A multi-centre retrospective study of rituximab use in the treatment of relapsed or resistant warm autoimmune haemolytic anaemia
Su W. Maung
Department of Haematology, University Hospital Limerick, Limerick, Ireland
Department of Haematology, Tallaght Hospital (AMNCH), Dublin, Ireland
Search for more papers by this authorMaeve Leahy
Department of Haematology, University Hospital Limerick, Limerick, Ireland
Search for more papers by this authorHilary M. O'Leary
Department of Haematology, University Hospital Limerick, Limerick, Ireland
Search for more papers by this authorIrfan Khan
Department of Haematology, Cork University Hospital, Cork, Ireland
Search for more papers by this authorMary R. Cahill
Department of Haematology, Cork University Hospital, Cork, Ireland
Search for more papers by this authorOonagh Gilligan
Department of Haematology, Cork University Hospital, Cork, Ireland
Search for more papers by this authorPhilip Murphy
Department of Haematology, Beaumont Hospital, Dublin, Ireland
Search for more papers by this authorSuzanne McPherson
Department of Haematology, Waterford Regional Hospital, Waterford, Ireland
Search for more papers by this authorFred Jackson
Department of Haematology, Waterford Regional Hospital, Waterford, Ireland
Search for more papers by this authorMary Ryan
Department of Haematology, Waterford Regional Hospital, Waterford, Ireland
Search for more papers by this authorBrian Hennessy
Department of Haematology, Waterford Regional Hospital, Waterford, Ireland
Search for more papers by this authorJohnny McHugh
Department of Haematology, Tallaght Hospital (AMNCH), Dublin, Ireland
Search for more papers by this authorMatthew Goodyer
Department of Haematology, Mater Misericordiae University Hospital, Dublin, Ireland
Search for more papers by this authorLarry Bacon
Department of Haematology, Mater Misericordiae University Hospital, Dublin, Ireland
Search for more papers by this authorPeter O'Gorman
Department of Haematology, Mater Misericordiae University Hospital, Dublin, Ireland
Search for more papers by this authorAisling Nee
Department of Haematology, University College Hospital, Galway, Ireland
Search for more papers by this authorMichael O'Dwyer
Department of Haematology, University College Hospital, Galway, Ireland
Search for more papers by this authorHelen Enright
Department of Haematology, Tallaght Hospital (AMNCH), Dublin, Ireland
Search for more papers by this authorJean Saunders
Statistical Consulting Unit/CSTAR @ UL, University of Limerick, Limerick, Ireland
Search for more papers by this authorCorresponding Author
Denis O'Keeffe
Department of Haematology, University Hospital Limerick, Limerick, Ireland
Correspondence: Dr Denis O'Keeffe, Department of Haematology, University Hospital Limerick, Dooradoyle, Limerick, Ireland.
E-mail: [email protected]
Search for more papers by this authorSu W. Maung
Department of Haematology, University Hospital Limerick, Limerick, Ireland
Department of Haematology, Tallaght Hospital (AMNCH), Dublin, Ireland
Search for more papers by this authorMaeve Leahy
Department of Haematology, University Hospital Limerick, Limerick, Ireland
Search for more papers by this authorHilary M. O'Leary
Department of Haematology, University Hospital Limerick, Limerick, Ireland
Search for more papers by this authorIrfan Khan
Department of Haematology, Cork University Hospital, Cork, Ireland
Search for more papers by this authorMary R. Cahill
Department of Haematology, Cork University Hospital, Cork, Ireland
Search for more papers by this authorOonagh Gilligan
Department of Haematology, Cork University Hospital, Cork, Ireland
Search for more papers by this authorPhilip Murphy
Department of Haematology, Beaumont Hospital, Dublin, Ireland
Search for more papers by this authorSuzanne McPherson
Department of Haematology, Waterford Regional Hospital, Waterford, Ireland
Search for more papers by this authorFred Jackson
