How should I evaluate and treat a 45-year-old man with recurrent severe anemia (hemoglobin 3 g/dL), bone‑marrow‑confirmed pure red‑cell aplasia, negative parvovirus B19 PCR, and suspected lymphoma?

Management of Pure Red Cell Aplasia with Negative Parvovirus B19 PCR in a 45-Year-Old Man

Initiate cyclosporine A at 3–5 mg/kg/day divided twice daily (targeting trough levels of 100–200 ng/mL) as second-line immunosuppressive therapy, while simultaneously completing the diagnostic workup with immunohistochemistry on bone marrow slides to exclude lymphoproliferative disorders and obtaining chest CT to rule out thymoma. 1, 2

Complete the Diagnostic Evaluation Immediately

Your hematologist's plan to perform immunohistochemistry on bone marrow is correct and essential:

• Order flow cytometry on bone marrow and peripheral blood, plus serum protein electrophoresis with immunofixation to detect chronic lymphocytic leukemia or large granular lymphocyte leukemia, which are the most common lymphoproliferative causes of PRCA. 1

• Obtain chest CT immediately to identify thymoma, which is surgically curable and will not respond to immunosuppression alone; delaying this imaging is a critical pitfall. 1

• Review all medications systematically, focusing on azathioprine, mycophenolate mofetil, tacrolimus, erythropoiesis-stimulating agents, and ganciclovir, as drug-induced PRCA often resolves with simple discontinuation. 1, 2

• Measure serum erythropoietin levels if the patient has any history of chronic kidney disease or prior ESA exposure to detect anti-EPO antibodies; if present, permanently discontinue all ESAs as they are ineffective and harmful. 1, 2

• Verify the reticulocyte count is <1% and direct antiglobulin test (DAT) is negative to confirm PRCA and exclude autoimmune hemolytic anemia. 1

Immunosuppressive Treatment Algorithm

First-Line: High-Dose Corticosteroids

• Start prednisone 1 mg/kg/day (approximately 60–80 mg daily for a 45-year-old man) or dexamethasone 20 mg/day as initial therapy if no reversible cause is identified. 1

• Monitor weekly reticulocyte counts; an increase precedes hemoglobin rise by 1–2 weeks and signals treatment response. 1

Second-Line: Cyclosporine A (Current Plan)

• Add cyclosporine A at 3–5 mg/kg/day divided BID when steroids fail or as steroid-sparing therapy; this has demonstrated efficacy in refractory PRCA and is the appropriate next step your hematologist has chosen. 1, 2, 3

• Target trough levels of 100–200 ng/mL and check levels 5–7 days after initiation, then every 2 weeks until stable. 1

• Case series demonstrate cyclosporine can achieve remission even after steroid failure, though response may take 8–12 weeks. 3

Adjunctive Therapy: Rituximab

• Add rituximab 375 mg/m² weekly for 4 weeks if immunohistochemistry reveals any lymphoproliferative disorder or if steroids plus cyclosporine are insufficient; rituximab provides steroid-sparing effects. 1

Reserve IVIG for Specific Scenarios

• Consider intravenous immunoglobulin (IVIG) 1 g/kg daily for 1–2 days only if parvovirus infection remains clinically suspected despite negative PCR (immunocompromised patients can have intermittent viremia causing false negatives) or as adjunctive therapy in refractory cases. 1, 3

• Do not rely on a single negative parvovirus PCR to definitively exclude infection; immunohistochemical staining of bone marrow for parvovirus B19 can detect infection when serology and PCR are negative. 1, 4

Supportive Care During Treatment

• Transfuse packed red blood cells to maintain hemoglobin >7 g/dL; given his current hemoglobin of 3 g/dL, he requires immediate transfusion to prevent cardiovascular complications. 1, 2

• Use irradiated blood products to prevent transfusion-associated graft-versus-host disease in this immunosuppressed patient. 1, 2

• Monitor ferritin serially; initiate iron chelation when ferritin exceeds 1,000 ng/mL to prevent iron overload from chronic transfusions. 1

Monitoring Treatment Response

• Check reticulocyte counts weekly after starting cyclosporine; expect an increase within 2–4 weeks if therapy is effective, with hemoglobin normalization by 6–12 weeks in responders. 1

• If no hematologic response after 8–12 weeks of immunosuppression, repeat bone marrow examination to evaluate for evolving myelodysplastic syndrome or other marrow pathology. 1, 5

Management of Refractory Disease

• Consider splenectomy for PRCA refractory to medical therapy, though efficacy is lower than in immune thrombocytopenia. 1

• Explore clinical trial enrollment or experimental agents (alemtuzumab, eltrombopag) for patients unresponsive to standard immunosuppression. 1

Critical Pitfalls to Avoid

• Do not overlook thymoma; chest CT must be performed urgently as thymectomy is potentially curative and immunosuppression alone will fail. 1

• Do not continue or switch ESA products if anti-EPO antibody-mediated PRCA is confirmed; neutralizing antibodies cross-react with all erythropoietin molecules. 2

• Do not assume a single negative parvovirus PCR excludes infection in immunosuppressed patients; bone marrow immunohistochemistry can reveal persistent infection when serology is negative. 1, 4

• Do not delay medication review; drug-induced PRCA (especially from tacrolimus or mycophenolate in transplant recipients) can be curative with simple discontinuation. 1, 6