再生障碍性贫血患儿骨髓间充质干细胞体外造血支持作用的研究

目的：骨髓间充质干细胞（mesenchymal stem cell, MSC）具有造血支持作用，再生障碍性贫血（aplastic anemia, AA）的发病机制涉及到造血微环境的异常，将两方面联系起来，体外研究再障患儿骨髓MSC的造血支持作用与再障的造血微环境异常的关系。方法：采集24例再障患儿和19例对照儿童的骨髓标本，分离、培养和扩增MSC；观察细胞形态及骨髓MSC成纤维细胞集落形成单位（CFU-F）计数分析；应用MTT法检测骨髓MSC粘附造血细胞的能力；应用ELISA检测骨髓MSC分泌干细胞生长因子（SCF）的浓度；对骨髓MSC进行贴壁培养，接种骨髓单个核细胞，计数扩增细胞数和红系爆式集落生成单位（BFU-E），粒细胞巨噬细胞集落生成单位（CFU-GM），混合细胞集落生成单位（CFU-GMME）。结果：①再障患儿骨髓MSC传代时间延长，CFU-F计数15.70±5.78显著低于对照组21.73±5.74，P<0.05；②再障患儿骨髓MSC培养上清中SCF的浓度30.69±16.82 pg/mL显著低于对照组50.74±14.83 pg/mL，P<0.01；③再障患儿骨髓MSC支持下的单个核细胞（MNC）细胞扩增总数和红系爆式集落生成单位（BFU-E），粒细胞巨噬细胞集落生成单位（CFU-GM），混合细胞集落生成单位（CFU-GMME）计数显著低于对照组，P<0.01。结论： 再障患儿骨髓MSC体外造血支持作用较对照儿童骨髓MSC显著降低，其发生机制可能与再障患儿骨髓MSC增殖能力减低及分泌SCF减少有关。     

再生障碍性贫血患儿骨髓间充质干细胞分离及培养

目的 分离再生障碍性贫血(再障)患儿骨髓间充质干细胞,进行体外培养,为进一步研究打下实验基础.方法 从再障患儿及正常志愿者骨髓中分离骨髓间充质干细胞,进行体外培养,诱导向成骨细胞、成脂细胞分化和流式细胞仪检测表面标志CD34、CD45、CD73和CD90.绘制生长曲线描述原代和传代细胞生长情况.结果 分离的贴壁细胞经向成骨细胞和脂肪细胞分化诱导培养,分别显示茜素红染色和油红染色阳性;CD73和CD90阳性.生长曲线显示,与正常志愿者相比再障患儿体外培养的骨髓间充质干细胞传代培养中生长能力减低.结论 再障患儿骨髓间充质干细胞存在异常,可能在再障发病机制中起着重要作用.     

再生障碍性贫血患儿骨髓间充质干细胞免疫调节特性和造血支持作用的研究

目的研究再生障碍性贫血(AA)患儿骨髓间充质干细胞(MSCs)的免疫调节特性和支持造血的功能。方法从AA患儿和成人骨髓中分离、培养、扩增MSCs,用流式细胞仪测定免疫标记;用3H-TdR法检测PHA刺激后,正常淋巴细胞转化以及MSCs对转化的影响;用造血祖细胞集落培养法(CFU-c)检测MSCs对造血的支持作用。结果从AA患儿骨髓中分离得到了MSCs,与正常骨髓MSCs具有相似的细胞形态和表面标志,但其增殖能力低于正常骨髓MSCs。AA-MSCs体外可抑制脐血淋巴细胞的转化,其抑制能力随细胞数量增加而增强,但与正常骨髓MSCs相比,抑制作用较弱。AA-MSCs体外可以支持脐血造血细胞的生长,但其支持能力只有正常骨髓MSCs的一半。结论AA-MSCs与正常MSCs虽体外生长形态相似,但传代能力、免疫抑制力及对造血集落生长的支持作用均较正常骨髓MSCs减低,提示间充质干细胞参与再生障碍性贫血的发病机制。     

