title: A 5-day cytoreductive chemotherapy followed by haplo-identical hsct (FA5-BUCY) as a tumor-ablative regimen improved the survival of patients with advanced hematological malignancies.
abstract: Haplo-HSCT has been used when HLA-matched siblings are not available. Conditioning regimens aim to reduce tumor burden prior to HSCT and provide sufficient immunoablation. We report the outcome of haplo-HSCT in 63 consecutive patients from 2/2013 to 12/2015 (19 females/44 males) with high-risk or relapsed/refractory hematological malignancies (n=29-AML; 8-sAML; 19-ALL; 5-advanced-MDS; 2-CML-BC). Median age was 20 years (range: 1.1-49). Twenty-one patients achieved remission prior to transplant, while 42 did not. Patients received FA5-BUCY, i.e., 5-day salvage chemotherapy (Fludarabine/Ara-C) and conditioning (Busulfan/Cyclophosphamide). GvHD prophylaxis included ATG, CsA, MMF and short-term MTX. All patients received stem cells from bone marrow and peripheral blood, and achieved successful engraftment, except two who died before. With a median follow-up of 269 days (120-1081), 42/63 patients are still alive and disease-free. Two-year OS and RFS were similar in patients not in remission and in those in complete remission (61.3% vs 56.3%, p=0.88; 58.3% vs 56.3%, p=0.991). Non-relapse mortality and relapse incidence were 22.2% and 11.1%, respectively. Severe acute-GvHD occurred in 4/63 patients. Transplant-related mortality was low at day+100 (17.5%) and for the entire study period (20.6%). Unexpectedly, few patients experienced mild-to-moderate toxicity, and main causes of death were infection and GvHD. BM blast counts, age, and donor-recipient gender-pairs did not affect the outcome. Less chemotherapy cycles prior to HSCT might result in more favorable outcome. Thus, haplo-HSCT with FA5-BUCY appears promising for advanced disease, especially when TBI and amsacrine, used for FLAMSA, are not available and in pediatric patients for whom TBI is not recommended.
authors.affiliation: Department of Hematology, Fujian Institute of Hematology, Fujian Provincial Key Laboratory on Hematology, Fujian Medical University Union Hospital, Fuzhou 350001, Fujian, P. R. China.
authors.forename: Ting
authors.initials: T
authors.lastname: Yang
authors.affiliation: Department of Hematology, Fujian Institute of Hematology, Fujian Provincial Key Laboratory on Hematology, Fujian Medical University Union Hospital, Fuzhou 350001, Fujian, P. R. China.
authors.forename: Qiaoxian
authors.initials: Q
authors.lastname: Lin
authors.affiliation: Department of Hematology, Fujian Institute of Hematology, Fujian Provincial Key Laboratory on Hematology, Fujian Medical University Union Hospital, Fuzhou 350001, Fujian, P. R. China.
authors.forename: Jinhua
authors.initials: J
authors.lastname: Ren
authors.affiliation: Department of Hematology, Fujian Institute of Hematology, Fujian Provincial Key Laboratory on Hematology, Fujian Medical University Union Hospital, Fuzhou 350001, Fujian, P. R. China.
authors.forename: Ping
authors.initials: P
authors.lastname: Chen
authors.affiliation: Department of Hematology, Fujian Institute of Hematology, Fujian Provincial Key Laboratory on Hematology, Fujian Medical University Union Hospital, Fuzhou 350001, Fujian, P. R. China.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Yuan
authors.affiliation: Department of Hematology, Fujian Institute of Hematology, Fujian Provincial Key Laboratory on Hematology, Fujian Medical University Union Hospital, Fuzhou 350001, Fujian, P. R. China.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Luo
authors.affiliation: Department of Hematology, Fujian Institute of Hematology, Fujian Provincial Key Laboratory on Hematology, Fujian Medical University Union Hospital, Fuzhou 350001, Fujian, P. R. China.
authors.forename: Tingbo
authors.initials: T
authors.lastname: Liu
authors.affiliation: Department of Hematology, Fujian Institute of Hematology, Fujian Provincial Key Laboratory on Hematology, Fujian Medical University Union Hospital, Fuzhou 350001, Fujian, P. R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zheng
authors.affiliation: Department of Hematology, Fujian Institute of Hematology, Fujian Provincial Key Laboratory on Hematology, Fujian Medical University Union Hospital, Fuzhou 350001, Fujian, P. R. China.
