Excellent Outcome of Concomitant Intensive Immunosuppression and Eculizumab in Aplastic Anemia/Paroxysmal Nocturnal Hemoglobinuria Syndrome

A 21 year men was referred to our Institution in 2007 for mild cytopenia and laboratory signs of hemolysis (Figure 1); based on flow cytometry, the diagnosis of PNH in the context of moderate AA was made. The patient did not receive any etiologic treatment until March 2009, when he started eculizumab because of severe anemia due to overt symptomatic hemolysis. The patient had no benefit from anticomplement treatment, with increasing transfusional need; after 3 months, the diagnosis of severe AA was documented. In absence of a suitable donor, Immunosuppressive Treatment (IST) was chosen as etiologic treatment [6]; the patients was enrolled in the trial NCT00895739 [7], which investigated the anti-CD52 alemtuzumab and cyclosporine A (CyA) as an alternative IST for AA. Given the persistent major PNH population, we decided to not discontinue eculizumab to minimize the risk of massive intravascular hemolysis and possible thrombotic complications. Alemtuzumab was administered subcutaneously (3-10-30-30 mg in 4 consecutive days), without relevant side effect. Irrespective of eculizumab, immediate and profound lymphocytopenia (absolute lymphocyte count <50/μL) was observed, as in patients not receiving alemtuzumab [7]. The IST resulted in a substantial increase of neutrophil, reticulocyte and platelet counts, with the best hematological response achieved at 4 months from treatment. Unfortunately, in the following months, irrespective of chronic CyA maintenance, blood counts felt down, thus the relapse of SAA prompted us to consider a second-line treatment. Given that the best unrelated donor was 5/6 HLA matched, we opted for a second course of IST using the rabbit Anti-Thymocyte Globuline (r-ATG) associated with CyA. The treatment was completed as scheduled (3.75 mg/kg for 5 days) without any side effect, and again lymphocyte depletion was observed irrespective of continuous eculizumab treatment. After this second IST the patient experienced progressive improvement of his blood counts, finally resulting in complete response (Figure 1). Notably, reappearance of intravascular hemolysis required transient increase of eculizumab dosage; with the progressive reduction of the PNH population, eculizumab was tapered to the standard dosage. The patient now shows normal blood counts, in absence of maintenance CyA treatment and without any sign or symptom of hemolysis.