The pathophysiology of pure red cell aplasia: implications for therapy

Abstract

To determine the utility of marrow culture in defining the natural history and therapeutic response of pure red cell aplasia we have studied 37 patients. Patients were evaluated at the University of Washington before specific therapies (n = 21) or at the time of treatment failure in = 16). Evaluation included a medical and drug exposure history, a physical examination, a chest x-ray or computed tomography to rule out thymoma, lymphocyte immunophenotype studies, anti-nuclear antibody and rheumatoid factor determinations, marrow cytogenetics, and marrow progenitor cell cultures. Retrospective Southern analyses to detect human parvovirus B19 was performed in the 27 patients for whom sera was stored. Clinical follow-up was obtained to document therapeutic responses. Normal burst forming unit-erythroid (BFU-E) growth (>30 bursts/10(5) marrow mononuclear cells [MMNC]) in culture proved an outstanding predictor of clinical response, as 27 of 29 individuals with normal frequencies of erythroid bursts in culture responded to immunomodulating therapies (sensitivity 96%, specificity 78%, predictive value 93%, P = .0001 with two-tailed chi square analysis). Overall, 28 patients responded to either immunomodulating therapies or drug withdrawal. Twenty-four patients obtained a normal hematocrit (complete response [CR] and 4 additional patients became transfusion independent (partial response). Although responding patients often required several therapies, 20 of 24 (83%) patients who obtained a CR have sustained a normal hematocrit without maintenance therapy at the time of last follow-up (median 5 years). In contrast, of 8 patients with poor in vitro BFU-E growth (<6 bursts/10(5) MMNC), 7 failed to respond to any therapy and all died (median survival time 17 months). Our data suggest that in individuals, from whom BFU-E mature appropriately in culture, immunosuppressive drugs should be used sequentially until a CR is obtained and a durable remission is the expected outcome.

Successful treatment with cyclosporin A for myelodysplastic syndrome with erythroid hypoplasia associated with T‐cell receptor gene rearrangements

“…Immunosuppressive treatments, including cyclosporin A (CsA), are successfully used in PRCA (Charles et al, 1996). Several well-documented reports of successful immunosuppressive treatments after failure of other kinds of therapies in certain forms of MDS have been published (Biesma et al, 1997;Jonasova et al, 1998).…”

Simultaneous occurrence of pure red cell aplasia and papular‐purpuric ‘gloves and socks’ syndrome in parvovirus B‐19 infection

“…5 Parvovirus B-19 infection produces characteristic absence of maturing erythroid precursors and the presence of giant pronormoblasts, with eosinophilic nuclear inclusion bodies in marrow smears. 6 This morphological finding led us to consider parvovirus B-19 infection as the most likely cause of PRCA in our patient in the first place. The predominantly unconjugated hyperbilirubinaemia could be also attributed to the B-19-induced lytic destruction of the red cell precursors in the bone marrow.…”

Rituximab to treat chronic lymphoproliferative disorder‐associated pure red cell aplasia

“…PRCA is quite a rare disorder characterized by normochromic, normocytic anemia, reticulocytopenia, almost complete absence of red-cell precursors in the bone marrow with essentially normal myeloid and megakaryocytic maturation (1,2). A large body of evidence suggests that autoimmune mechanisms underlie in most PRCA cases (8)(9)(10)(11). Serum of some patients with PRCA have been shown to have antibodies inhibiting erythropoietin (12)(13)(14).…”