Different types of allogeneic hematopoietic stem cell transplantation for Philadelphia chromosome-positive acute lymphoblastic leukemia: therapeutic efficacy and safety

doi:10.3969/j.issn.2095-4344.2017.25.018

Abstract

Abstract:

BACKGROUND: With the optimization of transplantation scheme and the emergence of graft-versus-host disease (GVHD) therapy drugs, allogeneic hematopoietic stem cell transplantation (allo-HSCT) in recent years has made great progress that makes patients with hematological malignancies have more long-term survival opportunities.
OBJECTIVE: To compare the efficiency and safety of three types of allo-HSCT used in the treatment of adults with Philadelphia chromosome (Ph) in acute lymphoblastic leukemia (Ph+ALL).
METHODS: A total of 69 patients with Ph+ALL who received allo-HSCT from June 2006 to November 2013 were enrolled, including 23 cases of sib-matched donor transplantation, 24 cases of unrelated-matched donor transplantation, and 22 cases of haploidentical donor transplantation. There were 54 cases of CR1, 13 cases of CR2 to CR3 and 3 cases of relapse. The bone marrow or/and peripheral blood stem cells were used for transplantation. All patients were subjected to pretreatment consisting of cytarabine, busulfan, cyclophosphamide and total body irradiation. GVHD was prevented by combined use of immunosuppressants including cyclosporine A, short-term methotrexate, mycophenolate mofetil and anti-human thymocyte globulin, etc.
RESULTS AND CONCLUSION: The results showed that 68 patients acquired hematopoietic reconstitution, and only 1 case of haploidentical donor transplantation failed. The mean follow-up period was 20.4 months. The acute GVHD incidence of the sibling matched-HSCT, unrelated donor HSCT and related haploidentical allo-HSCT was 30%, 33% and 45%, respectively; the chronic GVHD incidence (cGVHD) incidence was 22%, 29% and 36%, respectively; the incidence of aGVHD and cGVHD between groups showed no statistically significant difference. Transplant related mortality (TRM) was 9%, 29% and 41%, respectively, and there was a significant difference among groups (0.01 < P < 0.05). Recurrence rates were 17%, 21% and 14%, respectively, and there was no significant difference among groups. The 3-year overall survival rates were 68%, 49% and 43%, respectively; there were significant differences between sib-matched-HSCT and the other two groups, but no statistically significant difference was found between unrelated donor HSCT and related haploidentical allo-HSCT groups. The 3-year overall survival rate was 58% for 54 patients in CR1 and 41% for 15 patients in non-CR1 states. To conclude, the sib-matched HSCT has better effect than unrelated donor transplantation and related haploidentical allo-HSCT; Ph+ALL patients should do transplantation as early as possible in the state of CR1.

中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程

Key words: Philadelphia Chromosome, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Hematopoietic Stem Cell Transplantation, Tissue Engineering

CLC Number:

R394.2

Hu Xiao-hui, Zhou Jie, Zhou Hai-xia, Zhang Ri, Wu De-pei. Different types of allogeneic hematopoietic stem cell transplantation for Philadelphia chromosome-positive acute lymphoblastic leukemia: therapeutic efficacy and safety[J]. Chinese Journal of Tissue Engineering Research, 2017, 21(25): 4044-4049.

Figures/Tables 2

2.2 干细胞回输数量同胞全相合组回输单个核细胞中位数7.06(1.7-13.11)×108/kg，CD34+细胞中位数4.18 (1.02-6.55)×106/kg；无关全相合组单个核细胞中位数7.76 (4.75-15.00)×108/kg，CD34+细胞中位数4.38(2.84-10.00)× 106/kg；单倍型组单个核细胞中位数9.65(1.27-20.39)× 108/kg，CD34+细胞中位数3.22(1.73-8.56)×106/kg。 2.3 造血重建同胞全相合及无关全相合组全部造血重建，中性粒细胞≥0.5×109 L-1的中位时间分别为12(10- 15) d，12(11-15) d；血小板≥20×109 L-1的中位时间分别为13(10-30) d，12.5(10-15) d。亲缘单倍型移植组有2例巨核系未达到植活指标，其余重建患者中性粒细胞≥0.5× 109 L-1的中位时间为13(10-21) d，血小板≥20×109 L-1的中位时间为21(11-66) d。移植后定期监测供受者嵌合度水平，68例患者移植2周后供受者嵌合度持续大于95%。1例单倍型移植患者移植后1个月时供受者嵌合度下降至25.4%，考虑植入失败。 2.4 移植物抗宿主病 ①同胞全相合移植患者中，发生急性移植物抗宿主病7例，发生率30%(7/23)，其中Ⅱ度移植物抗宿主病4例，Ⅲ-Ⅳ度3例；发生慢性移植物抗宿主病5例，发生率22%(5/23)，其中3例为局限性，2例广泛性；②无关全相合移植患者中，发生急性移植物抗宿主病8例，发生率33%(8/24)，其中Ⅱ度4例，Ⅲ-Ⅳ度4例；发生慢性移植物抗宿主病7例，发生率29%(7/24)，4例为局限性，3例广泛性；③亲缘单倍型移植患者中，发生急性移植物抗宿主病10例，发生率45%(10/22)，其中Ⅱ度5例，Ⅲ度3例，Ⅳ度2例；发生慢性移植物抗宿主病8例，发生率36%(8/22)，4例为局限性，4例广泛性。统计学分析显示，各移植组间急慢性移植物抗宿主病发生率差异无显著性意义(P > 0.05)，见表1。 2.5 白血病复发随访至2014年11月底，同胞全相合移植组患者共有4例(17%)复发，其中1例发生中枢神经系统白血病，经三联鞘注化疗后缓解并存活；无关全相合组5例(21%)复发；单倍型移植组3例(14%)复发，其中1例发生中枢神经系统白血病，经三联鞘注治疗后脑脊液幼稚细胞转阴，但最终死于重度慢性移植物抗宿主病。各移植组间复发率比较，差异无显著性意义(P > 0.05)，见表1。 2.6 其他并发症移植后动态监测CMV-DNA，EBV-DNA拷贝数，发现CMV血症35例，EBV血症10例，接受系统性抗病毒、美罗华等治疗。移植后出现发热、咳嗽、低氧血症等患者，及时行肺部CT、肺功能等检查，并进行相应的抗感染及抗移植物抗宿主病治疗。 2.7 疗效分析 69例患者自移植日起，随访至2014年11月底，患者3年总体生存率54%(图2)。同胞全相合组中位随访时间23.8(5.5-60)个月，死亡5例，其中移植相关死亡2例、复发死亡3例，1例患者移植后出现中枢神经系统白血病经三联鞘注化疗后缓解并生存，总体生存率68%。无关全相合组中位随访时间17.4(1.5-60)个月，死亡12例，其中移植相关死亡7例，复发死亡5例，3年总体生存率为49%。单倍型组中位随访时间17.7(1.5-40)个月，死亡12例，其中移植相关死亡9例，复发死亡3例，3年总体生存率为43%(图3)。同胞全相合组与无关供体全相合组、亲缘单倍型组分别比较，差异均有显著性意义(P均< 0.05)，而无关供体全相合组与亲缘单倍型组差异无显著性意义。 54例CR1状态下行移植患者，3年总体生存率58%；15例于非CR1状态移植患者，3年总体生存率为41%，但两组间差异无显著性意义，见图4。"

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