非血缘关系造血干细胞移植61例分析

Objective To study the therapeutic effectiveness, associated complications and related factors of unrelated allogeneic hematopoietic stem cell transplantation (URD-HSCT). Methods Sixty-one patients with malignant hematological diseases received URD-HSCT. All cases were subjected to myeloablative or nonmyeloablative conditioning regimen according to primary diseases. Among 61 patients, 21 were donor-recipient 6/6 HLA-matched, 5 were 5/6 HLA antigen-matched, 24 were 1 HLA gene subtype-mismatched, 11 were 2 HLA gene subtype-mismatched. Eighteen patients were ABO-compatible with donors, while 43 ABO-incompatible with donors. The median of infused donor nucleated cells was 4.5×108/kg, and the median of CD34+ cells were 4.3×106/kg. The graft-versus-host disease (GVHD) prevention regimens were based on short-term MTX, cyclosporin A and mycophenolate mofetil (MMF) regimen. Forty-nine cases also received CD25 Mab on the day of transplantation, and the day 4 after transplantation. Nine cases were also administrated with antilymphocyte globulin (ALG) or antithymocyte globulin (ATG). Two cases received ALG and CD25 Mab. Results Among 61 patients, 59 cases were successfully engrafted, which was identified by blood type, chromosome test and DNA polymorphism. Twenty-three cases developed grade Ⅱ～Ⅳ acute GVHD. Twenty-five patients experienced chronic GVHD. Infection of bacterial and/or fungal within 100 days after URD-HSCT was documented in 48 cases. Thirty-six cases had cytomegalovirus infection. Major infection site was lower respiratory tract. Eighteen cases died after URD-HSCT, and the 2-year disease-free survival rate was (68.0±6.4)%. Among these 18 deaths, 12 cases died because of transplantation related complications with the transplantation related mortality (TRM) being 19.7 %, and the remaining 6 cases died of relapse with the relapse rate being 9. 8 %, respectively. Conclusions URD-HSCT is an effective therapeutic strategy for malignant hematopoietic diseases when related donor is not available Acute GVHD and infection are risk factors of therapeutic effect and prognosis after URD-HSCT. Early prediction and prevention of acute GVHD and infection are essential problems to overcome.     

非血缘关系造血干细胞移植61例分析

Objective To study the therapeutic effectiveness, associated complications and related factors of unrelated allogeneic hematopoietic stem cell transplantation (URD-HSCT). Methods Sixty-one patients with malignant hematological diseases received URD-HSCT. All cases were subjected to myeloablative or nonmyeloablative conditioning regimen according to primary diseases. Among 61 patients, 21 were donor-recipient 6/6 HLA-matched, 5 were 5/6 HLA antigen-matched, 24 were 1 HLA gene subtype-mismatched, 11 were 2 HLA gene subtype-mismatched. Eighteen patients were ABO-compatible with donors, while 43 ABO-incompatible with donors. The median of infused donor nucleated cells was 4.5×108/kg, and the median of CD34+ cells were 4.3×106/kg. The graft-versus-host disease (GVHD) prevention regimens were based on short-term MTX, cyclosporin A and mycophenolate mofetil (MMF) regimen. Forty-nine cases also received CD25 Mab on the day of transplantation, and the day 4 after transplantation. Nine cases were also administrated with antilymphocyte globulin (ALG) or antithymocyte globulin (ATG). Two cases received ALG and CD25 Mab. Results Among 61 patients, 59 cases were successfully engrafted, which was identified by blood type, chromosome test and DNA polymorphism. Twenty-three cases developed grade Ⅱ～Ⅳ acute GVHD. Twenty-five patients experienced chronic GVHD. Infection of bacterial and/or fungal within 100 days after URD-HSCT was documented in 48 cases. Thirty-six cases had cytomegalovirus infection. Major infection site was lower respiratory tract. Eighteen cases died after URD-HSCT, and the 2-year disease-free survival rate was (68.0±6.4)%. Among these 18 deaths, 12 cases died because of transplantation related complications with the transplantation related mortality (TRM) being 19.7 %, and the remaining 6 cases died of relapse with the relapse rate being 9. 8 %, respectively. Conclusions URD-HSCT is an effective therapeutic strategy for malignant hematopoietic diseases when related donor is not available Acute GVHD and infection are risk factors of therapeutic effect and prognosis after URD-HSCT. Early prediction and prevention of acute GVHD and infection are essential problems to overcome.     

