Long-term Follow-up of Patients with Moderate Aplastic Anemia and Pure Red Cell Aplasia Treated with Daclizumab

Overview

Journal Haematologica

Specialty Hematology

Date 2010 Mar 9

PMID 20207845

Citations 9

Authors

Elaine M Sloand

Matthew J Olnes

Barbara Weinstein

Colin Wu

Jaroslaw Maciejewski

Phillip Scheinberg

Neal S Young

Affiliations

Soon will be listed here.

Abstract

Background: Pure red cell aplasia and moderate aplastic anemia are marrow failure states with an immune pathogenesis. Previously, we described short-term improvements in blood counts in two pilot studies treating moderate aplastic anemia (mAA) and pure red cell aplasia (PRCA) patients with daclizumab, a humanized monoclonal antibody to the interleukin-2 receptor; we now report our long-term experience with a larger cohort of patients.

Design And Methods: After a median follow-up period of 4.8 years, 19 of 45 (42%) evaluable mAA patients and 10 of 26 (38%) patients with PRCA responded by three months and 2 additional mAA patients responded by six months following administration of the drug.

Results: Seven of 28 (25%) mAA patients achieved long-term packed red blood cell PRBC transfusion independence, and all PRCA responders achieved long-term transfusion PRBC transfusion independence.

Conclusions: Red cell transfusion-independence prior to treatment in mAA patients predicted response. The only significant adverse treatment-related events were transient rashes and arthralgias. Daclizumab is safe and effective, and produces lengthy remissions in patients with PRCA and mAA.

Citing Articles

Treatment strategy for acquired pure red cell aplasia: a systematic review and meta-analysis.

Lobbes H, Lega J, Le Guenno G, Ruivard M, Mainbourg S Blood Adv. 2023; 7(21):6451-6465.

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Clinical characteristics and outcomes of 100 adult patients with pure red cell aplasia.

Wu X, Cheng L, Liu X, Sun Y, Li B, He G Ann Hematol. 2022; 101(7):1493-1498.

PMID: 35460389 DOI: 10.1007/s00277-022-04847-2.

Distinctive and common features of moderate aplastic anaemia.

Patel B, Barot S, Kuzmanovic T, Kerr C, Przychodzen B, Thota S Br J Haematol. 2020; 189(5):967-975.

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Diagnosis and Treatment of Aplastic Anemia.

Peslak S, Olson T, Babushok D Curr Treat Options Oncol. 2017; 18(12):70.

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Pure Red Cell Aplasia Following Interleukin-2 Therapy.

Dutcher J, Fan W, Wiernik P J Investig Med High Impact Case Rep. 2016; 4(2):2324709616643991.

PMID: 27144182 PMC: 4840614. DOI: 10.1177/2324709616643991.

References

Sloand E, Scheinberg P, Maciejewski J, Young N . Brief communication: Successful treatment of pure red-cell aplasia with an anti-interleukin-2 receptor antibody (daclizumab). Ann Intern Med. 2006; 144(3):181-5. DOI: 10.7326/0003-4819-144-3-200602070-00006. View

Chen W, Jin W, Hardegen N, Lei K, Li L, Marinos N . Conversion of peripheral CD4+CD25- naive T cells to CD4+CD25+ regulatory T cells by TGF-beta induction of transcription factor Foxp3. J Exp Med. 2003; 198(12):1875-86. PMC: 2194145. DOI: 10.1084/jem.20030152. View

Przepiorka D, Kernan N, Ippoliti C, Papadopoulos E, Giralt S, Khouri I . Daclizumab, a humanized anti-interleukin-2 receptor alpha chain antibody, for treatment of acute graft-versus-host disease. Blood. 1999; 95(1):83-9. View

Gabler C, Blank N, Hieronymus T, Schiller M, Berden J, Kalden J . Extranuclear detection of histones and nucleosomes in activated human lymphoblasts as an early event in apoptosis. Ann Rheum Dis. 2004; 63(9):1135-44. PMC: 1755110. DOI: 10.1136/ard.2003.011452. View

Vlad G, Ho E, Vasilescu E, Fan J, Liu Z, Cai J . Anti-CD25 treatment and FOXP3-positive regulatory T cells in heart transplantation. Transpl Immunol. 2007; 18(1):13-21. DOI: 10.1016/j.trim.2007.03.001. View

Maciejewski J, Sloand E, Nunez O, Boss C, Young N . Recombinant humanized anti-IL-2 receptor antibody (daclizumab) produces responses in patients with moderate aplastic anemia. Blood. 2003; 102(10):3584-6. DOI: 10.1182/blood-2003-04-1032. View

