2006-2016年宫崎县某医院造血干细胞移植的临床特点及治疗结果

N. Kawano, S. Yoshida, Hidemi Shimonodan, Takuro Kuriyama, N. Ono, D. Himeji, T. Tochigi, Takashi Nakaike, Tomonori Shimokawa, S. Urata, K. Yamashita, Masaki Ito, Hideki Koketsu, Atsushi Toyofuku, T. Muranaka, K. Marutsuka, K. Mashiba, I. Kikuchi, S. Makino, H. Ochiai, K. Shimoda, K. Nagafuji, Y. Mori, T. Miyamoto, K. Akashi
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Results: Consistent with previous Japan Marrow Donor Program annual reports, the overall survival(OS)rate of allo-HSCT and auto-HSCT patients were 59% and 84% at five years, respectively. Among patients receiving allo-HSCT, severe regimen-related toxicity(RRT)(grade ≥ 3)events included cardiomyopathy due to cyclophospha-mide(1), idiopathic pulmonary syndrome(1), acute graft-versus-host disease(GVHD)Ⅲ-Ⅳ(3), acute-exacer-bated chronic GVHD(2), engraftment failure(2), human herpesvirus-6 encephalitis(2), and fungal infection(7). Moreover, univariate analysis identified disease risk index(DRI)and non-CR status before allo-HSCT as prognostic factors of OS. Among patients receiving auto-HSCT, the severe RRT event was thrombotic microangiopathy (1). The relapse after auto-HSCT in three patients with malignant lymphoma was a serious concern. Conclusion: Our study revealed critical issues in non-CR patients and those with high/very high DRI before allo-HSCT. Fur -thermore, the occurrence of severe RRT indicated the need for improvements in allo- and auto-HSCT. fusion gene. He achieved complete remission after multi-agent chemotherapy and received an unrelated CBT from a two HLA loci mismatched donor. The patient tested positive for antibodies (IgG) against HHV6 before conditioning for the CBT. The conditioning regimen consisted of total body irradiation (12 Gy) and high-dose cyclophosphamide (60 mg/ kg/day for 2 days). The number of infused nucleated cells in the cord blood was 2.1 × 10 7 /kg body weight. Prophylaxis for graft-versus-host disease (GVHD) consisted of a combination of tacrolimus (0.02 mg/kg/day) and mycophenolate mofetil (30 mg/kg/day). Prophylaxis for herpesvirus infection consisted of oral aciclovir (1,000 mg/day). Grade II acute GVHD of the skin developed on day 12 post-transplantation, and prednisolone (0.5 mg/kg/day) was administered. GVHD responded promptly, and prednisolone was discontinued by We report the case of a 45-year-old male patient who developed human herpesvirus 6 (HHV6)-associated pleurisy after an unrelated cord blood transplantation (CBT) for acute lymphoblastic leukemia. A large amount of pleural effusion accompanied by interstitial pneumonitis was noted on the right side on day 37 post-transplantation. A real-time quantitative PCR (RQ-PCR) assay revealed that the HHV6 viral load was substantially higher in the pleural effusion than in the peripheral blood plasma at the onset of pleurisy, with 2.2 × 10 2 and 7.9 × 10 3 copies of HHV6 DNA/mL in the peripheral blood plasma and the supernatant of the pleural effusion, respectively. Moreover, HHV6 DNA was still detected in the pleural effusion after antiviral therapy. Therefore, the pleural cavity may have been the primary site of HHV6 replication in the present case. 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引用次数: 0

