[匈牙利儿童获得性骨髓衰竭综合征治疗模式的转变]

[Change in paradigm in the treatment of pediatric acquired bone marrow failure syndromes in Hungary].

作者信息

Kállay Krisztián, Csomor Judit, Ádám Emma, Bödör Csaba, Kassa Csaba, Simon Réka, Kovács Gábor, Péter György, Ottóffy Gábor, Bartyik Katalin, Kiss Csongor, Masát Péter, Réti Marienn, Tóth Blanka, Kriván Gergely

机构信息

Dél-pesti Centrumkórház - Országos Hematológiai és Infektológiai Intézet Budapest, Albert Flórián út 5-7., 1097.

I. Patológiai és Kísérleti Rákkutató Intézet, Semmelweis Egyetem, Általános Orvostudományi Kar Budapest.

出版信息

Orv Hetil. 2018 Oct;159(42):1710-1719. doi: 10.1556/650.2018.31171.

DOI:10.1556/650.2018.31171

PMID:30334483

Abstract

INTRODUCTION

Acquired bone marrow failures are rare but fatal diseases in childhood. Since 2013, Hungary has been participating as a full member in the work of the European Working Group on uniform diagnostics and therapy in patients with acquired bone marrow failure syndromes. Hypocellular refractory cytopenia of childhood has been emphasized as a frequent entity, transplanted by reduced intensity conditioning with excellent outcomes.

AIM

To analyse and compare the results of treatment before and after our joining.

METHOD

A total of 55 patients have been treated in the 8 centres of the Hungarian Pediatric Oncology Network during 5 years between 2013 and 2017 (severe aplastic anemia: 9, myelodysplastic syndrome: 41, juvenile myelomonocytic leukemia: 5 patients). Allogeneic hematopoietic stem cell transplantation was performed in severe aplastic anemia in 7 cases, while antithymocyte globulin was administered in one case and one patient died before diagnosis. In patients with myelodysplastic syndromes, watch and wait strategy was applied in 4, while transplantation in 37 cases. Reduced intensity conditioning was used in 54 percent of these cases. Transplantation was the treatment of choice in all 5 patients with juvenile myelomonocytic leukemia.

RESULTS

In the whole patient cohort, the time from diagnosis to treatment was median 92 (3-393) days, while in severe aplastic anemia median 28 (3-327) days only. Grade II-IV acute graft versus host disease occurred in 22.6%, grade III-IV in 6.8% and chronic in 11.2%. All the patients treated with severe aplastic anemia are alive and in complete remission (100%). The overall estimated survival rate is 85.1% in myelodysplastic syndrome, while 75% in juvenile myelomonocytic leukemia. The median follow-up was 30.4 (1.1-62.5) months. There was a remarkable increase in overall survival comparing the data before (1992-2012) and after (2013) joining the international group, 70% vs. 100% (p = 0.133) in severe aplastic anemia and 31.3% vs. 85.1% (p = 0.000026) in myelodysplastic syndrome.

CONCLUSION

Due to a change in the paradigm of the conditioning regimen in hypocellular refractory cytopenia of childhood, the overall survival rate has significantly increased. Orv Hetil. 2018; 159(42): 1710-1719.

摘要

引言

获得性骨髓衰竭是儿童期罕见但致命的疾病。自2013年以来，匈牙利一直作为正式成员参与欧洲获得性骨髓衰竭综合征患者统一诊断和治疗工作组的工作。儿童低细胞难治性血细胞减少症被视为一种常见病症，采用减低强度预处理进行移植，效果良好。

目的

分析和比较我们加入该工作组前后的治疗结果。

方法

2013年至2017年的5年间，匈牙利儿科肿瘤网络的8个中心共治疗了55例患者（严重再生障碍性贫血：9例，骨髓增生异常综合征：41例，青少年粒单核细胞白血病：5例）。7例严重再生障碍性贫血患者接受了异基因造血干细胞移植，1例使用了抗胸腺细胞球蛋白，1例患者在诊断前死亡。对于骨髓增生异常综合征患者，4例采用观察等待策略，37例进行了移植。其中54%的病例采用了减低强度预处理。所有5例青少年粒单核细胞白血病患者均选择移植作为治疗方法。

结果

在整个患者队列中，从诊断到治疗的时间中位数为92（3 - 393）天，而严重再生障碍性贫血患者仅为28（3 - 327）天。II - IV级急性移植物抗宿主病发生率为22.6%，III - IV级为6.8%，慢性移植物抗宿主病为11.2%。所有接受治疗的严重再生障碍性贫血患者均存活且完全缓解（100%）。骨髓增生异常综合征的总体估计生存率为85.1%，青少年粒单核细胞白血病为75%。中位随访时间为30.4（1.1 - 62.5）个月。与加入国际组织之前（1992 - 2012年）的数据相比，总体生存率有显著提高，严重再生障碍性贫血从70%提高到100%（p = 0.133），骨髓增生异常综合征从31.3%提高到85.1%（p = 0.000026）。