Atraumatic splenic rupture following IVIg for parvovirus B19 pure red cell aplasia post renal transplant

Parvovirus B19 (PB19) associated pure red cell aplasia (PRCA) is an uncommon but well described complication of immunosuppression post solid organ transplantation. We report a unique case of a renal transplant patient with PB19 associated PRCA who developed a spontaneous splenic rupture after receiving IVIg for persistent anemia. He subsequently required splenectomy. Within the spleen we subsequently identified PB19 affected cells.     

Pure red cell aplasia associated with parvovirus B19 infection occurring late after allogeneic bone marrow transplantation

Differential diagnosis for anemia late after allogeneic stem cell transplantation is broad. In this report, we describe a case of severe anemia secondary to pure red cell aplasia associated with human parvovirus B19 infection over 8 years after allogeneic bone marrow transplantation. Characteristics of parvovirus B19 infection and the immunosuppressed state after allogeneic stem cell transplantation are reviewed.     

Pure red cell aplasia due to parvovirus B19 infection after liver transplantation： A case report and review of the literature

Pure red cell aplasia （PRCA） due to parvovirus B19 （PVB19） infectiori after solid organ transplantation has been rarely reported and most of the cases were renal transplant recipients, Few have been described after liver transplantation. Moreover, little information on the management of this easily recurring disease is available at present. We describe the first case of a Chinese liver transplant recipient with PVB19-induced PRCA during immunosuppressive therapy. The patient suffered from progressive anemia with the lowest hemoglobin level of 21 g/L. Bone marrow biopsy showed selectively inhibited erythropoiesis with giant pronormoblasts. Detection of PVB19-DNA in serum with quantitative polymerase chain reaction （PCR） revealed a high level of viral load. After 2 courses of intravenous immunoglobulin （IVIG） therapy, bone marrow erythropoiesis recovered with his hemoglobin level increased to 123 g/L. He had a lowlevel PVB19 load for a 5-too follow-up period without recurrence of PRCA, and finally the virus was cleared. Our case indicates that clearance of PVB19 by IVIG in transplant recipients might be delayed after recovery of anemia.     

Successful treatment of thymoma-associated pure red cell aplasia with intravenous immunoglobulins

Repeated cycles of intravenous immunoglobulins (IVIG) have been reported to be successful in a few patients with idiopathic pure red cell aplasia (PRCA) or associated with another pathology. The efficacy of this treatment for PRCA with thymoma has not been reported previously. We describe here the case of a 75-yr-old man who presented with PRCA associated with a benign thymoma. After failure of thymectomy, corticosteroids and octreotide, a complete durable remission was obtained after a single 5-d cycle of IVIG.     

Pure red cell aplasia. Stable complete remission following antilymphocyte globulin administration

A 25-yr-old woman with idiopathic pure red cell aplasia achieved complete remission following a single 5-day course of antilymphocyte globulin at a dose of 50 mg/kg daily by intravenous injection as initial and sole therapy. Apart from transient arthralgia and asymptomatic thrombocytopenia there were no side effects. At 2 yr, the patient has normal peripheral blood, bone marrow and in vitro culture studies. This approach offers an alternative to conventional immunosuppressive therapy where there is evidence of an underlying immune disorder.     

Successful high-titer immunoglobulin therapy for persistent parvovirus B19 infection in a lymphoma patient treated with rituximab-combined chemotherapy

A 40-year-old female diagnosed with follicular lymphoma was treated with rituximab-combined chemotherapy. Although she achieved complete remission, she developed progressive anemia and reticulocytopenia. Bone marrow examination revealed features of pure red cell aplasia and hemophagocytosis. In addition, the appearance of large pronormoblasts suggested that she was infected with parvovirus B19. Excess viral DNA in her bone marrow confirmed that her illness was caused by persistent parvovirus B19 infection. Serum immunoglobulin levels decreased beyond the lower normal limit, which indicated that her humoral immunity was impaired after rituximab-combined chemotherapy. Although she had been infected with parvovirus B19, she was re-infected and failed to control the viral expansion. High-titer immunoglobulin against parvovirus B19 was intravenously administrated and resulted in remarkable reticulocytosis and improvement of anemia. High-titer immunoglobulin, which contained a sufficient amount of neutralizing antibodies against parvovirus B19, likely inactivated most viruses in vivo. We successfully eradicated the virus after 2 courses of high-dose therapy at 0.5 g/kg/day every week followed by 8 courses of maintenance therapy at 0.1 g/kg/day every other week. It is important to consider that parvovirus B19 infection is a possible cause of progressive anemia in B-cell lymphoma patients treated with rituximab-combined chemotherapy. We propose that the use of high-titer immunoglobulin against parvovirus B19 may enable such immunocompromised patients to eradicate the virus before sufficient immune system reconstruction.     

