Infectious complications in patients receiving autologous CD34-selected hematopoietic stem cell transplantation for severe autoimmune diseases.

Long-term analysis of infectious complication after high-dose immunosuppressive therapy with CD34-selected autologous hematopoietic stem cell transplantation for patients with severe autoimmune diseases (AD) was performed. Theoretically, CD34 selection can reduce the risk of reinfusion of autoreactive lymphocytes. However, it is also associated with a significant reduction in T cells, natural killer cells, and monocytes, which in turn may compromise immune reconstitution, thereby increasing the risk of infection. Moreover, AD compromises host immunity and causes organ damage resulting in dysfunction of the cutaneous or mucosal barrier. In this study, the incidence rate of infections is reported in 14 patients who underwent high-dose (200 mg/kg) cyclophosphamide therapy followed by reinfusion of CD34-selected autologous peripheral blood stem cells. Bacterial complication occurred in 3 of 14 (21%) patients. Cytomegalovirus reactivation and adenovirus hemorrhagic cystitis were observed in 9 (64%) and 2 (14%) patients, respectively. As for late infectious complications, 7 patients (50%) developed dermatomal varicella zoster virus infection. No infection-related mortality was seen in this case series. Because the risk for infections approaches that seen in allogeneic transplant recipients, infection surveillance, diagnostic workup, and prophylactic strategies similar to those applicable to allogeneic recipients are warranted.

Rituximab does not compromise the mobilization and engraftment of autologous peripheral blood stem cells in diffuse-large B-cell lymphoma.

To investigate effects of the preautografting administration of rituximab on the mobilization and engraftment of peripheral blood stem cells (PBSC), we retrospectively analyzed the outcomes of 43 newly diagnosed diffuse-large B-cell lymphoma patients who received CHOP chemotherapy with or without rituximab as a first-line treatment before autologous PBSC transplantation (PBSCT). There was no difference in the number of CD34(+) cells among PBSC between the non-rituximab and the rituximab groups. Although B-cells were completely depleted from PBSC in the rituximab group, we found no difference in the expression of CXCR-4, VLA-4 and c-Kit on PBSC, indicating that rituximab did not affect the expression of these adhesion molecules, which might be involved in the mechanism of mobilization. There was no significant difference in the recovery of neutrophils and platelets, transplant-related toxicity and post-transplant complications between the two groups. Despite the short follow-up, there was no significant difference in progression-free survival between the two groups. These results indicated no adverse effect of rituximab on the mobilization and engraftment of PBSC. Larger studies are required to determine the impact of rituximab on the mobilization and function of PBSC as well as whether a survival advantage exists in patients who undergo auto-PBSCT with rituximab.

Cidofovir for treating adenoviral hemorrhagic cystitis in hematopoietic stem cell transplant recipients.

Adenovirus (AdV) infection is an important cause of morbidity and mortality in hematopoietic stem cell transplant (HSCT) recipients. We treated 16 patients with AdV hemorrhagic cystitis (HC) following HSCT with cidofovir (CDV; 1 mg/kg/day, three times weekly for 3 weeks). Patients included 10 males and six females with a median age of 50 years (range 10-62). Two of the 16 patients were unevaluable because of early death from nonadenoviral causes. CDV therapy cleared AdV from urine in 12 of 14 patients (86%). Of 14 patients, 10 (71%) showed clinical improvements in HC. Among 14 patients, seven (50%) had avoided renal damage, the most important CDV toxicity. One patient previously treated with foscarnet for cytomegalovirus (CMV) required hemodialysis, and CDV treatment was discontinued. In another patient, CDV treatment was discontinued because of grade 2 nephrotoxicity. Four patients became positive for CMV antigenemia while being treated with CDV, and two developed herpes simplex virus (HSV) stomatitis while being treated with CDV. CDV proved effective in treating AdV HC in transplant patients. However, CDV at 1 mg/kg/day given three times weekly failed to prevent breakthrough infection with CMV and HSV in some patients.

Influence of transplanted dose of CD56+ cells on development of graft-versus-host disease in patients receiving G-CSF-mobilized peripheral blood progenitor cells from HLA-identical sibling donors.