非血缘关系造血干细胞移植61例分析

Objective To study the therapeutic effectiveness, associated complications and related factors of unrelated allogeneic hematopoietic stem cell transplantation (URD-HSCT). Methods Sixty-one patients with malignant hematological diseases received URD-HSCT. All cases were subjected to myeloablative or nonmyeloablative conditioning regimen according to primary diseases. Among 61 patients, 21 were donor-recipient 6/6 HLA-matched, 5 were 5/6 HLA antigen-matched, 24 were 1 HLA gene subtype-mismatched, 11 were 2 HLA gene subtype-mismatched. Eighteen patients were ABO-compatible with donors, while 43 ABO-incompatible with donors. The median of infused donor nucleated cells was 4.5×108/kg, and the median of CD34+ cells were 4.3×106/kg. The graft-versus-host disease (GVHD) prevention regimens were based on short-term MTX, cyclosporin A and mycophenolate mofetil (MMF) regimen. Forty-nine cases also received CD25 Mab on the day of transplantation, and the day 4 after transplantation. Nine cases were also administrated with antilymphocyte globulin (ALG) or antithymocyte globulin (ATG). Two cases received ALG and CD25 Mab. Results Among 61 patients, 59 cases were successfully engrafted, which was identified by blood type, chromosome test and DNA polymorphism. Twenty-three cases developed grade Ⅱ～Ⅳ acute GVHD. Twenty-five patients experienced chronic GVHD. Infection of bacterial and/or fungal within 100 days after URD-HSCT was documented in 48 cases. Thirty-six cases had cytomegalovirus infection. Major infection site was lower respiratory tract. Eighteen cases died after URD-HSCT, and the 2-year disease-free survival rate was (68.0±6.4)%. Among these 18 deaths, 12 cases died because of transplantation related complications with the transplantation related mortality (TRM) being 19.7 %, and the remaining 6 cases died of relapse with the relapse rate being 9. 8 %, respectively. Conclusions URD-HSCT is an effective therapeutic strategy for malignant hematopoietic diseases when related donor is not available Acute GVHD and infection are risk factors of therapeutic effect and prognosis after URD-HSCT. Early prediction and prevention of acute GVHD and infection are essential problems to overcome.     

非血缘关系造血干细胞移植61例分析

Objective To study the therapeutic effectiveness, associated complications and related factors of unrelated allogeneic hematopoietic stem cell transplantation (URD-HSCT). Methods Sixty-one patients with malignant hematological diseases received URD-HSCT. All cases were subjected to myeloablative or nonmyeloablative conditioning regimen according to primary diseases. Among 61 patients, 21 were donor-recipient 6/6 HLA-matched, 5 were 5/6 HLA antigen-matched, 24 were 1 HLA gene subtype-mismatched, 11 were 2 HLA gene subtype-mismatched. Eighteen patients were ABO-compatible with donors, while 43 ABO-incompatible with donors. The median of infused donor nucleated cells was 4.5×108/kg, and the median of CD34+ cells were 4.3×106/kg. The graft-versus-host disease (GVHD) prevention regimens were based on short-term MTX, cyclosporin A and mycophenolate mofetil (MMF) regimen. Forty-nine cases also received CD25 Mab on the day of transplantation, and the day 4 after transplantation. Nine cases were also administrated with antilymphocyte globulin (ALG) or antithymocyte globulin (ATG). Two cases received ALG and CD25 Mab. Results Among 61 patients, 59 cases were successfully engrafted, which was identified by blood type, chromosome test and DNA polymorphism. Twenty-three cases developed grade Ⅱ～Ⅳ acute GVHD. Twenty-five patients experienced chronic GVHD. Infection of bacterial and/or fungal within 100 days after URD-HSCT was documented in 48 cases. Thirty-six cases had cytomegalovirus infection. Major infection site was lower respiratory tract. Eighteen cases died after URD-HSCT, and the 2-year disease-free survival rate was (68.0±6.4)%. Among these 18 deaths, 12 cases died because of transplantation related complications with the transplantation related mortality (TRM) being 19.7 %, and the remaining 6 cases died of relapse with the relapse rate being 9. 8 %, respectively. Conclusions URD-HSCT is an effective therapeutic strategy for malignant hematopoietic diseases when related donor is not available Acute GVHD and infection are risk factors of therapeutic effect and prognosis after URD-HSCT. Early prediction and prevention of acute GVHD and infection are essential problems to overcome.     

非血缘关系造血干细胞移植61例分析

Objective To study the therapeutic effectiveness, associated complications and related factors of unrelated allogeneic hematopoietic stem cell transplantation (URD-HSCT). Methods Sixty-one patients with malignant hematological diseases received URD-HSCT. All cases were subjected to myeloablative or nonmyeloablative conditioning regimen according to primary diseases. Among 61 patients, 21 were donor-recipient 6/6 HLA-matched, 5 were 5/6 HLA antigen-matched, 24 were 1 HLA gene subtype-mismatched, 11 were 2 HLA gene subtype-mismatched. Eighteen patients were ABO-compatible with donors, while 43 ABO-incompatible with donors. The median of infused donor nucleated cells was 4.5×108/kg, and the median of CD34+ cells were 4.3×106/kg. The graft-versus-host disease (GVHD) prevention regimens were based on short-term MTX, cyclosporin A and mycophenolate mofetil (MMF) regimen. Forty-nine cases also received CD25 Mab on the day of transplantation, and the day 4 after transplantation. Nine cases were also administrated with antilymphocyte globulin (ALG) or antithymocyte globulin (ATG). Two cases received ALG and CD25 Mab. Results Among 61 patients, 59 cases were successfully engrafted, which was identified by blood type, chromosome test and DNA polymorphism. Twenty-three cases developed grade Ⅱ～Ⅳ acute GVHD. Twenty-five patients experienced chronic GVHD. Infection of bacterial and/or fungal within 100 days after URD-HSCT was documented in 48 cases. Thirty-six cases had cytomegalovirus infection. Major infection site was lower respiratory tract. Eighteen cases died after URD-HSCT, and the 2-year disease-free survival rate was (68.0±6.4)%. Among these 18 deaths, 12 cases died because of transplantation related complications with the transplantation related mortality (TRM) being 19.7 %, and the remaining 6 cases died of relapse with the relapse rate being 9. 8 %, respectively. Conclusions URD-HSCT is an effective therapeutic strategy for malignant hematopoietic diseases when related donor is not available Acute GVHD and infection are risk factors of therapeutic effect and prognosis after URD-HSCT. Early prediction and prevention of acute GVHD and infection are essential problems to overcome.     

