de Latour Régis Peffault, Mary Jean Yves, Salanoubat Célia, Terriou Louis, Etienne Gabriel, Mohty Mohamad, Roth Sophie, de Guibert Sophie, Maury Sebastien, Cahn Jean Yves, Socié Gerard
Service d'Hématologie-Greffe, Université Paris 7, France.
Blood. 2008 Oct 15;112(8):3099-106. doi: 10.1182/blood-2008-01-133918. Epub 2008 Jun 5.
The natural history of paroxysmal nocturnal hemoglobinuria (PNH) clinical subcategories (classic PNH and aplastic anemia [AA]/PNH syndrome) is still unknown. We retrospectively studied 460 PNH patients diagnosed in 58 French hematologic centers from 1950 to 2005. The median (SE) follow-up time was 6.8 (0.5) years. The median survival time (SE) was 22 (2.5) years. We identified 113 patients with classic PNH, 224 patients with AA-PNH syndrome, and 93 (22%) intermediate patients who did not fit within these 2 categories. At presentation, classic PNH patients were older, with more frequent abdominal pain and displayed higher levels of GPI-AP-deficient granulocytes. A time-dependent improved survival was observed. In classic PNH, diagnoses before 1986 (hazard ratio [HR]: 3.6; P = .01) and increasing age (P < .001) were associated with worse survival prognoses, whereas use of androgens within the first year after diagnosis was protective (HR, 0.17; P = .01). Transfusions before 1996 (HR, 2.7; P = .007) led to lower survival rates in patients with AA-PNH syndrome, whereas immunosuppressive treatment was associated with better outcomes (HR, 0.33; P = .03). Evolution to thrombosis affected survival in both subcategories (classic PNH: HR, 7.8 [P < .001]; AA-PNH syndrome: HR, 33.0 [P < .001]). Evolution to bicytopenia or pancytopenia for classic PNH (HR, 7.3, P < .001) and malignancies for AA-PNH syndrome (HR, 48.8; P < .001) were associated with worse outcomes. Although clinical presentation and prognosis factors are different, classic PNH and AA-PNH syndrome present roughly similar outcomes, affected mainly by complications.
阵发性睡眠性血红蛋白尿（PNH）临床亚类（典型PNH和再生障碍性贫血[AA]/PNH综合征）的自然病程仍不清楚。我们回顾性研究了1950年至2005年在法国58家血液学中心诊断的460例PNH患者。中位（SE）随访时间为6.8（0.5）年。中位生存时间（SE）为22（2.5）年。我们确定了113例典型PNH患者、224例AA-PNH综合征患者以及93例（22%）不符合这两类的中间型患者。初诊时，典型PNH患者年龄较大，腹痛更频繁，且GPI-AP缺陷粒细胞水平更高。观察到生存情况随时间改善。在典型PNH中，1986年前诊断（风险比[HR]：3.6；P = 0.01）和年龄增加（P < 0.001）与较差的生存预后相关，而诊断后第一年内使用雄激素具有保护作用（HR，0.17；P = 0.01）。1996年前输血（HR，2.7；P = 0.007）导致AA-PNH综合征患者生存率降低，而免疫抑制治疗与更好的预后相关（HR，0.33；P = 0.03）。发展为血栓形成影响了这两个亚类的生存（典型PNH：HR，7.8[P < 0.001]；AA-PNH综合征：HR，33.0[P < 0.001]）。典型PNH发展为双系血细胞减少或全血细胞减少（HR，7.3，P < 0.001）以及AA-PNH综合征发展为恶性肿瘤（HR，48.8；P < 0.001）与较差的结局相关。尽管临床表现和预后因素不同，但典型PNH和AA-PNH综合征的结局大致相似，主要受并发症影响。
