造血干细胞移植治疗恶性血液病、实体瘤回顾分析

Effect of hematopoietic stem cell transplantation in patients with malignant hematologic diseases and solid tumors

目的探讨不同预处理方案以及不同移植方法治疗恶性血液病、实体瘤的疗效,对其移植效果及移植风险进行评价。方法回顾分析非净化自体骨髓移植(auto-HSCT)31例,外周血干细胞加自体骨髓活化移植(PBSCT+ABM)26例,清髓性异基因骨髓移植(allo-HSCT)18例,非清髓性异基因骨髓/外周血移植(allo-NSCT)43例,脐带血干细胞移植(CBT)7例的临床资料。PBSCT+ABM、auto-HSCT和allo-HSCT均采用MAC方案预处理。PBSCT+ABM系采用自身外周血干细胞及体外活化自体骨髓液750ml回输;allo-HSCT采集供者骨髓液于移植0d回输;allo-NSCT是采用低强度的FAAC或MAAC两种方案预处理,移植后根据嵌合体形成的情况,以递增方式将供体淋巴细胞输注(DLI)给患者。allo-CBT患儿,2例采用脐血库的干细胞,HLA配型4个以上的位点相合,5例采用同胞的脐带血干细胞,预处理采用CTX/ATG,移植的程序与上述一致。异基因移植患者常规使用免疫抑制剂(环胞霉素、氨甲蝶呤/骁悉),并根据白细胞、血小板、骨髓恢复,ABO血型分析,STR测定嵌合体形成等情况作为植活的证据。aGVHD按Glucksberg标准分析,cGVHD根据Shul man标准分析。结果125例患者中除有1例慢性髓性白血病(CML)NSCT移植后40d时植入失败死于骨髓衰竭,1例急性髓性白血病(AML)NSCT在造血恢复前死于脑出血外,其余123例都预期恢复造血。异基因移植aGVHD发生率9.69%,cGVHD发生率22.23%。auto-HSCT31例,截止资料分析时生存8例(25.80%)。PBSCT+ABM26例,生存15例(57.69%),allo-HSCT18例,生存11例(61.11%),NSCT43例,生存19例(45%)。CBT7例生存2例。结论异基因造血干细胞移植是一种根治性的治疗手段,尤其非清髓性预处理的异基因造血干细胞移植方法不仅扩大了移植的应用范围及适应证,而且提高了移植的安全性并降低了移植费用。

Objective To explore the clinical effectiveness of different preconditioning regimens and different transplantation methods in the treatment of malignant hematological diseases and solider tumors, and to evaluate the effectiveness and the risks associated with transplantation. Methods All 125 cases of transplantation were analyzed retrospectively, including 31 cases of auto-HSCT without cleaning （auto-HSCT） ,26 cases of peripheral blood stem cells plus auto-activated bone marrow transplantation （PBSCT ＋ ABM）, 18 cases of myeloablative allogenic bone marrow transplantation （allo-HSCT） ,43 cases of nonmyeloablative allogenic bone marrow or peripheral blood stem cell transplantation （allo-NSCT） and 7 cases of cord blood stem cell transplantation （CBT）. The cases of PBSCT ＋ ABM, auto-HSCT and allo-HSCT were preconditioned with MAC regimen chemotherapy. The cases of PBSCT ＋ ABM were infused with autologous peripheral blood stem cells and activated bone marrow about 750 ml. The cases of allo-HSCT were infused at the 0 day of transplantation with donor＇ s bone marrow stem cells. The cases of allo-NSCT was preconditioned with low dose conditioning regimen FAAC or MAAC, and after transplantation, the donor lymphocyte infusion increased progressively according to the formation of chimera. Among the patients who accepted CBT,2 adopted stem cells from cord bank with more than 4 matching sites of HLA zygosity, and 5 adopted sibling＇ s cord stem cells; and all were preconditioned with CTX/ATG, and procedures were the same as above mentioned. Those with allogenic transplantation used Cyclosporin A and methotrexate or mycophenolic acid routinely. The recovery of leukocytes, platelets and bone marrow, the analysis of blood type and the formation of chimera were regarded as the evidences of successful implantation, aGVHD was analyzed by Glucksberg standard, and cGVHD was analyzed by Shulman standard. Results Among 125 patients, 1 patient with CML died of bone marrow failure at day 40 after nonmyeloablative transplantation, 1 patient with AML died of cerebral hemorrhage before the recovery of haematogenesis, and 123 cases succeeded with haematogenesis recovery. The incidence rates of aGVHD and cGVHD in allogenic transplantation were 9.69% and 22.23% ,respectively. Until the time of collecting materials, the survival rates were 25.80% for auto-HSCT （n = 31 ）, 57.69% for PBSCT ＋ ABM （n = 26）,61.11% for allo-HSCT （n=18）, 45% for NSCT （n=43） and28.9% for CBT（n=7） respectively. Conclusion Hemopoietic stem cell transplantation is a curable method for malignant diseases. Especially, nonmyeloablative transplantation not only enlarge applieation and indication, but also are safer and cheaper. But relapse and GVHD remain the mainly causes of transplantation failure.