非血缘关系造血干细胞移植61例分析

Objective To study the therapeutic effectiveness, associated complications and related factors of unrelated allogeneic hematopoietic stem cell transplantation (URD-HSCT). Methods Sixty-one patients with malignant hematological diseases received URD-HSCT. All cases were subjected to myeloablative or nonmyeloablative conditioning regimen according to primary diseases. Among 61 patients, 21 were donor-recipient 6/6 HLA-matched, 5 were 5/6 HLA antigen-matched, 24 were 1 HLA gene subtype-mismatched, 11 were 2 HLA gene subtype-mismatched. Eighteen patients were ABO-compatible with donors, while 43 ABO-incompatible with donors. The median of infused donor nucleated cells was 4.5×108/kg, and the median of CD34+ cells were 4.3×106/kg. The graft-versus-host disease (GVHD) prevention regimens were based on short-term MTX, cyclosporin A and mycophenolate mofetil (MMF) regimen. Forty-nine cases also received CD25 Mab on the day of transplantation, and the day 4 after transplantation. Nine cases were also administrated with antilymphocyte globulin (ALG) or antithymocyte globulin (ATG). Two cases received ALG and CD25 Mab. Results Among 61 patients, 59 cases were successfully engrafted, which was identified by blood type, chromosome test and DNA polymorphism. Twenty-three cases developed grade Ⅱ～Ⅳ acute GVHD. Twenty-five patients experienced chronic GVHD. Infection of bacterial and/or fungal within 100 days after URD-HSCT was documented in 48 cases. Thirty-six cases had cytomegalovirus infection. Major infection site was lower respiratory tract. Eighteen cases died after URD-HSCT, and the 2-year disease-free survival rate was (68.0±6.4)%. Among these 18 deaths, 12 cases died because of transplantation related complications with the transplantation related mortality (TRM) being 19.7 %, and the remaining 6 cases died of relapse with the relapse rate being 9. 8 %, respectively. Conclusions URD-HSCT is an effective therapeutic strategy for malignant hematopoietic diseases when related donor is not available Acute GVHD and infection are risk factors of therapeutic effect and prognosis after URD-HSCT. Early prediction and prevention of acute GVHD and infection are essential problems to overcome.     

非血缘关系造血干细胞移植61例分析

Objective To study the therapeutic effectiveness, associated complications and related factors of unrelated allogeneic hematopoietic stem cell transplantation (URD-HSCT). Methods Sixty-one patients with malignant hematological diseases received URD-HSCT. All cases were subjected to myeloablative or nonmyeloablative conditioning regimen according to primary diseases. Among 61 patients, 21 were donor-recipient 6/6 HLA-matched, 5 were 5/6 HLA antigen-matched, 24 were 1 HLA gene subtype-mismatched, 11 were 2 HLA gene subtype-mismatched. Eighteen patients were ABO-compatible with donors, while 43 ABO-incompatible with donors. The median of infused donor nucleated cells was 4.5×108/kg, and the median of CD34+ cells were 4.3×106/kg. The graft-versus-host disease (GVHD) prevention regimens were based on short-term MTX, cyclosporin A and mycophenolate mofetil (MMF) regimen. Forty-nine cases also received CD25 Mab on the day of transplantation, and the day 4 after transplantation. Nine cases were also administrated with antilymphocyte globulin (ALG) or antithymocyte globulin (ATG). Two cases received ALG and CD25 Mab. Results Among 61 patients, 59 cases were successfully engrafted, which was identified by blood type, chromosome test and DNA polymorphism. Twenty-three cases developed grade Ⅱ～Ⅳ acute GVHD. Twenty-five patients experienced chronic GVHD. Infection of bacterial and/or fungal within 100 days after URD-HSCT was documented in 48 cases. Thirty-six cases had cytomegalovirus infection. Major infection site was lower respiratory tract. Eighteen cases died after URD-HSCT, and the 2-year disease-free survival rate was (68.0±6.4)%. Among these 18 deaths, 12 cases died because of transplantation related complications with the transplantation related mortality (TRM) being 19.7 %, and the remaining 6 cases died of relapse with the relapse rate being 9. 8 %, respectively. Conclusions URD-HSCT is an effective therapeutic strategy for malignant hematopoietic diseases when related donor is not available Acute GVHD and infection are risk factors of therapeutic effect and prognosis after URD-HSCT. Early prediction and prevention of acute GVHD and infection are essential problems to overcome.     

