应用改良BU/CY方案预处理联合自体外周血造血干细胞移植治疗青年中、低危急性髓系白血病疗效观察
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摘要
目的:观察青年中、低危急性髓系白血病(AML)在第1次完全缓解期(CR1)接受白消安(BU)/环磷酰胺(CY)改良方案预处理后行自体外周血造血干细胞移植(auto-PBHSCT)的安全性及疗效。方法:采用回顾性分析方法探讨改良BU/CY预处理联合auto-PBSCT的疗效。本院2013年5月至2016年12月期间10例青年中、低危AML患者,无异基因干细胞移植条件、CR1期接受以改良的BU/CY方案预处理联合auto-PBSCT,移植后3个月开始白介素-2(IL-2)或IL-2+二盐酸组胺维持治疗18个月。观察预处理方案的毒副作用、造血恢复时间、移植后100 d及1年内死亡率、复发率、2年及3年无白血病生存率(LFS)、3年及4年总生存率(OS)。结果:常见的非血液学毒性反应为胃肠道反应(轻度7例、中度3例、重度1例)、轻度肝损害(4例)、出血性膀胱炎0例、轻中度感染10例(血流感染5例,肠道感染2例,肛周感染3例,口腔感染2例)。患者均达到清髓效果,中性粒细胞(ANC)<0.5×10~9/L中位时间为1.5(0-3 d)d,血小板(Plt)<20×10~9/L中位时间为3(2-5)d。移植后中性粒细胞植入中位时间为13(10-19)d,血小板植入中位时间为32(10-72)d。移植后100 d及1年内死亡率为0。1例移植后半年复发,1例移植后14个月复发。移植后中位随访时间48.1个月,至随访日中位生存时间54.7个月。2年LFS为100%(10例),3年LFS为80%(8例);3年OS为80%(8例),4年OS为70%(7例)。结论:改良的BU/CY+auto-PBSCT治疗模式可达到清髓目的,对青年中、低危AML疗效明确,移植相关死亡率低,LFS及OS时间较长,可作为无异基因造血干细胞移植条件患者的另一个治疗选择。
Objective: To investigate the safety and efficacy of autologous peripheral blood hematopoietic stem cell transplantation(auto-PBHSCT) using modified BU/CY conditioning regimen for young AML patients of low and middle risk in the first complete remission(CR1). Methods: Ten young AML patients of low and middle risk who did not want to accept allogeneic hematopoietic stem cell transplantation(allo-HSCT)and underwent autoPBHSCT in CR1 during May 2013 to December 2016 were retrospectively analyzed. From 3 months after autoPBHSCT, the maintenance therapy with interleukin-2(IL-2) or IL-2 combined with histamine dihydrochloride was performed for these patients in the next 18 months. The side effects of the conditioning regimen, hematopoietic recovery time, transplant-related mortality(TRM) within 100 days and 1 year after auto-PBHSCT, relapse rate, leukemiafree survival(LFS) rate at 2 years and 3 years, overall survival(OS) were evaluated at 3 years and 4 years. Results:Gastrointestinal side effects were the major non-hematologic toxicity reaction, among which, 7 cases relatively mild and 3 cases displayed moderate, just one case suffered from severe reaction. In 4 cases, the mild liver damage occurred,but no hemorrhagic cystitis occurred. All the patients experienced different kinds of infection, including 5 cases of bloodstream infection, 2 cases of gastrointestinal infection, 3 cases of crissum infection and 2 cases of oral infection. The myeloablative effect occurred in all ten patients. The median times for absolute neutrophil count(ANC)<0.5×10~9/L and for platelet count <20.0×10~9/L were 1.5(0-3) days and 3(2-5) days after transplantation, respectively. The patients achieved ANC>0.5×10~9/L at 10 to 19 days, median was 13 days after auto-PBHSCT. The patients achieved platelet count >20×10~9/L at 10 to 72 days; median was 32 days after auto-PBHSCT. The TRM within 100 days and 1 year after transplantation was 0. The relapse occurred in 2 cases at 6 and 14 months after auto-PBHSCT raspectively. The median follow-up time was 48.1 months, and the median survival time was 54.7 months after transplantation. The 2-year and 3-year LFS were 100%(10 cases) and 80%(8 cases), respectively. The 3-year and 4-year OS were 80%(8 cases) and70%(7 cases), respectively. Conclusion: Modified BU/CY as conditioning regimen for auto-PBHSCT can achieve the myeloablative effect without raising TRM and obtain good LFS and OS. As for young AML patients without high risk, it is a valuable therapeutic option, especially for those lacking the chance of allo-HSCT.
