"微移植"治疗难治性原发中枢神经系统淋巴瘤的临床分析
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摘要
目的:观察以大剂量甲氨蝶呤(MTX)为基础的化疗联合亲缘单倍体相合供者G-CSF动员后外周血造血干细胞(G-PBHSC)输注组成的"微移植",治疗3例难治性原发中枢神经系统淋巴瘤(PCNSL)患者的疗效。方法:2014年3月至2015年9月火箭军总医院血液科收治的3例难治性PCNSL患者。"微移植"治疗时首先给予患者大剂量MTX为基础的化疗,在化疗结束后48 h给予亲缘单倍体相合供者G-PBHSC输注,输注的单个核细胞(MNC)中位数1.34×108/kg,不进行移植物抗宿主病(GVHD)预防。结果:3例患者在确诊后分别接受过化疗或放疗,在"微移植"治疗前病情处于进展状态,"微移植"治疗后1例患者获得完全缓解,并已持续15个月。2例患者获得部分缓解,病情稳定10个月和7个月,此后病情再次进展而死亡。患者对"微移植"治疗的耐受性好,不良反应主要是与大剂量MTX化疗相关的中性粒细胞减少、血小板减少和感染,但在G-PBHSC输注后患者中性粒细胞和血小板恢复的中位时间分别为11 d、12.5 d。在治疗期间未观察到GVHD相关临床表现。结论:对于难治性PCNSL患者,"微移植"是一个值得尝试的挽救性治疗方法。
Objective: To investigate the efficacy and safety of high-dose methotrexate-based chemotherapy combined with granulocyte-colony stimulating factor( G-CSF)-mobilized family related haploidentical donor peripheral blood hematopoietic stem cell( G-PBHSC) infusion for the treatment of patients with refractory primary central nervouse system lymphoma( PCNSL). Methods: Three patients with refractory PCNSL were treated in Department of Hematology of the General Hospital of the PLA's Rocket Force from March 2014 to September 2015. The sex ratio of male to female was 1:2 and the median age was 54( 48-66) years old. All patients received programmed infusions of GPBHSC after high-dose methotrexate-based chemotherapy without prophylaxis for graft-versus-host disease( GVHD).Results: Three patients had received initial chemotherapy or radiotherapy after diagnosis, one patient achieved complete remission( CR) after 3 courses of treatment and remained in CR until the end of follow-up, 2 cases achieved partial remission( PR) and the progression-free survival( PFS) time was 10 and 7 months, respectively. The patients generally well-tolerated this therapy. The main adverse effects of patients were neutropenia, thromboytopenia and infection related with chemotherapy after each course of treatment, the median recovery times of neutrophils and platelets were 11 and12. 5 days, respectively after of programmed infusions of G-PBHSC. No GVHD was observed in any of the patients during treatment. Conclusion: The combination of high-dose methotrexate-based chemotherapy with programmed haploidentical G-PBHSC infusion is a potential treatment alternative for refractory PCNSL patients.
Objective: To investigate the efficacy and safety of high-dose methotrexate-based chemotherapy combined with granulocyte-colony stimulating factor( G-CSF)-mobilized family related haploidentical donor peripheral blood hematopoietic stem cell( G-PBHSC) infusion for the treatment of patients with refractory primary central nervouse system lymphoma( PCNSL). Methods: Three patients with refractory PCNSL were treated in Department of Hematology of the General Hospital of the PLA's Rocket Force from March 2014 to September 2015. The sex ratio of male to female was 1:2 and the median age was 54( 48-66) years old. All patients received programmed infusions of GPBHSC after high-dose methotrexate-based chemotherapy without prophylaxis for graft-versus-host disease( GVHD).Results: Three patients had received initial chemotherapy or radiotherapy after diagnosis, one patient achieved complete remission( CR) after 3 courses of treatment and remained in CR until the end of follow-up, 2 cases achieved partial remission( PR) and the progression-free survival( PFS) time was 10 and 7 months, respectively. The patients generally well-tolerated this therapy. The main adverse effects of patients were neutropenia, thromboytopenia and infection related with chemotherapy after each course of treatment, the median recovery times of neutrophils and platelets were 11 and12. 5 days, respectively after of programmed infusions of G-PBHSC. No GVHD was observed in any of the patients during treatment. Conclusion: The combination of high-dose methotrexate-based chemotherapy with programmed haploidentical G-PBHSC infusion is a potential treatment alternative for refractory PCNSL patients.
引文
1 Korfel A,Schlegel U.Diagnosis and treatment of primary CNS lymphoma.Nat Rev Neurol,2013;9(6):317-327.
2 Hoang-Xuan K,Bessell E,Bromberg J,et al.Diagnosis and treatment of primary CNS lymphoma in immunocompetent patients:guidelines from the European Association for Neuro-Oncology.Lancet Oncol,2015;16(7):e322-332.
3 朱铁楠,王书杰,张薇,等.37例原发中枢神经系统淋巴瘤患者的临床特征及预后分析.中华血液学杂志,2015;36(10):849-852.
4 付丽,陈力,魏娜,等.原发性中枢神经系统淋巴瘤31例临床特点及预后分析.中国实验血液学杂志,2016;24(4):1061-1065.
5 Guo M,Hu KX,Yu CL,et al.Infusion of HLA-mismatched peripheral blood stem cells improves the outcome of chemotherapy for acute myeloid leukemia in elderly patients.Blood,2011;117(3):936-941.