非血缘关系造血干细胞移植61例分析

Objective To study the therapeutic effectiveness, associated complications and related factors of unrelated allogeneic hematopoietic stem cell transplantation (URD-HSCT). Methods Sixty-one patients with malignant hematological diseases received URD-HSCT. All cases were subjected to myeloablative or nonmyeloablative conditioning regimen according to primary diseases. Among 61 patients, 21 were donor-recipient 6/6 HLA-matched, 5 were 5/6 HLA antigen-matched, 24 were 1 HLA gene subtype-mismatched, 11 were 2 HLA gene subtype-mismatched. Eighteen patients were ABO-compatible with donors, while 43 ABO-incompatible with donors. The median of infused donor nucleated cells was 4.5×108/kg, and the median of CD34+ cells were 4.3×106/kg. The graft-versus-host disease (GVHD) prevention regimens were based on short-term MTX, cyclosporin A and mycophenolate mofetil (MMF) regimen. Forty-nine cases also received CD25 Mab on the day of transplantation, and the day 4 after transplantation. Nine cases were also administrated with antilymphocyte globulin (ALG) or antithymocyte globulin (ATG). Two cases received ALG and CD25 Mab. Results Among 61 patients, 59 cases were successfully engrafted, which was identified by blood type, chromosome test and DNA polymorphism. Twenty-three cases developed grade Ⅱ～Ⅳ acute GVHD. Twenty-five patients experienced chronic GVHD. Infection of bacterial and/or fungal within 100 days after URD-HSCT was documented in 48 cases. Thirty-six cases had cytomegalovirus infection. Major infection site was lower respiratory tract. Eighteen cases died after URD-HSCT, and the 2-year disease-free survival rate was (68.0±6.4)%. Among these 18 deaths, 12 cases died because of transplantation related complications with the transplantation related mortality (TRM) being 19.7 %, and the remaining 6 cases died of relapse with the relapse rate being 9. 8 %, respectively. Conclusions URD-HSCT is an effective therapeutic strategy for malignant hematopoietic diseases when related donor is not available Acute GVHD and infection are risk factors of therapeutic effect and prognosis after URD-HSCT. Early prediction and prevention of acute GVHD and infection are essential problems to overcome.     

非血缘关系造血干细胞移植61例分析

Objective To study the therapeutic effectiveness, associated complications and related factors of unrelated allogeneic hematopoietic stem cell transplantation (URD-HSCT). Methods Sixty-one patients with malignant hematological diseases received URD-HSCT. All cases were subjected to myeloablative or nonmyeloablative conditioning regimen according to primary diseases. Among 61 patients, 21 were donor-recipient 6/6 HLA-matched, 5 were 5/6 HLA antigen-matched, 24 were 1 HLA gene subtype-mismatched, 11 were 2 HLA gene subtype-mismatched. Eighteen patients were ABO-compatible with donors, while 43 ABO-incompatible with donors. The median of infused donor nucleated cells was 4.5×108/kg, and the median of CD34+ cells were 4.3×106/kg. The graft-versus-host disease (GVHD) prevention regimens were based on short-term MTX, cyclosporin A and mycophenolate mofetil (MMF) regimen. Forty-nine cases also received CD25 Mab on the day of transplantation, and the day 4 after transplantation. Nine cases were also administrated with antilymphocyte globulin (ALG) or antithymocyte globulin (ATG). Two cases received ALG and CD25 Mab. Results Among 61 patients, 59 cases were successfully engrafted, which was identified by blood type, chromosome test and DNA polymorphism. Twenty-three cases developed grade Ⅱ～Ⅳ acute GVHD. Twenty-five patients experienced chronic GVHD. Infection of bacterial and/or fungal within 100 days after URD-HSCT was documented in 48 cases. Thirty-six cases had cytomegalovirus infection. Major infection site was lower respiratory tract. Eighteen cases died after URD-HSCT, and the 2-year disease-free survival rate was (68.0±6.4)%. Among these 18 deaths, 12 cases died because of transplantation related complications with the transplantation related mortality (TRM) being 19.7 %, and the remaining 6 cases died of relapse with the relapse rate being 9. 8 %, respectively. Conclusions URD-HSCT is an effective therapeutic strategy for malignant hematopoietic diseases when related donor is not available Acute GVHD and infection are risk factors of therapeutic effect and prognosis after URD-HSCT. Early prediction and prevention of acute GVHD and infection are essential problems to overcome.     

