• alemtuzumab;
  • humoral immunodeficiency;
  • parvovirus B19;
  • red cell aplasia;
  • intravenous immunoglobulin

Alemtuzumab is a humanized monoclonal antibody directed against the CD52 antigen, expressed on most normal and malignant peripheral blood B and T cells. It was recently shown to give excellent disease control in T-cell prolymphocytic leukaemia (Deardon et al, 2001). Alemtuzumab causes profound and durable B- and T-cell depletion, and therefore induces significant cellular and humoral immunodeficiency. Opportunistic infections associated with cellular immunodeficiency have been reported with this drug, including Pneumocystis carinii pneumonia, cytomegalovirus infection, aspergillosis and herpes simplex viral infections (Lundin et al, 1998). To our knowledge, we report the first case of parvovirus B19-induced red cell aplasia associated with alemtuzumab therapy.

A 73-year-old woman was investigated for unsteady gait and poor balance. She was noted to have palpable lymph glands in the right axilla. A blood count revealed lymphocytosis of 6 × 109/l and mild anaemia (Hb 10·2 g/dl). The lymphocytes were medium-sized with irregular nuclei, indistinct nucleolous and basophilic cytoplasm. They were positive for CD3, CD4, CD38, CD52 and CD59, and negative for CD8, CD19, CD20, CD22, CD23 and CD79b. A probe derived from the T-cell receptor (TCR) βα chain locus hybridized to bands in addition to germ line hybridization with both of the restriction enzymes used, indicating T-cell clonality. A diagnosis of T-cell prolymphocytic leukaemia was established.

Seven months later, the patient's white cell count was 82 × 109/l and she began deoxycoformycin therapy. The white cell count fell to 27 × 109/l over the next 3 months but then began to rise. Treatment with alemtuzumab was started 14 months after initial diagnosis. She received 3 mg on d 1 and 2, 10 mg on d 3 and 30 mg on d 4. Thereafter, she received 30 mg three times a week for 4 weeks and entered complete remission with T cells comprising 0·35% of the bone marrow. Following treatment, she became progressively anaemic (Hb 8·6 g/dl) and required transfusion. At this point, there were no reticulocytes in her blood and the direct Coombes test was negative, while liver function tests and serum haptoglobins were normal. A bone marrow aspirate revealed complete absence of erythroid precursors consistent with red cell aplasia. Myelopoiesis and thrombopoiesis were normal. These findings prompted testing for parvovirus B19 infection. Quantitative DNA dot blot hybridization using serum (109 genome copies/ml) confirmed parvovirus B19 viraemia. Immune electron microscopy (Fig 1), which involved the addition to the patient's sample of parvovirus B19-specific immune serum to agglutinate parvovirus B19 particles making them easier to detect, further confirmed active parvovirus B19 infection. She had no history of contact with any individual with a rash in the previous 3 months. She received daily infusions of immunoglobulin (0·4 g/kg/d i.v. for 5 d) after which her reticulocyte count rose to 33 × 109/l and 52 × 109/l on d 7 and 14 respectively. Parvovirus B19 DNA dot blot analysis on serum collected on d 14 was negative. Further tests for parvovirus B19 DNA at 3, 6 and 18 months were negative, while haematological markers, including reticulocyte count, have remained normal since.


Figure 1. Immune electron microscopy showing aggregates of parvovirus B19 particles in serum, confirming viraemia during the patient's illness.

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Alemtuzumab impairs humoral immunity, and was the most likely explanation for parvovirus B19-induced red cell aplasia in our patient. Although bone marrow examination revealed erythroid hypoplasia, giant pronormoblasts considered pathognomic of this infection were not seen; a finding noted previously (Abkowitz et al, 1993). Destruction of erythroid precursors constitutes the main source of morbidity and mortality associated with this infection (Harris, 1992). Clearance of parvovirus B19 viraemia and hence recovery of erythropoiesis are dependent on an adequate antibody response, otherwise a chronic transfusion-dependent anaemic state might develop. Commercial intravenous immunoglobulin contains IgG antibodies to parvovirus B19 and thereby can control it (Kurtzman et al, 1987). However, monitoring for evidence of relapse is needed, by measurement of reticulocyte counts, and assays for parvovirus B19 viraemia until humoral immunity recovers from the effects of alemtuzumab.

Parvovirus B19 is a remediable cause of red cell aplasia in patients receiving alemtuzumab.


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  2. References
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  • Deardon, C.E., Matutes, E. & Cazin, B. (2001) High remission rates in T-cell prolymphocytic leukemia with CAMPATH-1H. Blood, 98, 17211726.
  • Harris, J.W. (1992) Parvovirus B19 for the hematologist. American Journal of Hematology, 39, 119130.
  • Kurtzman, G.J., Ozawa, K., Cohen, B., Hanson, G., Oseas, R. & Young, N.S. (1987) Chronic bone marrow failure due to persistent B19 parvovirus infection. New England Journal of Medicine, 317, 287294.
  • Lundin, J., Osterborg, A. & Brittinger, G. (1998) CAMPATH-1H monoclonal antibody for previously treated low-grade non-Hodgkin's lymphomas: a phase 2 multicenter study. Journal of Clinical Oncology, 16, 32573263.