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Biomedical subjects

Masahiro Kami

Publications and source records attributed to Masahiro Kami.

At least 55 records · Page 3Linked to original sources

Allogeneic hematopoietic stem cell transplantation with a reduced-intensity conditioning regimen for treatment of metastatic renal cell carcinoma: single institution experience with a minimum 1-year follow-up.

OBJECTIVE: The aim of this study was to evaluate the safety and efficacy of allogeneic hematopoietic stem cell transplantation with a reduced-intensity conditioning regimen (RIST) for interferon-alpha-refractory metastatic renal cell carcinoma (RCC). PATIENTS AND METHODS: Of 26 patients referred to the National Cancer Center Hospital for possible RIST between June 2000 and April 2002, an HLA-identical relative was identified for 12 patients. Nine patients underwent RIST. The conditioning regimen consisted of fludarabine 180 mg/m2 or cladribine 0.66 mg/kg, plus busulfan 8 mg/kg and rabbit antithymocyte globulin 5 mg/kg. Graft-vs-host disease (GVHD) prophylaxis was cyclosporine alone. RESULTS: All patients achieved engraftment without grade III to IV nonhematologic regimen-related toxicity. All patients achieved complete donor-type chimerism without donor lymphocyte infusion by day 60. Four patients developed acute GVHD, and four developed chronic GVHD. One patient (11%) achieved partial response. As of July 2003, six patients were alive at median follow-up of 681 days. The actuarial overall survival rate was 89% at 1 year and 74% at 2 years. The overall survival rate tended to be higher in the 12 patients with a matched donor than in the other 14 patients without a matched donor (p = 0.088). CONCLUSION: Our RIST procedure is feasible without severe toxicity. The efficacy of RIST for RCC should be confirmed in phase II/III clinical trials.

Acute Disease↗

Balance between acute graft-versus-host disease and graft-versus-tumor effect after reduced-intensity transplantation for metastatic renal cell carcinoma.

We describe a patient who had received reduced-intensity stem cell transplantation (RIST) for metastatic renal cell carcinoma (RCC). A 37-year-old man developed rapid progression of RCC during steroid therapy for immune-mediated thrombocytopenia and graft-versus-host disease (GVHD). After discontinuation of corticosteroid, RCC achieved long stable disease with the presence of chronic GVHD, despite low dose of prednisolone. This case suggests the impact of immunosuppression on progression of metastatic RCC after RIST.

Acute Disease↗

Vesicles as initial skin manifestation of disseminated fusariosis after non-myeloablative stem cell transplantation.

A 52-year-old man underwent non-myeloablative stem cell transplantation from his HLA identical sister for the treatment of mantle cell lymphoma. On day 0, he developed a high-grade fever, watery diarrhea and vesicles scattered on the skin. Well experienced dermatologists diagnosed these lesions as VZV reactivation. High dose antiviral agents were ineffective, and Fusarium solani was cultured from his stool and sputum. Systemic fusariosis progressed rapidly and he died of multiorgan failure on day 18. It is sometimes difficult to differentiate between viral and fungal blisters based on macroscopic examinations. We recommend early histopathological examination of the skin, when HSCT recipients develop vesicles.

Blister↗

Fatal hepatic failure associated with graft rejection following reduced-intensity stem-cell transplantation for chronic idiopathic myelofibrosis (CIMF).

A 54-year-old man with chronic idiopathic myelofibrosis (CIMF) underwent RIST. His clinical course had been uneventful until day 60, when splenomegaly reappeared. Hepatic dysfunction developed on day 75. Recipient-type hematopoiesis increased to 51% on day 90. After rapid tapering of cyclosporin, serum levels of AST and ALP normalized in parallel with recovery of complete chimerism on day 134. Yet, jaundice progressed. He died of liver failure on day 176. Postmortem examination revealed neither GVHD nor VOD. Graft rejection following RIST for CIMF may lead to fatal hepatic damage through extramedullary hematopoiesis in the liver or cytokine-mediated immune dysregulations.

Chronic Disease↗

Reduced-intensity hematopoietic stem cell transplantation (RIST) for solid malignancies.

