The incidence and prevalence of patients with paroxysmal nocturnal haemoglobinuria and aplastic anaemia PNH syndrome: A retrospective analysis of the UK's population-based haematological malignancy research network 2004-2018.

OBJECTIVES: A retrospective population-based study to determine the incidence and prevalence of patients with the rare blood disease paroxysmal nocturnal haemoglobinuria (PNH). METHODS: All patients were identified by flow cytometric detection of blood cells deficient in glycosylphosphatidylinositol (GPI) linked proteins at a single diagnostic reference laboratory that serves the Yorkshire based, Haematological Malignancy Research Network (HMRN) with a population of 3.8 million. RESULTS: One hundred and ninety-seven patients with detectable PNH clones at a level of >0.01% in at least two lineages of cells (neutrophils, monocytes and/or red cells) were identified over a 15-year period (2004-2018). Of these, 88% had aplastic anaemia (AA), 8% classical PNH and 3% myelodysplastic syndrome. The overall incidence rate was estimated at 0.35 cases per 100 000 people per year. This equates to 220 cases newly diagnosed in the United Kingdom each year. The overall prevalence rate was 3.81 per 100 000, this equates to an estimated 2400 prevalent cases in the UK. The overall and relative 5-year survival rates were 72% and 82.7%, respectively. CONCLUSIONS: This study showed that classical haemolytic PNH is a rare disease and represents only a small proportion overall of patients with detectable PNH cells, the majority of which have aplastic anaemia.

Incidence and outcome of acquired aplastic anemia: real-world data from patients diagnosed in Sweden from 2000-2011.

A plastic anemia is a rare life-threatening disease. However, since the introduction of immunosuppressive therapy and allogeneic stem cell transplantation, the outcome has improved considerably, and the 5-year survival is reported to be 70-80% in selected patient cohorts. Yet, contemporary population-based data on incidence and survival are lacking. We performed a national retrospective study to determine the incidence, treatment, and survival of patients with aplastic anemia diagnosed in Sweden from 2000-2011. Patients were included via the National Patient Registry, and diagnosed according to the Camitta criteria. In total, 257 confirmed cases were identified, with an overall incidence of 2.35 (95% CI: 2.06-2.64) cases per million inhabitants per year. Median age was 60 years (range: 2-92), and median follow up was 76 (0-193) months. Primary treatments included immunosuppressive therapy (63%), allogenic stem cell transplantation (10%), or single-agent cyclosporine/no specific therapy (27%). The 5-year survival was 90.7% in patients aged 0-18 years, 90.5% in patients aged 19-39 years, 70.7% in patients aged 40-59 years, and 38.1% in patients aged ≥60 years. Multivariate analysis showed that age (both 40-59 and ≥60 age groups), very severe aplastic anemia and single-agent cyclosporine/no specific therapy were independent risk factors for inferior survival. In conclusion, younger aplastic anemia patients experience a very good long-term survival, while that of patients ≥60 years in particular remains poor. Apparently, the challenge today is to improve the management of older aplastic anemia patients, and prospective studies to address this medical need are warranted.

Revisiting the death of Eleanor Roosevelt: was the diagnosis of tuberculosis missed?

Controversy has surrounded the death of Eleanor Roosevelt in 1962. There has been a persistent sense that doctors missed the diagnosis of miliary tuberculosis, thereby jeopardizing her life. This article, using Roosevelt's medical chart and other previously unreviewed documents, revisits her illness and death. What disease actually killed Eleanor Roosevelt? Did her physicians miss the diagnosis? These questions are of particular importance in light of the recent Institute of Medicine report estimating that almost 100,000 Americans die each year from medical mistakes. Why has the possibility of error clouded the care of Roosevelt for almost 40 years? What can Roosevelt's case reveal about ongoing efforts to reduce mistakes in clinical practice?

Aplastic anemia before bone marrow transplantation and antilymphocyte globulin.

In severe aplastic anemia, disease-dependent mortality was high before allogeneic bone marrow transplantation (BMT) and immunosuppressive therapies (IST) including antilymphocyte globulin became available. However, under supportive therapy alone, spontaneous remissions were observed in up to 20% of severe cases, reflecting the natural course of the disease. Therefore, in evaluating new forms of treatment, one has to keep in mind that remission is not necessarily response, and that final proof of utility of any new therapy still requires a randomized study design. Transition to leukemia or myelodysplasia was rarely observed if the initial diagnosis was accurate. The much higher incidence of leukemias in patients treated by IST, but not by BMT is probably due to the better life expectancy of patients at risk, rather than to a leukemogenic potential of IST itself. 'Outdated' therapeutic modalities, such as androgens or splenectomy, may still be justified as an adjuvant therapy in selected cases.