Objective: To investigate the safety and efficacy of autologous peripheral blood hematopoietic stem cell transplantation(auto-PBHSCT) using modified BU/CY conditioning regimen for young AML patients of low and middle risk in the first complete remission(CR1). Methods: Ten young AML patients of low and middle risk who did not want to accept allogeneic hematopoietic stem cell transplantation(allo-HSCT)and underwent autoPBHSCT in CR1 during May 2013 to December 2016 were retrospectively analyzed. From 3 months after autoPBHSCT, the maintenance therapy with interleukin-2(IL-2) or IL-2 combined with histamine dihydrochloride was performed for these patients in the next 18 months. The side effects of the conditioning regimen, hematopoietic recovery time, transplant-related mortality(TRM) within 100 days and 1 year after auto-PBHSCT, relapse rate, leukemiafree survival(LFS) rate at 2 years and 3 years, overall survival(OS) were evaluated at 3 years and 4 years. Results:Gastrointestinal side effects were the major non-hematologic toxicity reaction, among which, 7 cases relatively mild and 3 cases displayed moderate, just one case suffered from severe reaction. In 4 cases, the mild liver damage occurred,but no hemorrhagic cystitis occurred. All the patients experienced different kinds of infection, including 5 cases of bloodstream infection, 2 cases of gastrointestinal infection, 3 cases of crissum infection and 2 cases of oral infection. The myeloablative effect occurred in all ten patients. The median times for absolute neutrophil count(ANC)<0.5×10~9/L and for platelet count <20.0×10~9/L were 1.5(0-3) days and 3(2-5) days after transplantation, respectively. The patients achieved ANC>0.5×10~9/L at 10 to 19 days, median was 13 days after auto-PBHSCT. The patients achieved platelet count >20×10~9/L at 10 to 72 days; median was 32 days after auto-PBHSCT. The TRM within 100 days and 1 year after transplantation was 0. The relapse occurred in 2 cases at 6 and 14 months after auto-PBHSCT raspectively. The median follow-up time was 48.1 months, and the median survival time was 54.7 months after transplantation. The 2-year and 3-year LFS were 100%(10 cases) and 80%(8 cases), respectively. The 3-year and 4-year OS were 80%(8 cases) and70%(7 cases), respectively. Conclusion: Modified BU/CY as conditioning regimen for auto-PBHSCT can achieve the myeloablative effect without raising TRM and obtain good LFS and OS. As for young AML patients without high risk, it is a valuable therapeutic option, especially for those lacking the chance of allo-HSCT.
引文
1Kumar CC. Genetic abnormalities and challenges in the treatment of acute myeloid leukemia. Genes Cancer, 2011; 2(2):95–107.
2 Suh JK, Lee SW, Koh KN, et al. Hematopoietic stem cell transplantation in pediatric patients with acute myeloid leukemia without favorable cytogenetics. Pediatr Transplant, 2017; 21(7):e13004.
3 Yoon JH,Kim HJ,Park SS, et al. Clinical outcome of autologous hematopoietic cell transplantation in adult patients with acute myeloid leukemia:who may benefit from autologous hematopoietic cell transplantation? Biol Blood Marrow Transplant, 2017; 23(4):588-597.
4 Helbig G, Kocl?ga A, Wo?niczka K, et al. Long-term outcome of autologous hematopoietic stem cell transplantation(AHSCT)for acute myeloid leukemia(AML)-single center retrospective analysis.Pathol Oncol Res, 2017; doi:10.1007/s12253-017-0266-7.
5 Simancikova I, Bojtarova E, Hrubisko M, et al. Autologous hematopoietic stem cell transplantation for acute myeloid leukemiasingle center experience. Neoplasma, 2017; 64(5):738-744.
6 中华医学会血液学分会白血病淋巴瘤学组.成人急性髓系白血病(非急性早幼粒细胞白血病)中国诊疗指南(2017年版).中华血液学杂志, 2017; 38(3):177-182.
7 曹易耕,姜尔烈,何祎等.自体外周血造血干细胞移植治疗55例急性髓系白血病患者的疗效及预后分析.中华血液学杂志,2016; 37(6):464-468.
8 Cioch M, Jawniak D, Wach M, et al. Autologous hematopoietic stem cell transplantation for adults with acute myeloid leukemia.Transplant Proc, 2016; 48(5):1814-1817.
9 Wong RSM, Saleh MN, Khelif A, et al. Safety and efficacy of longterm treatment of chronic/persistent ITP with eltrombopag:final results of the EXTEND study. Blood, 2017; 130(23):2527-2536.