再生障碍性贫血患儿骨髓核素显像特点及其临床意义分析

目的 应用99mTc-硫胶体全身骨髓显像检测再生障碍性贫血（再障）患儿全身骨髓显影特点,探讨其在再障诊治中的价值。方法　对2009年1月至2012年1月青岛大学医学院附属医院小儿血液科收治的45例再障患儿（再障组）及15名对照组进行99mTc-硫胶体全身骨髓显像。99mTc-硫胶体注射放射剂量10～15 MBq/kg,分析骨髓核素显像的特异性、敏感性及不同类型再障患儿骨髓显像特点和临床转归的相关性。结果　再障组45例骨髓显像中活性减低33例（73.3%,包括0级11例、1级22例）,表现为全身骨髓显像有不同程度受抑,其特点是全身骨髓显影不良、显影骨髓总量减少;2级12例（26.7%）,骨髓活性正常。45例再障组临床诊断为急性再障（SAA）组19例、慢性再障（CAA）组26例,其中SAA组骨髓显像表现为中央＋外周骨髓均抑制者15例,仅中央骨髓抑制2例;CAA组中央＋外周骨髓均抑制6例,仅中央周骨髓抑制6例,仅外周抑制4例;两组骨髓显像抑制部位差异有统计学意义（χ2= 10.37,P＜0.05）;提示慢性再障骨髓显像受抑程度较轻,可仅有中央或外周骨髓的抑制并多存在灶状增生。对再障患儿骨髓显像与早期治疗反应进行统计分析,结果示不同骨髓显像分级间疗效差异有统计学意义（χ2=12.49,P＜0.05）,骨髓显像0级组有效率为36.3%,较1级组、2级组（77.3%、83.4%）疗效差。结论　全身骨髓显影不良、显影骨髓总量减少及显像特点有助于对儿童再障的诊断、分型及预后判断。骨髓显像与临床转归和预后关系仍需进一步扩大病例研究。     

儿童再生障碍性贫血临床特点及临床分型探讨

目的探讨儿童再生障碍性贫血(再障)临床特点及临床分型。方法2003-01—2005-12在中山大学附属第二医院儿科确诊儿童再障50例,年龄2～15岁,其中37例接受免疫抑制治疗(IST),观察再障发病诱因、临床表现、血象、骨髓象变化特点、临床分型及治疗转归。结果86%的儿童再障为特发性,70%患儿病程≤6个月,按疾病严重程度分型,临床诊断重型再障(SAA)38例,轻型再障(MAA)12例,骨髓有核细胞增生程度除与病情严重程度相关外,还与取材部位、病程及是否接受IST等因素有关。特发性再障患儿强化IST(IIST)及单用环孢菌素A(CsA)治疗6个月有效率分别为78.3%(18/23)和40.0%(4/10,χ2=4.59,P<0.05),多数患儿于IIST后2～3个月起效,仅1例病程2年余的SAA于IIST后7个月达部分缓解。结论儿童再障多数为特发性,起病急,病情重,临床表现及血象改变严重程度与骨髓增生减低程度相关,特发性再障患儿IIST疗效显著优于单用CsA治疗者,宜按国际标准根据病情严重程度分为重型和轻型。     

