Molecular impact and inducible factors associated with adenovirus infection in hematopoietic stem [corrected] cell transplant patients.

BACKGROUND AND PURPOSE OF STUDY: Latent and active adenovirus infections are detected in 5% to 20% of hematopoietic stem cell transplant (HSCT) patients. In addition to the significant role of adenoviral infection in the pathogenesis of late-onset hemorrhagic cystitis in HSCT patients, adenovirus infections may have possible roles in undefined posttransplant clinical complications. Therefore, pre- and posttransplantation we studied the prevalence and role of adenoviral infections among HSCT clinical syndromes using molecular methods. MATERIALS AND METHODS: In this cross-sectional study between 2005 and 2008. We collected 470 EDTA-treated blood samples from 125 HSCT recipients, including 70 (56%) men and 55 (44%) women. The 52 (41.6%) HSCT patients underwent autologous grafts and the other 73 (58.4%), from related donors. One EDTA-treated blood sample was collected from all recipients pretransplantation. Also once per week for 3 months we were collected blood samples from HSCT patients to evaluate the prevalence of adenovirus DNA infection by a qualitative in house polymerase chain reaction method. RESULTS: The adenovirus genome was diagnosed in 2/75 (2.7%) HSCT patient samples pretransplantation. There were 28/395 (7.1%) plasma samples of transplant patients infected with adenovirus DNA. Graft-versus-host disease (GVHD) clinical complications were observed in six adenovirus-infected transplant recipients; there was a significant correlation between these viral infections and GVHD clinical presentation. CONCLUSION: The high prevalence of adenovirus infection in HSCT recipients pre- and posttransplantation, was significantly related to GVHD symptoms, enforcing the important pathogenic role of these viral infections in clinical complications post-HSCT.

Bone marrow transplantation in thalassemia major patients using "short" anti-thymocyte globulin therapy in Shiraz, Southern Iran.

Allogeneic bone marrow transplantation (BMT) was performed on 113 Iranian transfusion-dependent thalassemia major patients from May 1993 through September 2003. To have at least 2 years follow-up, we report BMT on 90 patients transplanted up to December 2001. The donors were human leukocyte antigen (HLA)-identical, mixed lymphocyte culture (MLC)-nonreactive siblings (n = 74) on parents (n = 6); HLA-identical MLC-reactive siblings (n = 5) or parents (n = 1); and one HLA antigen-mismatched sibling (n = 4). The induction regimen in 11 patients was oral busulfan (BU) (14 mg/kg) and IV cyclophosphamide (CY; 200 mg/kg); in fifteen patients it was BU (15 mg/kg) and cyclophosphamide (CY; 200 mg/kg); in 47 patients, BU (15 mg/kg), CY (200 mg/kg), and short course of anti-thymocyte globulin (ATG, horse; 40 mg/kg including 10 mg/kg on days -2, -1, +1, +2); and in 15 patients, BU (15 mg/kg) CY (200 mg/kg), and ATG (60 to 100 mg/kg; 10 mg/kg at 3 to 5 days before and after BMT). Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine and prednisolone. The group who received BU (14 mg/kg) and CY (200 mg/kg), as compared to the group receiving BU (15 mg/kg) and CY (200 mg/kg), was of younger age and lower risk; median age 7 versus 10 years, and 46% versus 7% in Lucarelli's risk group class I (the best prognostic group), respectively. These patients showed a lower disease-free survival (DFS), namely 64% versus 73%, with a follow up of 2 to 10.5 years. Thus from 9.5 years ago, our standard protocol for BU has been 15 mg/kg. The group who received "short" ATG (40 mg/kg), BU (15 mg/kg), and CY (200 mg/kg) showed almost the same outcome as the group who received a higher dose of ATG (60 to 100 mg/kg), namely DFS 72% versus 73%, respectively, despite the fact that half of both groups were included in the Lucarelli's risk group class III (the worst prognostic group) 49% versus 53%. We showed the same DFS for the patients who received BU (15 mg/kg), CY (200 mg/kg), and no ATG compared with the ATG group (73% vs 72%), but 27% of the group without ATG developed grade IV acute GVHD and 54% developed chronic GVHD. In the group with short ATG, 15% and 17% of patients developed grade IV acute and chronic GVHD, respectively. There was no significant difference for falls in platelets and white blood cell or engraftment days and the number of packed red blood cell transfusions among the groups. The median hospital stay was longer for the group with BU (15 mg/kg), CY (200 mg/kg) namely 81 versus 61 to 65 days. Second bone marrow infusions were needed in 6% and 20% of patients who received ATG doses of (40 versus 60 to 100 mg/kg; respectively (1 to 2 month post-BMT). BU at a dose of 15 mg/kg was more effective than 14 mg/kg BU for its myeloablative properties. By adding "short" ATG course to the conditioning regimen, the incidence of grade IV acute and chronic GVHD was reduced in thalassemic patients, especially when an HLA disparity was present.

