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Chronic Lymphocytic Leukemia

Rituximab–cyclophosphamide–dexamethasone combination in the management of autoimmune cytopenias associated with chronic lymphocytic leukemia

Leukemia volume 25, pages 473–478 (2011)Cite this article

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Abstract

We report our experience on rituximab–cyclophosphamide–dexamethasone (RCD) combination therapy for the treatment of autoimmune disorders (AIDs) in 48 chronic lymphocytic leukemia (CLL) patients. Overall, 81% of patients were relapsing for AID after previous treatment with corticosteroids, splenectomy, rituximab or alemtuzumab. Diagnosis of AID was autoimmune hemolytic anemia (AIHA) in 26 (54%), autoimmune thrombocytopenia (AITP) in 9 (18.8%), Evan's syndrome in 8 (16.7%) and pure red cell aplasia (PRCA) in 5 patients (10.5%). Median time of autoimmune disorder (AID) onset from CLL diagnosis was 60 months (range: 0–240), and CLL was considered progressive in 40% of subjects upon AID diagnosis (complex AID). Median hemoglobin pre-treatment was 7.7 g/100 ml, and median platelet count 36.5 × 109/l, returning to a median of 12.5 /100ml and 37.5 × 109/l, respectively. Overall, an 89.5% response rate was obtained with this combination, irrespective of the AID type. Relapse occurred in 19 patients (39.6%). Median duration of response for autoimmunity (DR-AI) was 24 months, but DR-AI was higher for patients presenting: (1) AID early during CLL course (<3 years), or (2) both PRCA and AIHA. Median time to CLL progression in 48 patients was 16 months, but this time was statistically shorter for Evan's syndrome and AITP patients as compared with AIHA and PRCA patients. This study emphasizes the relevance of CLL-directed immune chemotherapy in the management of CLL-associated AID.

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References

  1. Hamblin TJ . Autoimmune complications of chronic lymphocytic leukemia. Semin Oncol 2006; 33: 230–239.

    Article  CAS  PubMed  Google Scholar 

  2. Karlsson C, Hansson L, Celsing F, Lundin J . Treatment of severe refractory autoimmune hemolytic anemia in B-cell chronic lymphocytic leukemia with alemtuzumab (humanized CD52 monoclonal antibody). Leukemia 2007; 21: 511–514.

    Article  CAS  PubMed  Google Scholar 

  3. Hallek M, Cheson BD, Catovsky D, Caligaris-Capio F, Dighiero G, Döhner H et al. International workshop on chronic lymphocytic leukemia (2008) Guidelines for the diagnosis and treatment of chronic lymphocytic leukemia: a report from the international workshop on chronic lymphocytic leukemia updating the National Cancer Institute-working group 1996 guidelines. Blood 2008; 111: 5446–5456.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Dearden C . Disease-specific complications of chronic lymphocytic leukemia. Hematology Am Soc Hematol Educ Program 2008; 2008: 450–456.

    Article  Google Scholar 

  5. Hall AM, Vickers MA, McLeod E, Barker RN . Rh autoantigen presentation to helper T cells in chronic lymphocytic leukemia by malignant B cells. Blood 2005; 105: 2007–2015.

    Article  CAS  PubMed  Google Scholar 

  6. Gupta N, Kavuru S, Patel D, Janson D, Driscoll N, Ahmed S et al. Rituximab-based chemotherapy for steroid-refractory autoimmune hemolytic anemia of chronic lymphocytic leukemia. Leukemia 2002; 16: 2092–2095.

    Article  CAS  PubMed  Google Scholar 

  7. Kaufman M, Limaye S, Driscoll N, Johnson C, Caramanica A, Lebowicz Y et al. A combination of rituximab, cyclophosphamide and dexamethasone effectively treats immune cytopenias of chronic lymphocytic leukemias. Leuk Lymphoma 2009; 50: 892–899.

    Article  CAS  PubMed  Google Scholar 

  8. Bowen DA, Call TG, Shanafelt T, Kay N, Schwager S, Reinalda M et al. Treatment of autoimmune cytopenia complicating progressive chronic lymphocytic leukemia/small lymphocytic lymphoma with rituximab, cyclophosphamide, vincristine, and prednisone. Leuk Lymphoma 2010; 51: 620–627.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Zent CS, Ding W, Schwager S, Reinalda M, Hoyer D, Jelinek D et al. The prognostic significance of cytopenia in chronic lymphocytic leukaemia/small lymphocytic lymphoma. Br J Haematol 2008; 141: 615–621.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Mauro F, Foa R, Cerretti R, Giannarelli D, Coluzzi S, Girelli G . Autoimmune hemolytic anemia in chronic lymphocytic leukemia: clinical, therapeutic, and prognostic features. Blood 2000; 95: 2786–2792.

    CAS  PubMed  Google Scholar 

  11. Zent CS, Kay NE . Autoimmune complications in chronic lymphocytic leukemia. Best Pract Res Clin Haematol 2010; 23: 47–59.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Visco C, Ruggeri M, Evangelista ML, Stasi R, Zanotti R, Giaretta I et al. Impact of immune thrombocytopenia on the clinical course of chronic lymphocytic leukemia. Blood 2008; 111: 1110–1116.

    Article  CAS  PubMed  Google Scholar 

  13. Ghazal H . Successful treatment of pure red cell aplasia with rituximab in patients with chronic lymphocytic leukemia. Blood 2002; 99: 1092–1094.

    Article  CAS  PubMed  Google Scholar 

  14. Narra K, Borghaei H, Al-Saleem T, Höglund M, Smith MR . Pure red cell aplasia in B-cell lymphoprliferative disorder treated with rituximab: report of two cases and review of the literature. Leukemia Res 2006; 30: 109–114.

    Article  CAS  Google Scholar 

  15. D’Arena G, Laurenti L, Capalbo S, D’Arco AM, De Filippi R, Marcacci G et al. Rituximab therapy for chronic lymphocytic leukemia-associated autoimmune hemolytic anemia. Am J Hematol 2006; 81: 598–602.

    Article  PubMed  Google Scholar 

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Acknowledgements

We are grateful to patients and their referring physicians. In addition, we would like to thank Professor G Laurent, Professor O Tournilhac, Professor B Coiffier, Professor G Salles, and Professor M Michallet for their helpful contribution in reading and discussing the manuscript.

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Author notes

  1. B Cazin and L Ysebaert: These authors are senior co-authors.

Authors and Affiliations

  1. Department of Hematology, Claude Huriez University Hospital, Lille, France

    J Rossignol, R Dulery, X Leleu & B Cazin

  2. Department of Hematology, Hospices Civils de Lyon, Lyon-Sud University Hospital, Pierre-Bénite, France

    A-S Michallet & A Garon

  3. Department of Hematology, Purpan University Hospital, Toulouse, France

    L Oberic, M Picard, C Willekens & L Ysebaert

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  1. J Rossignol
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Correspondence to L Ysebaert.

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Rossignol, J., Michallet, AS., Oberic, L. et al. Rituximab–cyclophosphamide–dexamethasone combination in the management of autoimmune cytopenias associated with chronic lymphocytic leukemia. Leukemia 25, 473–478 (2011). https://doi.org/10.1038/leu.2010.278

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