儿童骨髓增生异常综合征28例临床分析

目的：探讨儿童骨髓增生异常综合征(MDS)的临床特点、诊断及治疗。方法：回顾性分析2006年1月至2012年3月确诊的28例MDS患儿的临床症状、体征、实验室检查、治疗及疾病转归。结果：患儿临床表现主要为贫血（96%）、出血（68%）、发热（68%）或肝脾肿大（61%）。3例（11%）患儿分别转变为急性单核细胞白血病（M5）、红白血病（M6）、急性巨核细胞白血病（M7）,转为白血病的时间为1~2个月。患儿骨髓增生程度以活跃和明显活跃为主,病态造血以一系和二系病态为主;铁代谢存在明显紊乱;染色体异常核型检出率为45%,以数量异常为主;T细胞、B细胞、NK细胞总数减低,Th细胞表达减低,Ts细胞表达增高,Th /Ts比值倒置。8例患儿确诊后即放弃治疗;8例仅予对症支持治疗,其中1例失访,1例疾病稳定,6例疾病进展;诱导分化和刺激骨髓造血各1例,均发生疾病进展;10例行化疗,其中2例单药化疗,骨髓均无缓解,另8例联合化疗,其中4例骨髓部分缓解或完全缓解。结论：儿童MDS具有临床表现不典型、转为白血病风险高的特点;骨髓增生程度以活跃为主;病态造血以一系和二系病态为主;染色体畸变以数量异常为主;铁代谢明显紊乱,细胞免疫异常。多药联合化疗可延缓病程。     

再生障碍性贫血患儿骨髓造血干细胞端粒酶活性及相关基因表达的研究

目的：探讨再生障碍性贫血（简称再障）患儿骨髓造血干细胞端粒酶活性及端粒酶逆转录酶（hTERT）基因和端粒酶RNA组分（hTERC）基因的表达变化和关系。方法：用重复序列扩增（TRAP）银染法和实时荧光定量RT-PCR法分别检测52例慢性再障患儿（CAA组）、13例急性再障患儿（SAA组）和21例骨髓造血正常儿童（对照组）端粒酶活性及hTERT和hTERC mRNA的表达。结果：CAA组、SAA组端粒酶活性和hTERT mRNA水平均高于对照组（P<0.01）,且CAA组端粒酶活性和hTERT mRNA水平较SAA组升高（P<0.05）;hTERC mRNA在各组间表达差异无统计学意义（P=0.812）;hTERTmRNA的表达水平与端粒酶活性呈正相关（r＝0.660,P＜0.01）。结论：端粒酶活性的表达变化与儿童再障发病及发展过程有关,hTERT表达在端粒酶活性调节过程中起重要作用。     

小鼠骨髓间充质干细胞对植物血凝素诱导小鼠脾细胞增殖后趋化因子受体表达的影响

目的：观察小鼠骨髓间充质干细胞（mesenchymal stem cells,MSCs）在体外对小鼠脾细胞表达趋化因子受体的影响。方法：用密度梯度离心法从小鼠骨髓中分离出小鼠骨髓间充质干细胞,经低糖DMEM培养基培养扩增。C57BL/6小鼠脾细胞以1×106/孔的密度接种于24孔板,加入植物血凝素(PHA),培养72 h。实验分3组：A组按10%比例加入MSC;B组按1%比例加入MSC;对照组不加MSC。3 d后收集悬浮的脾细胞进行流式细胞术检测小鼠脾细胞趋化因子受体CXCR3,CCR5,CCR7表达的变化。结果：CD3+CCR5+、CD3+CCR7+在A,B组及对照组中表达的差异均有统计学意义（均P<0.01）;以A组表达率最高,B组次之,对照组最低;CD3+CXCR3+细胞在A组中表达较B组、对照组高（P<0.05）,B组和对照组之间的表达差异无统计学意义。结论：骨髓间充质干细胞在一定浓度下对小鼠脾细胞增殖后趋化因子受体CXCR3,CCR5,CCR7表达有上调作用。［中国当代儿科杂志,2007,9（6）：571-573］     