6 Guo M,Hu KX,Liu GX,et al.HLA-mismatched stem-cell micro transplantation as postremission therapy for acute myeloid leukemia:long-term follow-up.J Clin Oncol,2012;30(33):4084-4090.
7 赵红霞,孙万军,郭梅,等."微移植"治疗难治性淋巴瘤的临床观察.中华医学杂志,2013;93(34):2711-2714.
8 孙万军,赵红霞,黄雅静,等."微移植"治疗7例淋巴母细胞淋巴瘤/白血病的临床分析.中国实验血液学杂志,2014;22(4):995-998.
9 Abrey LE,Batchelor TT,Ferreri AJ,et al.Report of an international workshop to standardize baseline evaluation and response criteria for primary CNS lymphoma.J Clin Oncol,2005;23(22):5034-5043.
10 Bergner N,Monsef I,Illerhaus G,et al.Role of chemotherapy additional to high-dose methotrexate for primary central nervous system lymphoma(PCNSL).Cochrane Database Syst Rev,2012;11:CD009355.
11 Korfel A,Thiel E,Martus P,et al.Randomized phaseⅢstudy of whole-brain radiotherapy for primary CNS lymphoma.Neurology,2015;84(12):1242-1248.
12 Ferreri AJ,Illerhaus G.The role of autologous stem cell transplantation in primary central nervous system lymphoma.Blood,2016;127(13):1642-1649.
13 Langner-Lemercier S,Houillier C,Soussain C,et al.Primary CNS lymphoma at first relapse/progression:characteristics,management,and outcome of 256 patients from the French LOC network.Neuro Oncol,2016;18(9):1297-1303.
14 Chamberlain MC.Salvage therapy with bendamustine for methotrexate refaractory recurrent primary CNS lymphoma:a retrospective case series.J Neurooncol,2014;118(1):155-162.
15 Chamberlain MC.High-dose cytarabine salvage therapy for recurrent primary CNS lymphoma.J Neurooncol,2016;126(3):545-550.
16 Korfel A,Schlegel U,Herrlinger U,et al.Phase II trial of temsirolimus for relapsed/refractory primary CNS lymphoma.J Clin Oncol,2016;34(15):1757-1763.
2 Hoang-Xuan K,Bessell E,Bromberg J,et al.Diagnosis and treatment of primary CNS lymphoma in immunocompetent patients:guidelines from the European Association for Neuro-Oncology.Lancet Oncol,2015;16(7):e322-332.
3 朱铁楠,王书杰,张薇,等.37例原发中枢神经系统淋巴瘤患者的临床特征及预后分析.中华血液学杂志,2015;36(10):849-852.
4 付丽,陈力,魏娜,等.原发性中枢神经系统淋巴瘤31例临床特点及预后分析.中国实验血液学杂志,2016;24(4):1061-1065.
5 Guo M,Hu KX,Yu CL,et al.Infusion of HLA-mismatched peripheral blood stem cells improves the outcome of chemotherapy for acute myeloid leukemia in elderly patients.Blood,2011;117(3):936-941.
6 Guo M,Hu KX,Liu GX,et al.HLA-mismatched stem-cell micro transplantation as postremission therapy for acute myeloid leukemia:long-term follow-up.J Clin Oncol,2012;30(33):4084-4090.
7 赵红霞,孙万军,郭梅,等."微移植"治疗难治性淋巴瘤的临床观察.中华医学杂志,2013;93(34):2711-2714.
8 孙万军,赵红霞,黄雅静,等."微移植"治疗7例淋巴母细胞淋巴瘤/白血病的临床分析.中国实验血液学杂志,2014;22(4):995-998.
9 Abrey LE,Batchelor TT,Ferreri AJ,et al.Report of an international workshop to standardize baseline evaluation and response criteria for primary CNS lymphoma.J Clin Oncol,2005;23(22):5034-5043.
10 Bergner N,Monsef I,Illerhaus G,et al.Role of chemotherapy additional to high-dose methotrexate for primary central nervous system lymphoma(PCNSL).Cochrane Database Syst Rev,2012;11:CD009355.
11 Korfel A,Thiel E,Martus P,et al.Randomized phaseⅢstudy of whole-brain radiotherapy for primary CNS lymphoma.Neurology,2015;84(12):1242-1248.
12 Ferreri AJ,Illerhaus G.The role of autologous stem cell transplantation in primary central nervous system lymphoma.Blood,2016;127(13):1642-1649.
13 Langner-Lemercier S,Houillier C,Soussain C,et al.Primary CNS lymphoma at first relapse/progression:characteristics,management,and outcome of 256 patients from the French LOC network.Neuro Oncol,2016;18(9):1297-1303.
14 Chamberlain MC.Salvage therapy with bendamustine for methotrexate refaractory recurrent primary CNS lymphoma:a retrospective case series.J Neurooncol,2014;118(1):155-162.
15 Chamberlain MC.High-dose cytarabine salvage therapy for recurrent primary CNS lymphoma.J Neurooncol,2016;126(3):545-550.
16 Korfel A,Schlegel U,Herrlinger U,et al.Phase II trial of temsirolimus for relapsed/refractory primary CNS lymphoma.J Clin Oncol,2016;34(15):1757-1763.