异基因造血干细胞移植后纯红细胞再生障碍性贫血2例并文献复习
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摘要
背景:异基因造血干细胞移植后纯红细胞再生障碍性贫血的发生导致患者红系造血恢复延迟、血型转换时间延长,从而产生一系列并发症。因此,应重视异基因造血干细胞移植后纯红细胞再生障碍性贫血预防和诊断后的治疗对策,以加快移植后红系植入。目前纯红细胞再生障碍性贫血的发生率、高危因素尚无定论,诊疗尚无规范指南。目的:探讨异基因造血干细胞移植后纯红细胞再生障碍性贫血发病的高危因素和治疗对策。方法:2例患者,诊断为急性白血病,接受同胞供者的清髓性外周血干细胞移植,供受者血型均为A供O,分别于+44 d、+58 d出现纯红细胞再生障碍性贫血,复习诊治过程和相关文献。结果与结论:(1)1例经美罗华、大剂量甲强龙、血浆置换治疗后痊愈;另1例经大剂量甲强龙、美罗华和硼替佐米治疗后血象于5个月后逐渐恢复;(2)总结文献报道的93例发生移植后纯红细胞再生障碍性贫血病例,所有患者均为供受者ABO血型不合,明确血型的患者中A供O者占66%(47/71),同胞供者、非清髓预处理、病毒感染等是发生纯红细胞再生障碍性贫血的高危因素,主要治疗方法有血浆置换、激素、利妥昔单抗等;(3)异基因造血干细胞移植后纯红细胞再生障碍性贫血是少见的并发症,多种因素可促进其发生,目前尚无一致的治疗共识,部分患者可以自愈,对难治性患者,硼替佐米和艾曲波帕可作为新的靶向治疗药物。
BACKGROUND:The occurrence of pure red blood cell aplasia after allogeneic hematopoietic stem cell transplantation delays the recovery of erythroid hematopoiesis and prolongs the conversion time of blood type, eventually resulting in a series of complications. Therefore, attentions should be paid to the treatment and prevention of pure red blood cell aplasia after allogeneic hematopoietic stem cell transplantation to accelerate the erythroid implantation after transplantation. At present, the incidence and risk factors of pure red blood cell aplasia are inconclusive, and there is also no standard guide for the diagnosis and treatment.OBJECTIVE:To explore the risk factors and treatments of pure red cell aplasia following allogeneic hematopoietic stem cell transplantation.METHODS:Two patients with acute leukemia, who had received allogeneic hematopoietic stem cell transplantation with nonmyeloablative conditioning from sibling donor, were enrolled. The blood types of the patients and the donors were O positive and A positive, respectively.The two patients developed pure red cell aplasia at day +44 and day +58, respectively. Here, we reviewed the diagnosis and treatment process with literature.RESULTS AND CONCLUSION:One patient recovered by the treatment with rituximab, high-dose methylprednisolone, and plasma exchange.The other patient benefited from the treatment with high-dose methylprednisolone, rituximab, and bortezomib, and the patient's blood routine parameters recovered gradually after 5 months.(2) As previously reported in 93 cases of pure red blood cell aplasia after allogeneic hematopoietic stem cell transplantation, 66%(47/71) of the patients with determined blood type were O positive and the donors were A positive. The risk factors for pure red blood cell aplasia after allogeneic hematopoietic stem cell transplantation include sibling donor,nonmyeloablative conditioning, and virus infection; and the major treatment includes plasma exchange, steroid, and rituximab. Overall, pure red cell aplasia is a rare complication of allogeneic hematopoietic stem cell transplantation, and multiple factors can facilitate its occurrence. A consensus on the treatment of pure red cell aplasia has not been reached. Some patients can recover by themselves, and bortezomib and eltrombopag as new targeted drugs may be effective for refractory pure red cell aplasia.
