Atezolizumab‐induced pure red cell aplasia

A 45-year-old woman underwent a bone marrow biopsy for evaluation of persistent, severe transfusion-dependent normocytic anaemia, beginning approximately two months following initiation of olaparib and atezolizumab therapy for a metastatic BRCA1-mutated breast carcinoma. The anaemia had not improved despite discontinuation of olaparib for three months. The blood count on the day of the biopsy showed: haemoglobin concentration 82 g/l (post-transfusion), mean cell volume (MCV) 85 fl, neutrophils 1.53 × 109/l, platelets 167 × 109/l and reticulocytes 2 × 109/l (0.1%). A bone marrow aspirate and trephine biopsy specimen were normocellular, but exhibited a very striking reduction of erythropoiesis (top images). Proerythroblasts comprised 0.4% of all nucleated cells. There was no significant dysplasia. Trephine biopsy sections stained for glycophorin A (bottom right) confirmed the virtual absence of erythropoietic activity. CD3 staining (bottom left) demonstrated an increased number of T lymphocytes, interstitially and in small aggregates. Serology for human immunodeficiency virus (HIV) 1 and 2 and serology and polymerase chain reaction (PCR) for parvovirus B19 were negative. Serum vitamin B12 (659 pmol/l) and folate (>45 nmol/l) were normal. Cytogenetic analysis showed a normal karyotype. Flow cytometry on the marrow aspirate demonstrated 85% T cells with no loss of pan-T markers and an equal number of CD4+ and CD8+ cells, but 7% of all lymphocytes were double negative (CD4−/CD8−) T cells of α/β type.