Sequential Intensified Conditioning Followed By Tapering Of Prophylactic Immunosupressants and Donor Lymphocyte Infusions In Allogeneic Hematopoietic Stem Cell Transplantation For Refractory Leukemia

• Published in: Blood 2013-11, Vol.122 (21), p.702-702
• Main Authors: Liu, Qifa, Xuan, Li, Zhang, Yu, Zhou, Hongsheng, Huang, Fen, Dai, Min, Li, Yonghua, Nie, Danian, Xu, Na, Guo, Xutao, Lin, Dongjun, Xiao, Yang, Liu, Can, Jiang, Qianli, Sun, Jing
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V122.21.702.702

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is perceived as the only curative option for refractory acute leukemia. However, the relapse rate exceeds 50% in these patients undergoing allo-HSCT with standard myeloablative regimen. To improve outcomes of allo-HSCT for refractory leukemia, we previously introduced a strategy of sequential intensified conditioning and early rapid tapering of prophylactic immunosupressants for graft-versus-host disease (GVHD). The results indicated this strategy could improve outcomes of refractory leukemia, with 5-year overall survival (OS) and disease-free survival (DFS) of 44.6% ± 8.1% and 38.2% ± 7.7%. However, the 3-year cumulative incidence of leukemia relapse reached to 33.3%. To reduce the relapse rate but without increasing regimen-related toxicities (RRT), we increased the dose of etoposide (VP-16) in conditioning and infused donor lymphocytes (DLI). The aim of this prospective study was to assess the feasibility and efficacy of this modified strategy in patients with refractory acute leukemia. A total of 123 patients with refractory acute leukemia undergoing allo-HSCT from January 2009 to December 2012 were enrolled. Ninety-four patients received related (73 sibling and 21 family donors), 29 unrelated donor transplants; 73 were HLA locus matched, 50 mismatched. Modified sequential intensified conditioning regimen was: fludarabine (30 mg/m2/day, -10 to -6 days) + cytarabine (2.0 g/m2/day, -10 to -6 days) plus TBI (total body irradiation, 4.5 Gy/day, -5, -4 days) + cyclophosphamide (60 mg/kg/ day, -3, -2 days) + VP-16 (15 mg/kg/day, -3, -2 days). Cyclosporine A (CsA) was withdrawn rapidly in a stepwise fashion (total dose reduced by 20%/week) if patients who did not experience acute GVHD (aGVHD) by day +30 post-transplantation. Donor lymphocytes (1.0×108/kg, once a month, 4 doses totally) would be infused in patients without II° or more than II° aGVHD by day + 60 post-transplantation. All patients achieved hematopoietic engraftment, except for two who died of infections and one who died of RRT during conditioning. All 120 evaluable patients achieved complete remission (CR) at the time of neutrophil engraftment and achieved complete donor chimerism by day +30 post-transplantation. The incidence of total RRT was 100%, and III-IV RRT was 22.0%. Within the first 100 days post-transplantation, 67 patients developed 95 episodes of infections. Twenty-one had bacterial infections, 7 had invasive fungal infectio