Multiple osteolytic bone lesions with high serum levels of interleukin-6 and CCL chemokines in a patient with adult T cell leukemia.

A 37-year-old woman was diagnosed as having chronic adult T-cell leukemia (ATL) of the skin by a skin biopsy and human T-cell leukemia virus type-1 serology at our hospital in August 1992. The skin lesions of ATL were improved by treatment with psoralen ultraviolet ray A. She complained of severe pain in her bilateral forearms, hands and ankles, and X-ray examination in July 1999 revealed multiple punched-out lesions of the extremities. Serum levels of parathyroid hormone-related peptide, interleukin-1beta (IL-1beta), tumor necrosis factor-alpha and total serum receptor activator of nuclear factor kappaB ligand were not elevated. However, serum levels of IL-6, CCL2 monocyte chemoattractant protein-1 (MCP-1), CCL3 [macrophage inflammatory protein-1alpha (MIP-1alpha)] and CCL4 (MIP-1beta) were markedly elevated. Here, we have discussed the possible mechanism underlying the onset of the osteolytic lesions.

Chimerism and T-cell receptor repertoire analysis after unrelated cord blood transplantation with a reduced-intensity conditioning regimen following autologous stem cell transplantation for multiple myeloma.

A 65-year-old Japanese male was diagnosed as multiple myeloma with Bence Jones kappa type, clinical stage IIIA. His disease status reached partial remission after chemotherapy. Thereafter, he received tandem transplantation, consisting of high-dose chemotherapy with autologous stem cell transplantation (ASCT), followed by unrelated cord blood transplantation (U-CBT). U-CBT with a reduced-intensity conditioning regimen (RI-CBT) was performed in August 2003. HLA mismatch between the patient and the CBT donor was present at two serological loci (B and DR). A total nucleated CBT cell dose of 2.45 x 10(7)/kg body weight was infused on day 0. Graft-vs.-host disease (GVHD) prophylaxis consisted of cyclosporine A and short-term methotrexate. Neutrophil engraftment (>0.5 x 10(9)/l) was obtained on day 46. He developed positive cytomegalovirus antigenemia, grade II acute GVHD involving skin and liver, varicella-zoster virus infection, septic shock, hemorrhagic cystitis caused by adenovirus and acute hepatitis B virus infection after U-CBT. We retrospectively analyzed T-cell receptor (TCR) repertoire diversity and found that TCR repertoire diversity decreased continuously after U-CBT. Therefore, low-TCR repertoire diversity in this patient appears to be associated with various infections caused by immunodeficiency.

Abnormal expansion of naïve B lymphocytes after unrelated cord blood transplantation--a case report.

A 33-year-old woman underwent unrelated cord blood transplantation (U-CBT) for myelodysplastic syndrome (MDS)-related secondary AML. She showed impressive increases in the number of CD19+ B cells in bone marrow and CD19+27-IgD+ B cells in peripheral blood from about 1 month to 3 months after U-CBT. The serum level of IL-6 temporarily increased after transplantation, and this increase seemed to be correlated with the expansion of CD19+ B cells. Although, compared with BMT, little is known about the kinetics of hematological and immunological reconstitution in U-CBT, there was initial B-cell recovery after CBT as some described. This B cell recovery may be associated with a high number of B-cell precursors present in cord blood (CB). The phenomenon of naïve B lymphocyte expansion that we found might be associated with a high number of B-cell precursors present in CB.

Differential expression of natural killer cell receptors (CD94/NKG2A) on T cells by the stimulation of G-CSF-mobilized peripheral blood mononuclear cells with anti-CD3 monoclonal antibody and cytokines: a study in stem cell donors.

We investigated the expression of the inhibitory NKR (CD94/NKG2A) of the G-CSF mobilized peripheral blood mononuclear cells (G-PBMC) on T cells after stimulation for 7 days by immobilized anti-CD3 monoclonal antibody (mAb) with or without cytokines. We demonstrated increased expression of CD94/NKG2A on CD3+/CD8+ T cells. Also, addition of IL-12 induced significantly more CD94/NKG2A expression than addition of IL-15: CD94+CD3+/NKG2A+CD3+; 43.8 +/- 11.6%/33.7 +/- 11.4% by IL-12 versus 32.8 +/- 13.2%/21.3 +/- 9.6% by IL-15, respectively (n = 9, P < .05). However, >90% purified CD94+ cells CD94+ obtained from IL-15-treated G-PBMC by magnetic cell sorting (MACS) exhibited higher cytolytic (CTL) activity against K562 cells than that from IL-12-treated G-PBMC: E:T = 20:1, 40.7 +/- 18.4% vs 15.1 +/- 5.2% (n = 5, P < .05). Therefore, the cytokine effects on inhibitory NKR expression on T cells and CTL activity are differently regulated. Based on these findings, it may be possible to establish the effective strategy to expand inhibitory NKR-expressing T cells with CTL activity for cell therapy.