儿童再生障碍性贫血免疫抑制剂治疗疗效及相关因素分析

目的：探讨免疫抑制疗法（IST）对儿童再生障碍性贫血（AA）的疗效及其影响疗效的相关因素。方法：对2003年2月至2009年11月住院接受IST治疗的、可进行疗效评估的110例AA患儿的临床资料进行回顾性分析。110例患儿中,重型AA（SAA）83例,非重型 AA（非SAA）27例。前者采用抗胸腺细胞球蛋白（ATG）联合环孢素（CSA）及泼尼松、雄激素四联治疗,后者采用CSA联合泼尼松、雄激素三联治疗。结果：SAA与非SAA组的总有效率分别为69.9%和70.4%。单因素分析显示病程、骨髓CD34+细胞比例、CD4+CD25+调节性T细胞比例与疾病严重程度相关,但与预后无关。治疗有效组患儿年龄、病程、骨髓CD3+、CD8+细胞比例显著低于治疗无效组（P<0.05）。多因素分析显示年龄＞10岁、骨髓CD8+细胞比例＞25%的患儿治疗失败的风险分别是对应组的3.36倍和3.59倍。结论：IST治疗儿童AA疗效确切。年龄、病程、CD3+、CD8+ T细胞水平与IST的疗效相关。     

再生障碍性贫血患儿骨髓内人巨细胞病毒活动性感染对造血功能的影响

目的探讨再生障碍性贫血(再障)患儿骨髓内人巨细胞病毒(HCMV)活动性感染与骨髓CD34 细胞/有核细胞的百分比之间的关系,了解骨髓HCMV活动性感染对再障患儿骨髓造血功能的影响。方法收集23例再障初诊患儿(再障组),5例非血液病患儿作为对照。所有患儿均于治疗前抽取骨髓液标本,一部分骨髓液采用Trizol法抽提骨髓液RNA,然后进行反转录聚合酶链反应,扩增后通过琼脂糖凝胶电泳检测患儿骨髓内是否存在HCMV活动性感染;将再障组和对照组患儿另一部分骨髓液进行多参数流式细胞术检测,分别检测二组患儿骨髓CD34 细胞/有核细胞百分比。结果23例再障患儿中9例患儿骨髓标本内可检测到HCMV RNA表达,阳性率为39.1%;5例对照组患儿骨髓标本内均未检测到HCMV RNA表达。流式细胞术检测显示再障患儿骨髓CD34 细胞/有核细胞为(0.27±0.21)%,明显低于对照组[(1.57±0.45)%](P<0.05)。骨髓HCMV RNA阳性再障患儿的CD34 细胞/有核细胞为(0.13±0.07)%,显著低于HCMV RNA阴性患儿[(0.36±0.22)%](P<0.05)。结论HCMV可感染再障患儿的骨髓组织,其活动性感染可导致骨髓CD34 细胞/有核细胞的百分比明显减少,提示骨髓内HCMV活动性感染对骨髓造血功能有抑制作用。     

Immunosuppressive therapy without hematopoietic growth factor exposure in pediatric acquired aplastic anemia

Immunosuppressive therapy (IST) is recommended for children with acquired aplastic anemia (AA) who lack a human leukocyte antigen (HLA)-matched sibling donor for hematopoietic cell transplantation (HCT). Hematopoietic growth factors have often been included in IST supportive care, but prolonged exposure may increase the risk of secondary clonal evolution. The authors evaluated response, survival, and the incidence of clonal evolution following cyclosporine-based IST without hematopoietic growth factor exposure in a population-based pediatric cohort, identified retrospectively. Forty-five patients with a median age of 7.3 years (range 1.2-17.0 years) were included. Partial (PR) and complete (CR) response was achieved in 82% and 64%, at a median of 55 days (range 11-414 days) and 7.6 months (range 2.8-82.2 months), respectively. Patients with associated seronegative hepatitis had an increased likelihood of PR and CR on multivariate analyses (PR: hazard ratio [HR] 3.15, 95% confidence interval [CI] 1.40, 7.11; CR: HR 2.99, 95% CI 1.35, 6.62), whereas older children were less likely to achieve IST response than children younger than 5 years at diagnosis. Five- and 10-year overall survival was 96% ± 4% and 90% ± 7%, respectively, and 5-year failure-free survival was 63% ± 8%. There was no infection-related mortality, although 16.4% of patients had at least 1 episode of documented bacteremia. The 5-year cumulative incidence of relapse was 12.9% and of clonal evolution was 3.2%. The authors conclude that children with AA who receive IST without hematopoietic growth factor support have excellent response and survival outcomes and a low incidence of clonal evolution.     

