Treatment of Acute Myeloid Leukemia With Hematopoietic Stem Cell Transplantation

Cortney V. Jones; Edward A. Copelan

Disclosures

Future Oncol. 2009;5(4):559-568. 

In This Article

Reduced Intensity Preparative Regimens

The median age at diagnosis of AML is 68 years. Results using standard chemotherapy in patients aged 60 years and older are particularly poor, with median survival of less than a year. With traditional myeloablative preparative regimens, transplant-related morbidity and mortality increase substantially with older age and with comorbidities. Many clinicians have been reluctant to perform allotransplantation in patients older than 50 years of age and myeloablative transplantation is rarely performed in those over 65 years of age. Reduced-intensity regimens were originally developed to improve the safety of the procedure in older individuals or those with comorbidities. They are sufficiently immunosuppressive to permit engraftment of donor cells, but have reduced marrow (and extramedullary) toxicity. This approach relies on the immunologic graft-versus-leukemia effect to eradicate residual leukemic cells, including leukemic stem cells. Evidence that an immunologic effect is sufficient to eliminate leukemia is provided by sustained relapse-free survival following donor lymphocytic infusions[70,71,72] (as treatment for relapse after transplantation), and reduced relapse rates in transplant recipients in whom GVHD develops compared with those in whom it does not.[73]

While the regimen of low dose TBI and fludarabine is truly nonablative, producing only mild neutropenia and thrombocytopenia,[74] some regimens are substantially more toxic to the marrow and other organs. Reduced-intensity regimens appear to be most effective in slow growing malignancies, for example, chronic lymphocytic leukemia,[75] but have proven effective in AML. Retrospective reports have generally indicated that transplant-related mortality may be reduced by half, but that substantially higher relapse rates result in roughly similar rates of sustained survival.[76,77,78,79,80] The adverse impact of age and comorbidities on outcome appears significantly less dramatic using reduced intensity compared with myeloablative regimens. Several studies have reported favorable results in older patients,[76,78,81,82] of particular interest in view of the dismal results with standard chemotherapy. Clinicians are optimistic that induction remission followed by reduced intensity transplantation in selected patients will improve cure rates in older patients with AML. Current clinical trials will prospectively assess the usefulness of reduced-intensity preparation for older patients in first complete remission.

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