Abstract
Although the recent introduction of eculizumab has had a significant impact on the management of paroxysmal nocturnal hemoglobinuria (PNH), bone marrow transplantation (BMT) remains the only therapeutic option for patients who develop severe aplasia in the clinical course of PNH. However, information regarding BMT for eculizumab-treated PNH patients is scarce, and two major points—the optimal duration of eculizumab therapy, and the optimal BMT conditioning regimen—remain unclear. Here, we describe the clinical course of a PNH patient who was successfully treated with unrelated reduced-intensity BMT. Eculizumab was discontinued 2 weeks prior to the initiation of the conditioning regimen, which consisted of fludarabine 180 mg/m2, cyclophosphamide 100 mg/kg, rabbit anti-thymocyte globulin 2 mg/kg, and TBI 3 Gy. Complete donor chimerism was rapidly achieved in association with a rapid decrease in the proportion of PNH erythrocytes. The patient became transfusion-free immediately after BMT, and had no recurrence of hemolysis. The present case suggests that discontinuation of eculizumab before BMT and the use of a highly lymphoablative conditioning regimen may act as a successful treatment strategy in BMT for PNH. Further studies are warranted to evaluate the efficacy and safety of this treatment strategy.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Takeda J, Miyata T, Kawagoe K, Iida Y, Endo Y, Fujita T, et al. Deficiency of the GPI anchor caused by a somatic mutation of the PIG-A gene in paroxysmal nocturnal hemoglobinuria. Cell. 1993;73(4):703–11.
Brodsky RA. Narrative review: paroxysmal nocturnal hemoglobinuria: the physiology of complement-related hemolytic anemia. Ann Intern Med. 2008;148(8):587–95.
Helley D, de Latour RP, Porcher R, Rodrigues CA, Galy-Fauroux I, Matheron J, et al. Evaluation of hemostasis and endothelial function in patients with paroxysmal nocturnal hemoglobinuria receiving eculizumab. Haematologica. 2010;95(4):574–81.
Hillmen P, Young NS, Schubert J, Brodsky RA, Socie G, Muus P, et al. The complement inhibitor eculizumab in paroxysmal nocturnal hemoglobinuria. N Engl J Med. 2006;355(12):1233–43.
Hillmen P, Muus P, Duhrsen U, Risitano AM, Schubert J, Luzzatto L, et al. Effect of the complement inhibitor eculizumab on thromboembolism in patients with paroxysmal nocturnal hemoglobinuria. Blood. 2007;110(12):4123–8.
Brodsky RA, Young NS, Antonioli E, Risitano AM, Schrezenmeier H, Schubert J, et al. Multicenter phase 3 study of the complement inhibitor eculizumab for the treatment of patients with paroxysmal nocturnal hemoglobinuria. Blood. 2008;111(4):1840–7.
Kanakura Y, Ohyashiki K, Shichishima T, Okamoto S, Ando K, Ninomiya H, et al. Safety and efficacy of the terminal complement inhibitor eculizumab in Japanese patients with paroxysmal nocturnal hemoglobinuria: the AEGIS clinical trial. Int J Hematol. 2011;93(1):36–46.
Kelly RJ, Hill A, Arnold LM, Brooksbank GL, Richards SJ, Cullen M, et al. Long-term treatment with eculizumab in paroxysmal nocturnal hemoglobinuria: sustained efficacy and improved survival. Blood. 2011;117(25):6786–92.
Nishimura Ji J, Hirota T, Kanakura Y, Machii T, Kageyama T, Doi S, et al. Long-term support of hematopoiesis by a single stem cell clone in patients with paroxysmal nocturnal hemoglobinuria. Blood. 2002;99(8):2748–51.
Dmytrijuk A, Robie-Suh K, Cohen MH, Rieves D, Weiss K, Pazdur R. FDA report: eculizumab (Soliris) for the treatment of patients with paroxysmal nocturnal hemoglobinuria. Oncologist. 2008;13(9):993–1000.
Engelhard D, Cordonnier C, Shaw PJ, Parkalli T, Guenther C, Martino R, et al. Early and late invasive pneumococcal infection following stem cell transplantation: a European Bone Marrow Transplantation survey. Br J Haematol. 2002;117(2):444–50.
Hill A, Hillmen P, Richards SJ, Elebute D, Marsh JC, Chan J, et al. Sustained response and long-term safety of eculizumab in paroxysmal nocturnal hemoglobinuria. Blood. 2005;106(7):2559–65.
Rother RP, Rollins SA, Mojcik CF, Brodsky RA, Bell L. Discovery and development of the complement inhibitor eculizumab for the treatment of paroxysmal nocturnal hemoglobinuria. Nat Biotechnol. 2007;25(11):1256–64.
Brodsky RA. Stem cell transplantation for paroxysmal nocturnal hemoglobinuria. Haematologica. 2010;95(6):855–6.
Santarone S, Bacigalupo A, Risitano AM, Tagliaferri E, Di Bartolomeo E, Iori AP, et al. Hematopoietic stem cell transplantation for paroxysmal nocturnal hemoglobinuria: long-term results of a retrospective study on behalf of the Gruppo Italiano Trapianto Midollo Osseo (GITMO). Haematologica. 2010;95(6):983–8.
Takahashi Y, McCoy JP Jr, Carvallo C, Rivera C, Igarashi T, Srinivasan R, et al. In vitro and in vivo evidence of PNH cell sensitivity to immune attack after nonmyeloablative allogeneic hematopoietic cell transplantation. Blood. 2004;103(4):1383–90.
Bacigalupo A, Socie G, Lanino E, Prete A, Locatelli F, Locasciulli A, et al. Fludarabine, cyclophosphamide, antithymocyte globulin, with or without low dose total body irradiation, for alternative donor transplants, in acquired severe aplastic anemia: a retrospective study from the EBMT-SAA working party. Haematologica. 2010;95(6):976–82.
Acknowledgments
We are grateful to Ms. Aya Yano, Ms. Kimiko Yamamoto, and Ms. Junko Ikemoto for their excellent technical assistance.
Conflict of interest
The authors declare that they have no conflicts of interest.
Author information
Authors and Affiliations
Corresponding author
About this article
Cite this article
Taniguchi, K., Okada, M., Yoshihara, S. et al. Strategy for bone marrow transplantation in eculizumab-treated paroxysmal nocturnal hemoglobinuria. Int J Hematol 94, 403–407 (2011). https://doi.org/10.1007/s12185-011-0931-7
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12185-011-0931-7