抗胸腺细胞球蛋白联合环孢菌素A治疗儿童再生障碍性贫血疗效及相关因素分析

目的探索采用抗胸腺细胞球蛋白(ATG)联合环孢菌素A(CSA)的免疫抑制疗法(IST)治疗儿童再生障碍性贫血(再障)的疗效及其相关影响因素,为进一步提高临床疗效提供参考依据。方法共40例再障患儿(重型再障28例,依赖成分输血的慢性再障12例)接受ATG联合CSA治疗。统计分析治疗前病程和外周血三系下降程度;ATG治疗后外周血淋巴细胞绝对计数(ALC)下降程度、血清病发生率及不同制剂ATG治疗等临床因素与远期疗效的相关性。结果中位随访时间19(9～44)个月,总有效率和显效率分别为78%和45%。疗效相关统计分析显示:(1)ATG治疗后2周内,ALC下降幅度≥2×109/L者的有效率明显高于下降幅度<2×109/L者,两组总有效率分别为89%和54%(P<0.05)。(2)从确诊再障到接受ATG治疗,病程≤6个月者有效率明显高于病程>6个月者,两组总有效率分别为92%和53%(P<0.05)。(3)采用两种ATG制剂(美国Genzyme或德国Fresenius)各治疗18例和22例,两组疗效差异无显著性(P>0.05)。结论 ATG联合CSA的免疫抑制治疗是儿童再障的有效疗法,目前常用的两种ATG制剂,均能获得显著疗效。再障确诊后早期治疗有助于提高疗效。治疗期间密切观察ALC下降程度,对于ALC下降不明显者,是否需要适当增加ATG剂量,有待进一步研究论证。     

Outcome of children with aplastic anemia treated with immunosuppressive therapy

Background

Immunosuppressive therapy (IST) is the alternative treatment in children with aplastic anemia (AA) who do not have an HLA‐matched sibling. The aim of this study is to evaluate the outcome of children with AA treated with IST.

Methods

We retrospectively reviewed the hospital records of children with AA from 1984 to 2004, treated at our institution with antithymocyte globulin (ATG), cyclosporine (CS), and short course of prednisone.

Result

Forty‐two patients were treated with IST (24 boys, 18 girls); of whom 26% received G‐CSF. The median age at diagnosis was 8.5 years. Sixty‐nine, 19, and 12% were diagnosed with severe, very severe, and moderate AA, respectively. Twenty‐one percent had hepatitis‐associated AA. Median follow‐up time was 53.3 months. Sixty‐two percent had complete response; 19% had partial response. Two patients relapsed and received a second course of ATG; both had a partial response. The actuarial 5 years survival rate was 67.5%. Two patients developed myelodysplastic syndrome (MDS); both received long‐term G‐CSF and had partial response after two courses of IST. Fifteen percent of survivors had significant hypertension which persisted after CS was discontinued.

Conclusions

This study shows promising response in children with AA treated with IST; however, the outcome was inferior to our institutional results with hematopoietic stem cell transplantation from a sibling donor. Hypertension and MDS are late complications. Longer follow‐up, larger cohorts, and prospective studies are warranted to evaluate late complications and risk factors. Pediatr Blood Cancer 2008;50:52–57. © 2007 Wiley‐Liss, Inc.     