Department of Haematology, Waterford Regional Hospital, Waterford, Ireland
Search for more papers by this authorMary Ryan
Department of Haematology, Waterford Regional Hospital, Waterford, Ireland
Search for more papers by this authorBrian Hennessy
Department of Haematology, Waterford Regional Hospital, Waterford, Ireland
Search for more papers by this authorJohnny McHugh
Department of Haematology, Tallaght Hospital (AMNCH), Dublin, Ireland
Search for more papers by this authorMatthew Goodyer
Department of Haematology, Mater Misericordiae University Hospital, Dublin, Ireland
Search for more papers by this authorLarry Bacon
Department of Haematology, Mater Misericordiae University Hospital, Dublin, Ireland
Search for more papers by this authorPeter O'Gorman
Department of Haematology, Mater Misericordiae University Hospital, Dublin, Ireland
Search for more papers by this authorAisling Nee
Department of Haematology, University College Hospital, Galway, Ireland
Search for more papers by this authorMichael O'Dwyer
Department of Haematology, University College Hospital, Galway, Ireland
Search for more papers by this authorHelen Enright
Department of Haematology, Tallaght Hospital (AMNCH), Dublin, Ireland
Search for more papers by this authorJean Saunders
Statistical Consulting Unit/CSTAR @ UL, University of Limerick, Limerick, Ireland
Search for more papers by this authorCorresponding Author
Denis O'Keeffe
Department of Haematology, University Hospital Limerick, Limerick, Ireland
Correspondence: Dr Denis O'Keeffe, Department of Haematology, University Hospital Limerick, Dooradoyle, Limerick, Ireland.
E-mail: [email protected]
Search for more papers by this authorSummary
This retrospective analysis assessed the response, safety and duration of response to standard dose rituximab 375 mg/m2 weekly for four weeks as therapy for patients with primary or secondary warm autoimmune haemolytic anaemia (WAIHA), who had failed initial treatment. Thirty-four patients received rituximab for WAIHA in seven centres in the Republic of Ireland. The overall response rate was 70·6% (24/34) with 26·5% (9/34) achieving a complete response (CR). The time to response was 1 month post-initiation of rituximab in 87·5% (21/24) and 3 months in 12·5% (3/24) of patients. The median duration of follow-up was 36 months (range 6–90 months). Of the patients who responded, 50% (12/24) relapsed during follow up with a median time to next treatment of 16·5 months (range 6–60 months). Three patients were re-treated with rituximab 375 mg/m2 weekly for four weeks at relapse and responded. There was a single episode of neutropenic sepsis. Rituximab is an effective and safe treatment for WAIHA but a significant number of patients will relapse in the first two years post treatment. Re-treatment was effective in a small number of patients, suggesting that intermittent pulse treatment or maintenance treatment may improve long-term response.
References
- Akpek, G., McAneny, D. & Weintraub, L. (1999) Comparative response to splenectomy in Coombs-positive autoimmune hemolytic anemia with or without associated disease. American Journal of Hematology, 61, 98–102.
10.1002/(SICI)1096-8652(199906)61:2<98::AID-AJH4>3.0.CO;2-G CAS PubMed Web of Science® Google Scholar
- Barcellini, W. & Zanella, A. (2011) Rituximab therapy for autoimmune haematological diseases. European Journal of Internal Medicine, 22, 220–229.
- Barcellini, W., Zaja, F., Zaninioni, A., Imperiali, F.G., Battista, M.L., Di Bona, E., Fattizzo, B., Consonni, D., Cortellezzi, A., Fanin, R. & Zanella, A. (2012) Low-dose rituximab in adult patients with idiopathic autoimmune hemolytic anemia: clinical efficacy and biologic studies. Blood, 119, 3691–3697.
- Bussone, G., Ribeiro, E., Dechartres, A., Viallard, J.F., Bonnotte, B., Fain, O., Godeau, B. & Michel, M. (2009) Efficacy and safety of rituximab in adults’ warm autoimmune haemolytic anemia: retrospective an analysis of 27 cases. American Journal of Hematology, 84, 153–157.
