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Katsumichi Fujimaki

Publications and source records attributed to Katsumichi Fujimaki.

At least 19 recordsLinked to original sources

Non-Hodgkin's lymphoma presenting as multiple bone lesions and hypercalcemia.

We report a rare case of a patient with non-Hodgkin's lymphoma who developed multiple bone lesions and hypercalcemia. A 50-year-old woman complained of drowsiness and multiple bone pain on admission. Radiographic examination revealed multiple bone fractures and osteolytic lesions. She was diagnosed with diffuse large B cell lymphoma by biopsy of an inguinal lymph node. Elevation of parathyroid hormone-related protein (PTHrP) and hypercalcemia were confirmed pretreatment, and those serum levels decreased during chemotherapy for lymphoma. However, the disease was resistant to chemotherapy combined with rituximab. These findings suggest that hypercalcemia is associated with PTHrP and the prognosis of patients with bone lymphoma in advanced stage is poor, although it is thought to be a relatively favorable prognosis in localized primary lymphoma of bone.

Antibodies, Monoclonal↗

Effect of blood cyclosporine concentration on the outcome of hematopoietic stem cell transplantation from an HLA-matched sibling donor.

We retrospectively evaluated the effect of the blood cyclosporine (CsA) concentration on the outcome of allogeneic hematopoietic stem cell transplantation from an HLA-matched sibling donor in 171 patients who received a continuous infusion of CsA and short-course methotrexate to prevent graft-versus-host disease (GVHD). CsA was started at 3.0 mg/kg/day and the dose was adjusted to maintain the blood CsA concentration between 250 and 350 ng/ml. The actual dose of CsA averaged 1.9 mg/kg/day at the 3rd week after transplantation. The incidence of grade II-IV acute GVHD was 29.9%. Patient age and sex were identified as independent significant risk factors for acute GVHD. The CsA concentration during the 3rd week after transplantation most strongly affected the incidence of grade II-IV acute GVHD (RR 0.995 for an increase in CsA concentration by 1 ng/ml, P = 0.037) adjusted for other risk factors. The incidence of acute GVHD was significantly lower in patients with a 3rd-week CsA concentration higher than 300 ng/ml than in those with values between 200 and 300 ng/ml (20% vs. 35%, P = 0.036). We concluded that the blood CsA concentration at peri-engraftment period may be important in preventing acute GVHD.

Cyclosporine↗

Phase II study of CHOP-GR therapy for advanced-stage follicular lymphoma.

Recently, the cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) regimen plus rituximab (R-CHOP) have been used widely to treat patients with follicular lymphoma. We investigated a fixed scheme of combination chemotherapy protocol including CHOP, granulocyte colony stimulating factor (G-CSF) and rituximab (CHOP-GR) for patients with advanced-stage grade 1 or grade 2 follicular lymphoma in a phase II clinical trial, assessing enhancement of antibody-dependent cellular cytotoxicity of rituximab by G-CSF. Twenty-one untreated patients received two courses of CHOP chemotherapy followed by four courses of CHOP-GR, including G-CSF (s.c.) on days 11 - 14 and rituximab on day 15. Overall response rate was 76% (16 of 21 patients). Two patients, one with no response and subsequent allogeneic hematopoietic stem cell transplantation and one with progressive disease, died of lymphoma. One patient refused to continue therapy, whereas two were rediagnosed and no longer met histologic criteria; these three patients were classified as nonresponders. After a median observation time of 23 months, the 19 histologically assessable patients showed a 2-year progression-free survival rate of 82%, whereas 2-year overall survival was 95%. Fifteen patients (79%) continued in remission during this median follow-up period. Of seven patients with initial bulky mass, five responded to therapy. The most frequent adverse events were leukocytopenia (100%) and neutropenia (100%), followed in turn by alopetia (94%) and nausea/vomiting (79%). Of 11 patients examined for bcl-2 translocation in peripheral blood or marrow by polymerase chain reaction (PCR), four were positive, whereas three of the four had complete remissions and converted to PCR negativity after therapy. According to short-term observation, CHOP-GR is a safe and effective therapy for patients with advanced-stage follicular lymphoma.