非血缘关系造血干细胞移植61例分析

Objective To study the therapeutic effectiveness, associated complications and related factors of unrelated allogeneic hematopoietic stem cell transplantation (URD-HSCT). Methods Sixty-one patients with malignant hematological diseases received URD-HSCT. All cases were subjected to myeloablative or nonmyeloablative conditioning regimen according to primary diseases. Among 61 patients, 21 were donor-recipient 6/6 HLA-matched, 5 were 5/6 HLA antigen-matched, 24 were 1 HLA gene subtype-mismatched, 11 were 2 HLA gene subtype-mismatched. Eighteen patients were ABO-compatible with donors, while 43 ABO-incompatible with donors. The median of infused donor nucleated cells was 4.5×108/kg, and the median of CD34+ cells were 4.3×106/kg. The graft-versus-host disease (GVHD) prevention regimens were based on short-term MTX, cyclosporin A and mycophenolate mofetil (MMF) regimen. Forty-nine cases also received CD25 Mab on the day of transplantation, and the day 4 after transplantation. Nine cases were also administrated with antilymphocyte globulin (ALG) or antithymocyte globulin (ATG). Two cases received ALG and CD25 Mab. Results Among 61 patients, 59 cases were successfully engrafted, which was identified by blood type, chromosome test and DNA polymorphism. Twenty-three cases developed grade Ⅱ～Ⅳ acute GVHD. Twenty-five patients experienced chronic GVHD. Infection of bacterial and/or fungal within 100 days after URD-HSCT was documented in 48 cases. Thirty-six cases had cytomegalovirus infection. Major infection site was lower respiratory tract. Eighteen cases died after URD-HSCT, and the 2-year disease-free survival rate was (68.0±6.4)%. Among these 18 deaths, 12 cases died because of transplantation related complications with the transplantation related mortality (TRM) being 19.7 %, and the remaining 6 cases died of relapse with the relapse rate being 9. 8 %, respectively. Conclusions URD-HSCT is an effective therapeutic strategy for malignant hematopoietic diseases when related donor is not available Acute GVHD and infection are risk factors of therapeutic effect and prognosis after URD-HSCT. Early prediction and prevention of acute GVHD and infection are essential problems to overcome.     

HLA单倍体相合与全相合外周血造血干细胞移植治疗恶性血液病的疗效比较

目的 观察和比较亲属间人类白细胞抗原(HLA)单倍体相合与全相合外周血造血干细胞移植(PBSCT)治疗恶性血液病的临床疗效.方法 2004年5月至2009年2月,共111例恶性血液病患者进行了异基因PBSCT(allo-PBSCT),其中单倍体相合移植受者51例(单倍体组),同期全相合移植受者60例(全相合组).两组的预处理方案均为清髓性;两组预防移植物抗宿主病(GVHD)均以经典环孢素A加短程甲氨蝶呤作为基础方案,HLA 1个抗原不合时,加用吗替麦考酚酯,HLA 2～3个抗原不合时,再加用抗胸腺细胞球蛋白(ATG)及抗CD25单克隆抗体.移植物为经粒细胞集落刺激因子动员的、未进行体外去除T淋巴细胞的外周血造血干细胞(PBSC).结果 111例受者均获得完全、持久供者干细胞植入.单倍体组和全相合组受者中性粒细胞≥0.5×10~9/L的中位时间分别为14 d和12 d,血小板≥20×10~9/L的中位时间分别为15 d和13 d.单倍体组有25例受者发生急性GVHD(aGVHD),其中Ⅰ度20例,Ⅱ度5例;有33例发生慢性GVHD(cGVHD),其中局限型30例,广泛型3例;4年累积发病率为70.4%;无白血病存活40例,3年预期总无白血病存活率(LFS)为74.5%,其中标危型77.3%,高危型68.2%.全相合组有14例发生aGVHD,其中Ⅰ度10例,Ⅱ度2例,Ⅲ度2例;有37例发生cGVHD,其中局限型32例,广泛型5例;4年累积发病率为58.1%.无白血病存活46例,3年预期总LFS为72.1%,其中标危型77.6%,高危型52.7%.单倍体组受者移植后aGVHD发生率高于全相合组,差异有统计学意义(P<0.05);但cGVHD、原发病复发率和LFS差异均无统计学意义(P>0.05).结论 应用清髓性预处理联合多种免疫抑制剂进行非体外去T淋巴细胞的、亲属间HLA单倍体相合与全相合PBSCT均为治疗恶性血液病安全有效的方案.     

