Rao Aarati, Kelly Michael, Musselman Mark, Ramadas Jagadeesh, Wilson David, Grossman William, Shenoy Shalini
Washington University School of Medicine, St. Louis Children's Hospital, St. Louis, Missouri, USA.
Pediatr Blood Cancer. 2008 Apr;50(4):822-5. doi: 10.1002/pbc.21264.
Autoimmune hematologic cytopenias in children often require therapeutic intervention. We report a prospective pediatric multicenter trial of rituximab for refractory or steroid-dependent patients.
Four doses of rituximab (375 mg/m(2)/dose) were administered weekly. Patients without response after three doses were offered dose escalation to 750 mg/m(2)/dose/week x 3. Safety, efficacy, and immunologic tests were evaluated after therapy.
Twenty-nine of 30 children (2-18 years) with thrombocytopenia (21), hemolytic anemia (6), Evans syndrome (2), and neutropenia (1) received at least four doses of rituximab. One developed anaphylaxis with the first dose. One patient was subsequently diagnosed with monosomy 7 myelodysplasia. Of 28 remaining patients, 9 received dose escalation. Responders discontinued other therapy following rituximab. The overall response rate was 72% with median follow-up of 18 months. Complete remission was observed in 14 (50%); all received four doses of rituximab. Partial remission (PR) was observed in six (22%); five had received dose escalation. Of four relapses, 4-24 months after therapy, two were retreated with rituximab and achieved second remission. No major infections were encountered. Circulating B-cells were depleted by 1 month and normalized by 1 year. IgM, Ig A, and IgG levels decreased 6, 9, and 12 months after therapy, respectively, but remained near normal range. Tetanus toxoid antibody titers remained detectable.
Rituximab was well tolerated, and induced sustained remissions in children with refractory immune cytopenias. Dose escalation and re-treatment after relapse elicited additional responses. Rituximab therapy should be considered prior to potential interventions with higher toxicity.
儿童自身免疫性血细胞减少症常需进行治疗干预。我们报告了一项针对难治性或依赖类固醇患者的利妥昔单抗前瞻性儿科多中心试验。
每周给予四剂利妥昔单抗（375mg/m²/剂）。三剂后无反应的患者可将剂量增至750mg/m²/剂/周×3。治疗后评估安全性、疗效和免疫检测。
30名2至18岁的儿童患者中，29例患有血小板减少症（21例）、溶血性贫血（6例）、伊文氏综合征（2例）和中性粒细胞减少症（1例），接受了至少四剂利妥昔单抗治疗。1例在首剂时发生过敏反应。1例患者随后被诊断为7号染色体单体型骨髓发育异常。其余28例患者中，9例接受了剂量增加。有反应者在使用利妥昔单抗后停用了其他治疗。总体缓解率为72%，中位随访时间为18个月。14例（50%）观察到完全缓解；均接受了四剂利妥昔单抗。6例（22%）观察到部分缓解（PR）；5例接受了剂量增加。在治疗后4至24个月的4例复发中，2例再次使用利妥昔单抗治疗并获得第二次缓解。未发生重大感染。循环B细胞在1个月时减少，1年时恢复正常。治疗后6、9和12个月时，IgM、IgA和IgG水平分别下降，但仍接近正常范围。破伤风类毒素抗体滴度仍可检测到。
利妥昔单抗耐受性良好，可诱导难治性免疫性血细胞减少症患儿持续缓解。复发后增加剂量和再次治疗可引发额外反应。在考虑进行毒性更高的潜在干预之前，应考虑利妥昔单抗治疗。
