Shah Sandip A, Shah Kamlesh M, Patel Kinnari A, Anand Asha S, Talati Shailesh S, Panchal Harsha P, Patel Apurva A, Parikh Sonia K, Parekh Bhavesh B, Shukla Shilin N, Raut Shreeniwas S
GCRI, Ahmedabad, India.
Indian J Hematol Blood Transfus. 2015 Mar;31(1):9-13. doi: 10.1007/s12288-014-0391-3. Epub 2014 Jun 19.
Beta thalassemia major, one of the most prevalent hemoglobinopathy throughout the word, can be cured by allogenic stem cell transplantation (SCT) (Bone Marrow Transplant 36:971-975, 2005). Many patients, however, lack a suitably matched related sibling donor. Unrelated umbilical cord blood (UCB) can be used as an alternative stem cell source for these patients. This report describes SCT for nine children with beta-thalassemia major using partially HLA-matched unrelated UCB. Conditioning included oral busulfan 16 mg/kg (day -10 to -7), cyclophosphamide (Cy) 200 mg/kg (day -5 to -2), fludarabine 90 mg/kg (day -13 to -11), and antithymocyte globulin (rabbit) 7.5 mg/kg (day -3 to -1). The infused cell dose was 10.71 × 10(7)/kg total nucleated cells (TNC) (range 6.5-17 × 10(7)/kg TNC). The patients ranged in age from 1.5 to 7 years, in weight from 10.5 to 17 kg. A second transplant with two unrelated cord blood units was attempted in two patients who had primary graft failure. The retransplant recipients were preconditioned with i.v Cy 120 mg/kg (day -3 to -2). Five of the nine patients engrafted promptly with 50-100 % donor chimerism (56 %). They engrafted at a median of 17 days (range 12-19). One patient is transfusion free for 36 months; a second patient is transfusion free for 18 months and a third is transfusion free for 9 months. There was no transplant related mortality. Four of the nine children had autologous recovery without engraftment. Primary graft rejection is the major complication. Post transplant complications were mild hepatic veno-occlusive disease, acute GVHD grade II, and CMV interstitial pneumonia. The chronic GVHD was limited and could be controlled by Methylprednisolone combined with Mycophenolate. The lack of a marrow donor registry in India makes UCBT from related and unrelated donors a good alternative. Transplant should be delayed until the child is at least 18 months of age. The dose of UCB stem cells is the most important factor for engraftment. UCB has the advantages of rapid availability and low risk of severe GVHD despite donor-recipient HLA disparity (Transplant Proc 37:2667-2669, 2005). We demonstrate the feasibility of this procedure in the setting of a developing country.
重型β地中海贫血是全球最常见的血红蛋白病之一，可通过异基因干细胞移植（SCT）治愈（《骨髓移植》36:971 - 975, 2005）。然而，许多患者缺乏匹配度合适的同胞供体。无关脐血（UCB）可作为这些患者的替代干细胞来源。本报告描述了使用部分HLA匹配的无关脐血对9例重型β地中海贫血患儿进行的干细胞移植。预处理方案包括口服白消安16 mg/kg（第 - 10天至 - 7天）、环磷酰胺（Cy）200 mg/kg（第 - 5天至 - 2天）、氟达拉滨90 mg/kg（第 - 13天至 - 11天）以及抗胸腺细胞球蛋白（兔）7.5 mg/kg（第 - 3天至 - 1天）。输注的细胞剂量为10.71×10⁷/kg总核细胞（TNC）（范围为6.5 - 17×10⁷/kg TNC）。患者年龄在1.5至7岁之间，体重在10.5至17 kg之间。两名原发性移植物失败的患者尝试了使用两个无关脐血单位进行二次移植。二次移植受者接受静脉注射Cy 120 mg/kg（第 - 3天至 - 2天）预处理。9例患者中有5例迅速植入，供体嵌合率为50% - 100%（平均56%）。他们的植入中位时间为17天（范围12 - 19天）。1例患者已36个月未输血；第2例患者18个月未输血，第3例患者9个月未输血。无移植相关死亡。9名儿童中有4例出现自体恢复但未植入。原发性移植物排斥是主要并发症。移植后并发症包括轻度肝静脉闭塞病、急性II级移植物抗宿主病（GVHD）和巨细胞病毒（CMV）间质性肺炎。慢性GVHD较局限，可通过甲泼尼龙联合霉酚酸酯控制。印度缺乏骨髓供体登记系统，使得来自相关和无关供体的脐血移植成为一个很好的选择。移植应推迟至儿童至少18个月大。脐血干细胞剂量是植入的最重要因素。尽管供受者HLA存在差异，但脐血具有快速可得且严重GVHD风险低的优点（《移植过程》37:2667 - 2669, 2005）。我们证明了在发展中国家背景下该手术的可行性。