Immunosuppressive treatment of aplastic anemia in Chinese children with antithymocyte globulin and cyclosporine

Fifty-one children with aplastic anemia (AA) from 1993 to 2004 in the authors' institution were treated by 3 therapies: 11 patients in group 1 received the SSL-6 protocol; 16 patients in group 2 had CsA alone, where the dose of CsA began from 9-12 mg/kg in the initial 2 weeks and tapered off to 5 mg/kg later; 24 patients in group 3 were treated combining rabbit ATG (Pasteur, Merieux) 2.5 mg/kg for 5 days with CsA, which was the same dose as in group 2. The response was 27, 50, and 79%, respectively. The statistical analysis showed that the protocol of intensive immunosuppressive treatment (IST) was the most effective one and CsA was better than that of SSL-6. None of our patients developed clone diseases although the follow-up was as long as more than to 9 years. The data suggest that children with AA should receive IST as first-line therapy in developing countries.

Hematopoietic stem cell transplantation (HSCT) is effective treatment for patients with aplastic anemia (AA). However, HSCT is not widely used in China for economic reasons and lack of donors. Immunosuppressive therapy (IST) is now the mainstay treatment for AA. To evaluate the effect of immunosuppressive therapy, combining antithymocyte globulin (ATG) with cyclosporine (CsA), a retrospective study on 51 children with AA from January 1993 to December 2004 treated in the authors' department was performed.     

兔抗人胸腺细胞免疫球蛋白治疗儿童再生障碍性贫血所致的血清病单中心回顾性研究

目的探讨兔抗人胸腺细胞免疫球蛋白(ATG)治疗再生障碍性贫血(AA)患儿发生血清病的相关因素,总结临床经验,分析血清病是否影响AA预后。方法收集并分析首都医科大学附属北京儿童医院血液肿瘤中心2016年3月至2018年12月AA应用免疫抑制治疗(IST)后出现血清病患儿的临床数据,分析其发生时间、临床表现、治疗及预后。结果共收集AA患儿48例。中位年龄5岁5个月(2岁1个月~15岁6个月),男女比例1.4∶1.0;75.0%(36/48例)发生血清病,中位发病时间为IST第11天,72.2%(26/48例)发生在第7-14天;临床表现前3位为关节痛(63.9%,23例)、发热(52.7%,19例)、皮疹(52.7%、19例)等。血清病组与无血清病组IST前和血清病发生时的外周血白细胞、中性粒细胞绝对值、淋巴细胞绝对值计数差异均无统计学意义(均P>0.05)。IST结束后持续应用糖皮质激素预防血清病的患儿发病率(2/12例,16.6%)低于未应用者(34/36例,94.4%),差异有统计学意义(χ^2=29.037,P<0.001)。发生血清病后经糖皮质激素[甲泼尼龙2~4 mg/(kg·d)]治疗症状均好转。随访至IST治疗后6个月及6个月以上的患儿共37例,发生血清病者25例,19例达到治愈或明显进步标准,6例未愈;不发生血清病12例,10例达到治愈或明显进步标准,2例未愈。2组患儿预后差异无统计学意义(P>0.05)。结论AA患儿IST治疗易出现血清病,发病高峰期为IST第2周,以关节痛、发热、皮疹为主要临床表现,血清病发病情况与治疗前及发病时的白细胞、中性粒细胞、淋巴细胞绝对值无相关性;IST结束后继续应用糖皮质激素开展预防性治疗可降低其发生率,发生后再应用糖皮质激素也可有效控制病情;血清病发生与否不影响IST治疗AA的预后。     

Outcome of Pediatric Acquired Aplastic Anemia: A Developing World Experience

Introduction: Outcome data of children with acquired aplastic anemia (AA) are lacking from the developing world. Here, we describe the same from a centre in North India. Methods: Retrospective data regarding medical history, physical examination, complete blood count, bone marrow aspirate, and biopsy were retrieved for all children <18 years, with acquired AA admitted between January 2005 and June 2012. In addition, the outcome data after immunosuppressive therapy (IST) or bone marrow transplant (BMT) was obtained. Results: A total of 61 children were diagnosed with AA (Inherited-18 and acquired-43). Among 43 children with acquired AA, 3 had nonsevere and 40 had severe. One patient with nonsevere AA died of sepsis and 2 recovered spontaneously. Of the 40 remaining children with severe AA, 10 refused therapy and 3 died due to severe sepsis prior to any therapy. Five underwent upfront matched sibling donor BMT and one post-IST failure. Four year overall survival (OS) and event free survival (EFS) for children undergoing BMT was 100% and 80 ± 17.9, respectively. Out of 22 treated with IST, 20 were evaluable for response. Seventeen received one course and 3 received two course of IST. The overall response to IST was seen in 14/20 (70%). Only two achieved complete response while remaining 12 had partial response. The 4-year estimated OS and EFS for children treated with IST was 74.4 ± 12.1% and 65.6 ± 12.2. Conclusion: Outcomes for children with AA are encouraging in the developing world although barriers like sepsis and treatment abandonment remain. BMT offers faster and complete recovery.     