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Zheng
authors.affiliation: Department of Hematology, Fujian Institute of Hematology, Fujian Provincial Key Laboratory on Hematology, Fujian Medical University Union Hospital, Fuzhou 350001, Fujian, P. R. China.
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Zheng
authors.affiliation: Department of Hematology, Fujian Institute of Hematology, Fujian Provincial Key Laboratory on Hematology, Fujian Medical University Union Hospital, Fuzhou 350001, Fujian, P. R. China.
authors.forename: Xinji
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Hematology, Fujian Institute of Hematology, Fujian Provincial Key Laboratory on Hematology, Fujian Medical University Union Hospital, Fuzhou 350001, Fujian, P. R. China.
authors.forename: Langhui
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Hematology, Fujian Institute of Hematology, Fujian Provincial Key Laboratory on Hematology, Fujian Medical University Union Hospital, Fuzhou 350001, Fujian, P. R. China.
authors.forename: Hao
authors.initials: H
authors.lastname: Zheng
authors.affiliation: Department of Hematology, Fujian Institute of Hematology, Fujian Provincial Key Laboratory on Hematology, Fujian Medical University Union Hospital, Fuzhou 350001, Fujian, P. R. China.
authors.forename: Zaisheng
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Hematology, Fujian Institute of Hematology, Fujian Provincial Key Laboratory on Hematology, Fujian Medical University Union Hospital, Fuzhou 350001, Fujian, P. R. China.
authors.forename: Xueling
authors.initials: X
authors.lastname: Hua
authors.affiliation: Department of Hematology, Fujian Institute of Hematology, Fujian Provincial Key Laboratory on Hematology, Fujian Medical University Union Hospital, Fuzhou 350001, Fujian, P. R. China.
authors.forename: Shaohua
authors.initials: S
authors.lastname: Le
authors.affiliation: Department of Hematology, Fujian Institute of Hematology, Fujian Provincial Key Laboratory on Hematology, Fujian Medical University Union Hospital, Fuzhou 350001, Fujian, P. R. China.
authors.forename: Jian
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Hematology, Fujian Institute of Hematology, Fujian Provincial Key Laboratory on Hematology, Fujian Medical University Union Hospital, Fuzhou 350001, Fujian, P. R. China.
authors.forename: Zhizhe
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Hematology, Fujian Institute of Hematology, Fujian Provincial Key Laboratory on Hematology, Fujian Medical University Union Hospital, Fuzhou 350001, Fujian, P. R. China.
authors.forename: Jianda
authors.initials: J
authors.lastname: Hu
mesh_terms: D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002066:Busulfan / Q000008:administration & dosage; D017024:Chemotherapy, Adjuvant; D002648:Child; D002675:Child, Preschool; D003520:Cyclophosphamide / Q000008:administration & dosage; D003561:Cytarabine / Q000008:administration & dosage; D018450:Disease Progression; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D019337:Hematologic Neoplasms / Q000235:genetics / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000401:mortality; D006801:Humans; D007223:Infant; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000009:adverse effects / Q000401:mortality; D016016:Proportional Hazards Models; D012008:Recurrence; D012074:Remission Induction; D013997:Time Factors; D019172:Transplantation Conditioning / Q000009:adverse effects / Q000379:methods* / Q000401:mortality; D000075442:Transplantation, Haploidentical; D016896:Treatment Outcome; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives; D055815:Young Adult
chemical_list: D003561:Cytarabine; D003520:Cyclophosphamide; D014740:Vidarabine; D002066:Busulfan; C024352:fludarabine
keywords: cytoreductive chemotherapy; disease control; haplo-identical HSCT; hematological malignancies; refractory