M, mitoxantrone; A, ara-C; DFS, disease-free survival; D, daunorubicin; I, idarubicin; E, etoposide; T, thioguanine; O, vincristine; Pred, prednisone; GM-CSF, granulocyte-macrophage colony-stimulating factor; G-CSF, granulocute colony-stimulating factor; ND, not done; NS, not significant (though actual value not reported).

Reprinted from Stone RM, O'Donnell MR, Sekeres MA: Acute myeloid leukemia. Hematology AM Soc Hematol Educ Program 98-117, 2004, copyright American Society of Hematology, U.S.A.

Protracted postremission chemotherapy

There does not appear to be any additional survival benefit attained from administering one to two cycles of postremission therapy, or in treating older AML patients with maintenance therapy. In the MRC AML 11 trial, 371 patients who entered a CR following anthracycline- or anthracenedione-based remission induction therapy were randomized to receive either one cycle of DAT consolidation therapy or DAT along with three additional cycles of ara-C-based consolidation therapy (for a total of four cycles of postremission therapy).29 Of patients randomized to the long consolidation course, 61% were able to complete all four cycles. Survival was similar at 5 years for patients randomized to the short and long consolidation arms.

In the phase III trial performed by the Leukemia Cooperative Group of the European Organization for the Research and Treatment of Cancer and the Dutch-Belgian Hemato-oncology Cooperative Hovon Group, patients over 60 years of age were randomized to remission induction regimens consisting of mitox-antrone and ara-C versus daunorubicin and ara-C.4 Following one cycle of consolidation therapy, 151 patients in CR were further randomized to receive low-dose ara-C maintenance therapy, or to no further treatment. Actuarial disease-free survival was longer for those receiving low-dose postremission therapy compared to those not receiving therapy, with 5-year DFS being 13 and 7% respectively. OS, though, was similar.

Postremission stem cell transplantation

An even more aggressive approach than induction therapy followed by consolidation or intensification for older adults with AML consists of stem cell transplantation. This topic will be covered in greater detail in Chapter 100. Nonmyeloablative allogeneic stem cell transplants take advantage of a graft-versus-leukemia effect using a less intensive preparative regimen with lower up-front mortality. The reduced treatment-related mortality and ability to perform these transplants in the outpatient setting make them an appealing option for the older AML patient with few comorbidities and an adequate performance status. Preliminary studies that include older AML patients have demonstrated that durable CRs are attainable with this treatment,8687 though follow up is still less than 3 years.

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