摘要
Objective To investigate if low dose total body irradiation (TBI, 6.0- 9.0 Gy) combined with intensified chemotherapy followed by autologous peripheral blood stem cell transplantation results in better survival in children with refractory leukemia or solid tumors.Methods Twenty-one children with malignant tumors were included in this study. There were 14 males and 7 females aged 3.5- 12 years. Underlying disease included high-risk acute lymphoblastic leukemia (ALL, CR1 in 3 children and CR2 in 5 children), acute myeloblastic leukemia (AML, 9 children), nonHodgkin' s lymphoma stage Ⅳ (2 children), and neuroblastoma stage Ⅳ (2 children). The peripheral hematopoietic stem cells were collected six to eleven months after complete response, mobilized with high dose chemotherapy alone or combined with GM-CSF or G-CSF. The conditioning regimen consisted of chemotherapy with two to three combinations of the following drugs: cyclophosphamide,arabinosylcytosine, McNU, etopside, and Idarubicin on the basis of TBI (6.0-9.0Gy). A mean of (1.8 ± 0.5) × 108/kg autologous mononuclear cells were transplanted. The patients were followed up after transplantation.Results Severe bone marrow suppression occurred in all patients around day + 7. Peripheral white blood cell count decreased to 0 in all patients at day + 4.8 ± 2.9, and platelet count decreased to less than 20× 109/L at day + 9.0 ± 2.6. Successful engraftment was achieved in 21 patients, but four died of infection at day + 17, + 20, + 31 and + 67, respectively. Recovery of white blood cell (WBC) to 10 × 109/L, absolute neutrophil count to 0.5 × 109/L, platelet count to 20 × 109/L occurred on 21 ± 12,26± 13, and 27 ± 10 days, respectively. During the follow up period, three patients relapsed at + 5months, + 1.5 years, and + 2 years 10 months, respectively. One patient died of intracranial hemorrhage at +8 months. Thirteen patients had event-free survival for 2 - 12 years, with a mean of 6.7±3.4 years.Conclusion Our preliminary data suggest that myeloablative therapy with low dose TBI (6.0 - 9.0 Gy)combined with intensified chemotherapy followed by autologous paripheral blood stem cell transplantation might be associated with favorable results in children with refractory leukemia or solid tumors.
目的 探讨讨低剂量全身照射 (6 0 - 9 0Gy)联合强烈化疗后行自体外周血造血干细胞移植能否在儿童难治性白血病或实体瘤中取得良好疗效。方法 2 1例患儿进入本文研究 ,男 14例 ,女 7例 ,年龄 3 5 - 12岁。基础疾病包括高危急性淋巴细胞白血病(CR1) 3例 ,急性淋巴细胞白血病二次缓解 5例 ,急性非淋巴细胞白血病 9例 ,非何杰金氏淋巴瘤Ⅳ期 2例。完全缓解后 6- 11个月采集外周血造血干细胞 ,用大剂量化疗或化疗与G CSF/GM CSF合用进行采集前的动员。预处理方案包括下列药物中 2 - 3种联合 :环磷酰胺、阿糖胞苷、司莫司丁、足叶乙甙、去甲氧柔红霉素 ,并加用全身照射 (6 0 - 9 0Gy)。结果 所有病例在约 +7天出现严重骨髓抑制 ,外周血白细胞在 +4 8± 2 9天降至 0 ,血小板在 +9 0± 2 6天降至 2 0± 10 9/L以下。 17例外周血植入成功 ,另 4例分别于 +17、+2 0、+31和 +67天死于感染。白细胞升至 10×10 9/L ,中性粒细胞升至 0 5× 10 9/L ,血小板升至 2 0× 10 9/L的时间分别为 2 1± 12、2 6± 13和 2 7± 10天。随访研究显示 3例分别于 +5个月、1 5年和 2年 10个月复发 ,一例在 +8个月时死于颅内出血。 13例获得 2至 12年 (平均 6 7± 3 4年 )的无病生存。