alexa Excellent Outcome of Concomitant Intensive Immunosuppression and Eculizumab in Aplastic Anemia/Paroxysmal Nocturnal Hemoglobinuria Syndrome | OMICS International
ISSN: 2329-8790
Journal of Hematology & Thromboembolic Diseases
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Excellent Outcome of Concomitant Intensive Immunosuppression and Eculizumab in Aplastic Anemia/Paroxysmal Nocturnal Hemoglobinuria Syndrome

Serena Marotta,Serena Marotta,Giovanna Giagnuolo,Santina Basile,Simona Pagliuca,Francesco Grimaldi,Fabrizio Pane,Antonio Maria Risitano*
Department of Clinical Medicine and Surgery, Federico II University of Naples, Via Pansini 5, 80131 Naples, Italy
Corresponding Author : Antonio Maria Risitano
Hematology, Department of Clinical Medicine and Surgery
Federico II University of Naples
Via Pansini 5, 80131 Naples, Italy
Tel: +39 081 746 2111-2037
Fax: +39 081 746 4728
E-mail: [email protected]
Received January 05, 2014; Accepted January 20, 2014; Published January 22, 2014
Citation: Marotta S, Giagnuolo G, Basile S, Pagliuca S, Grimaldi F, et al. (2014) Excellent Outcome of Concomitant Intensive Immunosuppression and Eculizumab in Aplastic Anemia/Paroxysmal Nocturnal Hemoglobinuria Syndrome. J Hematol Thromb Dis 2:128. doi: 10.4172/2329-8790.1000128
Copyright: © 2014 Marotta S, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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Dear Editor:
Paroxysmal Nocturnal Hemoglobinuria (PNH) is characterized by complement-mediated intravascular hemolysis, thrombophilia and Aplastic Anemia (AA) [1,2]. The treatment of PNH has been rebuilt by the anti-C5 eculizumab, which results in transfusion independence in half of the patients [3,4], while the others remain severely anemic due C3-mediated extravascular hemolysis [5] and/or concomitant AA.
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 anti-complement 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.
The occurrence of severe AA is a possible event during the course of PNH [2] and eventually hampers the hematological benefit from eculizumab. Treatment options include IST or Bone Marrow Transplantation (BMT) [6]. Here we provide evidence that intensive IST based on either polyclonal or monoclonal anti-lymphocyte antibodies can be delivered even concomitantly to eculizumab treatment, without any side effect or pharmacological interference. Our observation is the first proof, in vivo, that the terminal effector complement, namely the membrane attack complex, is not needed for the lympholytic effect of both thymoglobuline and alemtuzumab, suggesting a major role for antibody-dependent cellular cytotoxicity or even programmed cell death, rather than complement-dependent cytotoxicity [8]. On the other hand, our patient demonstrates that intensive IST, even combined with eculizumab, is a worth treatment option for AA/PNH syndrome, possibly resulting in excellent clinical outcome.
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