Low Expression of Basic Fibroblastic Growth Factor in Mesenchymal Stem Cells and Bone Marrow of Children with Aplastic Anemia

Background: Our previous experiments with gene chip suggested that basic fibroblastic growth factor (FGF2) levels were lower in mesenchymal stem cell (MSC) from aplastic anemia patients. The purpose of this study was to determine the expression of FGF2 in MSC and in bone marrow of children with aplastic anemia to better understand the role of low FGF2 expression in the pathogenesis of aplastic anemia. Procedure: MSCs from the bone marrow of aplastic anemia children and control group were cultured in vitro. Growth curves of primary and passage MSC were plotted. FGF2 gene expression in MSCs was detected using quantitative real-time polymerase chain reaction (RT-PCR). FGF2 protein expression in mononuclear cells and FGF2 protein level in extracellular fluid of bone marrow were also investigated. Result: Decreased growth of MSCs from aplastic anemia children was observed after passage 8 in serial subcultivation, and FGF2 gene expression was downregulated. Within the patients’ bone marrow, low FGF2 expression was validated both in mononuclear cells and in the extracellular fluid. Conclusion: Low FGF2 gene expression in MSCs and low FGF2 protein level in bone marrow of aplastic anemia may involve to pathogenesis of aplastic anemia.     

Diagnosis and treatment of children with aplastic anemia

BACKGROUND: Long-term survival rates among children diagnosed with severe aplastic anemia (SAA) are excellent due to the success of human leukocyte antigen (HLA)-identical related hematopoietic stem cell transplantation (HSCT), concurrent advances in immunosuppressive treatment (IST), and improved supportive care. The challenge in making treatment recommendations for children with SAA, therefore, is to balance the apparent chronicity and morbidity following IST, with the potential up-front toxicity and complications of HSCT. METHODS: This review provides an update on the diagnosis and a risk-based treatment algorithm for children with acquired SAA. Recent experience using alternative donor HSCT and efforts to extend HSCT eligibility through advances in donor matching, de-escalation of conditioning regimens, and potential marrow graft engineering are highlighted. We discuss IST response rates, risks of relapse, and complications including clonal evolution. CONCLUSIONS: While good treatment options exist for a majority of children diagnosed with SAA, novel non-transplantation treatments for unresponsive and relapsed patients without suitable transplant donors are needed. Further improvements in outcome will ultimately require a more complete understanding of the pathophysiology of aplastic anemia (AA).     

Complete response to tacrolimus in a child with severe aplastic anemia resistant to cyclosporin A

Aplastic anemia (AA) is a rare disorder in children, usually treated with immunosuppressive therapy (IST) including antithymocyte globulin (ATG) and cyclosporin A. There are no current widely used alternative therapies with comparable efficacy. We describe a child with severe aplastic anemia (SAA), who developed severe gingival hyperplasia secondary to cyclosporin A, unresponsive to intensive dental intervention. When IST was changed to tacrolimus there was a significant improvement in the gingival hyperplasia, but equally important, he achieved complete response of his AA within several months. The use of tacrolimus in children with AA may be a potential modality of treatment. Pediatr Blood Cancer 2009;52:525–527. © 2008 Wiley‐Liss, Inc.