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.     

Pure red cell aplasia induced by B19 parvovirus during allogeneic bone marrow transplantation

We report a patient who had abrupt onset of pure red cell aplasia (PRCA) induced by B19 parvovirus during allogeneic bone marrow transplantation (BMT). A 14-year-old girl with APL in complete remission was admitted in February 1988, for the purpose of BMT. She was received marrow from HLA identical sister on March 17, 1988 (day 0). She received 120 mg/kg cyclophosphamide and 12 Gy total body irradiation for conditioning of BMT. For graft-versus-host disease (GVHD) prophylaxis she was given cyclosporine and short term methotrexate. She did not develop acute GVHD after BMT, but on the day 28 a bone-marrow aspirate revealed findings of PRCA. During this course the number of white blood cell and platelet favorably recovered. B 19 parvovirus DNA was detected in the serum of the day 30 and day 42. Antihuman B 19 parvovirus (HPV) antibody titers were increased: the values of anti-HPV IgM were suddenly elevated and those of anti-HPV IgG were elevated. Serum on the day 42 inhibited erythroid progenitors (CFU-E, BFU-E) but not inhibited myeloid progenitors (CFU-C). A reticulocyte count recovered on the day 50. As the patient was HPV-IgG negative prior to BMT and the donor was HPV-IgG seronegative, the source of infection may be platelet transfusion (day 7 through 14).     

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 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.     

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.     

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.     

Recovery of erythropoiesis following allogeneic bone marrow transplantation for chronic lymphocytic leukaemia-associated pure red cell aplasia

Pure red cell aplasia is a rare condition, that can be either idiopathic or associated with a lymphoproliferative disorder. The latter is considered to result from T cell-mediated suppression of haematopoiesis, and usually responds well to treatment with immunosuppressive medication. We describe a patient with B-CLL-associated pure red cell aplasia who did not respond to several courses of immunosuppressive treatment. Erythropoiesis was finally restored after allogeneic bone marrow transplantation.     

Impact of nonmyeloablative conditioning regimens on the occurrence of pure red cell aplasia after ABO-incompatible allogeneic haematopoietic stem cell transplantation

BACKGROUND AND OBJECTIVES: In the setting of major ABO-incompatible allogeneic haematopoietic stem cell transplantation (HSCT), pure red cell aplasia (PRCA) is linked to the persistence of host residual plasma cells secreting antidonor isohaemagglutinins (HA) after transplantation. There are conflicting results regarding the impact of the intensity of conditioning regimen on the occurrence of PRCA after major ABO-mismatched HSCT. MATERIAL AND METHODS: To address this question, we compared two cases occurring after nonmyeloablative (NMA) and myeloablative (MA) HSCT and reviewed previous cases reported in the NMA setting. RESULTS AND CONCLUSIONS: We observed a delayed disappearance of antidonor HAs in the NMA setting, associated to a more prolonged period of red blood cells transfusion dependence than in the MA setting. In our case as in several others, the disappearance of antidonor HAs and resolution of PRCA were observed after reinforcement of the graft-versus-host effect (i.e. immunosuppression removal or donor leukocytes infusion).     

Human parvovirus B19 infection in bone marrow transplantation patients

We report the results of a survey of parvovirus B19 infection carried out with the aim to evaluate the frequency and the role of this infection in bone marrow transplant (BMT) recipients, as it is known that B19 virus can persist in clinical circumstances of immunodeficiency. Fifty-one patients subjected to BMT in the Bone Marrow Transplantation Center of Florence were enrolled in this study. Immunological and virological indications of B19 infection were tested weekly during the stay in hospital. A high rate of seroconversion or B19 antibody rise was observed, but, in absence of B19 IgM or B19 DNA presence, this result seems to be attributable to a passive immunization, rather than to a recent viral infection. In these 51 patients, as well as in 59 others not included in this study, clinical manifestations imputable to B19 infection have never been observed. It is possible that the isolation measures and the intravenous immunoglobulins (IVIG) administration may contribute in preventing B19 infection in the BMT recipients at least until the hospital discharge. © 1993 Wiley-Liss, Inc.     

Cyclosporine as prophylaxis for graft versus host disease in adults undergoing allogeneic bone marrow transplantation

Fifteen adult patients undergoing allogeneic bone marrow transplantation (BMT) received cyclosporine (CSP) as prophylaxis of graft versus host disease (GVHD). In our patients eleven were hematologic malignancies, and four were severe aplastic anemia. Twelve patients were HLA-matched, and three were one locus mismatched. Three patients received CSP only, twelve received CSP and short term methotrexate. Seven patients had acute GVHD, but GVHD over Grade II were seen in only 3 patients who were transplanted from HLA-one locus mismatched donor. 7 patients had chronic GVHD. CSP were given intravenously at 3-5 mg/kg, starting 1 day before BMT. From about day 30, CSP was given orally. CSP concentrations when patients were given orally were lower in patients who had chronic GVHD. Although hypertension and water retention were seen in 8 patients, and renal dysfunction was seen in 3 patients, the side effects of CSP were mild and transient. There were no correlations between serum concentrations and the side effects of CSP. Three patients had the disturbance of hematopoiesis. Ten of fifteen patients are alive at median follow-up of 18.5 months (8-41 months) after BMT.     

骨髓移植术后急性移植物抗宿主病的肠镜及病理表现

目的 探讨非亲缘异基因骨髓移植术后出现肠道症状的急性移植物抗宿主病(GVHD)患者的结肠镜、病理特征及治疗情况.方法 分析总结4例急性GVHD中、重度肠道受损患者的内镜病理资料.结果 4例患者分别于移植后的21～57 d发生不同程度肠道黏膜受损所致的腹痛、腹泻等症状,肠镜和活检病理示肠黏膜允血水肿或上皮层坏死脱落,肠腔正常结构消失,直、结肠多发性溃疡,见较多淋巴细胞和浆细胞浸润,未见巨细胞病毒(CMV)包涵体和巨细胞,诊断为急性GVHD.予以糖皮质激素等治疗,1例治疗无效死亡,其余得到有效控制.结论 非亲缘异基因骨髓移植后发生急性GVHD的肠道受损,诊断有赖于肠镜和活检病理,据此及时正确治疗后多能得到有效控制.