BACKGROUND:The occurrence of pure red blood cell aplasia after allogeneic hematopoietic stem cell transplantation delays the recovery of erythroid hematopoiesis and prolongs the conversion time of blood type, eventually resulting in a series of complications. Therefore, attentions should be paid to the treatment and prevention of pure red blood cell aplasia after allogeneic hematopoietic stem cell transplantation to accelerate the erythroid implantation after transplantation. At present, the incidence and risk factors of pure red blood cell aplasia are inconclusive, and there is also no standard guide for the diagnosis and treatment.OBJECTIVE:To explore the risk factors and treatments of pure red cell aplasia following allogeneic hematopoietic stem cell transplantation.METHODS:Two patients with acute leukemia, who had received allogeneic hematopoietic stem cell transplantation with nonmyeloablative conditioning from sibling donor, were enrolled. The blood types of the patients and the donors were O positive and A positive, respectively.The two patients developed pure red cell aplasia at day +44 and day +58, respectively. Here, we reviewed the diagnosis and treatment process with literature.RESULTS AND CONCLUSION:One patient recovered by the treatment with rituximab, high-dose methylprednisolone, and plasma exchange.The other patient benefited from the treatment with high-dose methylprednisolone, rituximab, and bortezomib, and the patient's blood routine parameters recovered gradually after 5 months.(2) As previously reported in 93 cases of pure red blood cell aplasia after allogeneic hematopoietic stem cell transplantation, 66%(47/71) of the patients with determined blood type were O positive and the donors were A positive. The risk factors for pure red blood cell aplasia after allogeneic hematopoietic stem cell transplantation include sibling donor,nonmyeloablative conditioning, and virus infection; and the major treatment includes plasma exchange, steroid, and rituximab. Overall, pure red cell aplasia is a rare complication of allogeneic hematopoietic stem cell transplantation, and multiple factors can facilitate its occurrence. A consensus on the treatment of pure red cell aplasia has not been reached. Some patients can recover by themselves, and bortezomib and eltrombopag as new targeted drugs may be effective for refractory pure red cell aplasia.
引文
[1]马威,张定宇,尹建平,等.异基因造血干细胞移植后纯红细胞再生障碍性贫血发生的影响因素分析[J].中国输血杂志,2013,26(7):603-606.
[2]黄晓军,许兰平,江倩,等.主要ABO血型不合异基因造血干细胞移植后纯红细胞再生障碍[J].中华血液学杂志,2005,26(9):548-550.
[3]万长春,李云涛,冯四洲,等.ABO血型不合异基因造血干细胞移植后纯红细胞再生障碍分析[J].中华医学杂志,2006,86(18):1289-1292.
[4]Booth GS,Gehrie EA,Bolan CD,et al.Clinical guide to ABO-incompatible allogeneic stem cell transplantation.Biol Blood Marrow Transplant.2013;19(8):1152-1158.
[5]鹿全意,牛小青,郭勇,等.G-CSF动员的异基因外周血干细胞和骨髓联合移植治疗白血病[J].中国实验血液学杂志,2005,13(2):326-328.
[6]Nakamura N,Ninomiya S,Matsumoto T,et al.Recovery of Pure Red Cell Aplasia Following Hematopoietic Stem Cell Transplantation Associated with IL-6 Elevation Caused by Odontogenic Infection.Intern Med.2018 Jun 6.doi:10.2169/internalmedicine.0869-18.[Epub ahead of print]
[7]Griffith LM,Mc Coy JP Jr,Bolan CD,et al.Persistence of recipient plasma cells and anti-donor isohaemagglutinins in patients with delayed donor erythropoiesis after major ABOincompatible non-myeloablativehaematopoietic cell transplantation.Br J Haematol.2005;128(5):668-675.
[8]吴超,韩明哲.ABO血型不合异基因造血干细胞移植后继发纯红细胞再生障碍性贫血研究进展[J].中国医药生物技术,2007,2(3):222-225.
[9]Varela Gómez R,Vázquez Vázquez G,et al.Successful treatment of pure red cell aplasia with high-dose dexamethasone after ABO-incompatible allogeneic hematopoietic stem cell transplantation.HematolOncol Stem Cell Ther.2018;11(1):44-46.
[10]Busca A,Dellacasa C,Giaccone L,et al.Eltrombopag for the Treatment of Refractory Pure RBC Aplasia after Major ABOIncompatible Hematopoietic Stem Cell Transplantation.Biol Blood Marrow Transplant.2018;24(8):1765-1770.
