Führer M, Burdach S, Ebell W, Gadner H, Haas R, Harbott J, Janka-Schaub G, Klingebiel T, Kremens B, Niemeyer C, Rampf U, Reiter A, Ritter J, Schulz A, Walther U, Zeidler C, Bender-Götze C
Kinderpoliklinik der LMU München.
Klin Padiatr. 1998 Jul-Aug;210(4):173-9. doi: 10.1055/s-2008-1043875.
Since the introduction of combined immunosuppressive therapy (IST) into management of aplastic anemia (AA) in childhood response and probability of survival improved. In contrast to bone marrow transplantation (BMT), however, patients after IST are not considered cured as high rates of relapse and development of clonal disease demonstrate. From 11/93 to 9/97 114 children (65 m, 49 f; median age 9.5 y.) from 37 centers in Germany and Austria were registered in the SAA 94 study. 86 patients lacking a matched sibling donor received IST. Most of the patients suffered from very severe (VSAA: PMN < 200/microliter) or severe AA (SAA: PMN < 500/microliter). All patients were treated with combined IST consisting of ALG and Cyclosporin A (CSA). VSAA and SAA patients were additionally treated with G-CSF. Therapy response was evaluated at day 112, after 6, 12 and 18 months. 8/86 patients died, the probability of survival being 87% after 4 years. At d 112 61% of evaluable patients became independent of transfusions (IST response: CR + PR), 13% with normal blood counts (CR). After 6 months 33% showed CR. At 12 and 18 months response improved to 74% resp. 80%, 39% resp. 55% CR. The best response was achieved in the subgroup of VSAA with 90% (PR + CR) and 65% CR after 18 months. 4 patients developed AML 3-19 months after the beginning of IST. In 2/4 pts. an aberrant clone (-7; 5q-) could be detected retrospectively in BM at diagnosis of AA. 3 nonresponders developed chromosomal aberrations (+19; -7, +12; +8) after 4, 12 and 16 months without morphological signs of AML or MDS. Overall 11 relapses occurred at a median time of 12 months (range 5-27 months) after the beginning of IST. 2 of them relapsed under CSA therapy, 2 under tapering of CSA and 7 after cessation of CSA. 7 patients responded again to CSA monotherapy. Overall response rate is 77% with a probability of event free survival (EFS) of 54% after 4 years regarding all complications mentioned as events.
自从联合免疫抑制疗法（IST）被引入儿童再生障碍性贫血（AA）的治疗后，缓解率和生存率都有所提高。然而，与骨髓移植（BMT）不同的是，接受IST治疗的患者不被认为已治愈，因为复发率高和克隆性疾病的发生表明了这一点。从1993年11月到1997年9月，来自德国和奥地利3x7个中心的114名儿童（65名男性，49名女性；中位年龄9.5岁）被纳入SAA 94研究。86名缺乏匹配同胞供体的患者接受了IST治疗。大多数患者患有极重型（VSAA：中性粒细胞<200/微升）或重型AA（SAA：中性粒细胞<500/微升）。所有患者均接受由抗淋巴细胞球蛋白（ALG）和环孢素A（CSA）组成的联合IST治疗。VSAA和SAA患者还接受了粒细胞集落刺激因子（G-CSF）治疗。在第112天、6个月、12个月和18个月时评估治疗反应。8/86名患者死亡，4年后生存率为87%。在第112天，61%可评估的患者不再依赖输血（IST反应：完全缓解+部分缓解），13%血常规正常（完全缓解）。6个月后，33%显示完全缓解。在12个月和18个月时，缓解率分别提高到74%和80%，完全缓解率分别为39%和55%。在VSAA亚组中，18个月后获得了最佳反应，完全缓解率为90%（部分缓解+完全缓解），完全缓解率为65%。4名患者在IST开始后3-19个月发生急性髓系白血病（AML）。在4例患者中的2例中，在AA诊断时可回顾性地在骨髓中检测到异常克隆（-7；5q-）。3名无反应者在4、12和16个月后出现染色体异常（+19；-7，+12；+8），无AML或骨髓增生异常综合征（MDS）的形态学迹象。总体而言，在IST开始后的中位时间12个月（范围5-27个月）发生了11次复发。其中2例在CSA治疗期间复发，2例在CSA减量期间复发，7例在CSA停药后复发。7名患者对CSA单一疗法再次有反应。关于所有提及为事件的并发症，总体反应率为77%，4年后无事件生存率（EFS）为54%。
