Wu Bingyi, Guo Kunyuan, Song Zhaoyang, Yan Dingan, Yang Yulian, Xiao Lulu
Hematology Department, Zhujiang Hospital, Guangzhou 510280, China.
Zhonghua Xue Ye Xue Za Zhi. 2002 Apr;23(4):194-7.
To observe the influence of decreasing conditioning regimen intensity on the engraftment of HLA haplotype peripheral blood stem cell transplantation.
Twelve patients with leukemia, including 4 in complete remission, whose HLAs were full matched with donors, and 8 with refractory leukemia, whose HLAs were mismatched, were transplanted with G-CSF mobilized allogeneic peripheral blood stem cells after conditioned with a regimen consisting of fludarabine (30 mg/m(2) x 6 days), busulfan (4 mg/kg x 2 days) and cyclophosphamide (30 approximately 60 mg/kg x 2 days) (FBC). Donor lymphocytes were infused at day + 30, + 60 and + 90 after transplantation, respectively. Hematopoietic reconstitution was observed. Engraftment was documented by the analysis of short tandem repeats with polymerase chain reaction (STR-PCR).
Patients in HLA haplotype group received a mean number of 4.87 x 10(8)/kg donor mononuclear cells (MNC), with CD(34)(+) cells of 4.58 x 10(6)/kg and patients in HLA identical group a mean number of 4.85 x 10(8)/kg MNC with CD(34)(+) cells of 4.47 x 10(6)/kg. The mean time of white blood cell count more than 1.0 x 10(9)/L was 14 (10 approximately 18) days in HLA matched patients and 29 (11 approximately 90) days in HLA haplotype group. One three locus mismatched patient failed to engraft, but auto-hematopoiesis was recovered on day + 50. Full donor chimerism was observed in all patients except one with mixed chimera. The mixed chimera was converted into full donor chimera after three times donor lymphocyte infusion. One each died from severe acute GVHD, severe VOD and severe chronic GVHD in HLA haplotype group, and one from chronic GVHD in HLA identical group.
Patients survived engraftment was not influenced by decreasing conditioning intensity as in this regimen. Haplotype stem cells could be engrafted durable in recipients by this regimen combined with donor lymphocyte infusion.
观察降低预处理方案强度对HLA单倍型外周血干细胞移植植入的影响。
12例白血病患者,其中4例处于完全缓解期,其HLA与供者完全匹配,8例为难治性白血病,其HLA不匹配,在接受氟达拉滨(30mg/m²×6天)、白消安(4mg/kg×2天)和环磷酰胺(30~60mg/kg×2天)(FBC)方案预处理后,接受G-CSF动员的异基因外周血干细胞移植。分别在移植后第30、60和90天输注供者淋巴细胞。观察造血重建情况。通过聚合酶链反应(STR-PCR)分析短串联重复序列记录植入情况。
HLA单倍型组患者平均接受4.87×10⁸/kg供者单个核细胞(MNC),CD34⁺细胞为4.58×10⁶/kg,HLA全相合组患者平均接受4.85×10⁸/kg MNC,CD34⁺细胞为4.47×10⁶/kg。HLA匹配患者白细胞计数超过1.0×10⁹/L的平均时间为14(10~18)天,HLA单倍型组为29(11~90)天。1例三位点不匹配患者未植入,但在第50天自体造血恢复。除1例混合嵌合体患者外,所有患者均观察到完全供者嵌合。在三次输注供者淋巴细胞后,混合嵌合体转化为完全供者嵌合体。HLA单倍型组分别有1例死于严重急性移植物抗宿主病(GVHD)、严重肝静脉闭塞病(VOD)和严重慢性GVHD,HLA全相合组有1例死于慢性GVHD。
在本方案中,植入存活的患者不受降低预处理强度的影响。通过本方案联合供者淋巴细胞输注,单倍型干细胞可在受者体内持久植入。