Purine analog regimens for allogeneic transplant?

Abstract

regimens. Attempts to improve the outcomes of allogeneic transplantation by altering the conditioning regimen have been explored. Clift et al 1 observed that intensification of the conditioning regimen by increasing the total dose of irradiation significantly decreased the risk of leukemic relapse; however, treatment-related mortality (TRM) was increased, resulting in no improvement in survival. Recently, several groups evaluated less intense conditioning regimens in an attempt to reduce treatment-related toxicity. Such low-intensity conditioning regimens could improve disease-free survival if the reduction in TRM was not offset by increased relapse risk. These regimens would be safer to administer to high-risk patients who may not have historically been considered candidates for this procedure because of advanced age or concurrent medical illnesses. Khouri et al 2 and Giralt et al 3 presented outcomes of patients who underwent allogeneic transplantation with purine analog‐based conditioning regimens which are immunosuppressive but not myeloablative. Khouri et al2 treated 15 patients with chronic lymphocytic leukemia or lymphoma and observed that this regimen was well tolerated, with one TRM (6.7%) and rare $ grade 3 nonhematologic toxicity. Eleven patients had engraftment of donor cells, but only five of these patients had complete (100%) donor chimerism early after transplantation. Four patients did not engraft donor cells but recovered with autologous hematopoiesis. Because only two of the 15 patients had assessment of chimerism beyond 6 months after transplantation, it is unclear whether durable donor engraftment can be achieved with this regimen. In this report, control of disease was also of concern. Although eight patients (53%) achieved complete response (CR) after transplantation, an earlier report from the same institution using an intense conditioning regimen reported that 80% of similar patients achieved CR.4 Giralt et al3 treated 15 patients with advanced leukemia or myelodysplasia with purine analog‐based nonmyeloablative conditioning regimens for allogeneic transplantation. The regimen was well tolerated, with only two patients developing $ grade 3 nonhematologic toxicity. However, only one of 12 assessable patients had complete donor chimerism after transplantation, whereas seven patients had mixed chimerism and four patients failed to engraft donor cells. Disease control was also relatively poor, with only eight patients achieving CR, of whom two persisted. The median survival time was only 78 days (range, 0 to 1751 days), with the most common cause of death being not toxicity, but leukemia.