OKT-3-based reconditioning regimen for early graft failure in HLA-non-identical stem cell transplants

Primary non-engraftment or early rejection after transplantation of haemato poietic stem cells represent life-threatening complications of allogeneic s tem cell transplantation. Management of early graft failure has been proble matic, as the risk of fatal infectious complications increases with the tim e of pancytopenia and as a second transplant preceded by a conventional mye loablative conditioning regimen has been associated with high rates of cumu lative organ toxicity. For paediatric patients with early graft failure fol lowing the transplantation of highly purified major histocompatibility comp lex (MHC)-disparate haematopoietic stem cells, we have evaluated an immunos uppressive OKT-3/methylprednisolone-based reconditioning regimen with low t oxicity in preparation for a secondary transplant of purified haematopoieti c stem cells from the same donor. This report presents the results from a 4 -year pilot study including six patients with early graft failure. The resu lts demonstrate that this antibody-based regimen can be used effectively to prepare patients for secondary transplantation. Successful engraftment aft er a second transplant procedure was achieved in five of these six high-ris k patients. The median interval between first and second transplant was 27 d (range 22-51 d), and the median time for engraftment was 10 d (range 9-13 d). Chimaerism analysis of microsatellite regions by polymerase chain reac tion (PCR) demonstrated complete donor chimaerism in four of these patients within the first month after secondary transplant and revealed mixed chima erism in one patient who converted to complete chimaerism after T-cell add- back.