Ducassou Stéphane, Leverger Guy, Fernandes Helder, Chambost Hervé, Bertrand Yves, Armari-Alla Corinne, Nelken Brigitte, Monpoux Fabrice, Guitton Corinne, Leblanc Thierry, Fisher Alain, Lejars Odile, Jeziorski Eric, Fouissac Fanny, Lutz Patrick, Pasquet Marlène, Pellier Isabelle, Piguet Christophe, Vic Philippe, Bayart Sophie, Marie-Cardine Aude, Michel Marc, Perel Yves, Aladjidi Nathalie
Paediatric Oncology Haematology Unit/CEREVANCE/CIC 1401, Inserm CICP, University Hospital of Bordeaux, Paediatric Hospital, Bordeaux, France.
Paediatric Onco-Haematology Unit, Hôpital Trousseau, APHP, Paris, France.
Br J Haematol. 2017 Jun;177(5):751-758. doi: 10.1111/bjh.14627. Epub 2017 Apr 26.
Childhood autoimmune haemolytic anaemia (AIHA) requires second-line immunosuppressive therapy in 30-50% of cases. It appears that rituximab is indicated in such circumstances. This prospective national study reports the practice, efficacy and tolerance of rituximab in children with isolated AIHA and AIHA in the setting of Evans syndrome (ES). Sixty-one children were given rituximab between 2000 and 2014. The median interval from diagnosis to rituximab was 9·9 [interquartile range (IQR) 1·6-28·5] months. Forty-six patients responded (75%) and the 6-year relapse-free survival (RFS) was 48%. Twenty patients relapsed at a median interval of 10·8 (IQR 3·9-18·7) months, rituximab allowed steroid withdrawal in 44/61 (72%) of children. In isolated AIHA, complete response and 6-year RFS were significantly higher than in ES (P < 0·05). Ten out of 61 patients were infants, seven of who responded with a 6-year RFS of 71%. Among patients without immunoglobulin substitution before rituximab, 4 are still receiving substitutions. Five patients died, including one potentially attributable to rituximab. This large observational series of childhood AIHA established the rituximab benefit-risk ratio, allowing steroid withdrawal, with 37% of long-term responders, mainly in isolated AIHA. All subgroups of patients drew benefit. Our long-term results indicate the baseline to be challenged by new treatment approaches.
30%-50%的儿童自身免疫性溶血性贫血（AIHA）病例需要二线免疫抑制治疗。在这种情况下，利妥昔单抗似乎是适用的。这项前瞻性全国性研究报告了利妥昔单抗在患有孤立性AIHA和Evans综合征（ES）背景下的AIHA儿童中的应用情况、疗效和耐受性。2000年至2014年间，61名儿童接受了利妥昔单抗治疗。从诊断到使用利妥昔单抗的中位间隔时间为9.9[四分位间距（IQR）1.6-28.5]个月。46例患者有反应（75%），6年无复发生存率（RFS）为48%。20例患者复发，中位间隔时间为10.8（IQR 3.9-18.7）个月，利妥昔单抗使44/61（72%）的儿童停用了类固醇。在孤立性AIHA中，完全缓解率和6年RFS显著高于ES（P<0.05）。61例患者中有10例为婴儿，其中7例有反应，6年RFS为71%。在使用利妥昔单抗前未进行免疫球蛋白替代治疗的患者中，有4例仍在接受替代治疗。5例患者死亡，其中1例可能归因于利妥昔单抗。这项关于儿童AIHA的大型观察性系列研究确定了利妥昔单抗的获益风险比，可使类固醇停用，37%的患者长期缓解，主要是在孤立性AIHA中。所有患者亚组均有获益。我们的长期结果表明，新的治疗方法将对基线情况提出挑战。
