title: Chronic treatment of paroxysmal nocturnal hemoglobinuria patients with eculizumab: safety, efficacy, and unexpected laboratory phenomena.
abstract: The terminal complement inhibitor eculizumab has become the standard of treatment in patients with symptomatic paroxysmal nocturnal hemoglobinuria (PNH). In this retrospective study, 19 PNH patients received chronic therapy with eculizumab with a median duration of 16 months (range 6-46 months). Parameters of hemolysis, transfusion requirements, and serum iron parameters were analyzed. Lactate dehydrogenase levels were significantly decreased by 85% from a median of 1897 U/l (range 293-3360) to 283 U/l (range 143-667), with an 86% reduction of transfusion requirements, whereas other parameters of hemolysis remained abnormal. Six patients (31.6%) became completely transfusion independent. A significant increase in ferritin levels from a median of 104 μg/l before to a median of 528 μg/l (p = 0.011) during treatment with eculizumab was observed. This was more pronounced in patients with low reticulocyte production index and/or requiring blood transfusions. Monospecific direct Coombs test was positive in most PNH patients, indicating a shift to extravascular hemolysis. Positive immunofixation for IgG kappa was observed, due to the presence of eculizumab in the serum. Eculizumab was safe and well tolerated long term in our study population. Iron should not be routinely supplemented in PNH patients treated with eculizumab without close monitoring of iron parameters, and iron depletion therapy should be considered in the case of overload.
authors: Department of Hematology, University Hospital Essen, Hufelandstrasse 55, 45122, Essen, Germany. alexander.roeth@uk-essen.de.
authors: Alexander
authors: A
authors: Röth
authors: Department of Hematology, University Hospital Essen, Hufelandstrasse 55, 45122, Essen, Germany.
authors: Christina
authors: C
authors: Hock
authors: Department of Hematology, University Hospital Essen, Hufelandstrasse 55, 45122, Essen, Germany.
authors: Anna
authors: A
authors: Konik
authors: Department of Hematology, University Hospital Essen, Hufelandstrasse 55, 45122, Essen, Germany.
authors: Sandra
authors: S
authors: Christoph
authors: Department of Hematology, University Hospital Essen, Hufelandstrasse 55, 45122, Essen, Germany.
authors: Ulrich
authors: U
authors: Dührsen
references: Ser Haematol. 1972;5(3):3-23
references: 4565712
references: JAMA. 2005 Apr 6;293(13):1653-62
references: 15811985
references: N Engl J Med. 2006 Sep 21;355(12):1233-43
references: 16990386
references: Br J Haematol. 2008 Jun;142(2):263-72
references: 18503589
references: Dtsch Med Wochenschr. 2009 Feb;134(9):404-9
references: 19224425
references: Blood. 2009 Apr 16;113(16):3885-6
references: 19372265
references: Ann N Y Acad Sci. 2009 Sep;1173:108-23
references: 19758139
references: Int J Hematol. 2003 Feb;77(2):113-20
references: 12627845
references: Mol Immunol. 1996 Dec;33(17-18):1389-401
references: 9171898
references: Blood. 2005 Dec 1;106(12):3699-709
references: 16051736
references: Cytometry B Clin Cytom. 2007 May;72(3):167-77
references: 17285629
references: Blood. 1982 Jul;60(1):20-3
references: 7044450
references: Blood. 2007 Dec 1;110(12):4123-8
references: 17702897
references: N Engl J Med. 2009 Jan 29;360(5):542-4
references: 19179328
references: Lancet. 2006 Feb 4;367(9508):397-403
references: 16458763
references: Haematologica. 2010 Apr;95(4):567-73
references: 20145265
references: Am J Hematol. 2010 Aug;85(8):553-9
references: 20658586
references: Eur J Immunol. 1992 Oct;22(10):2669-73
references: 1382994
references: N Engl J Med. 1990 Oct 25;323(17):1184-9
references: 1699124
references: Medicine (Baltimore). 1966 Sep;45(5):331-63
references: 5975900
references: Cell. 1993 May 21;73(4):703-11
references: 8500164
references: Br J Haematol. 2010 May;149(3):414-25
references: 20230403
references: Blood. 2009 Apr 23;113(17):4094-100
references: 19179465
references: N Engl J Med. 2009 Jan 29;360(5):544-6
references: 19179329
references: Blood. 2008 Oct 15;112(8):3099-106
references: 18535202
references: Blood. 2008 Jul 15;112(2):449-51
references: 18606894
references: N Engl J Med. 1995 Nov 9;333(19):1253-8
references: 7566002
references: Blood. 2008 Feb 15;111(4):1840-7
references: 18055865
references: Am J Transplant. 2009 Jan;9(1):231-5
references: 18976298
references: Int J Hematol. 2010 Mar;91(2):159-60
references: 20140782
references: Clin Lab Haematol. 2001 Apr;23(2):81-90
references: 11488846
references: Stem Cells. 1996 Jul;14(4):396-411
references: 8843541
references: EMBO J. 1994 Jan 1;13(1):110-7
references: 8306954