Incidence of acquired pure red cell aplasia: a nationwide epidemiologic analysis with 2 registry databases in Japan

Abstract

Acquired pure red cell aplasia (PRCA) is a rare syndrome characterized by anemia with reticulocytopenia and a marked reduction in erythroid precursors. Given its rarity, the true incidence is largely unknown, and epidemiological data representing the general population, with a description of the full spectrum of etiologies, are scarce. An epidemiological study on PRCA in Japan conducted 30 years ago estimated the annual incidence as 0.3 per million. To update the data and investigate the incidence and demographics of PRCA, we conducted a nationwide epidemiological study using the Japanese Society of Hematology (JSH) Hematologic Disease Registry, a hematologic disease registration database managed by the JSH and the Diagnosis Procedure Combination (DPC) study data available at a website of the Ministry of Health, Labor, and Welfare (MHLW) of Japan. A total of 1055 patients with newly diagnosed acquired PRCA were identified between 2012 and 2019, and the average annual incidence was calculated at 1.06 (95% confidence interval [CI], 0.83-1.28) per million. The median age was 73 (range, 18-99) years. The female-to-male ratio was 1.5:1, and the female predominance was most prominent in the child-bearing age group. Sixty-nine percent of acquired PRCA was idiopathic. The incidence of PRCA was approximately 20% of that of aplastic anemia (AA) during the same period. Approximately 0.98 patients per million per year (95% CI, 0.89-1.07) required hospitalization for the treatment of PRCA. These results are expected to contribute to the discussion of resource allocation for PRCA in the aging population in many countries, including Japan.

Graphical abstract

Figure 1.

Age and etiological distributions of acquired PRCA in the Ptosh cohort. A total of 1055 patients with PRCA were identified in Ptosh. (A) A violin plot showing the age distribution of the patients. A total of 76% of them were >60 years old. (B) Distributions of the age of the patients with PRCA were depicted by sex, and we did not find a significant difference in age distributions (P = .3). (C) The pie chart shows an etiological distribution of PRCA in the present study. Among the 1055 patients with acquired PRCA, 69.0% had idiopathic PRCA. Other underlying causes included thymoma (9.4%), LGLL (2.5%), CLL (0.6%), and others (14.3%). (D) Age distributions in the 3 major subtypes of acquired PRCA were depicted in a violin plot, and a statistical difference was recognized between idiopathic and thymoma-associated PRCA, with median ages of 75 (range, 20-99) years old and 67 (range, 33-90) years old, respectively (P = .0006). A bimodal age distribution was observed in those with LGLL-associated PRCA. (E) The age distributions were not different between genders in respective subtypes of PRCA. The bimodal distribution in those with LGLL-associated PRCA was preserved in each gender group.

Figure 2.

Female predominance of PRCA in different age groups. Green and red bars represent the number of female and male patients, respectively. The number on the top of the green bar indicates the female-to-male ratio of the patients in each age group. The ratio was the highest in those <40 years old or in a child-bearing age group. The decreasing trend in the female-to-male ratio along with their increased age was statistically significant (P = .0485 with Cochran-Armitage test).

Figure 3.

The OS of PRCA in the Ptosh database. (A) A Kaplan-Meier curve of the OS of 153 patients with PRCA in the Ptosh registration was depicted. The OS was defined as the period from the date of the diagnosis to the date of the outcome. The median period of observation was 400 days, and the presumed OS rate at 1 year was 87.6% (95% CI, 80.5-92.2%). (B) The OS curves for idiopathic and thymoma-associated PRCA were juxtaposed, while PRCA with “other” etiologies conferred an inferior survival (P = .0019). The estimated 1-year OS rates were 91.4% (95% CI, 83.4-95.6%), 92.9% (95% CI, 59.1-99.0%), and 63.1% (95% CI, 35.8-81.3%) for idiopathic, thymoma, and others, respectively.

Figure 4.

Geographical distribution of PRCA occurrence in Japan. The prefectural disparities in (A) the number of patients with PRCA registered in Ptosh and (B) the numbers of JSH hematologists. Although a regional PRCA incidence varies between 1.04 and 21.6 per million, it was not correlated with a hematologist density (Pearson’s product-moment correlations 0.0462; 95% CI, −0.244 to 0.329; P = .0758).