dierickx.qxp 14/3/08 16:39 Page 58
Anaemia and Haemaglobinopathies
Table 2: Responses with Rituximab in Idiopathic Thrombocytopenic Purpura
Author Year Number of Age Prior Splenectomy Response Response
Patients (years) (n) ORR (%) CR (%)
Stasi 2001 25 22–74 8 52 20
Giagounidis 2002 12 28–71 11 75 41
Zaja 2003 20 16–76 2 65 45
Narang 2003 6 30–70 6 100 67
Shanafelt 2003 12 31–79 1 50 42
Cooper 2004 57 21–79 31 54 32
Sanal 2004 15 20–83 8 87 67
Zalzaleh 2004 10 NR NR 60 2
Jacoub 2004 11 20–79 6 91 81
Braendstrup 2005 35 17–82 16 49 20
Case 2005 22 24–83 20 59 32
Garcia-Chaves 2005 14 17–70 NR 92 36
Ahn 2005 12 22–87 3 83 50
Narat 2005 6 19–74 NR 83 67
Bennett 2006 36 2–18 7 31 NR
Penalver 2006 89 4–98 47 55 46
Dierickx 2007 29 16–89 22 64 58
Total 370 2–87 165/340 reported 64 45
n = number of patients; ORR = overall response rate; CRR = complete response rate; NR = not reported.
rituximab-coated B cells, similar to the mechanism of rapid response of mechanism of cell lysis is similar to that of rituximab. There has
anti-D in Rh+ patients with ITP.
8
been very limited experience with alemtuzumab in autoimmune
cytopenia, with only one report showing responses in 15 of
Currently, no pre-treatment patient or disease characteristics that 21 patients treated. Compared with rituximab, toxicity is expected to
predict response have been identified. So far, no consistent significant be much greater due to the profound immunosuppression that lasts
correlation between response and sex, age, prior splenectomy, platelet for several months after cessation of treatment.
17
Humanised anti-
count or haemoglobin concentration when rituximab was started, CD154 MAb is another potentially interesting molecule in the
duration of disease before start of rituximab and presence of treatment of ITP. By blocking the interaction between CD40 on APCs
underlying condition have been identified. and CD154 (=CD40 ligand) on activated CD4-positive T cells, the
autoimmune response is selectively suppressed (see Figure 1).
Preliminary experience suggests that re-treatment with rituximab Although a phase I trial showed encouraging results, no further trials
in patients relapsing after a successful treatment with anti-CD20 were set up because of the occurrence of unacceptable adverse
therapy is beneficial, although concern has been raised. (thromboembolic) events.
18
Reactivation of the disease may be attributable to the production
of autoantibodies by long-lived plasma cells that are not targeted Based on growing literature and experience, rituximab has emerged
by rituximab due to the absence of CD20 expression on as an effective and well-tolerated immunotherapeutic treatment
their surface.
2
option in patients with immune anaemia and thrombocytopenia.
However, due to the lack of controlled data, no conclusions
Apart from rituximab, other targeted immunotherapy has been regarding the true efficacy, optimal timing, dose and safety of
described in immune-mediated haematological disorders. rituximab administration can currently be made and no valid
Alemtuzumab is a humanised rat anti-CD52 MAb that binds to comparison with the classic treatments of immune cytopenia is
most normal and malignant lymphocytes, both of T and B type. The currently available. ■
1. Cheung MC, Haynes AE, Meyner RM, et al., Rituximab in anaemia, Semin Hematol, 2005;42(3):131–6. anaemia of chronic lymphocytic leukaemia, Leukemia,
lymphoma: a systematic review and consensus guideline from 8. Cines DB, Bussel JB, How I treat idiopathic thrombocytopaenic 2002;16(10):2092–5.
Cancer Care Ontario, Cancer Treat Rev, 2007;33(2):161–76. purpura (ITP), Blood, 2005;106(7):2244–51. 14. Arnold DM, Dentali F, Crowther MA, et al., Systematic review:
2. Edwards JC, Cambridge G, B-cell-targeting in rheumatoid 9. Maloney DG, Smith B, Rose A, Rituximab: mechanism of action efficacy and safety of rituximab for adults with idiopathic
arthritis and other autoimmune diseases, Nat Rev Immunol, and resistance, Semin Oncol, 2002;29(Suppl. 2):2–9. thrombocytopaenic purpura, Ann Intern Med, 2007;146:25–33.
2006;6(5):394–403. 10. Dierickx D, De Rycke A, Vanderschueren S, et al., New 15. Kimby E, Tolerability and safety of rituximab (Mabthera
®
),
3. Gehrs BC, Friedberg RC, Autoimmune haemolytic anaemia, treatment options for immune-mediated haematological Cancer Treatm Rev, 2005;31(6):456–73.
Am J Hematol, 2002;69(4):258–71. disorders, Eur J Intern Med, in press. 16. Tsutsumi Y, Kanamori H, Mori A, et al., Reactivation of
4. Cooper N, Bussel J, The pathogenesis of immune 11. Berentsen S, Ulvestad E, Gjertsen BT, et al., Rituximab for hepatitis B virus with rituximab, Expert Opin Drugs Saf,
thrombocytopaenic purpura, Br J Haematol, primary chronic cold agglutinin disease: a prospective study of 2005;4:599–608.
2006;133(4):364–74. 37 courses of therapy in 27 patients, Blood, 17. Willis F, Marsh JC, Bevan DH, et al., The effect of treatment
5. Norton A, Roberts I, Management of Evans syndrome, 2004;103(8):2925–8. with Campath-1H in patients with autoimmune cytopaenias,
Br J Haematol, 2006;132(2):125–37. 12. Schöllkopf C, Kjeldsen L, Bjerrum OW, et al., Rituximab in Br J Haematol, 2001;114(4):891–8.
6. Semple JW, Freedman J, Autoimmune pathogenesis and chronic cold agglutinin disease: a prospective study of 20 18. Kuwana M, Normura S, Fujimura K, et al., Effect of a single
autoimmune haemolytic anaemia, Semin Hematol, patients, Leuk Lymphoma, 2006;47(2):253–60. injection of humanised anti-CD154 monoclonal antibody on the
2005;42(3):122–30. 13. Gupta N, Kavuru S, Patel D, et al., Rituximab-based platelet-specific autoimmune response in patients with immune
7. King KE, Ness PM, Treatment of autoimmune haemolytic chemotherapy for steroid-refractory autoimmune haemolytic thrombocytopaenic purpura, Blood, 2004;103:1229–36.
58 EUROPEAN HAEMATOLOGY 2007
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