FBC预处理方案在HLA半相合异基因外周血干细胞移植中的应用

目的　观察降低预处理强度对HLA半相合异基因干细胞植入的影响。方法　用氟达拉宾 (30mg m2 × 6d)、白消安 (4mg kg× 2d)、环磷酰胺 [(30～ 6 0 )mg kg× 2d]组成FBC方案。将 12例白血病患者分成两组 ,HLA完全相合移植组 4例 ,移植前患者处完全缓解状态 ;HLA半相合移植组 8例 ,皆为难治性白血病 ,其中 1例HLA 3个位点不合 ,6例二个位点不合 ,1例一个位点不合 ,接受本处理方案后 ,进行G CSF动员的异基因外周血干细胞移植 ,并于移植后第 30天 (+30天 )、+6 0天、+90天输注供者淋巴细胞 ,观察异基因干细胞植入和长期植入情况。结果　HLA半相合组患者平均接受 4.87× 10 8 kg供者外周血单个核细胞 ,其中CD3 4+细胞平均数为 4.5 8× 10 6 kg,HLA全相合组平均接受 4.85× 10 8 kg供者外周血单个核细胞 ,其中CD3 4+细胞 4.47× 10 6 kg。HLA半相合组 7例白细胞升至 1.0×10 9 L的平均时间为 2 9d(11～ 90d) ,血小板升至 2 0× 10 9 L的时间为 36d(14～ 96d) ,1例HLA 3个位点不合的患者移植失败 ,但该患者于 +5 0天恢复自体造血。而HLA全相合的 4例患者白细胞升至 1.0×10 9 L平均需 14d(11～ 18d) ,血小板升至 2 0× 10 9 L平均需 15d(11～ 18d)。经STR PCR检测 ,两组患者除 1例表现为混合嵌合体 ,其余均呈完

Application of FBC conditioning regimen in HLA haplotype peripheral blood stem cell transplantation 基金项目:全军医学科学技术研究"十五"计划重点课题资助项目(01Z0250)

OBJECTIVE: To observe the influence of decreasing conditioning regimen intensity on the engraftment of HLA haplotype peripheral blood stem cell transplantation. METHOD: 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). RESULT: 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. CONCLUSION: 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.