Graft failure occurs at relatively low frequency, but commonly in hemophagocytic lymphohistiocytosis (HLH), especially with umbilical cord blood transplant (UCBT). No standard approaches to management of graft failure exist. We present a challenging case of relapsed HLH following first UCBT with primary graft failure following second UCBT. We report a novel reduced intensity conditioning regimen of alemtuzumab, 4 Gy total body irradiation and fludarabine for salvage of primary graft failure followed by double UCBT. The reported patient successfully engrafted with 100% donor chimerism following salvage UCBT with no occurrence of acute or chronic graft-versus-host disease.