Adult↗

Acute myelomonocytic leukemia with dysplastic bone marrow eosinophils showing t(5;17)(q13;q11) and a secondary chromosomal aberration, inv(16)(p13q22).

inv(16)(p13q22) is associated with de novo acute myelomonocytic leukemia with dysplastic bone marrow eosinophils (AMML Eo), which has a relatively favorable clinical course with a longer remission duration and better survival prospects. On the other hand, t(5; 17)(q13;q11), although relatively rare, has been reported to be a component of complex chromosomal abnormalities in myelodysplastic syndromes and secondary acute myeloid leukemia (AML). We treated a 29-year-old woman with the first reported case of de novo AMML Eo with inv(16)(p13q22) in addition to t(5; 17)(q13;q11). Although she attained complete remission (CR) immediately after induction therapy, the disease recurred 1 year after the completion of consolidation therapies. She underwent HLA-matched unrelated allogeneic bone marrow transplantation (UBMT), together with a myeloablative conditioning regimen, after achieving a second CR and has survived without a recurrence for more than 24 months since UBMT. In general, certain secondary chromosomal abnormalities are associated with the phenotype of the disease, which retains its essential biologic characteristics established by the primary abnormality. Accordingly, the primary nature of the leukemic cells in this case differs from the findings for core-binding factor AML with inv(16)(p13q22). We believe this report is the first of de novo AMML Eo with t(5; 17)(q13;q11) showing as a secondary chromosomal aberration with inv(16)(p13q22).

Adult↗

Human herpesvirus 6 meningoencephalitis in allogeneic hematopoietic stem cell transplant recipients.

We retrospectively investigated the clinical characteristics of human herpesvirus 6 (HHV-6) meningoencephalitis within 100 days after allogeneic hematopoietic stem cell transplantation (HSCT). Of 1148 patients who received transplants between January 1999 and December 2003, 11 patients (0.96%) with HHV-6 meningoencephalitis were identified. Ten of 11 recipients received hematopoietic stem cells from donors other than HLA-identical siblings. Confusion was the most frequent central nervous system (CNS) symptom, and a skin rash with high-grade fever preceded the CNS symptoms in 9 patients. Magnetic resonance imaging of the brain showed an abnormal increased T2 signal in the hypothalamus of 5 patients. Eight patients were treated with ganciclovir, and an improvement of CNS symptoms was obtained in 3 patients; 3 patients treated with acyclovir showed no improvement. Improvement in the meningoencephalitis seemed less frequent in patients with abnormal findings in the hypothalamus than in those without such findings. Because the symptoms of HHV-6 meningoencephalitis mimicked those of cyclosporine- or tacrolimus-induced encephalopathy, the drugs were withdrawn at the onset of CNS symptoms in 10 patients, resulting in the development of grade IV graft-versus-host disease (GVHD) in 5 patients. Three patients died of HHV-6 meningoencephalitis, and 6 died of other causes, including GVHD. In conclusion, HHV-6 meningoencephalitis is a rare but potentially life-threatening complication in patients who undergo allogeneic HSCT. Careful assessment of the clinical findings and the brain may allow early and precise diagnosis of HHV-6 meningoencephalitis and contribute to improving its prognosis.

Adolescent↗

[Multiple myeloma presenting as cavernous sinus syndrome].

We report on a 70-year-old male who developed cavernous sinus syndrome as the initial symptom of multiple myeloma. He was admitted with diplopia and ptosis in October 2004. The diagnosis of multiple myeloma and cavernous sinus syndrome due to a gross mass at the sinus base were made. Cerebral computed tomography revealed that the lesion occupied the sphenoid sinus and involved the oculomoter nerve. He underwent local irradiation of the mass followed by systemic chemotherapy. The symptoms caused by the mass disappeared after the treatment. Clinicians need to be aware of the rare manifestation of multiple myeloma.

Aged↗

A possible association between the presence of interleukin-4-secreting cells and a reduction in the risk of acute graft-versus-host disease.