10 Komrokji RS. Use of eltrombopag for treatment of myelodysplastic syndromes. Lancet Haematol, 2017; 4(3):e99-e100.
11 Gill H, Wong RSM, Kwong YL. From chronic immune thrombocytopenia to severe aplastic anemia:recent insights into the evolution of eltrombopag. Ther Adv Hematol, 2017; 8(5):159-174.
12 Han Y, Tang Y, Chen J, et al. Low-dose decitabine for patients with thrombocytopenia following allogeneic hematopoietic stem cell transplantation:a pilot therapeutic Study. JAMA Oncol, 2015; 1(2):249-251.
13 Wetzel D, Mueller BU, Mansouri Taleghani B, et al. Delayed haematological recovery after autologous stem cell transplantation is associated with favourable outcome in acute myeloid leukaemia.Br J Haematol, 2015; 168(2):268-273.
14 Walter RB, Buckley SA, Pagel JM, et al. Significance of minimal residual disease before myeloablative allogeneic hematopoietic cell transplantation for AML in first and second complete remission.Blood, 2013; 122(10):1813-1821.
15 BuckleySA,AppelbaumFR,WalterRB.Prognosticand therapeutic implications of minimal residual disease at the time of transplantation in acute leukemia. Bone Marrow Transplant, 2013;48(5):630-641.
2 Suh JK, Lee SW, Koh KN, et al. Hematopoietic stem cell transplantation in pediatric patients with acute myeloid leukemia without favorable cytogenetics. Pediatr Transplant, 2017; 21(7):e13004.
3 Yoon JH,Kim HJ,Park SS, et al. Clinical outcome of autologous hematopoietic cell transplantation in adult patients with acute myeloid leukemia:who may benefit from autologous hematopoietic cell transplantation? Biol Blood Marrow Transplant, 2017; 23(4):588-597.
4 Helbig G, Kocl?ga A, Wo?niczka K, et al. Long-term outcome of autologous hematopoietic stem cell transplantation(AHSCT)for acute myeloid leukemia(AML)-single center retrospective analysis.Pathol Oncol Res, 2017; doi:10.1007/s12253-017-0266-7.
5 Simancikova I, Bojtarova E, Hrubisko M, et al. Autologous hematopoietic stem cell transplantation for acute myeloid leukemiasingle center experience. Neoplasma, 2017; 64(5):738-744.
6 中华医学会血液学分会白血病淋巴瘤学组.成人急性髓系白血病(非急性早幼粒细胞白血病)中国诊疗指南(2017年版).中华血液学杂志, 2017; 38(3):177-182.
7 曹易耕,姜尔烈,何祎等.自体外周血造血干细胞移植治疗55例急性髓系白血病患者的疗效及预后分析.中华血液学杂志,2016; 37(6):464-468.
8 Cioch M, Jawniak D, Wach M, et al. Autologous hematopoietic stem cell transplantation for adults with acute myeloid leukemia.Transplant Proc, 2016; 48(5):1814-1817.
9 Wong RSM, Saleh MN, Khelif A, et al. Safety and efficacy of longterm treatment of chronic/persistent ITP with eltrombopag:final results of the EXTEND study. Blood, 2017; 130(23):2527-2536.
10 Komrokji RS. Use of eltrombopag for treatment of myelodysplastic syndromes. Lancet Haematol, 2017; 4(3):e99-e100.
11 Gill H, Wong RSM, Kwong YL. From chronic immune thrombocytopenia to severe aplastic anemia:recent insights into the evolution of eltrombopag. Ther Adv Hematol, 2017; 8(5):159-174.
12 Han Y, Tang Y, Chen J, et al. Low-dose decitabine for patients with thrombocytopenia following allogeneic hematopoietic stem cell transplantation:a pilot therapeutic Study. JAMA Oncol, 2015; 1(2):249-251.
13 Wetzel D, Mueller BU, Mansouri Taleghani B, et al. Delayed haematological recovery after autologous stem cell transplantation is associated with favourable outcome in acute myeloid leukaemia.Br J Haematol, 2015; 168(2):268-273.
14 Walter RB, Buckley SA, Pagel JM, et al. Significance of minimal residual disease before myeloablative allogeneic hematopoietic cell transplantation for AML in first and second complete remission.Blood, 2013; 122(10):1813-1821.
15 BuckleySA,AppelbaumFR,WalterRB.Prognosticand therapeutic implications of minimal residual disease at the time of transplantation in acute leukemia. Bone Marrow Transplant, 2013;48(5):630-641.