Abstract
Allogeneic stem cell transplantation (SCT) from an HLA-haploidentical relative provides a potentially curative treatment option for hematologic malignancies patients who lack a suitably HLA-matched donor. The greatest challenge to performing HLA-haploidentical SCT has been high rates of graft failure and severe graft-versus-host disease (GVHD). Our group has been exploring high dose, post-transplantation cyclophosphamide (Cy) as prophylaxis of GVHD after nonmyeloablative, HLA-haploidentical bone marrow transplantation, or mini-haploBMT. Among 210 recipients of mini-haploBMT, 87% of patients have experienced sustained donor cell engraftment. The cumulative incidences of grades II-IV acute GVHD and chronic GVHD are 27% and 13%, respectively. Five-year cumulative incidence of non-relapse mortality is 18%, relapse is 55%, and actuarial overall survival and event-free survivals are 35% and 27%, respectively. These outcomes suggest that mini-haploBMT with post-transplantation Cy is associated with acceptably low toxicities and can provide longterm survival, if not cure, for many patients with advanced hematologic malignancies.
Highlights
Post-transplantation Cy as a form tioning comprised cyclophosphamide 14.5 cipient. mg/kg/day on days -6 and -5, fludarabine 30 of drug-induced immunologic tolerance mg/m2/day for five consecutive days starting on day -6, and 2 Gy total body irradiation given in Engraftment and donor chimerism
Three year overall survival was loidentical BMT after myeloablative conditioning have shown that increasing HLA mismatch between donor and recipient was associated with worse survival due to an increased incidence of graft-versus-host disease (GVHD) and NRM, which outweighed any potential reduction in the incidence of relapse.[10,11,12]
Since our regimen incorporated nonmyeloablative conditioning and novel GVHD prophylaxis, we examined the impact of increasing HLA disparity on outcome.[9]
Summary
Based upon encouraging results from a phase I/II trial,[7,8] we recently completed a phase II trial of nonmyeloablative, HLA-haploidentical BMT with high-dose, post-transplantation Cy for patients with advanced hematologic malignancies. These nonmyeloablative, HLA-haploidentical trans- Fifty-eight patients had experienced relapse of outcomes suggest that mini-haploBMT with post-transplantation Cy is associated with acceptably low toxicities and can provide longterm survival, if not cure, for many patients with advanced hematologic malignancies.
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