[11]Bolan CD,Leitman SF,Griffith LM,et al.Delayed donor red cell chimerism and pure red cell aplasia following major ABO-incompatible nonmyeloablative hematopoietic stem cell transplantation.Blood.2001;98(6):1687-1694.
[12]Helbig G,Stella-Holowiecka B,Wojnar J,et al.Pure red-cell aplasia following major and bi-directional ABO-incompatible allogeneic stem-cell transplantation:recovery of donor-derived erythropoiesis after long-term treatment using different therapeutic strategies.Ann Hematol.2007;86(9):677-683.
[13]Schetelig J,Breitschaft A,Kr?ger N,et al.After major ABO-mismatched allogeneic hematopoietic progenitor cell transplantation,erythroid engraftment occurs later in patients with donor blood group A than donor blood group B.Transfusion.2005;45(5):779-787.
[14]侯相麟,马海珍,刘正国,等.ABO血型不合的异基因外周血干细胞移植[J].临床血液学杂志,2001,14(4):172-173.
[15]许伟,朱梅,李燕萍,等.ABO血型不合的异基因造血干细胞采集及移植效果研究[J].中国实验血液学杂志,2011,9(5):1237-1240.
[16]范辉,靖彧,李红华,等.ABO血型不合异基因造血干细胞移植后并发纯红系再生障碍[J].中国实验血液学杂志,2008,16(2):364-367.
[17]牟海霞,马劼,蔡正文,等.ABO血型不合同胞间异基因外周血干细胞移植后纯红细胞再生障碍性贫血3例报告[J].内科急危重症杂志,2006,12(6):267-269.
[18]章卫平,王健民,宋献民,等.ABO血型不合异基因外周血干细胞移植对红系造血重建的影响[J].中华血液学杂志,2005,26(2):113-114.
[19]孟凡义,孙竞,刘启发,等.ABO血型不合异基因外周血干细胞移植对红系造血重建的影响[J].解放军医学杂志,2002,27(4):357-358.
[20]刘生全,符粤文,王倩,等.ABO血型不合异基因造血干细胞移植后单纯红细胞再生障碍性贫血二例并文献复习[J].白血病·淋巴瘤,2012,21(12):757-759.
[21]张东华,李登举,肖毅,等.ABO主血型不合的非清髓性异基因造血干细胞移植2例[J].临床血液学杂志,2004,17(2):92-94.
[22]王恒湘,纪树荃,陈惠仁.红细胞生成素联合甲泼尼龙治愈异基因骨髓移植后纯红细胞再生障碍性贫血一例[J].中华血液学杂志,2000,21(10):532.
[23]巫进明,陈嘉榆,黄振倩,等.激素治疗ABO血型不合异基因造血干细胞移植后纯红细胞再生障碍性贫血--1例报告及文献复习[J].白血病·淋巴瘤,2005,14(1):24-26.
[24]翁文骏,陈志峰,夏修贤,等.减停免疫抑制剂诱发移植物抗宿主病治疗儿童ABO血型不合移植后纯红细胞再生障碍性贫血1例及文献复习[J].中国小儿血液与肿瘤杂志,2012,17(5):211-214.
[25]蔡正文,赖永榕,马劼,等.血浆置换联合免疫抑制剂治疗干细胞移植后移植物抗宿主病和纯红细胞再生障碍性贫血疗效分析[J].中国肿瘤临床,2008,35(3):149-151.
[26]胡俊斌,郭涛,邹萍.血浆置换与强的松治疗allo-BMT后纯红细胞再生障碍性贫血[J].中国输血杂志,1999,12(3):151-152.
[27]邵晓雁,欧阳建,孙雪梅,等.血型不合的异基因造血干细胞移植治疗恶性血液病[J].实用临床医药杂志,2006,10(9):49-51.
[28]曹星玉,吴彤,张耀臣,等.异基因造血干细胞移植后同时发生纯红细胞再生障碍性贫血和EVANS综合征1例并文献复习[J].临床血液学杂志,2010,23(5):520-522.