非血缘关系造血干细胞移植61例分析

目的 探讨非血缘关系造血干细胞移植(URD-HSCT)的临床疗效,移植相关并发症及影响预后的危险因素.方法 回顾性分析61例接受URD-HSCT患者的临床资料.所有患者根据原发病分别给予非清髓性及清髓性预处理;供、受者HLA配型6/6抗原位点全相合21例,5/6相合5例,1个基因亚型不合24例,2个基因亚型不合11例;供、受者间ABO血型相合18例,不合43例;受者接受供者的有核细胞中位数为4.5×108/kg,CD34+细胞中位数为4.3×106/kg.术后移植物抗宿主病(GVHD)的预防采用以短程甲氨蝶呤+环孢素A+霉酚酸酯为基础的方案,49例加用抗CD25单克隆抗体,9例加用抗淋巴细胞或抗胸腺细胞免疫球蛋白;并常规采用促进造血功能恢复、抗感染等治疗.术后观察受者的造血功能重建、并发症以及预后情况.结果 61例患者中,59例术后经血型、染色体及DNA多态性检测证实供者细胞植活.术后23例受者发生Ⅱ～Ⅳ度急性GVHD,25例发生慢性GVHD;术后100 d内,48例受者发生细菌和(或)真菌感染,36例发生巨细胞病毒感染,以下呼吸道感染较多.术后有18例受者死亡,受者总的2年无病存活率为(68.0±6.4)%,其中12例因移植相关并发症死亡,移植相关死亡率19.7%;6例原发病复发的受者均死亡,复发率9.8%.其余受者经治疗后好转.结论 URD-HSCT是治疗造血系统恶性疾病的有效方法.急性GVHD和感染是严重影响移植疗效和预后的危险因素,需早期预防.     

Nonmyeloablative stem cell transplantation and cell therapy for malignant and non-malignant diseases

The conditioning prior to allogeneic stem cell transplantation was originally designed as a myeloablative conditioning, designed to eliminate malignant or genetically abnormal cells and then use the transplant procedure for rescue of the patients or to replace missing bone marrow products. However, allografts can induce effective graft vs. malignancy effects and can also eliminate undesirable hematopoietic stem cells in patients with genetic disorders and autoimmune diseases, thus documenting that alloreactive effects mediated by donor lymphocytes post-grafting can play a major role in eliminating hematopoietic cell of host origin, as well as provide effective immunotherapy for the treatment of disease recurrence. The efficacy of donor lymphocyte infusion (DLI) could be improved by activation with rIL-2 or by donor immunization. The cumulative experience over the years suggesting that alloreactive donor lymphocytes were most effective in eliminating tumor cells of host origin resulted in an attempt to reduce the intensity of the conditioning in preparation for the transplant procedure used for the treatment of hematological and other malignancies as well as life-threatening non-malignant disorders for which allogeneic stem cell transplantation may be indicated. Our working hypothesis proposed that the myeloablative conditioning which is hazardous and may be associated with early and late side effects, may not be required for treatment of patients with any indication for allogeneic stem cell transplantation. Instead, nonmyeloablative conditioning based on the use of reduced intensive preparatory regimen, also known as nonmyeloablative stem cell transplantation, may be sufficient for engraftment of donor stem cells while avoiding procedure-related toxicity and mortality, followed by elimination of undesirable cells of host origin by post-transplant effects mediated by alloreactive donor lymphocytes infused along with donor stem cells or administered subsequently as DLI. Improvement of the immediate outcome of stem cell transplantation using NST due to a significant decrease in transplant related mortality has broadened the spectrum of patients eligible for allogeneic stem cell transplantation, including elderly patients and other patients with less than optimal performance status. Likewise, the safer use of stem cell transplantation prompted expanding the scope of potential indications for allogeneic stem cell transplantation, such as metastatic solid tumors and autoimmune disorders, which now are slowly becoming much more acceptable. Current strategies focus on the need to improve the capacity of donor lymphocytes to eliminate undesirable malignant and non-malignant hematopoietic cells of host origin, replacing abnormal or malignant stem cells or their products with normal hematopoietic stem cells of donor origin, while minimizing procedure-related toxicity and mortality and improving the quality of life by reducing the incidence and severity of hazardous acute and chronic GVHD.     

非清髓性造血干细胞移植后并发移植物抗宿主病的相关因素分析

目的 探讨和分析非清髓性造血干细胞移植(NST)后并发移植物抗宿主病(GVHD)的相关因素.方法 选择34例血液病患者,其中重型再生障碍性贫血(SAA)15例,重型β-地中海贫血(TM)1例,肿瘤性血液病18例;进行无关供者脐带血造血干细胞移植(UCBT)11例,同胞供者骨髓联合外周血干细胞移植7例,外周血造血干细胞移植(PBSCT)16例.移植前采用以抗胸腺细胞球蛋白(ATG)、抗淋巴细胞球蛋白(ALG)或者氟达拉滨强效免疫抑制为基础的非清髓性预处理方案.GVHD的预防采用短程的甲氨蝶呤(MTX)联合环孢素A(CsA).观察非清髓性造血干细胞移植后的临床特点以及急、慢性移植物抗宿主病的发生情况;分析发生慢性移植物抗宿主病(cGVHD)的相关因素.结果 NST的植入率为91.2%.移植后7例肿瘤性血液病患者形成了供、受者造血细胞混合嵌合体(MC),给予供者淋巴细胞输注(DLI)2～9次后,例由MC转变为供者造血细胞完全嵌合体(FDC).随访12(3～96)个月,共发生Ⅰ～Ⅱ度急性移植物抗宿主病(aGVHD)5例,GVHD 15例.经统计学分析,发现年龄大的肿瘤性血液病患者经以ATG为基础的NST后,再给予DLI,其cGVHD的发生率高,且合并感染,对治疗的反应差;而以氟达拉滨为基础的NST患者发生cGVHD后治疗反应较好.移植100 d前后患者分别死亡3例和5例,其中3例死于广泛性cGVHD.结论 患者的年龄大、有合并症、以ATG为基础的预处理方案、肿瘤性血液病是NST后患者并发cGVHD的危险因素.     