We investigated effects of variations in the cellular composition of G-CSF-mobilized peripheral blood progenitor cell (G-PBPC) allografts on clinical outcomes of allogeneic PBPC transplantation. We retrospectively analyzed transplanted doses of various immunocompetent cells from 27 HLA-identical sibling donors in relation to engraftment, incidence of graft-versus-host disease (GVHD), and survival. Significant variability was documented in both absolute numbers and relative proportions of CD34+, CD2+, CD3+, CD4(high)+, CD4+25+, CD8(high)+, CD19+, CD56+, and CD56+16+ cells contained in these allografts. Stepwise Cox regression analysis revealed that the CD56+ cell dose was significantly inversely correlated with the incidence of GVHD. Thus, there was a significantly higher incidence of grade II acute GVHD in patients receiving a lower CD56+16+ cell dose (hazard ratio (HR) 0.0090; 95% confidence interval (CI), <0.00001-3.38; P=0.031), a higher incidence of chronic GVHD in those receiving allografts with a lower CD56+16+ to CD34+ ratio (HR <0.00001; 95% CI <0.00001-0.0007; P=0.0035), and a higher incidence of extensive chronic GVHD in those receiving allografts with a lower CD56+ to CD34+ ratio (HR <0.00001; 95% CI <0.00001-0.053; P=0.0083). These results suggest that CD56+ cells in G-PBPC allografts from HLA-identical sibling donors may play an important role in preventing the development of GVHD.

Role of autotransplantation in the treatment of acute promyelocytic leukemia patients in remission: Fukuoka BMT Group observations and a literature review.

We retrospectively analyzed the outcomes of 26 patients with acute promyelocytic leukemia (APL) in the first CR (CR1) or second CR (CR2), who underwent autologous PBSCT (auto-PBSCT) between 1992 and 2008. All patients received all-trans retinoic acid-based induction therapy. After two courses of consolidation chemotherapy, upfront auto-PBSCT was performed in 20 patients in the CR1. Five patients had a high WBC count of more than 10 × 10(9)/L (high risk), while 15 patients had a count of less than 10 × 10(9)/L (low risk) at initial presentation. In addition, six patients, who were considered as low-risk patients at presentation, had a relapse after three cycles of consolidation and 2 years of maintenance therapy, but gained the molecular remission after re-induction and consolidation, and underwent auto-PBSCT in the CR2. In 26 recipients, engraftment was rapid and no TRM was documented. All 20 patients autotransplanted in CR1 were still in CR at a median of 133 months (73-193 months), and six patients who underwent auto-PBSCT in CR2 were also still in CR at a median of 41 months (2-187 months) without maintenance therapy. PML/RARα chimeric mRNA was undetectable in PBSC or BM samples examined before auto-PBSCT. Despite a small number of cases studied, our retrospective observations suggest that auto-PBSCT may be an effective treatment option to continue durable CR in the treatment of high-risk APL. We review previous reports and discuss the role of autotransplantation in the treatment of APL patients in CR.

Long-term outcomes of autologous PBSCT for peripheral T-cell lymphoma: retrospective analysis of the experience of the Fukuoka BMT group.

Peripheral T-cell lymphoma (PTCL) is generally characterized by poor prognosis after conventional chemotherapy compared with aggressive B-cell lymphoma. To elucidate the role of high-dose chemotherapy (HDCT) with auto-SCT, we retrospectively analyzed the outcomes of 39 patients with PTCL who received HDCT and auto-SCT between 1990 and 2005. Eleven patients were histologically typed as angioimmunoblastic, nine as anaplastic large-cell lymphoma, seven as natural killer/T-cell lymphoma and twelve as PTCL unspecified. Clinical conditions at transplantation were complete response (CR) in 27 patients and non-CR in 12 patients. Thirty-two patients received a pre-transplant conditioning regimen (MCEC) comprising ranimustine, carboplatin, etoposide and CY, and seven did other TBI-based regimens. Rapid engraftment was obtained in all cases, and transplant-related death was not seen. An estimated 5-year OS was 62.1% with a median follow-up of 78 months. The 5-year OS was significantly higher in patients transplanted during complete response than in those during other disease status (71.4% vs 27.3%, P=0.046). HDCT supported by auto-SCT may therefore be effective as consolidation in CR for PTCL treatment.

A phase I-II trial of autologous peripheral blood stem cell transplantation in the treatment of refractory autoimmune disease.