Koon H, Severy P, Hagg D, Butler K, Hill T, Jones A . Antileukemic effect of daclizumab in CD25 high-expressing leukemias and impact of tumor burden on antibody dosing. Leuk Res. 2005; 30(2):190-203. DOI: 10.1016/j.leukres.2005.06.007. View

Yeh S, Wroblewski K, Buggage R, Li Z, Kurup S, Sen H . High-dose humanized anti-IL-2 receptor alpha antibody (daclizumab) for the treatment of active, non-infectious uveitis. J Autoimmun. 2008; 31(2):91-7. PMC: 2742388. DOI: 10.1016/j.jaut.2008.05.001. View

Tkaczuk J, Yu C, Baksh S, Milford E, Carpenter C, Burakoff S . Effect of anti-IL-2Ralpha antibody on IL-2-induced Jak/STAT signaling. Am J Transplant. 2002; 2(1):31-40. DOI: 10.1034/j.1600-6143.2002.020107.x. View

10.

Bumgardner G, Hardie I, Johnson R, Lin A, Nashan B, Pescovitz M . Results of 3-year phase III clinical trials with daclizumab prophylaxis for prevention of acute rejection after renal transplantation. Transplantation. 2001; 72(5):839-45. DOI: 10.1097/00007890-200109150-00017. View

11.

Shimamoto T, Tohyama K, Okamoto T, Uchiyama T, Mori H, Tomonaga M . Cyclosporin A therapy for patients with myelodysplastic syndrome: multicenter pilot studies in Japan. Leuk Res. 2003; 27(9):783-8. DOI: 10.1016/s0145-2126(03)00008-0. View

12.

Cortes J, Faderl S, Estey E, Kurzrock R, Thomas D, Beran M . Phase I study of BMS-214662, a farnesyl transferase inhibitor in patients with acute leukemias and high-risk myelodysplastic syndromes. J Clin Oncol. 2005; 23(12):2805-12. DOI: 10.1200/JCO.2005.09.005. View

13.

Young N, Tisdale J . High-dose cyclophosphamide for treatment of aplastic anemia. Ann Intern Med. 2002; 137(6):549-50; author reply 549-50. DOI: 10.7326/0003-4819-137-6-200209170-00030. View

14.

Perales M, Ishill N, Lomazow W, Weinstock D, Papadopoulos E, Dastigir H . Long-term follow-up of patients treated with daclizumab for steroid-refractory acute graft-vs-host disease. Bone Marrow Transplant. 2007; 40(5):481-6. DOI: 10.1038/sj.bmt.1705762. View

15.

Ali E, Healy B, Stazzone L, Brown B, Weiner H, Khoury S . Daclizumab in treatment of multiple sclerosis patients. Mult Scler. 2009; 15(2):272-4. DOI: 10.1177/1352458508097468. View

16.

Rosenfeld S, Follmann D, Nunez O, Young N . Antithymocyte globulin and cyclosporine for severe aplastic anemia: association between hematologic response and long-term outcome. JAMA. 2003; 289(9):1130-5. DOI: 10.1001/jama.289.9.1130. View

17.

Wang Z, Xiao L, Shi B, Qian Y, Bai H, Chang J . Short-term anti-CD25 monoclonal antibody treatment and neogenetic CD4(+)CD25(high) regulatory T cells in kidney transplantation. Transpl Immunol. 2008; 19(1):69-73. DOI: 10.1016/j.trim.2008.01.005. View

18.

Fujishima N, Sawada K, Hirokawa M, Oshimi K, Sugimoto K, Matsuda A . Long-term responses and outcomes following immunosuppressive therapy in large granular lymphocyte leukemia-associated pure red cell aplasia: a Nationwide Cohort Study in Japan for the PRCA Collaborative Study Group. Haematologica. 2008; 93(10):1555-9. DOI: 10.3324/haematol.12871. View

19.

Mor E, Yussim A, Chodoff L, Schwartz M . New immunosuppressive agents for maintenance therapy in organ transplantation. BioDrugs. 2007; 8(6):469-88. DOI: 10.2165/00063030-199708060-00007. View

20.

Vincenti F, Kirkman R, LIGHT S, Bumgardner G, Pescovitz M, Halloran P . Interleukin-2-receptor blockade with daclizumab to prevent acute rejection in renal transplantation. Daclizumab Triple Therapy Study Group. N Engl J Med. 1998; 338(3):161-5. DOI: 10.1056/NEJM199801153380304. View