The risk of persistent carriage of methicillin-resistant Staphylococcus aureus in hematopoietic stem cell transplantation.

The clinical course of hematopoietic stem cell transplantation (HSCT) recipients was retrospectively analyzed to determine whether carriage of methicillin-resistant Staphylococcus aureus (MRSA) is a risk factor for MRSA infection during the neutropenic period. We studied four patients in whom MRSA colonies developed before HSCT. Two patients were previously diagnosed as having MRSA infection and two were carriers of MRSA. We tried to eliminate MRSA before HSCT and succeeded in eradication in two patients. MRSA infection did not develop in one patient who received prophylactic administration of vancomycin (VCM), but MRSA-induced phlegmon developed during neutropenia in one patient who did not receive prophylaxis. Of the other two patients who had been persistently positive for MRSA, MRSA did not develop in one patient who received prophylaxis, but the another patient who did not receive prophylaxis died from MRSA-induced sepsis in the early post-transplant period. We therefore recommend that MRSA be eliminated by prophylactic administration of anti-MRSA drugs such as VCM before HSCT when patients have persistent MRSA.

Chronic eosinophilic leukemia with t(6;11)(q27;q23) translocation.

We report a rare case of chronic eosinophilic leukemia (CEL) with a chromosomal abnormality of t(6;11)(q27;q23). The patient was diagnosed as having thyroid cancer with metastases to the lung and cervical lymph nodes in 1993. Percutaneous ethanol injection therapy (PEIT), total thyroidectomy, and radiotherapy were performed. The patient was also diagnosed as having prostatic cancer with bone metastasis in July 1999, and hormonal therapy was performed. At the time of the diagnosis of prostatic cancer, leukocytosis with eosinophilia was also revealed. Thereafter, cytogenetical analysis and reverse transcriptase polymerase chain reaction (RT-PCR) analysis of bone marrow showed t(6;11)(q27;q23) translocation and MLL/AF6 fusion products, respectively. No transcripts of the BCR/ABL chimeric gene were found by RT-PCR in bone marrow. Analysis of serum cytokines revealed a slight elevation of GM-CSF but no elevation of IL-3 or IL-5. Tissue damage due to infiltration of eosinophils was not observed throughout the clinical course. On the basis of the cytogenetic and molecular abnormality, the patient was diagnosed as having CEL, rather than reactive eosinophilia due to thyroid or prostatic cancer or other reactive inflammation. This is the first case report of CEL with t(6;11)(q27;q23) translocation.

Peripheral T-cell lymphoma in a patient with osteopetrosis.

Osteopetrosis is a rare genetic disorder in which the function of osteoclasts is defective, resulting in impaired bone resorption. This disease is usually accompanied by myelosuppression due to decreased marrow space and by osteomyelitis, especially in the submandibular bone. We report the case of a 72-year-old woman with an autosomal dominant form of osteopetrosis who suffered from peripheral T-cell lymphoma. Accurate clinical and pathological diagnoses and staging were difficult due to nonspecific reactive hyperplasia of the lymph nodes, even though we used several scintigraphic techniques and [18F]fluorodeoxyglucose positron emission tomography. We also paid special attention to myelosuppression and exacerbation of osteomyelitis after combination chemotherapy. Severe infectious complications were avoided by early administration of G-CSF for leukocytopenia and by continuous oral administration of antibiotics. The patient achieved complete remission after four courses of chemotherapy and this status has been maintained for 6 months.

Increased proportion of HLA-class-I-specific natural killer cell receptors (CD94) on peripheral blood mononuclear cells after allogeneic bone marrow transplantation.