Successful re‐transplantation in patient with recurrent parvovirus B19 pure red cell aplasia

Impaired cell‐mediated, as well as antibody‐mediated immunity predisposes a renal transplant recipient to a wide variety of atypical infection. With an increasing number of re‐transplant, the balance between immunosuppression and the risk of recurrent disease poses a clinical and therapeutic challenge. Here, we report a successful re‐transplantation in a case of parvovirus B19 infection leading to anaemia and collapsing glomerulopathy in the allograft managed with intravenous immunoglobulin (IVIG) and reduction of immunosuppression. This case emphasizes re‐consideration to renal transplant after clearance of the virus in a previous renal allograft lost to PVB19 infection.     

Pure red cell aplasia due to parvovirus B19 infection transmitted probably through hematopoietic stem cell transplantation

Abstract: Human parvovirus B19 is a very common infectious pathogen in humans. In healthy subjects, B19 infection is the cause of a self-limiting subclinical erythroid aplasia, followed by rash or arthralgia. In immunocompromised patients B19 can cause chronic anemia. This report presents the case of a 19-year-old male who developed severe anemia shortly after successful allogeneic hematopoietic stem cell transplantation. His marrow showed selective erythroid aplasia, and real-time polymerase chain reaction assay confirmed parvovirus B19 infection. Despite repeated high-dose immunoglobulin treatment, he remained anemic. His hematological status markedly improved after cessation of immunosuppression. Retrospective examination of the donor's blood suggests that hematopoietic stem cells could be the source of infection.     

Rituximab to treat chronic lymphoproliferative disorder‐associated pure red cell aplasia

We report four patients (mean age 65 yr; range 40–77 yr) affected by acquired pure red cell aplasia (PRCA) complicating chronic lymphoid disorders and treated with anti‐CD20 monoclonal antibody rituximab. Three out of four patients were given packed red cell transfusion. Steroids and recombinant erythropoietin (r‐Epo) were also administered as first‐line therapy without response. After a mean time of 57 d (range 23–62 d) from PRCA diagnosis, all patients received rituximab at a dosage of 375 mg/m²/wk for four consecutive weeks. First injection side effects of rituximab were minimal. All patients showed an increase in hemoglobin levels in response to rituximab, in one patient just after the first dose, in another patient after the second and in two other patients after the third dose. Three patients (75%) were considered in complete remission (CR) and one patient (25%) in partial remission 4 wk after the last rituximab infusion, despite a CR was obtained later (16 wk following the beginning of the therapy). Finally, at the last follow‐up (mean 18.5 months, range 2–60 months), all patients were alive and in continue CR. Despite very limited in number, these results suggest that rituximab is very effective in the treatment of PRCA complicating B‐cell chronic lymphoproliferative disorders.     

Development of pure red cell aplasia by transmission and persistent infection of parvovirus B19 through a kidney allograft

We report a case of pure red cell aplasia (PRCA) caused by parvovirus B19 (PVB19) infection, which was transmitted through a kidney allograft. The patient underwent a living‐donor kidney transplant from his wife at the age of 60. Despite successful engraftment with a normal creatinine level, he developed severe anemia that required frequent blood transfusions 2 months after transplantation. Renal anemia was unlikely as his serum erythropoietin level was extremely high. A bone marrow aspiration test demonstrated the existence of large proerythroblasts. Although anti‐PVB19 IgM antibody levels were not increased, polymerase chain reaction (PCR) detected PVB19 DNA in his serum. Thus, he was diagnosed as having PRCA induced by PVB19 infection. PCR analysis of total DNA isolated from 0‐hour biopsy sections showed the existence of PVB19 DNA. Furthermore, PVB19 proteins was detected on renal tubules of 0‐hour allograft by immunoperoxidase staining. Thus, transmission of PVB19 through the allograft was confirmed. A single course of intravenous immunoglobulin (IVIG) therapy resulted in substantial improvement; however, the effect was limited, and severe anemia relapsed after 5‐6 months. Several courses of IVIG with adjustment of immunosuppressive drugs resulted in long‐term remission. Our case demonstrates that donor‐transmitted PVB19 infection should be suspected in kidney transplant recipients who develop refractory anemia during the early post‐operative phase.     