[29]白庆咸,陈协群,王文清,等.异基因造血干细胞移植治疗白血病的临床研究[J].临床血液学杂志,2004,17(6):321-323.
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[32]李成文,韩明哲,冯四洲,等.异基因外周血干细胞移植后发生纯红细胞再生障碍--一例报告附文献复习[J].中华血液学杂志,1999,20(7):359.
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[34]Hirokawa M,Fukuda T,Ohashi K,et al.Efficacy and long-term outcome of treatment for pure red cell aplasia after allogeneic stem cell transplantation from major ABO-incompatible donors.Biol Blood Marrow Transplant.2013;19(7):1026-1032.
[35]Yang X,Levis M.Pulsed-high-dose dexamethasone as a treatment for pure red cell aplasia following ABO-incompatible allogeneic stem cell transplantation.Transfus Med.2014;24(4):246-248.
[36]Helbig G,Stella-Holowiecka B,Krawczyk-Kulis M,et al.Successful treatment of pure red cell aplasia with repeated,low doses of rituximab in two patients after ABO-incompatible allogeneic haematopoietic stem cell transplantation for acute myeloid leukaemia.Haematologica.2005;90 Suppl:ECR33.
[37]Benson DM Jr,Smith MK,Krugh D,et al.Successful therapy of chronic graft-versus-host disease manifesting as pure red cell aplasia with single-agent rituximab.Bone Marrow Transplant.2008;41(6):595-596.
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[39]Khan F,Linden MA,Zantek ND,et al.Subcutaneous bortezomib is highly effective for pure red cell aplasia after ABO-incompatible haematopoietic stem cell transplantation.Transfus Med.2014;24(3):187-188.
[40]Townsley DM,Scheinberg P,Winkler T,et al.Eltrombopag Added to Standard Immunosuppression for Aplastic Anemia.N Engl J Med.2017;376(16):1540-1550.
[41]Saleh MN,Bussel JB,Cheng G,et al.Safety and efficacy of eltrombopag for treatment of chronic immune thrombocytopenia:results of the long-term,open-label EXTEND study.Blood.2013;121(3):537-545.
[2]黄晓军,许兰平,江倩,等.主要ABO血型不合异基因造血干细胞移植后纯红细胞再生障碍[J].中华血液学杂志,2005,26(9):548-550.
[3]万长春,李云涛,冯四洲,等.ABO血型不合异基因造血干细胞移植后纯红细胞再生障碍分析[J].中华医学杂志,2006,86(18):1289-1292.
[4]Booth GS,Gehrie EA,Bolan CD,et al.Clinical guide to ABO-incompatible allogeneic stem cell transplantation.Biol Blood Marrow Transplant.2013;19(8):1152-1158.
[5]鹿全意,牛小青,郭勇,等.G-CSF动员的异基因外周血干细胞和骨髓联合移植治疗白血病[J].中国实验血液学杂志,2005,13(2):326-328.
[6]Nakamura N,Ninomiya S,Matsumoto T,et al.Recovery of Pure Red Cell Aplasia Following Hematopoietic Stem Cell Transplantation Associated with IL-6 Elevation Caused by Odontogenic Infection.Intern Med.2018 Jun 6.doi:10.2169/internalmedicine.0869-18.[Epub ahead of print]
[7]Griffith LM,Mc Coy JP Jr,Bolan CD,et al.Persistence of recipient plasma cells and anti-donor isohaemagglutinins in patients with delayed donor erythropoiesis after major ABOincompatible non-myeloablativehaematopoietic cell transplantation.Br J Haematol.2005;128(5):668-675.
[8]吴超,韩明哲.ABO血型不合异基因造血干细胞移植后继发纯红细胞再生障碍性贫血研究进展[J].中国医药生物技术,2007,2(3):222-225.
[9]Varela Gómez R,Vázquez Vázquez G,et al.Successful treatment of pure red cell aplasia with high-dose dexamethasone after ABO-incompatible allogeneic hematopoietic stem cell transplantation.HematolOncol Stem Cell Ther.2018;11(1):44-46.