Reduced intensity stem cell transplantation (RIST) is a new approach of stem cell transplantation, which has shown promising features as reported in multiple phase I and II studies. Elderly patients, who are not eligible for conventional myeloablative hematopoietic stem cell transplantation (HSCT), are now treatable with RIST. It has also reduced regimen-related toxicity and provided better prognosis in short-term follow-up than conventional HSCT. Among solid tumors, metastatic renal cell carcinoma was found to respond well to RIST. Clinical studies are currently being conducted to evaluate the efficacy of RIST in other types of solid tumors. However, the mechanism of graft-versus-host disease (GVHD) and graft-versus-tumor (GVT) effects remains unclear. More knowledge on the mechanism is crucial to enhance the antitumor effect and to improve the prognosis further.

Animals↗

Comparative analysis of clinical outcomes after allogeneic bone marrow transplantation versus peripheral blood stem cell transplantation from a related donor in Japanese patients.

A reduced incidence of graft versus host disease (GvHD) has been documented among Japanese allogeneic bone marrow transplantation (BMT) patients, as the Japanese are genetically more homogeneous than western populations. To clarify whether this ethnic difference affects the results of allogeneic peripheral blood stem cell transplantation (PBSCT), we conducted a nationwide survey to compare clinical outcomes of allogeneic PBSCT (n = 214) and BMT (n = 295) from a human leucocyte antigen-identical-related donor in Japanese patients. The cumulative incidence of grades II-IV acute GvHD was 37.4% for PBSCT and 32.0% for BMT. The cumulative incidence of extensive chronic GvHD at 1 year was significantly higher after PBSCT than BMT (42% vs. 27%; P < 0.01). The organ involvement patterns of GvHD were different between the two groups. By multivariate analyses, the incidence of chronic GvHD was significantly increased in PBSCT, whereas the stem cell source did not affect the incidence of acute GvHD, transplant-related mortality, relapse or survival. We concluded that Japanese PBSCT patients have an increased risk of chronic GvHD compared with BMT patients, but the incidence of acute GvHD was still lower than in western populations. Thus, the choice of haematopoietic stem cell source should be considered based on data for individual ethnic populations.

Acute Disease↗

EBV-positive Burkitt lymphoma as a late-onset posttransplantion lymphoproliferative disorder after allogeneic stem cell transplantation.

Posttransplantation lymphoproliferative disorder (PTLD) is one of the well-recognized complications after allogeneic stem cell transplantation (SCT). It generally occurs early after SCT, and only a few reports of late-onset cases are available. We report a 58-year-old male patient who developed lymphoma 4 years after allogeneic SCT for chronic myeloid leukemia. The presence of c-myc translocation and Epstein-Barr virus-encoded RNA in the lymphoma cells, without rearrangement of the 3'-bcr region, confirmed the histopathologic diagnosis of Burkitt lymphoma. DNA chimerism analysis revealed that the lymphoma cells were of donor origin. The patient achieved complete response with intensive chemotherapy. To our knowledge, this is the first report of Burkitt lymphoma as a PTLD occurring after allogeneic SCT.

Burkitt Lymphoma↗

The lower pole of the earlobe is an alternative site for painless blood sampling in the self-assessment of blood glucose concentrations.

OBJECTIVES: Measurement of blood glucose is essential for better control of diabetes mellitus. The pain associated with repeated blood sampling is a significant problem, and a less painful technique would be advantageous. This study was conducted to establish a less painful method of blood sampling for monitoring of blood glucose concentrations. METHODS: Fourteen healthy doctors and nurses at the age of 22 to 32 years were enrolled into this study. The earlobe was divided into 20 areas. Each area was punctured with a fine needle and the pain was assessed by the visual analog scale (VAS). Then, localized cooling or warming was applied before puncture and the pain was assessed by the VAS. RESULTS: The VAS tended to be lower toward the lower part of the earlobe. The VAS in the uppermost area was 53.1 +/- 19.1 mm and 28.9 +/- 16.8 mm in the lowest part of the earlobe. The VAS was higher in the uppermost area than in the lowest area in six of the seven volunteers (p=0.028). We did not find significant differences in the VAS and blood glucose levels between the control sampling and the warming, or cooling sampling. The localized warming shortens the time to obtain blood by 4.4 seconds (p=0.0426). CONCLUSION: The area of the ear, but not localized cooling or warming, significantly affects the pain in sampling blood from the earlobe. Blood sampling for glucose tests are recommended to be obtained at the lower pole of the earlobe.

