OBJECTIVETo explore the efficacy of tumor-ablative individualized allogeneic hematopoietic stem cell transplantation for the treatment of patients with high risk/refractory leukemia.

METHODSFivety-seven patients with high risk/refractory leukemia were enrolled. Tumor-ablative individualized conditioning regimens included HDAra-C + Bu/Cy, Ara-C + Bu/Fludarabine, G-CSF primed HDAra-C + Bu/Cy, and FLAG followed by reduced-intensified BuCy. Overall survival (OS), disease free survival (DFS), graft versus host disease, infection and relapse post grafting were analyzed.

RESULTSFifty-six patients attained durable engraftment. The median follow-up duration was 17.5 (2 - 34) months. The 18 months probabilities of OS and DFS were (74.7 ± 6.1)% and (62.4 ± 6.7)%, respectively. In addition, the 18 months probabilities of OS and DFS in patients who attained complete remission (CR) before transplantation were (74.2 ± 7.1)% and (58.8 ± 8.1)%, respectively, while in those not attained CR were (77.0 ± 11.8)% and (72.7 ± 11.7)%, respectively. Twenty nine patients developed acute GVHD (aGVHD) (grade I in 18, grade II in 4, grade III in 2 and grade IV in 5). The probabilities of aGVHD was (50.9 ± 6.6)% by Kaplan-Meier curve analysis. The probabilities of grades 2-4 and grades 3-4 aGVHD were (19.3 ± 5.2)% and (12.3 ± 4.3)% respectively. Extensive chronic GVHD (cGVHD) was observed in 36 patients. The probabilities of cGVHD was (64.3 ± 6.4)% by Kaplan-Meier curve analysis. Cytomegaloviremia (CMV) was observed in 39 (68.42%) patients, hemorrhagic cystitis in 13 (22.8%) patients, fungous infection in 16 (28.07%) patients and bacterial infection in 38 (66.67%) patients. Relapse occurred in 14 patients (hematologic relapse in 11 and extramedullary relapse in 3), probabilities of relapse being (24.6 ± 5.7)%. The 17.5-month probability of relapse in patients who attained CR before transplantation was (28.1 ± 7.7)%, while in those not attained CR was (15.6 ± 10.2)%. Fifteen patients died (6 from hematological relapse, 5 from infection of bacterial and fungous, 4 from cGVHD) after 100 days.

CONCLUSIONTumor-ablative individualized allogeneic hematopoietic stem cell transplantation is a promising and safe choice for treatment of high risk/refractory leukemia, even with high leukemia burden.