Pure Red Cell Aplasia and Chromosomal Abnormality in a Patient With Lung Adenocarcinoma Receiving Immune Checkpoint Inhibitors: A Case Report

Discussion

We reported a case with lung adenocarcinoma, presenting with pure red cell aplasia and chromosomal abnormality during treatment with an ICI-containing regimen. It was necessary to discriminate this diagnosis from myelosuppression because the patient had received combined therapy with cytotoxic agents plus pembrolizumab. Furthermore, myelodysplasia syndrome was suspected owing to the chromosomal abnormality and treatment history of chemotherapy and radiation. A marked improvement was observed after the initiation of prednisolone (1 mg/kg/day).

The association between pure red cell aplasia and chromosomal abnormality is complicated. Although a case with idiopathic pure red cell aplasia presenting chromosomal abnormality was reported, pure red cell aplasia can onset as a prodrome of myelodysplastic syndrome (2), and cases with myelodysplastic syndrome with pure red cell aplasia have been reported (3). Myelodysplastic syndrome with pure red cell aplasia has two distinct phenotypes. One shows increased blasts in the bone marrow, and anemia may be caused by a defect of maturation and proliferation of erythroid precursors, as a part of myelodysplasia syndrome. The other shows no blastic changes in the bone marrow, and an immunogenic mechanism is proposed because of the good response to immune suppressive therapy (3). In the present case, an immunogenic mechanism was likely associated with the onset of pure red cell aplasia, given the good response to steroid therapy, and we believe that ICI therapy induced the pathology of anemia. However, the possibility that chromosomal abnormality resulted from chemotherapy or radiation therapy cannot be excluded.

It has been reported that anemia of all grades and grades 3-4 were observed in 11% and 5.4% of patients treated with ICIs, respectively (4). Additionally, pure red cell aplasia was reported in 4 of the 118 patients who showed hematologic irAEs (5), which suggests that ICI-induced pure red cell aplasia is rare. However, pure red cell aplasia is considered an important adverse event of ICI therapy because it can result in severe anemia and affect the prognosis of patients.

Although steroids are commonly used for the treatment of patients showing hematologic irAEs, including hemolytic anemia, aplastic anemia, or thrombocytopenia, resistance to steroid therapy has been reported in 20% of the patients (5). Pure red cell aplasia induced by ICI therapy was reported in three patients with melanoma (5-7) and one patient with Hodgkin lymphoma (8). Among these four patients, three patients showed favorable responses to steroid therapy but one patient required additional intravenous immunoglobulin therapy because the anemia was not improved by steroid therapy. Furthermore, of the three patients showing an initial response to steroids, two patients required additional intravenous immunoglobulin therapy due to the recurrence of anemia. These previous reports suggest the efficacy of immunoglobulin therapy for pure red aplasia induced by ICI therapy.