Nephrotic syndrome after allogeneic hematopoietic stem cell transplantation as a late complication of chronic graft-versus-host disease

BACKGROUND: This study aims to determine the incidence and outcome of nephrotic syndrome in patients who underwent allogeneic stem cell transplantation in a single center. METHODS: Records of 279 adult patients with hematological diseases who underwent allogeneic hematopoietic stem cell transplantation were analyzed to evaluate the incidence and outcome of nephrotic syndrome. The diagnosis of chronic graft-versus-host disease was based on clinical evidence with histological confirmation whenever possible. RESULTS: Of the 279 patients, 105 with a minimum follow-up of 100 days developed chronic graft-versus-host disease: six of these had nephrotic syndrome. The cumulative incidence of nephrotic syndrome was 8% at day +1,681. Patients grafted with peripheral blood stem cells had a higher probability of developing nephrotic syndrome than did those grafted with bone marrow: 24% and 3%, respectively. The pathological diagnosis was membranous glomerulonephritis in four patients, and minimal change disease in one; the diagnosis could not be histologically confirmed in the sixth patient. All patients had extensive chronic graft-versus-host disease and were receiving treatment with cyclosporine A and steroids (four patients). Response to immunosuppressive therapy with cyclosporine A and steroids was achieved in all patients at a median time of 12 weeks after transplantation. CONCLUSION: Patients with chronic graft-versus-host disease may be considered to be at risk of nephrotic syndrome: careful monitoring of renal function is advisable, particularly in patients receiving allogeneic peripheral stem cell grafts.     

Myeloablative allogeneic hematopoietic stem cell transplantation in elderly patients

This study aimed to evaluate the outcome following myeloablative allogeneic hematopoietic stem cell transplantation (SCT) among patients older than 50 yr of age. A total of 215 patients with a median age of 57 yr underwent allogeneic hematopoietic SCT for early (41%) or advanced (59%) hematologic malignancies. After a median follow-up of 36 months a 10-yr survival estimate of 56 +/- 6% could be assessed for patients in early disease stages while patients with advanced diseases showed a significantly decreased survival probability of 31 +/- 5% (p < 0.0002). Transplant related mortality (TRM) at day 100 and 365 post-transplant was 13% and 30% for early but increased to 21% and 49% for advanced disease stages. As major determinants of TRM advanced disease stage (p < 0.0001) and occurrence of grades II-IV graft-vs.-host disease (GVHD) (p < 0.0001) were identified. These results show that hematopoietic SCT following myeloablative conditioning is also applicable to elderly patients whereas disease stage and high-grade GVHD represent the essential prognostic factors for outcome.     

不同动员方案对异基因造血干细胞移植临床疗效的影响

目的 探讨异基因造血干细胞移植中不同动员方案的临床效果.方法 回顾性分析71例异基因外周血造血干细胞移植的临床资料,根据供者采用动员剂的不同分为G-CSF动员组(G组,有24例受者)和G-CSF联合GM-CSF动员组(G+M组,有47例受者).比较两组供者的动员效果及移植物细胞成分,观察受者术后造血功能重建的情况和GVHD的发生情况,观察供者应用动员剂后的不良反应.结果 动员4 d后,G组供者的外周血白细胞计数为(49.6±19.5)×109/L,明显高于G+M组供者的(25.4±10.4)×109/L(P＜0.05).两组间CD34+细胞占单个核细胞比例的差异无统计学意义(P＞0.05),但G+M组CD34+CD38-细胞占CD34+细胞的比例为(37.7±5.7)%,明显高于G组的(31.4±4.5)%(P＜0.05).两组供者经过1～3次采集均能获取足够的CD34+细胞,两组采集的供者淋巴细胞计数及其亚群分布的差异均无统计学意义(P＞0.05).两组受者间CD34+细胞、CD34+CD38-细胞及T淋巴细胞亚群输入量的差异均无统计学意义(P＞0.05).术后所有受者的造血功能均顺利重建.术后对受者进行2～55个月的随访,无论是急性还是慢性GVHD,其发病率和严重程度在两组间的差异均无统计学意义(P＞0.05).术后共有17例受者死于原发病复发,10例死于GVHD和感染等移植相关并发症,G组和G+M组分别有14例(58.3%)和31例(66.0%)受者存活.在使用动员剂后,供者出现的主要不良反应为骨骼肌酸痛和发热,多发生在用药后36 h,给予解热镇痛药后缓解.结论 单用G-CSF与联合应用G-CSF和M-CSF进行动员的临床效果相当,但后者对CD34+CD38-细胞的选择性较强,而在异基因造血干细胞移植输入较多的CD34+细胞和CD34+CD38-细胞有利于受者造血功能的快速重建.     

