Parvovirus B19 infections occur fairly frequently in children, and the most common clinical picture is erythema infectiosum.1 In patients with an underlying hemolytic disorder, this can cause a transient aplastic crisis. In recipients of allogeneic stem cell transplantation (SCT)2 and in other patients with severe immunodeficiencies,3 the viremia can persist and cause chronic pure red cell aplasia. Here, we describe an allogeneic SCT recipient who developed severe pancytopenia with multiorgan failure (MOF) after parvovirus B19 infection. To our knowledge, this is the first report of this severe complication of parvovirus B19 infection following allogeneic SCT.
In September 2002, a 38-year-old male was admitted to our department with pancytopenia after a 2-week period of headache, fatigue, pharyngitis, polymyositis, polyarthralgia, nausea and vomiting. He had received an allogeneic T-cell-depleted bone marrow transplantation 1 year earlier from a matched unrelated donor for refractory chronic lymphocytic leukemia (CLL). The post transplant period was uneventful, apart from grade I acute graft-versus-host-disease. From 3 months after transplantation peripheral blood cell counts were normal and analysis of chimerism, determined in peripheral blood T- and non-T cells, demonstrated complete donor chimerism. At the time of admission he was anuric. Physical examination was normal apart from pallor and weakness. Peripheral blood counts revealed very severe pancytopenia (hemoglobulin, 4.6 mmol/l; leukocytes, 0.6 × 109/l; thrombocytes, 1 × 109/l). Blood chemistry values showed acute renal failure (creatinine 462 μmol/l). Hemodialysis was started 2 days after admission and continued for 2 weeks until a spontaneous diuresis occurred. Owing to epileptic seizures, an MRI was performed that revealed encephalopathy. He was treated with phenytoin. Transthoracic echocardiographic assessment was performed during a 2-week stay on ICU, for respiratory and circulatory instability. This demonstrated cardiomyopathy with diffuse left ventricular failure. He was treated with an ACE inhibitor, β-adrenergic blocker and diuretics. Electrocardiography was normal before and early after SCT. X-ray of the chest was normal as was an ultrasound of the abdomen. Bone marrow biopsy revealed decreased cellularity of 30% that included 5% CLL cells (by immunophenotypic analysis). Laboratory tests for hemolysis and paroxysmal nocturnal hemoglobinuria were negative. Complement proteins C3 and C4 were absent. All serology and PCR tests for human immunodeficiency virus (HIV), cytomegalovirus and Epstein–Barr virus were negative. No autoimmune antibodies were found. Plasma PCR for parvovirus DNA and serology for parvovirus B19 demonstrated a recent infection; prior tests before and after SCT were, retrospectively, negative for parvovirus B19 (Table 1). Also, a bronchoscopy with bronchoalveolar lavage was PCR positive for parvovirus B19. He received red cell and platelet transfusions (Figure 1), antibiotic and antifungal prophylaxis. Prednisone 100 mg/day was started for possible immune complex-mediated nephritis; however, no response occurred after 3 weeks of treatment. When the primary parvovirus B19 infection was diagnosed, 3 weeks after admission, he received immune globulin, 400 mg/kg/day, for 3 days. Within 2 weeks after the immune globulin he improved. The peripheral blood counts recovered, complement proteins became normal 4 weeks after immune globulin and the symptoms of heart failure resolved. A control MRI of the brain 4 months later showed no abnormalities. Phenytoin and the drugs given for heart failure were stopped and the patient is currently in good clinical health and in complete remission of the CLL (the bone marrow biopsy no longer showed any monoclonal B cells on immunophenotyping.)
Transient aplasia can be associated with parvovirus B19 infection in patients with a high erythrocyte destruction rate, including those with sickle cell disease, thalassemia or hereditary spherocytosis. It can be life threatening without blood transfusions. Most of the otherwise immune-competent patients will recover spontaneously. However, in immune-compromised patients, for example, allogeneic bone marrow transplant recipients or HIV-positive patients,4 parvovirus B19 infection can persist and may cause chronic pure red cell aplasia. The reason for leuko- and thrombocytopenia, which is also sometimes present, is possibly cytotoxicity of the viral nonstructural protein (NS1) and also hemophagocytosis.4, 5 Damage to erythrocyte precursor cells by parvovirus B19 takes place via the blood group P-antigen receptor.1 Recipients of SCT are more likely to acquire parvovirus B19 infection because immune globulin production and T-cell function are very poor during the first year post transplant, the time period of most reported cases of parvovirus B19-induced aplastic crises. Indeed, our patient had a very delayed immune response to the parvovirus infection as the T-cell-dependent switch from IgM to IgG occurred only 1 year after the primary infection. The significance of the high parvovirus load that remained (Table 1) is presently unknown, but is probably also related to the ongoing immunodeficiency.
The therapy of choice is immune globulin 400 mg/kg/day for 3–5 days.6, 7, 8 Immune globulin to parvovirus B19 can control the persistent infection when an adequate patient antibody response is absent.
In summary, parvovirus B19 infection can be very severe after allogeneic SCT and, in addition to the aplastic crises, can also cause severe MOF.
The Health Council of the Netherlands recently (2002) advised that immune-compromised patients who do not have detectable antibodies against parvovirus B19 should receive blood products only from donors who have antibodies against parvovirus B19, since parvovirus B19 can also be transmitted by blood products.9
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Health Council of the Netherlands. Blood Products and Parvovirus B1. Health Council of the Netherlands: The Hague, 2002; publication no. 2002/07E.
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Klümpen, HJ., Petersen, E. & Verdonck, L. Severe multiorgan failure after parvovirus B19 infection in an allogeneic stem cell transplant recipient. Bone Marrow Transplant 34, 469–470 (2004). https://doi.org/10.1038/sj.bmt.1704612
Parvovirus B19 infection in adult patients after allogeneic stem cell transplantation: our experience of five cases and literature review
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