- Carson, K. R., Evens, A.M., Richey, E.A., Habermann, T.M., Focosi, D., Seymour, J.F., Laubach, J., Bawn, S.D., Gordon, L.I., Winter, J.N., Furman, R.R., Vose, J.M., Zelenetz, A.D., Mamtani, R., Raisch, D.W., Dorshimer, G.W., Rosen, S.T., Muro, K., Gottardi-Littell, N.R., Talley, R.L., Sartor, O., Green, D., Major, E.O. & Bennett, CL.(2009) Progressive multifocal leukoencephalopathy after rituximab therapy in HIV-negative patients: a report of 57 cases from the Research on Adverse Drug Events and Reports project. Blood, 113, 4834–4840
- Chertkov, G. & Dacie, J.V. (1956) Results of splenectomy in auto-immune haemolytic anaemia. British Journal of Haematology, 2, 237–249.
- Crowther, M., Tracey Chan, Y.L., Garbett, I.K., Lim, W., Vickers, M.A. & Crowther, M.A. (2011) Evidence based focussed review of the treatment of idiopathic warm immune haemolytic anemia in adults. Blood, 118, 4036–4040.
- Dierickx, D., Verhoef, G., Van Hoof, A., Mineur, P., Roest, A., Triffet, A., Kentos, A., Pierre, P., Boulet, D., Bries, G., Lê, P.Q., Janssens, A. & Delannoy, A. (2009) Rituximab in auto-immune haemolytic anemia and immune thrombocytopenic purpura: a Belgian retrospective multicentric study. Journal of Internal Medicine, 266, 484–491.
- Garvey, B. (2008) Rituximab in the treatment of Autoimmune Haematological disorders. British Journal of Haematology, 141, 149–169.
- Gehrs, B.C. & Friedberg, R.C. (2002) Autoimmune haemolytic anemia. American Journal of Hematology, 69, 258–271.
- Genty, I., Michel, M., Hermine, O., Schaeffer, A, Godeau, B. & Rochant, H. (2002) Characteristics of autoimmune hemolytiv anemia in adults: retrospective analysis of 83 cases. Revue de Medecine Interne, 23, 901–909.
- Keystone, E., Fleischmann, R., Emery, P., Furst, D.E., van Vollenhoven, R., Bathon, J., Dougados, M., Baldassare, A., Ferraccioli, G., Chubick, A., Udell, J., Cravets, M.W., Agarwal, S., Cooper, S. & Magrini, F. (2007) Safety and efficacy of additional courses of rituximab in patients with active rheumatoid arthritis: an open-label extension analysis. Arthritis and Rheumatism, 56, 3896–3908.
- Lechner, L. & Jager, U. (2010) How I treat autoimmune haemolytic anemia in adults. Blood, 116, 1831–1838.
- Medeot, M., Zaja, F., Vianelli, N., Battista, M., Baccarani, M., Patriarca, F., Soldano, F., Isola, M., De Luca, S. & Fanin, R. (2008) Rituximab therapy in adult patients with relapsed or refractory immune thrombocytopenic purpura: long-term follow-up results. European Journal of Haematology, 81, 165–169.
- Merril, j., Buyon, J., Furie, R., Latinis, K., Gordon, C., Hsieh, H.J. & Brunetta, P. (2011) Assessment of flares in lupus patients enrolled in a phase II/III study of rituximab (EXPLORER). Lupus, 20, 709–716
- Murphy, S. & LoBuglio, A.F. (1976) Drug therapy of autoimmune haemolytic anemia. Seminars Hematology, 13, 323–334.
- Patel, V.L., Mahévas, M., Lee, S.Y., Stasi, R., Cunningham-Rundles, S., Godeau, B., Kanter, J., Neufeld, E., Taube, T., Ramenghi, U., Shenoy, S., Ward, M.J., Mihatov, N., Patel, V.L., Bierling, P., Lesser, M., Cooper, N. & Bussel, J.B. (2012) Outcomes five years after response to rituximab therapy in children and adults with immune thrombocytopenia. Blood, 119, 5989–5995.
- Serrano, J. (1992) Review of 200 cases studied in a period of 20 years (1970-1989). Sangre (Barc), 37, 265–274.