Paroxysmal nocturnal haemoglobinuria: long-term follow-up and prognostic factors

Background Paroxysmal nocturnal haemoglobinuria (PNH) is a rare acquired disorder of haematopoietic stem cells. Although knowledge about the pathophysiology of the disease is increasing, no multivariate analysis of factors influencing survival has been undertaken, mainly because the disease is rare. We undertook such an investigation. Methods Data were collected on 220 patients with PNH diagnosed over a 46-year period (1950–1995) from participating French centres. Diagnosis of the disease required, at least, an unequivocally positive Hamʹs test. Findings The Kaplan-Meier survival estimate was 65% (SE 4) at 10 years and 48% (6) at 15 years after diagnosis. 8-year cumulative incidence rates of the main complications (pancytopenia, thrombosis, and myelodysplastic syndrome) were 15% (3), 28% (4), and 5% (2), respectively. Demographic data, presenting features, initial treatment, complications, and causes of death were similar to those previously reported. In multivariate analysis, seven factors were significantly associated with survival in patients with PNH. Poor survival was associated with the occurrence of thrombosis as a complication (relative risk 10·2 [95% CI 6-17], p<0·0001), evolution to pancytopenia (5·5 [2·8-11], p<0·0001), myelodysplastic syndrome or acute leukaemia (19·1 [7·3-50], p<0·001), age over 55 years at diagnosis (4 [2·4-6·9], p<0·0001), need for additional treatment (2·1 [1·3-3·6], p<0·003), and thrombocytopenia at diagnosis (2·2 [1·3-3·8, p<0·003). Better survival was shown for patients in whom aplastic anaemia antedated PNH (0·32 [0·14-0·72], p<0·02). Factors associated in multivariate analysis with a high risk of thrombosis during the disease course were thrombosis at diagnosis (5·1 [2·5-10·6], p=0·0002), age over 54 years (2·6 [1·5-4·6, p=0·0014), and infection at diagnosis (2·6 [1·3-5·2], p=0·0099). The risk factors for progression to pancytopenia were absence at diagnosis of anaemia (4·03 [1·3-12·2], p=0·03) and neutropenia (2·45 [1·1-5·7], p=0·03). The risk factors for development of myelodysplastic syndrome or acute leukaemia were abdominal pain crisis at presentation (10·5 [2·5-44·0], p=0·004) and year of diagnosis after 1983 (8·45 [1·8-40·7], p=0·004). Interpretation This large number of cases permitted a detailed analysis of prognostic factors for the first time, in this rare disease. Estimates of PNH prognostic factors may serve as baseline data in the assessment of current and future treatments for this disease.