In the present study, we investigated the inhibitory natural killer cell receptor (NKR) expression of CD94/NKG2A on PBMC after allogeneic bone marrow transplantation (BMT). The proportion of CD94 expression on PBMC was higher in patients without chronic graft-versus-host disease (cGVHD) and also in cGVHD patients with good response to conventional immunosuppressive therapy than in cGVHD patients with poor response. Also, the proportions of CD94+/CD3+ cells and CD94+/CD8+ cells were higher in cGVHD patients showing good response. In addition, the proportion of NKG2A-expressing cells was higher in patients without cGVHD than in patients with cGVHD. Therefore, chronic allostimulation after allo-BMT may augment the proportion of CD94/NKG2A-positive cells, and these cells may play some role in the regulation of alloresponse in some patients.

Exfoliative esophagitis early after autologous peripheral blood stem cell transplantation.

Two patients with non-Hodgkin's lymphoma (NHL) suffered from hematemesis due to exfoliative esophagitis early after autologous peripheral blood stem cell transplantation (PBSCT). The chemotherapy regimens used for these 2 patients were the same and consisted of high-dose ranimustine, carboplatin, etoposide, and cyclophosphamide (MCVC regimen), which have been widely used in autologous PBSCT for NHL in Japan. Esophageal bleeding in both patients was stopped by conservative treatment without any special endoscopic manipulations. Gastrointestinal bleeding after hematopoietic stem cell transplantation is usually caused by viral infections, graft-versus-host disease, or conditioning chemo-radiotherapy. Although severe esophagitis is common in patients receiving stem cell transplantation, the exfoliative form detected by endoscopic examination has not been reported. We conclude that high-dose chemotherapy and frequent vomiting during treatment are risk factors for lower-esophageal bleeding in these cases.

Successful treatment of immunoblastic lymphadenopathy-like T-cell lymphoma with cyclosporin A.

Immunoblastic lymphadenopathy (IBL)-like T-cell lymphoma is considered to belong to peripheral T-cell lymphoma. Its prognosis is grave and effective treatments have not been established. Recently, we gave oral cyclosporin A (CsA) to a patient with IBL-like T-cell lymphoma, and succeeded in achieving dramatic remission. In this case, serum levels of interleukin-12 (IL-12) and tumor necrosis factor-alpha (TNF alpha) were elevated and decreased or returned to normal after achieving remission. Since CsA is a potent suppressor of the immune system and most notably T-cells, the immunosuppression of T-cell function might have played an important role in achieving remission in this case, although the precise mechanism still remains to be elucidated. The present case indicates that administration of CsA may be a very effective and safe selection of therapy for IBL-like T-cell lymphoma, as well as analogous disorders such as IBL and angioimmunoblastic lymphadenopathy with dysproteinemia (AILD), thereby will contribute to improving the prognosis of patients with these diseases.

[Bilateral non-Hodgkin's lymphoma of the adrenal glands with adrenal insufficiency].

A 66-year-old female presented with anorexia, fatigue, skin pigmentation, weight loss and low grade fever. Imaging studies demonstrated bilateral bulky masses confined to the adrenal glands. Ultrasonography guided needle biopsy of the mass showed findings of diffuse large B-sell lymphoma. Low levels of serum cortisol, urinary 17-OHCS and 17-KS, a high level of ACTH and a non-reactive pattern on the rapid ACTH test led to a diagnosis of Addison's disease. Only a partial regression was achieved by the first chemotherapy. She died due to disease progression, while the next course of chemotherapy had been postponed because of interstitial pneumonitis due to methotrexate.

[Studies on stress analysis of laminate veneers].

The stress distributions in the laminate veneers under the two kinds of loadings are analyzed numerically by use of FEM in order to make clear the defects of various enamel preparations and Young's modulus of laminate shell materials in restored teeth. The analytical results are summarized as follows, 1) In both cases of two loading conditions under in this study, the stress distribution in restored teeth varied much with Young's modulus of laminate shell materials. 2) Especially in the case of thin enamel preparation in marginal light-chamber configuration, the higher tensile stress is obtained under the higher Young's modulus in the resin cement layer near the labio-gingival margin. 3) When the high load is applied normal to the incisal edge, considering each material strength, however what kind of laminate shell materials are used, the restored teeth is quite within the bounds of possibility for exploration in facio-gingival region or fracture in vicinity of loading points.