造血干细胞移植治疗儿童髓系白血病26例疗效分析

目的 了解造血干细胞移植对儿童急性髓系白血病(AML)和慢性粒细胞白血病(CML)的治疗效果.方法 髓系白血病患儿26例,平均年龄为9.8岁,其中CML 8例,AML18例.CML患儿中,第1次慢性期(CPl)6例,加速期(AP)1例,第2次慢性期(CP2)1例;AML患儿中,第1次缓解(CRl)9例,第2次缓解(CR2)7例,2例未缓解(NCR).26例中,2例接受HLA全相合同胞供者的外周血与骨髓干细胞联合移植;2例接受由HLA半相合母亲供者外周血干细胞分离出的CD34+细胞输注;2例接受脐血移植;其余20例接受外周血造血干细胞移植.每例移植有核细胞(6.8±6.0)×108/kg,CD34+细胞(4.0±5.8)×106/kg,CD3+细胞(2.6±3.8)×108/kg.所有患儿均采用白消安及环磷酰胺进行清髓性预处理.移植后采用环孢素A和甲氨蝶呤联用预防移植物抗宿主病(GVHD),接受无关供者造血干细胞移植者加用抗胸腺细胞球蛋白,6例CML患儿加用霉酚酸酯.若发生Ⅱ度以上GVHD,则给予甲泼尼龙或巴利昔单抗治疗.结果 除2例HLA半相合移植失败外,其余24例均获得造血功能重建.24例植入成功的患儿中,2例未发生急性GVHD(aGVHD),15例(62.5%,15/24)出现Ⅰ～Ⅱ度aGVHD,7例(29.2%,7/24)出现Ⅲ～Ⅳ度aGVHD(重度aGVHD).7例重度aGVHD均为CML患儿.26例平均随访20.5个月,其中原发病复发死亡者4例,治疗相关死亡者5例,尚有17例(65.4%,17/26)患儿无病存活.结论 异基因造血干细胞移植有助于提高髓系白血病患儿的存活率,只要加强预防,无关供者造血干细胞移植产生的GVHD是可以控制的.而对于高危患儿,无关供者造血干细胞移植的效果与亲缘相关供者移植相似.

Outcome of allogeneic stem cell transplantation for 26 children with myeloid leukemia

Objective To clarify the role of hematopoietic stem cell transplantation treating patients with myeloid leukemia. Methods A total of 26 consecutive patients with acute myeloid leukemia (AML, 18 cases: CR1 = 9, CR2 = 7, Non CR = 2) and chronic myeloid leukemia (CML, 8 cases: CP1 = 6, AP = 1, CP2 = 1) in a single institution between May 200! and September 2006 were enrolled. Five out of 9 cases of AML got CR1 after at least 2 courses of chemotherapy. The average age was 9. 8 years old (range 2～17 years) and the average body weight 32.8 kg (11.5～79kg). Patients underwent allogeneic peripheral blood stem cell transplantation (allo-PBSCT) from HLA-identical siblings (n = 2), mismatched family donors (n = 4) and matched unrelated donors (n = 20). All patients received myeloablative regimens with 16～20 mg/kg busulfan and 20t1 mg/kg cyclophosphomide. For aGVHD prophylaxis patients with HLA-identical sibling donors received cyclosporine (CsA) and metbetraxate, while patients with matched unrelated donors received CsA, methotrexate and 15 mg/kg rabbit ATG (Fresenius). After Jan. 20{)4 mycophenolate mofetil were used to enhance GVHD prophylaxis for CML patients. Results After an average follow-up period of 20.5 months (9～55 months), 2(7.6%) patients' graft was rejected, 7(27%) patients developed grade 3～4 aGVHD (all with CML), and 5 patients had extensive cGVHD. At present, 9 patients have died of relapse (4/26) and TRM (GVHD 4/26 and infection 1/26), while 17 (65.4%) patients are still alive with disease-free survival. Conclusion Allogeneic stem cell transplantation is conducive to improve the survival rate for children with AML and the GVHD associated with unrelated donor transplants can be controlled after taking active prevention measures.