de Planque M M, Bacigalupo A, Würsch A, Hows J M, Devergie A, Frickhofen N, Brand A, Nissen C
Department of Immunohaematology and Blood Bank, University Hospital, Leiden, The Netherlands.
Br J Haematol. 1989 Sep;73(1):121-6. doi: 10.1111/j.1365-2141.1989.tb00230.x.
468 severe aplastic anaemia (SAA) patients registered in the EBMT-SAA registry who did not undergo bone marrow transplantation and were treated with immunosuppressive therapy (IS; 96% of patients received ATG) were evaluated. Their median age was 23 years (range 1-73) at initial IS therapy, 59% were males; in 69% the aetiology of SAA was idiopathic. Of these 468 patients, 245 had a follow-up of less than 2 years after IS 166/245 died, 71/245 are still alive, 8/245 are lost to follow-up. Of 223 patients who survived greater than or equal to 2 years (LTS long-term survivors), 191 are alive, 21 died greater than 2 years and 11 are lost. Median follow-up of 223 LTS was 4.1 years (range 2.0-10.9). Comparison of 166 patients who died less than 2 years and 223 LTS revealed no difference at time of initial IS therapy as regards sex, duration of AA, or its aetiology, but the age distribution and, in particular, severity of SAA differed significantly: more LTS were between 21 and 40 years old (44% v. 32%, P less than 0.02), less LTS had reticulocytes less than 20 x 10(9)/l (63% v. 80%, P less than 0.001), polymorphonuclear granulocytes (PMN) less than 0.2 x 10(9)/l (30% v. 57%, P less than 0.001), haemorrhages (58% v. 79%, P less than 0.002) and infection (30% v. 49%, P less than 0.005) at time of IS. A gradual improvement of blood counts was seen in patients alive greater than or equal to 2 years after IS. At 2 years after IS 80% had a normal haemoglobin and PMN greater than 0.5 x 10(9)/l, but only after 5 years 80% of cases had platelets greater than 50 x 10(9)/l. Development of clonal disease was reported of 31 LTS: 19 developed paroxysmal nocturnal haemoglobinuria (PNH), one acute leukaemia, 11 myelodysplastic syndromes and of these 11 five subsequently acute leukaemia. The majority of these patients (23/31) are still alive. Actuarial mortality of LTS is 22% at 8 years, but so far no plateau was achieved. It is concluded that SAA patients who become LTS following IS, show an improvement in haematological status but are probably not cured and are prone to develop clonal (malignant) disease.
对欧洲血液和骨髓移植协会严重再生障碍性贫血（SAA）登记处登记的468例未接受骨髓移植且接受免疫抑制治疗（IS；96%的患者接受了抗胸腺细胞球蛋白）的严重再生障碍性贫血患者进行了评估。初始IS治疗时他们的中位年龄为23岁（范围1 - 73岁），59%为男性；69%的SAA病因是特发性的。在这468例患者中，245例在IS治疗后随访时间不足2年，其中166/245例死亡，71/245例仍存活，8/245例失访。在223例存活时间大于或等于2年的患者（长期存活者，LTS）中，191例存活，21例在2年后死亡，11例失访。223例LTS的中位随访时间为4.1年（范围2.0 - 10.9年）。对166例在2年内死亡的患者和223例LTS进行比较，发现在初始IS治疗时，性别、再生障碍性贫血病程或病因方面无差异，但年龄分布，特别是SAA的严重程度有显著差异：更多LTS年龄在21至40岁之间（44%对32%，P<0.02），更少LTS在IS治疗时网织红细胞低于20×10⁹/L（63%对80%，P<0.001）、多形核粒细胞（PMN）低于0.2×10⁹/L（30%对57%，P<0.001）、有出血（58%对79%，P<0.002）和感染（30%对49%，P<0.005）。在IS治疗后存活时间大于或等于2年的患者中可见血细胞计数逐渐改善。IS治疗2年后，80%的患者血红蛋白正常且PMN大于0.5×10⁹/L，但仅在5年后80%的病例血小板大于50×10⁹/L。报告了31例LTS发生克隆性疾病：19例发生阵发性夜间血红蛋白尿（PNH），1例发生急性白血病，11例发生骨髓增生异常综合征，其中11例中有5例随后发生急性白血病。这些患者中的大多数（23/31）仍存活。LTS的8年精算死亡率为22%，但目前尚未达到平台期。结论是，IS治疗后成为LTS的SAA患者，血液学状态有所改善，但可能未治愈，且易于发生克隆性（恶性）疾病。
