Abstract
A 79-year-old female diagnosed with T cell/histiocyte-rich large B cell lymphoma in complete remission after six cycles of rituximab-combined chemotherapy developed severe anemia, reticulocytopenia, and bone marrow erythroid hypoplasia. She was diagnosed with pure red cell aplasia (PRCA) accompanied by Coombs-negative autoimmune hemolytic anemia evidenced by a lack of glycophorin-A-positive cells in the bone marrow, haptoglobin under the detection level, and a high titer of RBC-bound IgG. Anti-erythropoietin receptor (EPOR) antibody was detected in the serum, and oligoclonal α/β and γ/δ T cells were also detected in her peripheral blood by Southern blotting analysis. Parvovirus B19 DNA was not detected by PCR. Although the treatment with rituximab had limited efficacy (specifically, only for hemolysis), subsequent cyclosporine therapy led to prompt recovery of erythropoiesis with the disappearance of anti-EPOR antibody and oligoclonal T cells. This is the first case report of anti-EPOR antibody-associated PRCA in a patient with malignant lymphoma treated successfully with cyclosporine.
References
Dührsen U, Augener W, Zwingers T, Brittinger G. Spectrum and frequency of autoimmune derangements in lymphoproliferative disorders: analysis of 637 cases and comparison with myeloproliferative diseases. Br J Haematol. 1987;67:235–9.
Grønbaek K, D’Amore F, Schmidt K. Autoimmune phenomena in non-Hodgkin’s lymphoma. Leuk Lymphoma. 1995;18:311–6.
Hirokawa M, Sawada K, Fujishima N, Kawano F, Kimura A, Watanabe T, et al. Acquired pure red cell aplasia associated with malignant lymphomas: a nationwide cohort study in Japan for the PRCA Collaborative Study Group. Am J Hematol. 2009;84:144–8.
Hauswirth AW, Skrabs C, Schützinger C, Gaiger A, Lechner K, Jäger U. Autoimmune hemolytic anemias, Evans’ syndromes, and pure red cell aplasia in non-Hodgkin lymphomas. Leuk Lymphoma. 2007;48:1139–49.
Alter R, Joshi SS, Verdirame JD, Weisenburger DD. Pure red cell aplasia associated with B cell lymphoma: demonstration of bone marrow colony inhibition by serum immunoglobulin. Leuk Res. 1990;14:279–86.
Fisch P, Handgretinger R, Schaefer HE. Pure red cell aplasia. Br J Haematol. 2000;111:1010–22.
Handgretinger R, Geiselhart A, Moris A, Grau R, Teuffel O, Bethge W, et al. Pure red-cell aplasia associated with clonal expansion of granular lymphocytes expressing killer-cell inhibitory receptors. N Engl J Med. 1999;340:278–84.
Hara A, Furuichi K, Higuchi M, Iwata Y, Sakai N, Kaneko S, et al. Autoantibodies to erythropoietin receptor in patients with immune-mediated diseases: relationship to anaemia with erythroid hypoplasia. Br J Haematol. 2013;160:244–50.
Kamesaki T, Oyamada T, Omine M, Ozawa K, Kajii E. Cut-off value of red-blood-cell-bound IgG for the diagnosis of Coombs-negative autoimmune hemolytic anemia. Am J Hematol. 2009;84:98–101.
Sawada K, Hirokawa M, Fujishima N, Teramura M, Bessho M, Dan K, et al. Long-term outcome of patients with acquired primary idiopathic pure red cell aplasia receiving cyclosporine A. A nationwide cohort study in Japan for the PRCA Collaborative Study Group. Haematologica. 2007;92:1021–8.
De Wolf-Peeters C, Delabie J, Campo E, Jaffe ES, Delsol G. T cell/histiocyte-rich large B cell lymphoma. In: WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. 4th ed. Lyon: International Agency for Research on Cancer; 2008. p. 238–9.
Oyaizu N, Kozai Y, Kodo H, Sunaga S, Iwabuchi K, Higashihara M, et al. A case of pure red cell aplasia complicated with diffuse large B cell lymphoma, T-cell-rich/histiocyte-rich variant: effectiveness of rituximab and implications for a common immunopathogenic role of B lymphocytes. Acta Haematol. 2005;113:194–7.
Bennett CM, de Jong JL, Neufeld EJ. Targeted ITP strategies: do they elucidate the biology of ITP and related disorders? Pediatr Blood Cancer. 2006;47:706–9.
Taylor RP, Lindorfer MA. Antigenic modulation and rituximab resistance. Semin Hematol. 2010;47:124–32.
Červinek L, Černá O, Čaniga M, Konířová E, Hluší A, Šimkovič M, et al. Efficacy of rituximab in primary immune thrombocytopenia: an analysis of adult pretreated patients from everyday hematological practice. Int J Hematol. 2012;96:594–9.
Dearden C, Wade R, Else M, Richards S, Milligan D, Hamblin T, et al. The prognostic significance of a positive direct antiglobulin test in chronic lymphocytic leukemia: a beneficial effect of the combination of fludarabine and cyclophosphamide on the incidence of hemolytic anemia. Blood. 2008;111:1820–6.
Jourdan E, Topart D, Richard B, Jourdan J, Sotto A. Severe autoimmune hemolytic anemia following rituximab therapy in a patient with a lymphoproliferative disorder. Leuk Lymphoma. 2003;44:889–90.
Acknowledgments
The authors would like to thank Dr. Toyomi Kamesaki at the Center for Community Medicine, Jichi Medical University, Tochigi, Japan, for measuring RBC-bound IgG.
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
Fujimi, A., Kamihara, Y., Kanisawa, Y. et al. Anti-erythropoietin receptor antibody-associated pure red cell aplasia accompanied by Coombs-negative autoimmune hemolytic anemia in a patient with T cell/histiocyte-rich large B cell lymphoma. Int J Hematol 100, 490–493 (2014). https://doi.org/10.1007/s12185-014-1652-5
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12185-014-1652-5