Outcomes of a 1-Day Nonmyeloablative Preparative Regimen for Primary Graft Failure After Allogeneic Stem Cell Transplantation

Primary graft failure after allogeneic stem cell transplantation is a life-threatening complication because of prolonged neutropenia after the initial transplantation. A shortened conditioning regimen followed by re-transplantation may increase the chance of survival. Here, we report 11 patients with a median age of 44 (range, 25-67) years, who received a 1-day reduced-intensity preparative regimen and subsequent re-transplantation for primary graft failure. The diseases in these patients were as follows: acute myelogenous leukemia/myelodysplastic syndromes in 6, myeloproliferative diseases in 3, chronic lymphocytic leukemia in 1, and aplastic anemia in 1. All 11 patients experienced primary engraftment failure following a T-cell depleted, fludarabine-based nonmyeloablative transplantation from a haploidentical donor (n = 6), a matched sibling donor (n = 1), a matched unrelated donor (n = 2), or after myeloablative transplantation from dual umbilical cord blood units (n = 2). The 1-day preparative regimen for graft failure rescue consisted of 30 mg/m2 fludarabine, 2 g/m2 cyclophosphamide, 20 mg/body alemtuzumab, and 200 cGy total body irradiation, all delivered 1 day prior to transplantation. Five patients received grafts from the same haploidentical donor; 5, from a different haploidentical donor; and 1, from the same matched sibling donor. Out of the 11 patients, 9 engrafted. Of these, one developed Grade II acute GVHD, and one, Grade I acute GVHD. At present, 8 out of the 11 patients are alive with a median follow-up of 9.2 (range, 2.3-28.8) months from the initial transplantation and 7 are in remission. Three patients died, 1 due to infection and 2 secondary to multi-organ failure. In conclusion, although the number is small, this case-series suggest that our 1-day preparative regimen is feasible, leads to successful engraftment in a high proportion of patients, and might be appropriate for patients requiring immediate re-transplantation after primary graft failure.