Reduced Intensity Allografts for Acute Myeloid Leukemia: Defining the Role of Conditioning and Donor Alloreactivity.

The role of reduced intensity allografting in the treatment of patients with acute myeloid leukemia (AML) is unclear. While more patients may survive the initial period following allografting in comparison to those receiving full intensity transplants, the risk of relapse may be greater, particularly in patients not in remission at the time of transplantation. Here we report the results of allogeneic transplants using either cytokine mobilized peripheral blood (PB) or bone marrow (BM) following a reduced intensity conditioning (RIC) regimen. 131 patients with AML were all conditioned with an identical regimen containing Cyclophosphamide at 120mg/kg iv over 2 days (days −3 and −2) followed by a single dose of total body irradiation at 550cGy on day −1. HLA-identical (HLA-ID) siblings donated cytokine mobilized PB to 62 recipients and unrelated donor (UD) BM was used for 69 patients. GVHD prophylaxis consisted of single agent cyclosporine (CSP) for recipients of HLA-ID allografts and CSP, methotrexate, and methylprednisolone in recipients of UD BM. The median age of recipients was 45 years (range 21–70), with 55 males and 76 females. 43 pts were in CR1, 33 in CR2, and 55 had relapsed (rel) or refractory (ref) disease. 59 of 69 recipients of UD BM were serologically identical with their donors at 6/6 antigens. There were no graft failures in either group.With a median follow-up of over 18 months, the results of transplantation are presented in the Table.

Results of Transplantation

For pts transplanted in CR1, the results are comparable to those observed following fully ablative conditioning, particularly since many pts were transplanted due to high risk karyotype. In CR2, outcomes following RIC were superior in recipients of UD BM compared to HLA-ID PB, possibly due to a greater graft versus leukemia effect. UD BM was ineffective in pts with rel/ref AML. Of interest, the 2 year DFS in pts with rel/ref AML following receipt of HLA-ID PB was 17% overall, but was 28% in those that developed any acute GVHD versus 0% in those that did not (P<0.02). In conclusion, while the role of RIC in the treatment of pts with AML requires further clarification, our findings suggest that in pts beyond CR1, clinical evidence of donor alloreactivity appears to be critical for ensuring durable DFS.