How I manage acquired pure red cell aplasia in adults

Abstract

Pure red cell aplasia (PRCA) is a rare hematological disorder with multiple etiologies. The multifaceted nature of this disease is emphasized by the variety of concomitant clinical features. Classic idiopathic presentation aside, prompt recognition of pathogenetic clues is important because of their diagnostic and therapeutic implications. As a consequence, treatment of PRCA is diverse and strictly dependent on the presented clinical scenario. Here, we propose a series of clinical vignettes that showcase instructive representative situations derived from our routine clinical practice. Using these illustrative clinical cases, we review the diagnostic workup needed for a precise diagnosis and the currently available therapeutic options, discussing their applications in regard to the various PRCA-associated conditions and individual patients' characteristics. Finally, we propose a treatment algorithm that may offer guidance for personalized therapeutic recommendations.

Graphical abstract

Figure 1.

Common PRCA-associated disorders. Idealized circle plot showing PRCA and associated diseases according to our internal cohort of patients with PRCA, LGL, thymoma, and Good syndrome, and bar graph demonstrating frequencies of associations in our internal cohort of patients with PRCA. PB19, parvovirus B19.

Figure 2.

Pathogenesis of PRCA. Various mechanisms may lead to PRCA. (1) Viral infections (eg, B19 parvovirus) and a variety of drugs may have a direct cytotoxic effect against erythroid precursors or also exert an indirect pathogenic effect via a molecular mimicry mechanism. The resulting cross-reactive TCR recognition may lead to a breach of tolerance with polyclonal CTL responses. (2) This latter phenomenon may also be triggered by alteration of immune tolerance because of the presence of thymoma (or thymic dysfunction) with subsequent LGL clonal expansion (in some cases carrying STAT3 mutations). (3) Lack of viral clearance from immunodeficiency (eg, hypoglobulinemia) may be the cause of elicitation of aberrant CTLs responses. Alternatively, in the context of immunodeficiency antibody responses or the inability of TCR recognition may lead to generation of autoreactive T cells with alterations of TCR repertoires evading immune-tolerance mechanisms. For instance, the presence of T-cell subsets with predominant expression of γδ⁺ TCR rearrangements lacking HLA class I restriction could explain the attack of erythroid progenitors, which physiologically present downregulation of HLA class I antigens. GS, Good syndrome; STAT3, signal transducer and activator of transcription 3.

Figure 3.

Treatment algorithm of acquired PRCA. Cs, corticosteroids; CY, cyclophosphamide; M, maintenance; MGUS, monoclonal gammopathy of undetermined significance; PB19, parvovirus B19.