Vol 52, No 4 (2021)
Review article
Published online: 2021-08-31
Allogeneic hematopoietic stem cell transplantation for paroxysmal nocturnal hemoglobinuria in the era of complement inhibition
1
DOI: 10.5603/AHP.2021.0049
Acta Haematol Pol 2021;52(4):253-256.
Abstract
The only potentially curative treatment for paroxysmal nocturnal hemoglobinuria (PNH) is allogeneic hematopoietic stem cell transplantation (allo-HSCT).
However, its use has been largely abandoned following the introduction of efficient symptomatic treatment with complement inhibition. Nevertheless, the population of PNH patients is diverse, and some of them might still gain advantage from allo-HSCT, while anti-complement treatment would be the first choice for others. Both treatment modalities may be also sequentially applied in the same patient when needed.
This review aimed to present the current status of allo-HSCT in the treatment of patients with PNH, with special reference to Poland where the previous unavailability of anti-complement therapy enabled the acquisition of extensive experience in performing allo-HSCT for PNH, a treatment option currently restricted only to selected patients who are not candidates for eculizumab.
Keywords: paroxysmal nocturnal hemoglobinuriaallogeneic hematopoietic stem cell transplantationeculizumab
References
- Parker CJ. Update on the diagnosis and management of paroxysmal nocturnal hemoglobinuria. Hematology Am Soc Hematol Educ Program. 2016; 2016(1): 208–216.
- Hillmen P, Young NS, Schubert J, et al. The complement inhibitor eculizumab in paroxysmal nocturnal hemoglobinuria. N Engl J Med. 2006; 355(12): 1233–1243.
- Lee JW, Sicre de Fontbrune F, Wong Lee Lee L, et al. Ravulizumab (ALXN1210) vs eculizumab in adult patients with PNH naive to complement inhibitors: the 301 study. Blood. 2019; 133(6): 530–539.
- Kulasekararaj AG, Hill A, Rottinghaus ST, et al. Ravulizumab (ALXN1210) vs eculizumab in C5-inhibitor-experienced adult patients with PNH: the 302 study. Blood. 2019; 133(6): 540–549.
- DeZern AE, Uknis M, Yuan X, et al. Complement blockade with a C1 esterase inhibitor in paroxysmal nocturnal hemoglobinuria. Exp Hematol. 2014; 42(10): 857–861.e1.
- Risitano AM. Anti-complement treatment in paroxysmal nocturnal hemoglobinuria: where we stand and where we are going. Transl Med UniSa. 2014; 8: 43–52.
- Yuan X, Gavriilaki E, Thanassi JA, et al. Small-molecule factor D inhibitors selectively block the alternative pathway of complement in paroxysmal nocturnal hemoglobinuria and atypical hemolytic uremic syndrome. Haematologica. 2017; 102(3): 466–475.
- Alfinito F, Ruggiero G, Sica M, et al. Eculizumab treatment modifies the immune profile of PNH patients. Immunobiology. 2012; 217(7): 698–703.
- Risitano AM, Notaro R, Marando L, et al. Complement fraction 3 binding on erythrocytes as additional mechanism of disease in paroxysmal nocturnal hemoglobinuria patients treated by eculizumab. Blood. 2009; 113(17): 4094–4100.
- Risitano AM, Marotta S, Ricci P, et al. Anti-complement treatment for paroxysmal nocturnal hemoglobinuria: time for proximal complement inhibition? A position paper from the SAAWP of the EBMT. Front Immunol. 2019; 10: 1157.
- Brodsky RA, Young NS, Antonioli E, et al. Multicenter phase 3 study of the complement inhibitor eculizumab for the treatment of patients with paroxysmal nocturnal hemoglobinuria. Blood. 2008; 111(4): 1840–1847.
- Fattizzo B, Serpenti F, Giannotta JA, et al. Difficult cases of paroxysmal nocturnal hemoglobinuria: diagnosis and therapeutic novelties. J Clin Med. 2021; 10(5): 948.
- Donohue RE, Marcogliese AN, Sasa GS, et al. Standardized high-sensitivity flow cytometry testing for paroxysmal nocturnal hemoglobinuria in children with acquired bone marrow failure disorders: A single center US study. Cytometry B Clin Cytom. 2018; 94(4): 699–704.
- Brodsky RA. How I treat paroxysmal nocturnal hemoglobinuria. Blood. 2009; 113(26): 6522–6527.
- Takahashi Y, McCoy JP, Carvallo C, 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): 1383–1390.
- Vallet N, de Fontbrune FS, Loschi M, et al. Société Francophone de Greffe de Moelle et Thérapie Cellulaire. Hematopoietic stem cell transplantation for patients with paroxysmal nocturnal hemoglobinuria previously treated with eculizumab: a retrospective study of 21 patients from SFGM-TC centers. Haematologica. 2018; 103(3): e103–e105.
- DeZern AE, Jones RJ, Brodsky RA. Eculizumab bridging before bone marrow transplant for marrow failure disorders is safe and does not limit engraftment. Biol Blood Marrow Transplant. 2018; 24(12): e26–e30.
- Saso R, Marsh J, Cevreska L, et al. Bone marrow transplants for paroxysmal nocturnal haemoglobinuria. Br J Haematol. 1999; 104(2): 392–396.
- Santarone S, Bacigalupo A, Risitano AM, 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): 983–988.
- Peffault de Latour R, Schrezenmeier H, Bacigalupo A, et al. Allogeneic stem cell transplantation in paroxysmal nocturnal hemoglobinuria. Haematologica. 2012; 97(11): 1666–1673.
- Markiewicz M, Drozd-Sokolowska J, Biecek P, et al. Allogeneic hematopoietic stem cell transplantation for paroxysmal nocturnal hemoglobinuria: multicenter analysis by the Polish Adult Leukemia Group. Biol Blood Marrow Transplant. 2020; 26(10): 1833–1839.
- Liu L, Zhou H, Miao M, et al. Outcomes of haploidentical haematopoietic stem cell transplantation for paroxysmal nocturnal haemoglobinuria. Blood. 2019; 134(Suppl 1): 5730.
- Mei M, Gupta R, O'Donnell M, et al. Post-allogeneic hematopoietic stem cell transplantation eculizumab as prophylaxis against hemolysis and thrombosis for patients with hematologic disorders associated with paroxysmal nocturnal hemoglobinuria clones. Biol Blood Marrow Transplant. 2019; 25(5): e183–e185.