Reduced Intensity Stem Cell Transplant (RIST) as Salvage Treatment for Relapse Following Myeloablative Allogeneic Transplantation in Adult Acute Myeloid Leukemia.

Relapse of acute myeloid leukemia (AML) following myeloablative allogeneic stem cell transplantation portends a dismal prognosis. Therapy aimed at enhancing graft-versus-leukemia (GVL) effect, e.g., by donor leukocyte infusion, has limited success in AML, and a second ablative transplant is associated with prohibitive mortality in adults. From April 2001 to March 2006, nine patients, ranging in age from 21 to 57, with high risk myeloid malignancy (7 AML and 2 advanced myelodysplasia) and overt bone marrow relapse less than one year after ablative busulfan/cyclophosphamide conditioning have been treated with a cytoreductive regimen of fludarabine (30 mg/m²/day) and cytarabine (2g/m²/day) for 5 days (-7 through -3) and G-CSF administration (5 ug/kg daily starting day -8) with or without idarubicin (8 mg/m² days -7, -5, and -3) (8 cases) or fludarabine 30 mg/m² for 3 days and 200 cGy total body irradiation (1 case). G-CSF mobilized peripheral blood stem cells from their original HLA-matched donor (8 siblings, 1 unrelated) were infused. Graft versus host disease (GVHD) prophylaxis was mycophenolate mofetil for 30 days and cyclosporine with a rapid taper. The mean onset of relapse after the initial ablative transplant was day 172 (range 106–271). Fludarabine-based therapy was well tolerated with no treatment related mortality. Full donor chimerism was established by day 72 (range 26–113) in 6 patients (67%). Five patients died: 2 from relapse without GVHD at day +30 and +301 after RIST (one patient with complex and one with Ph+ cytogenetic abnormalities), 3 from relapse with evidence of GVHD. Four patients survive: one has relapsed at 91 days after RIST and is receiving alternate therapy, while three patients (30%) survive in complete remission at 100+, 635+ and 1795+ days after salvage RIST. In 5 cases (56%), the duration of complete remission after RIST was longer than after the initial ablative transplant. We conclude that fludarabine-based RIST is a safe and effective salvage therapy offering a chance for increased survival with low morbidity in patients relapsing after ablative transplant. In addition, RIST therapy has resulted in long-term disease free survival in over 20% of cases in this study.