic stem cell transplants are usually restricted to patients under the age of 60-65. However, recent studies have suggested that elderly patients can be transplanted safely with reduced intensity regimens (though relapse rates are high). This has prompted the search for effective anti-leukemia therapies that are not systemically toxic.

CD45 is a tyrosine phosphatase expressed on virtually all leukocytes, including myeloid and lymphoid precursors in bone marrow and mature lymphocytes in lymph nodes. It is also expressed on most myeloid and lymphoid leukemic cells but not on mature erythrocytes or platelets. A Phase I study showed that linking 131I to this antibody was a successful method of delivering high doses of irradiation to sites of marrow with less irradiation to organs such as the liver.[2] A subsequent Phase II study combined 131I-anti-CD45 with busulfan and cyclophosphamide for treating patients with AML in first complete remission.[3]

The current study involved 58 patients with advanced AML (n=47) or high-risk MDS (n=11). Nineteen of the 47 patients with AML had secondary AML. The median age for de novo AML patients was 59 years, while patients with secondary AML and MDS were a decade older. The oldest patient in this study was 74 years old. All patients in this study achieved a complete response. Transplant-related mortality was 12%. Forty percent of patients relapsed, and 40% survived at one year. One-year survivals were higher for patients with AML than for patients with MDS. Results were also better in patients who received higher doses of 131I-anti-CD45 antibody.

Comments: These data suggest that a significant fraction of patients over the age of 50 with AML can be salvaged with this approach.