OBJECTIVES: To carry out a phase I-II trial to elucidate the feasibility and efficacy of high dose cyclophosphamide (CY) supported by autologous peripheral blood stem cell transplantation (PBSCT) in the treatment of severe and refractory autoimmune disease (AD). METHODS: Peripheral blood stem cells (PBSCs) were mobilised during haematological recovery after relatively high dose CY (2 g/m2) for 2 days, followed by administration of granulocyte colony stimulating factor. After collecting PBSCs--more than 2x10(6) CD34+ cells/kg--by apheresis, CD34+ cells were immunologically selected and cryopreserved. Eight patients were enrolled--five had systemic sclerosis (SSc) alone, one had SSc with systemic lupus erythematosus, one amyopathic dermatomyositis (ADM), and one Wegener's granulomatosis (WG). All of the patients were treated with high dose CY (50 mg/kg) for 4 days and autologous PBSCT. RESULTS: Haematopoietic reconstitution was rapid and sustained. Toxicity due to the regimen included various infections such as pneumonia, sepsis, cystitis, herpes zoster, and acute heart failure. However, there was no treatment related mortality. Encouraging results were obtained after autologous PBSCT. Sclerosis of the skin was markedly improved in all of the patients with SSc. Interstitial pneumonia (IP), evaluated by PaO2, serum KL-6 levels, and pulmonary high resolution computed tomography, improved significantly. In a patient with ADM, severe and progressive IP also improved markedly. In a patient with WG, the size of the left orbital granuloma decreased substantially, resulting in reduction of the exophthalmos. CONCLUSIONS: These observations suggest that high dose CY with autologous PBSCT is feasible and may be effective in the treatment of severe and refractory AD.

[Colorimetric studies on hiding effect of Cosmotech porcelain for laminate restoration].

The hiding effect on color tone of discolored teeth restored with ceramic laminate veneer crown was examined. Translucent (T1, T2), Enamel (E1, E2, E3), Dentin (DA2, DA3, DB2, DB3), Masking dentin (MDA2, MDA3, MDB2, MDB3) in 13 colors and Modifire (M61, M62, M65, M66, M67, M68, M69, M70, M79) in 7 colors of the ceramic materials (Cosmotech porcelain G C Co., Ltd) were examined in this experiments. The colorimetric examination of the color tone backing with the white or black color was carried out by testing for color difference (delta E*ab), value difference (delta L*), chrom and hue of the samples. The result obtained were as follows; 1. Color difference was higher in order of T2 greater than T1 in Translucent greater than E1 greater than E3 greater than E2 in Enamel greater than DB3 greater than DA2 greater than DA3 greater than DB2 in Dentin greater than MDB3 greater than MDA2 greater than MDB2 greater than MDA3 in Masking dentin, and M69 greater than M79 greater than M70 greater than M68 greater than M66 greater than M61 greater than M62 greater than M67 greater than M65 in Modifire. 2. Value difference was higher in order of T2 greater than T1 in Translucent greater than E1 greater than E3 greater than E2 in Enamel greater than DB3 greater than DA2 greater than DB2 greater than DA3 in Dentin greater than MDA2 greater than MDB3 greater than MDB2 greater than MDA3 in Masking dentin, and M69 greater than M70 greater than M79 greater than M68 greater than M66 greater than M61 greater than M67 greater than M65 greater than M62 in Modifire.(ABSTRACT TRUNCATED AT 250 WORDS)

Study of estimation of color recognition on the dentist. On the ability of subjects to discriminate color in terms of hue, value and chroma.

The tooth crown color space model was manufactured and the improvement of the color representation and communication on the dental clinic have been trying. The study of color discrimination by dentist and student viewing with the use of tooth crown color chips reported here in basic knowledge on the color sensitivity of human eye. The test card were 55 x 90 mm in size and the color chip, 5 x 10 mm. The paired color chips were placed on the test card to have a 2 mm distance between them. Color difference of two tooth crown color chips on the test cards was 3.5 (delta E*ab), the combination of hue, value and chroma was constant of all cards. The subjects were 22 people, 6 dentists and 16 dental school students with normal color sensibility. In proportion of method of comparison for surface color (JIS Z 8723), the subject observed the test card which were different of hue, value and chroma on the their naked-eye, were investigated to evaluate their judgement of the test cards. The following results were obtained. The standard of judgment for the color discrimination was made firstly in terms of hue, secondly in terms of value, and thirdly in terms of chroma.