OBJECTIVE: We monitored cytokine-secreting cells using an enzyme-linked immunospot (ELISPOT) assay in a prospective study to assess the cytokine network after transplantation. PATIENTS AND METHODS: Peripheral blood mononuclear cells were collected from 23 patients who received allogeneic stem cell transplantation, from before the preconditioning regimen to 56 days after transplantation. The number of interleukin-4 (IL-4), interferon-gamma (IFN-gamma), and tumor necrosis factor-alpha (TNF-alpha)-secreting cells were measured by ELISPOT assay. For IL-4 and IFN-gamma, in vitro stimulation with phorbol 12-myristate 13-acetate and phytohemagglutinin was performed. RESULTS: The frequency of IL-4-secreting cells was significantly higher in five patients receiving peripheral blood stem cell transplantation (PBSCT) than that in 18 patients who received bone marrow transplantation (BMT). Based on IFN-gamma and TNF-alpha release, there was a trend toward a decrease in the number of cytokine-secreting cells in PBSCT compared with BMT. Furthermore, patients who did not develop acute graft-vs-host disease (GVHD, n=5) showed a significantly higher number of IL-4-secreting cells compared with those who developed acute GVHD (n=18). Both IFN-gamma-secreting cells and TNF-alpha-secreting cells showed a trend to increase in number in patients with acute GVHD. In patients who received reduced-intensity stem cell transplantation (n=7) compared with conventional stem cell transplantation (n=16), there was a large number of cytokine-secreting cells detected by IL-4 and IFN-gamma release. CONCLUSIONS: These results are consistent with the hypothesis that IL-4-producing cells inhibit the development of acute GVHD. In addition, the increased percentage of IL-4-secreting cells may be responsible for the unexpected low incidence of acute GVHD in PBSCT, despite the presence of large numbers of mature T cells in the donor infusion.

Adult↗

Idiopathic thrombocytopenic purpura and myasthenia gravis after fludarabine treatment for chronic lymphocytic leukemia.

We report a patient with chronic lymphocytic leukemia (CLL) who developed idiopathic thrombocytopenic purpura (ITP) and myasthenia gravis (MG) after fludarabine therapy. ITP developed after 6 cycles of fludarabine treatment, and MG occurred 2 months after the onset of ITP. MG was successfully treated with immunosuppressive therapy and plasma exchange, while rituximab was effective for CLL and ITP. Fludarabine seemed to have an important role in the onset of ITP and MG in this case.

Antibodies, Monoclonal↗

Atypical Burkitt lymphoma arising from follicular lymphoma: demonstration by polymerase chain reaction following laser capture microdissection and by fluorescence in situ hybridization on paraffin-embedded tissue sections.

A 77-year-old man with disseminated lymphadenopathy was referred to our hospital. An inguinal lymph node biopsy specimen had the appearance of composite lymphoma consisting of follicular lymphoma and atypical Burkitt lymphoma. The bone marrow was involved, and chromosomal analysis of the marrow showed t(8;14) and t(14;18) in identical cells. The patient underwent systemic chemotherapy but died of lymphoma 4 months later. Polymerase chain reactions performed on cells obtained from follicular and diffuse components by laser capture microdissection showed the two components to be clonally identical. Moreover, fluorescence in situ hybridization performed on paraffin-embedded tissue sections demonstrated an immunoglobulin heavy chain (IGH)/BCL2 translocation signal in both follicular and diffuse components, but an IGH/c-MYC translocation signal in only the diffuse component. Accordingly, the atypical Burkitt lymphoma arose from the follicular lymphoma as a consequence of the additional IGH/c-MYC translocation, then involving the bone marrow.

Aged↗

[Outcome of allogeneic stem cell transplantation for hematological disorders in patients older than 50].

We retrospectively evaluated the outcomes in patients older than 50 years of age who underwent allogeneic hematopoietic transplantation. Twenty-three patients received conventional stem cell transplantation (CST) and 9 patients received reduced intensity stem cell transplantation (RIST). Regimen-related toxicity was observed in 21 (91%) patients with CST and 4 (44%) patients with RIST. Early death occurred within 100 days after transplantation in 6 patients with CST and 2 patients with RIST. Among the patients with complete remission, the two-year probability rate of survival was 44% in patients with CST and 100% in patients with RIST (p=0.08). Among the patients without complete remission, the two-year probability rate of survival was 30% in patients with CST and 0% in those with RIST (p=0.08). For patients receiving RIST without complete remission, relapse and infection were the main causes of death. Our data suggest that patients without complete remission should receive CST to the degree possible.

Female↗

[Triple secondary malignancy of gingiva, palate and esophagus after an allogeneic bone marrow transplantation for cutaneous T-cell lymphoma].