Origin and subset distribution of peripheral blood dendritic cells in patients with chronic graft-versus-host disease

BACKGROUND: After allogeneic hematopoietic stem cell transplantation, donor T cells interact with an antigen-presenting cell environment that is distorted in number, level of activation, and origin. The role of antigen presentation in the development of chronic graft-versus host disease (cGVHD) is unknown. METHODS: The number and origin of peripheral blood immature myeloid (CD19- CD1c+) and plasmacytoid (BDCA-2+) dendritic cells (DCs) was determined in 30 patients at more than 100 days after allogeneic hematopoietic stem cell transplantation. RESULTS: Patients with cGVHD had significantly higher plasmacytoid DC numbers than individuals without this complication (9.1+/-2.0 x 10(6)/L versus 3.8+/-0.6 x 10(6)/L, =0.025). Chimerism studies demonstrated that DCs in patients with cGVHD were exclusively of donor origin, whereas persistence of host DCs was observed in some control patients. CONCLUSIONS: The antigen-presenting cell environment in patients with cGVHD, as represented by immature blood DCs, is of donor origin but distorted in terms of subset distribution.     

非清髓性造血干细胞移植后移植物抗宿主病的临床观察

目的 观察非清髓性造血干细胞移植（NST）后移植物抗宿主病（GVHD）的发生情况。方法 将18例患者分为3组：A组为6例重型再生障碍性贫血（SAA）成人患者，行无关供者脐血造血干细胞移植；B组为5例SAA患者，行同胞供者骨髓联合外周血造血干细胞移植；C组为7例肿瘤性血液病患者，其中3例行同胞供者骨髓移植，4例行外周血造血干细胞移植。均采用以抗胸腺细胞球蛋白或抗淋巴细胞球蛋白为基础的预处理方案。A组和B组应用环孢素A（CsA）和甲泼尼龙预防GVHD，C组应用CsA和甲氨蝶呤预防GVHD。C组形成混合性嵌合体后行供者淋巴细胞输注（DLI）。结果 A组有4例形成并维持混合性嵌合体状态，1例死于真菌性败血症，1例自动出院。移植后早期，B组有3例供者型嵌合体占94％以上，并在短期内转变并维持完全供者嵌合体状态，获得无病存活，其中1例在移植后8个月发生慢性GVHD；另2例行供者千细胞输注后，1例6个月后死于继发性纵隔淋巴瘤，1例造血功能恢复。C组患者早期均形成混合性嵌合体，获得血液学部分缓解，患者DLI前无急性GVHD发生，1例于2次DLI后死于严重感染，1例失访；另5例分别经过4、3、7、5、4次DLI，全部转为完全供者型嵌合体，并获得血液学完全缓解，4例并发慢性GVHD，2例并发急性GVHD。结论 对于SAA患者，NST的临床效果较好，GVHD的发生率较低；而对于肿瘤性血液病，NST后患者的早期死亡率低，急性GVHD发生率下降，但慢性GVHD和感染的发生率较高。     

Outcomes of Busulfan,Fludarabine, and 400 cGy Total Body Irradiation Compared With Busulfan and Fludarabine Reduced-Intensity Conditioning Regimens for Allogeneic Stem Cell Transplantation in Adult Patients With Hematologic Diseases: A Single-Center Experience

BackgroundReduced intensity conditioning (RIC) regimens decrease the risk for nonrelapse mortality (NRM) in adult patients undergoing allogeneic hematopoietic stem cell transplantation for hematologic malignancies but increase the risk for relapse. The aim of this study was to compare the outcomes of fludarabine–total body irradiation (TBI) with fludarabine among patients with hematologic diseases.Patients and MethodsThis retrospective study of 137 patients with different hematologic malignancies compared the outcomes of 63 patients who received a conventional RIC regimen with 2 days of IV busulfan (3.2 mg/kg/d × 2 days) and fludarabine with 74 patients who received the same regimen plus 400 cGy of fludarabine and busulfan (FB)-TBI divided in 2 doses over 1 day (200 cGy BID). Median follow-up was 4.62 years.ResultsThe donors were either HLA-matched siblings (36%) or HLA-matched unrelated donors (64%). The FB-TBI showed trends toward improvement in progression-free survival (PFS) and overall survival (OS) over FB (5-year PFS rates 50% vs 34%, P = .06, and 5-year OS rate 53% vs 39%, P = .13). Acute graft-vs-host disease (aGVHD), relapse, and NRM were similar between the 2 groups. The 5-year cumulative incidence of chronic GVHD (cGVHD) was lower in the FB-TBI group compared with the FB group (29% vs 52%, P = .003). Multivariable analysis revealed that grade III-IV aGVHD was the only independent risk factor for worse OS (P = .001) in both groups. A high disease risk index was possibly associated with inferior OS (P = .07) in both groups.ConclusionsThe FB-TBI is a safe and effective intensified RIC regimen for adult patients with hematologic malignancies. It predicted a lower risk for cGVHD and showed possibly improved PFS and OS compared with FB.