Nonmyeloablative allogeneic stem cell transplantation (NST) after truly nonmyeloablative and reduced intensity conditioning regimens

Abstract

Nonmyeloablative allogeneic stem cell transplantation (NST) has been explored to overcome transplant-related mortality (TRM). From the review of 39 published reports, 50% of the 1484 treated patients had NSTs with truly nonmyeloablative conditioning (NMC) and 417 patients (29%) received an unrelated donor transplant (UDT). Median age was 49 years (range 17-59). A median dose of 4.74 x 10(6) CD34+ per kg (range 1.7-7.5) was administered. Hematological recovery was rapid with all the regimens used. Sustained engraftment was obtained in 1267/1355 assessable patients (94%, range 67-100%). Complete donor chimerism was observed in 707/948 assessable patients (75%, range 22-100%). Both were higher after reduced intensity conditioning (RIC) than after NMC regimens. Reject was more frequent after UDT and NMC regimens. Grades II-IV and III-IV acute graft versus host disease (GVHD) occurred in 580/1400 (41%; range 7-72%) and 188/1093 (17%; range 0-29%) assessable patients, respectively; grades II-IV and III-IV acute GVHD were more frequent after UDT and RIC regimens, respectively. Chronic GVHD occurred in 407/1046 assessable patients (39%; range 0-79%) and extensive chronic GVHD in 166/835 patients (20%; range 0-69%); they were more frequent after RIC regimens and less frequent after UDT. Transplant-related mortality (TRM) rate of 20.6%, without differences between RIC and NMC regimens, was observed; TRM was higher with UDTs. The most frequent causes of TRM were acute or chronic GVHD after RIC regimens and infections after NMC regimens and UDTs. Indolent lymphoid malignancies and some solid tumors appear sensitive to the graft versus malignancy (GVM) effect. NSTs could guarantee relatively low TRM and toxicity in patients not eligible for conventional allogeneic transplantation and could represent a platform for successive specific immunotherapy.