摘要

背景:阐明死亡患者的临床特征对于改善恶性肿瘤造血干细胞移植(HSCT)的预后至关重要。患者和方法:回顾性分析我院2006 - 2016年接受同种异体造血干细胞移植(alloo -HSCT)和自体造血干细胞移植(auto-HSCT)治疗的81例难治性/复发恶性血液病患者(54例)。结果:与之前的日本骨髓捐赠计划年度报告一致,同种异体造血干细胞移植和自体造血干细胞移植患者的5年总生存率(OS)分别为59%和84%。在接受同种异体造血干细胞移植的患者中,严重的方案相关毒性(RRT)(等级≥3)事件包括由环磷酰胺引起的心肌病(1)、特发性肺综合征(1)、急性移植物抗宿主病(GVHD)Ⅲ-Ⅳ(3)、急性加重慢性GVHD(2)、移植失败(2)、人疱疹病毒-6脑炎(2)和真菌感染(7)。此外,单因素分析发现,疾病风险指数(DRI)和非cr状态在异基因造血干细胞移植前是OS的预后因素。在接受自体造血干细胞移植的患者中,严重的RRT事件是血栓性微血管病变(1)。三例恶性淋巴瘤患者自体造血干细胞移植后的复发是一个严重的问题。结论:我们的研究揭示了非cr患者和高/非常高DRI患者在移植前的关键问题。此外,严重RRT的发生表明需要改进同种异体移植和自体造血干细胞移植。融合基因。他在多药化疗后获得完全缓解,并接受了来自两个HLA位点不匹配供者的不相关CBT。患者在接受CBT前检测HHV6抗体(IgG)阳性。调理方案包括全身照射(12 Gy)和高剂量环磷酰胺(60 mg/ kg/天,持续2天)。脐带血输注有核细胞数为2.1 × 10.7 /kg体重。预防移植物抗宿主病(GVHD)包括他克莫司(0.02 mg/kg/天)和霉酚酸酯(30 mg/kg/天)的组合。预防疱疹病毒感染的方法包括口服阿昔洛韦(1000mg /天)。移植后第12天出现皮肤II级急性GVHD,给予强的松龙(0.5 mg/kg/天)。我们报告了一例45岁男性患者,在急性淋巴细胞白血病的非相关脐带血移植(CBT)后发生人类疱疹病毒6 (HHV6)相关胸膜炎。移植后第37天右侧可见大量胸腔积液伴间质性肺炎。实时荧光定量PCR (real-time quantitative PCR, RQ-PCR)检测结果显示,胸膜炎发病时,外周血和胸膜上清中HHV6病毒载量分别为2.2 × 10.2和7.9 × 10.3拷贝/mL,胸膜积液中HHV6病毒载量明显高于外周血和外周血。此外,抗病毒治疗后胸腔积液中仍检测到HHV6 DNA。因此,在本病例中,胸膜腔可能是HHV6病毒复制的主要部位。据我们所知,本研究是CBT后成人hhv6相关胸膜炎的第一份详细报告。当CBT后出现不明原因的胸腔积液时,即使外周血中没有HHV6 DNA, HHV6相关性胸膜炎也应被视为潜在的并发症。(造血细胞移植杂志3(2):59-63,2014。)
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Clinical Features and Treatment Outcomes of Hematopoietic Stem Cell Transplantation During 2006-2016 at a Single Institution in Miyazaki Prefecture
Background: The elucidation of clinical characteristics in deceased patients is essential to improve outcomes of hematopoietic stem cell transplantation(HSCT)for malignancy. Patients and Methods: We retrospectively examined 81 refractory/relapsed hematological malignancy patients treated with allogeneic HSCT(allo-HSCT)(54)and autologous HSCT(auto-HSCT)(27)in our hospital from 2006 to 2016. Results: Consistent with previous Japan Marrow Donor Program annual reports, the overall survival(OS)rate of allo-HSCT and auto-HSCT patients were 59% and 84% at five years, respectively. Among patients receiving allo-HSCT, severe regimen-related toxicity(RRT)(grade ≥ 3)events included cardiomyopathy due to cyclophospha-mide(1), idiopathic pulmonary syndrome(1), acute graft-versus-host disease(GVHD)Ⅲ-Ⅳ(3), acute-exacer-bated chronic GVHD(2), engraftment failure(2), human herpesvirus-6 encephalitis(2), and fungal infection(7). Moreover, univariate analysis identified disease risk index(DRI)and non-CR status before allo-HSCT as prognostic factors of OS. Among patients receiving auto-HSCT, the severe RRT event was thrombotic microangiopathy (1). The relapse after auto-HSCT in three patients with malignant lymphoma was a serious concern. Conclusion: Our study revealed critical issues in non-CR patients and those with high/very high DRI before allo-HSCT. Fur -thermore, the occurrence of severe RRT indicated the need for improvements in allo- and auto-HSCT. fusion gene. He achieved complete remission after multi-agent chemotherapy and received an unrelated CBT from a two HLA loci mismatched donor. The patient tested positive for antibodies (IgG) against HHV6 before conditioning for the CBT. The conditioning regimen consisted of total body irradiation (12 Gy) and high-dose cyclophosphamide (60 mg/ kg/day for 2 days). The number of infused nucleated cells in the cord blood was 2.1 × 10 7 /kg body weight. Prophylaxis for graft-versus-host disease (GVHD) consisted of a combination of tacrolimus (0.02 mg/kg/day) and mycophenolate mofetil (30 mg/kg/day). Prophylaxis for herpesvirus infection consisted of oral aciclovir (1,000 mg/day). Grade II acute GVHD of the skin developed on day 12 post-transplantation, and prednisolone (0.5 mg/kg/day) was administered. GVHD responded promptly, and prednisolone was discontinued by We report the case of a 45-year-old male patient who developed human herpesvirus 6 (HHV6)-associated pleurisy after an unrelated cord blood transplantation (CBT) for acute lymphoblastic leukemia. A large amount of pleural effusion accompanied by interstitial pneumonitis was noted on the right side on day 37 post-transplantation. A real-time quantitative PCR (RQ-PCR) assay revealed that the HHV6 viral load was substantially higher in the pleural effusion than in the peripheral blood plasma at the onset of pleurisy, with 2.2 × 10 2 and 7.9 × 10 3 copies of HHV6 DNA/mL in the peripheral blood plasma and the supernatant of the pleural effusion, respectively. Moreover, HHV6 DNA was still detected in the pleural effusion after antiviral therapy. Therefore, the pleural cavity may have been the primary site of HHV6 replication in the present case. To our knowledge, the present study is the first detailed report of adult HHV6-associated pleurisy after CBT. HHV6-associated pleurisy should be considered a potential complication when pleural effusion of unknown cause is encountered after CBT, even in the absence of HHV6 DNA in the peripheral blood. (Journal of Hematopoietic Cell Transplantation 3(2): 59-63, 2014.)
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