Bone marrow transplantation in thalassaemia patients in Shiraz, Islamic Republic of Iran.

We report the results of allogeneic bone marrow transplantation in 26 female and 37 male patients with beta-thalassaemia major (age range: 2-17 years), performed at Namazi Hospital over the period 1992-99. In all cases, standard conditioning and immunosuppressive regimens were employed. Currently, 50 patients remain thalassaemia-free, 9 of whom have developed chronic graft-versus-host disease. There were 8 deaths among the 13 unsuccessful transplant cases: 4 due to acute uncontrollable graft-versus-host disease, and 4 to non-transplant-related causes such as hypoglycaemia, hypersensitivity reactions and advanced disease. We conclude that allogeneic bone marrow transplantation is an effective therapy for the treatment of beta-thalassaemia major, particularly for patients classified as classes I and II.

Bone marrow transplantation in thalassaemia patients in Shiraz, Islamic Republic of Iran

We report the results of allogeneic bone marrow transplantation in 26 female and 37 male patients with beta-thalassaemia major [age range: 2-17 years], performed at Namazi Hospital over the period 1992-99. In all cases, standard conditioning and immunosuppressive regimens were employed. Currently, 50 patients remain thalassaemia-free, 9 of whom have developed chronic graft-versus-host disease. There were 8 deaths among the 13 unsuccessful transplant cases: 4 due to acute uncontrollable graft-versus-host disease, and 4 to non-transplant-related causes such as hypoglycaemia, hypersensitivity reactions and advanced disease. We conclude that allogeneic bone marrow transplantation is an effective therapy for the treatment of beta-thalassaemia major, particularly for patients classified as classes I and II

Acute graft-versus-host disease in thalassaemic marrow transplantation with low-dose antithymocyte globulin.

Our unit performed transplantations on 21 classes II and III thalassaemic patients (class II patients had either hepatomegaly or portal fibrosis and class III patients had both). We used busulfan (15 mg/kg) and cyclophosphamide (200 mg/kg). Graft-versus-host disease (GVHD) prophylaxis was cyclosporin, prednisolone and low-dose antithymocyte globulin. Our patient data showed a low incidence of acute GVHD following transplantation. We offer this regimen as an acceptable therapy for thalassaemic patients undergoing allogeneic marrow transplantation as a safe clinical procedure, irrespective of the class of patient.

Acute graft-versus-host disease in thalassaemic marrow transplantation with low-dose antithymocyte globulin

Our unit performed transplantations on 21 classes II and III thalassaemic patients [class II patients had either hepatomegaly or portal fibrosis and class III patients had both]. We used busulfan [15 mg/kg] and cyclophosphamide [200 mg/kg]. Graft-versus-host disease [GVHD] prophylaxis was cyclosporin, prednisolone and low-dose antithymocyte globulin. Our patient data showed a low incidence of acute GVHD following transplantation. We offer this regimen as an acceptable therapy for thalassaemic patients undergoing allogeneic marrow transplantation as a safe clinical procedure, irrespective of the class of patient