Persistent parvovirus B19 infection resulting in red cell aplasia after allogeneic hematopoietic stem cell transplantation

Persistent parvovirus B19 (PVB) infection has been reported sporadically in immunocompromised patients including hematopoietic stem cell and solid organ transplant recipients. However, the pathogenesis of persistent infection has yet to be fully elucidated. We report here a patient with multiple myeloma developing red cell aplasia during the hematopoietic recovery after allogeneic hematopoietic stem cell transplantation (HSCT) caused by PVB. The patient had already had PVB viremia before transplantation and remained asymptomatic. The route of PVB transmission was considered to be direct contact with the patient's family member with primary PVB infection 1 month before transplantation. Treatment with intravenous immunoglobulin resulted in prompt resolution of anemia. These findings suggest that monitoring of PVB DNA is recommended for patients undergoing HSCT and having contact with individuals with documented PVB infection, even if they are asymptomatic.     

Acquired pure red cell aplasia: updated review of treatment

Pure red cell aplasia (PRCA) is a syndrome characterized by a severe normocytic anaemia, reticulocytopenia, and absence of erythroblasts from an otherwise normal bone marrow. Primary PRCA, or secondary PRCA which has not responded to treatment of the underlying disease, is treated as an immunologically-mediated disease. Although vigorous immunosuppressive treatments induce and maintain remissions in a majority of patients, they carry an increased risk of serious complications. Corticosteroids were used in the treatment of PRCA and this has been considered the treatment of first choice although relapse is not uncommon. Cyclosporine A (CsA) has become established as one of the leading drugs for treatment of PRCA. However, common concerns have been the number of patients treated with CsA who achieve sustained remissions and the number that relapse. This article reviews the current status of CsA therapy and compares it to other treatments for diverse PRCAs.     

Pure red cell aplasia: further evidence of T cell clonal disorder

Summary. We report a patient with pure red cell aplasia and type I autoimmune polyglandular syndrome who also had an expansion of suppressor T lymphocytes in the peripheral blood. Southern blotting of DNA from these cells suggested T cell receptor (TCR) γ gene rearrangement. We confirmed true clonality of this by amplification of the gene rearrangement using the polymerase chain reaction and subsequent analysis of the product by gene cloning and DNA sequencing.     

Azathioprine-associated pure red cell aplasia

Abstract. Azathioprine-associated pure red cell aplasia in patients with a renal allograft is a rare complication. Although immunological inhibition of erythroid progenitor cell has been suggested, the cause of this phenomenon remains unclear. The patient we describe showed a decrease in the number of erythroid progenitor cells and no evidence for the presence of a serum inhibitor of these precursor cells. Discontinuation of azathioprine was associated with a complete recovery from anaemia as well, with an increase in the number of erythroid progenitor cells.     

A case of pure red cell aplasia and systemic lupus erythematosus caused by human parvovirus B19 infection

Human parvovirus B19 (B19) rarely induces pure red cell aplasia (PRCA) in healthy hosts. Meanwhile B19 infection is often clinically similar to systemic lupus erythematosus (SLE), and several cases have been reported wherein B19 actually stimulated SLE exacerbation in an immunocompetent subject. An 82-year-old healthy woman was diagnosed to have complicated with B19 infection and PRCA. Four weeks later, she had high fever, polyarthritis, and oral ulcers, additionally diagnosed with SLE, and subsequently, 15 mg of prednisone was started. This is the first case wherein B19 infection caused both PRCA and SLE in a healthy patient as far as our investigations are concerned.     

Pure red cell aplasia due to parvovirus B19 in a patient treated with rituximab

Rituximab is a chimeric monoclonal antibody directed against CD20 and used in the treatment of B-cell non-Hodgkin's lymphoma. Due to its ability to deplete B lymphocytes, rituximab can interfere with humoral immunity, causing it to be suppressed for several months after treatment. The reported case depicts a serious consequence of this effect of rituximab therapy: pure red cell aplasia resulting from chronic parvovirus B19 infection. The point of interest in this case is not only the association between rituximab therapy and pure red cell aplasia, but the diagnostic and therapeutic utility of the knowledge of parvovirus B19 as the likely etiologic link between the two. Given the known efficacy of intravenous immunoglobulin (IVIg) in the treatment of chronic parvovirus B19 infection, this therapy can cure some of these patients and successfully render most others transfusion-independent until recovery of their own humoral immune system.