[10]Busca A,Dellacasa C,Giaccone L,et al.Eltrombopag for the Treatment of Refractory Pure RBC Aplasia after Major ABOIncompatible Hematopoietic Stem Cell Transplantation.Biol Blood Marrow Transplant.2018;24(8):1765-1770.
[11]Bolan CD,Leitman SF,Griffith LM,et al.Delayed donor red cell chimerism and pure red cell aplasia following major ABO-incompatible nonmyeloablative hematopoietic stem cell transplantation.Blood.2001;98(6):1687-1694.
[12]Helbig G,Stella-Holowiecka B,Wojnar J,et al.Pure red-cell aplasia following major and bi-directional ABO-incompatible allogeneic stem-cell transplantation:recovery of donor-derived erythropoiesis after long-term treatment using different therapeutic strategies.Ann Hematol.2007;86(9):677-683.
[13]Schetelig J,Breitschaft A,Kr?ger N,et al.After major ABO-mismatched allogeneic hematopoietic progenitor cell transplantation,erythroid engraftment occurs later in patients with donor blood group A than donor blood group B.Transfusion.2005;45(5):779-787.
[14]侯相麟,马海珍,刘正国,等.ABO血型不合的异基因外周血干细胞移植[J].临床血液学杂志,2001,14(4):172-173.
[15]许伟,朱梅,李燕萍,等.ABO血型不合的异基因造血干细胞采集及移植效果研究[J].中国实验血液学杂志,2011,9(5):1237-1240.
[16]范辉,靖彧,李红华,等.ABO血型不合异基因造血干细胞移植后并发纯红系再生障碍[J].中国实验血液学杂志,2008,16(2):364-367.
[17]牟海霞,马劼,蔡正文,等.ABO血型不合同胞间异基因外周血干细胞移植后纯红细胞再生障碍性贫血3例报告[J].内科急危重症杂志,2006,12(6):267-269.
[18]章卫平,王健民,宋献民,等.ABO血型不合异基因外周血干细胞移植对红系造血重建的影响[J].中华血液学杂志,2005,26(2):113-114.
[19]孟凡义,孙竞,刘启发,等.ABO血型不合异基因外周血干细胞移植对红系造血重建的影响[J].解放军医学杂志,2002,27(4):357-358.
[20]刘生全,符粤文,王倩,等.ABO血型不合异基因造血干细胞移植后单纯红细胞再生障碍性贫血二例并文献复习[J].白血病·淋巴瘤,2012,21(12):757-759.
[21]张东华,李登举,肖毅,等.ABO主血型不合的非清髓性异基因造血干细胞移植2例[J].临床血液学杂志,2004,17(2):92-94.
[22]王恒湘,纪树荃,陈惠仁.红细胞生成素联合甲泼尼龙治愈异基因骨髓移植后纯红细胞再生障碍性贫血一例[J].中华血液学杂志,2000,21(10):532.
[23]巫进明,陈嘉榆,黄振倩,等.激素治疗ABO血型不合异基因造血干细胞移植后纯红细胞再生障碍性贫血--1例报告及文献复习[J].白血病·淋巴瘤,2005,14(1):24-26.
[24]翁文骏,陈志峰,夏修贤,等.减停免疫抑制剂诱发移植物抗宿主病治疗儿童ABO血型不合移植后纯红细胞再生障碍性贫血1例及文献复习[J].中国小儿血液与肿瘤杂志,2012,17(5):211-214.
[25]蔡正文,赖永榕,马劼,等.血浆置换联合免疫抑制剂治疗干细胞移植后移植物抗宿主病和纯红细胞再生障碍性贫血疗效分析[J].中国肿瘤临床,2008,35(3):149-151.
[26]胡俊斌,郭涛,邹萍.血浆置换与强的松治疗allo-BMT后纯红细胞再生障碍性贫血[J].中国输血杂志,1999,12(3):151-152.
[27]邵晓雁,欧阳建,孙雪梅,等.血型不合的异基因造血干细胞移植治疗恶性血液病[J].实用临床医药杂志,2006,10(9):49-51.
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