Adult↗

[Fungal prophylaxis following reduced-intensity stem cell transplantation (RIST)].

Hematopoietic stem cell transplantation has been established as a curative treatment for advanced hematologic malignancies. Transplantation with a reduced-intensity conditioning regimen has been developed. The minimal toxicity of reduced-intensity stem cell transplantation (RIST) has made transplantation available for patients of advanced age or with organ dysfunction. The response of malignant lymphoma and some solid tumors to RIST has been observed. RIST with unrelated donors and umbilical cord blood has been studied. Fungal infection is an important complication of RIST. Since the prognosis of fungal infection is poor, the management has been focused on its prophylaxis. Given recent progression in RIST management, the strategy of infectious prophylaxis has also changed. Equipment in the hospital is important for fungal infection; however, the median day of the development of fungal infection is day 100, when most patients are followed as outpatients. The focus of fungal management after RIST is oral antifungal agents rather than in-hospital equipment. Various antifungal agents have recently been developed and applied for clinical use. Many antifungals have been developed simultaneously for the first time. A major change in antifungal management will probably occur in the next several years.

Humans↗

High incidences of malignant lymphoma in patients infected with hepatitis B or hepatitis C virus.

It is still not clear whether there is an association between malignant lymphomas and hepatitis B or hepatitis C virus infections. Most studies from Italy and Japan support this association, but studies from other countries generally do not. We conducted a hospital-based case-control study to evaluate this association and show a significant association between the development of malignant lymphoma and infections by these viruses.

Adult↗

Fatal deep vein thrombosis after allogeneic reduced intensity hematopoietic stem cell transplantation for the treatment of metastatic gastric cancer.

A 61-year-old man received reduced intensity stem cell transplantation (RIST) for the treatment of metastatic gastric cancer. The cytoreductive course of RIST was uneventful until day 0, when fever suddenly developed and his performance status deteriorated. Edema developed in the bilateral lower extremities by day 7, which was diagnosed by Doppler ultrasonography as deep vein thrombosis (DVT) involving the femoral veins to the inferior vena cava. While the edema improved with anticoagulation treatment, gastrointestinal graft-versus-host disease (GVHD) followed on day 13. Diarrhea subsided spontaneously, but hypoalbuminemia persisted, with the subsequent development of oliguria and jaundice on day 18. He died of sepsis on day 30, without any evidence of cancer progression. This case demonstrates that DVT is a potentially significant problem following RIST for solid tumors.

Anticoagulants↗

Antithymocyte globulin affects the occurrence of acute and chronic graft-versus-host disease after a reduced-intensity conditioning regimen by modulating mixed chimerism induction and immune reconstitution.

BACKGROUND: There have been no detailed analyses of the induction of donor cell-type chimerism, the onset and incidence of acute and chronic graft-versus-host disease (GVHD), and the immune recovery kinetics after reduced-intensity stem cell transplantation (RIST). METHODS: To address these, with particular emphasis on the impact of the use of antithymocyte globulin (ATG) in RIST, we compared 39 consecutively registered patients who underwent RIST from an HLA-matched related donor and 33 patients who underwent conventional marrow-ablative transplantation. RESULTS: The incidences of grades II to IV acute and chronic GVHD tended to be less in RIST with ATG than in either RIST without ATG or conventional marrow-ablative transplantation. In a multivariate analysis, the predictive factors for acute and chronic GVHD included, respectively, ATG and grades II to IV acute GVHD. In a chimerism analysis, the achievement of complete donor chimera in T-cell lineage was delayed in RIST without ATG compared with RIST with ATG (P=0.038), which might explain the observed delayed onset of acute GVHD in RIST with ATG compared with the other two regimens. The ratio of type 1 and 2 dendritic cells did not affect the development of GVHD, whereas the number of naive CD4+ T cells did. No difference was observed in the incidence of clinically definitive infection, including cytomegalovirus, among the three cohorts, regardless of the use of ATG. CONCLUSIONS: We suggest that the conditioning regimen and immunosuppressive strategy after RIST should be carefully balanced against the risk of GVHD and of relapse of the basic disorder caused by the lack of a graft-versus-leukemia benefit.

Acute Disease↗