The muscle-related complications of fasciitis and myositis, caused by chronic GVHD after Allo-SCT are relatively rare, but at times will severely impair a patient's quality of life (QOL). We performed a retrospective analysis in Japanese Allo-SCT recipients to identify the incidence, risk factors and clinical features of fasciitis and myositis. In 1967 patients who underwent Allo-SCT between January 1994 and March 2005 and survived beyond 90 days post transplantation, eight patients developed fasciitis and nine patients developed myositis, with a 5-year cumulative incidence of 0.55% and 0.54%, respectively. The median time from SCT to the development of fasciitis and myositis was 991 and 660 days, respectively. PBSCT was a risk factor for developing fasciitis, but no risk factors were found for myositis. The response to immunosuppressive treatment was better in patients with myositis than fasciitis, and the overall survival after developing these symptoms was better in patients with myositis than those with fasciitis. An early diagnosis by a biopsy, which includes fascia and muscle or magnetic resonance imaging (MRI) and prompt treatment may be important to prevent an impairment of the patient's QOL with persistent disability.
Rheumatoid arthritis (RA) is associated with an increased risk of developing lymphoma. Although the pathogenesis is still unclear, the increased risk appears to be related to the high inflammatory activity of RA, immunosuppressive agents, or Epstein-Barr virus (EBV) infection. We investigated the relationship between EBV latent infection and methotrexate (MTX)-associated lymphoma in RA patients. Nine patients were diagnosed with non-Hodgkin's lymphoma (NHL) during MTX treatment for RA in a multicenter study. The pathologic findings were consistent with diffuse large B-cell lymphoma in 8 patients and peripheral T-cell lymphoma, unspecified in 1. EBV infection was detected in 3 patients by in situ hybridization. Among all 9 patients who were initially treated by MTX withdrawal alone, 2 obtained spontaneous complete response (CR), 1 had partial response, 2 had stable disease (SD), and 4 had progressive disease. Both patients who had a CR and 1 who had SD were positive for EBV. Further examination of the latent EBV infection patterns revealed that 2 patients who obtained a CR had latency Type III, and the other with SD had latency Type II. These results demonstrate that immunodeficiency caused by MTX treatment is associated with the development of EBV-related NHL in RA patients. In patients who were treated by MTX for RA and developed NHL, remission can be observed following MTX withdrawal especially in NHL with latency Type III EBV infection. The analysis of EBV infection, including the latency types, is useful to decide the optimum therapeutic strategy. Am. J. Hematol. 82:1106Hematol. 82: -1109Hematol. 82: , 2007
Epstein-Barr virus (EBV)-associated T/NK-cell lymphoproliferative disease (LPD) has been linked to several different disorders. Its prognosis is generally poor and a treatment strategy has yet to be established. There are reports, however, that hematopoietic stem cell transplantation (HSCT) can cure this disease. To clarify the current situation regarding allogeneic hematopoietic stem cell transplantation (allo-HSCT) for EBV-associated T/NK-LPD, a nationwide survey was performed in Japan. Data for 74 patients were collected. There were 42 cases of chronic active EBV infection (CAEBV), 10 cases of EBV-associated hemophagocytic lymphohistiocytosis (EBV-HLH), and 22 cases of EBV-associated lymphoma/leukemia (EBV-lymphoma/leukemia). Of those with CAEBV, 54% had the EBV-infected T-cell type and 59% with EBV-lymphoma/leukemia had the EBV-infected NK-cell type. Most patients with EBV-HLH and EBV-lymphoma/leukemia received allo-HSCT within 1 year after onset compared to only 14% of patients with CAEBV. The event-free survival (EFS) rate following allo-HSCT was 0.561 ± 0.086 for CAEBV, 0.614 ± 0.186 for EBV-HLH, and 0.309 ± 0.107 for EBV-lymphoma/leukemia. The EFS of allo-HSCT with conventional conditioning was 0.488 ± 0.074 and with reduced-intensity conditioning was 0.563 ± 0.124. Thus, in a substantial number of cases, EBV-associated T/NK-LPD can be cured by either allogeneic conventional stem cell transplantation or reduced-intensity stem cell transplantation. Am. J. Hematol. 83:721-727, 2008. V
Recently, animal studies have demonstrated the efficacy of endothelial progenitor cell (EPC) therapy for diabetic wound healing. Based on these preclinical studies, we performed a prospective clinical trial phase I/IIa study of autologous G-CSF-mobilized peripheral blood (PB) CD34(+) cell transplantation for nonhealing diabetic foot patients. Diabetic patients with nonhealing foot ulcers were treated with 2 × 10(7) cells of G-CSF-mobilized PB CD34(+) cells as EPC-enriched population. Safety and efficacy (wound closure and vascular perfusion) were evaluated 12 weeks posttherapy and further followed for complete wound closure and recurrence. A total of five patients were enrolled. Although minor amputation and recurrence were seen in three out of five patients, no death, other serious adverse events, or major amputation was seen following transplantation. Complete wound closure was observed at an average of 18 weeks with increased vascular perfusion in all patients. The outcomes of this prospective clinical study indicate the safety and feasibility of CD34(+) cell therapy in patients with diabetic nonhealing wounds.
Summary:To establish the most appropriate prophylactic therapy and risk factors for predicting hemorrhagic cystitis (HC) after stem cell transplantation (SCT), we retrospectively analyzed the clinical records of 450 transplant patients treated from 1982 to 2002. In all, 81 patients developed early-and/or late-onset HC (early ¼ 29, late ¼ 48, both ¼ 4). For the incidence of early-onset HC, administration of cyclophosphamide (CY) (P ¼ 0.0079, odds ratioCI ¼ 2.055-9.292), antithymocyte globulin (P ¼ 0.0009, OD ¼ 3.368, 95% CI ¼ 1.642-6.911), nonradiation (P ¼ 0.0163, OD ¼ 2.564, 95% CI ¼ 0.181-0.841), 2-mercaptoethane sodium sulfonate (Mesna) (P ¼ 0.0001, OD ¼ 7.519, 95% CI ¼ 2.847-19.858), and bladder irrigation (P ¼ 0.0001, OD ¼ 4.950, 95% CI ¼ 2.328-10.523) were risk factors. By Fisher's exact test, the combination of BU and Mesna was a more significant risk factor (Po0.001) than Mesna alone (P ¼ 0.008) compared to the administration of neither agent. By multivariate analysis, prophylactic administration of Mesna (P ¼ 0.0105, OD ¼ 5.301, 95% CI ¼ 1. 477-19.026) and bladder irrigation (P ¼ 0.0001, OD ¼ 9.469, 95% CI ¼ 3.872-23.156) were significant risk factors of early-onset HC. We conclude that (i) highdose BU as well as CY is a cause of HC, (ii) protective bladder irrigation has an opposite effect, and (iii) Mesna possibly has a toxic effect on bladder mucosa. Bone Marrow Transplantation (2003) 32, 903-907.
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