A 31-year-old man was diagnosed as having cutaneous T-cell lymphoma in January 1994. He received an allogeneic bone marrow transplantation (BMT) from an HLA-matched sibling donor in May 1995, because of refractoriness to chemotherapy. The patient had been treated with immunosuppressants including prednisolone and cyclosporin A for chronic graft-versus-host disease (GVHD) of the extensive type following acute GVHD. Five years after the BMT, he developed moderately differentiated squamous cell carcinoma (SCC) on the mandibular gingival mucosa and underwent surgical resection. Furthermore, 6 years after the BMT well differentiated SCC developed on his palate and was resected. Concurrently, he was diagnosed as having esophageal cancer (poorly differentiated SCC) and underwent a subtotal esophagotomy. One year later he had a recurrence of the esophageal cancer with dysphagia and was treated with radiation and chemotherapy. He remains free of triple cancer and lymphoma. It is suggested that total body irradiation, immunosuppressants, and chronic GVHD are associated with a risk of secondary malignancies following allogeneic BMT. These factors might have contributed to the onset of triple cancer in our patient.

Adult↗

[Hematopoietic stem cell transplantation in the second or later complete remission in acute promyelocytic leukemia initially treated with all-trans retinoic acid].

Despite the use of all-trans retinoic acid (ATRA) as the first-line treatment for acute promyelocytic leukemia (APL), relapse occurs in about 20% of cases. Most relapsing APL patients can achieve second remission (CR2) following ATRA combined with chemotherapy or arsenic trioxide. Stem cell transplantation (SCT) has been widely adopted in CR2, but optimal SCT (auto- or allo-SCT) remains controversial. We analyzed the outcomes for 8 APL patients initially treated using ATRA, who relapsed, achieved CR2 and underwent auto-SCT (n = 4) or allo-SCT (n = 4). The mean age of patients who underwent allo-SCT was 39 years. Minimal residual disease (MRD) just prior to SCT was positive in 1 patient and negative in 3. Engraftment was achieved in all patients, but 2 patients died of transplantation-related complications within 6 months. Complete molecular remission has been maintained in the remaining 2 patients. The mean age of patients who underwent auto-SCT was 48 years. MRD just prior to SCT was negative in all 4 patients. Complete molecular remission has been maintained in all 4 patients (mean follow-up, 3 years 9 months). The results for auto-SCT are favorable in patients with MRD-negative APL.

Adult↗

[Trial of front-line intensive chemotherapy followed by peripheral blood stem cell transplantation in high-intermediate and high risk non-Hodgkin's lymphoma patients].

High-intermediate (HI)- and high (H)-risk non-Hodgkin lymphoma was treated with front-line intensive chemotherapy followed by autologous peripheral blood stem cell transplantation (auto-PBSCT). Twenty-eight cases were enrolled after obtaining informed consent, from November, 1998 to October, 2003. Initial treatment was 2 or 3 cycles of CHOP-V regimen, followed by three high-dose therapy, one each of cyclophosphamide, methotrexate and etoposide. The final high-dose therapy was a combination of ranimustine, ifosphamide and etoposide, which was followed by auto-PBSCT. Patients with a bulky mass received involved-field radiation therapy (IF-RT) after auto-PBSCT. Complete remission (CR) was achieved in 16 cases (57%) and partial remission (PR) in 9 cases (32%), after auto-PBSCT The final responses after IF-RT were CR in 20 cases (71%) and PR in 5 cases (18%). Overall survival of cases with 2 cycles of CHOP-V regimen was 56% after a median observation time of 30 months, compared with 82% in cases with 3 cycles (p = 0.0732). The results suggested that the reduction of tumor size with the initial CHOP-V treatment was most important. In all cases, progression-free survival was 64% and the overall survival was 74% after a median observation time of 30 months, which showed a good outcome compared with that of HI- and H-risk group defined by the age-adjusted international prognostic index reported by Shipp et al.

Adolescent↗

[Pulmonary MALT lymphoma with macroglobulinemia].

An 84-year-old man was diagnosed as having pulmonary MALT lymphoma in January 1997. Six years later, he was admitted to our hospital with coughing and dyspnea in November 2003. Dissemination of MALT lymphoma was confirmed by findings of pleural effusion and bone marrow aspiration. A FISH analysis of cells from the pleural effusion revealed t(11;18)(q21;q21) and the serum level of IgM was 8,600 mg/dl (M-protein). The diagnosis of secondary macroglobulinemia was made. The patient received rituximab monotherapy because he was very elderly. Pleural effusion has not been seen after the administration of rituximab, although there have been no changes in the lung mass and serum values of M-protein.

Aged, 80 and over↗

Affixin interacts with alpha-actinin and mediates integrin signaling for reorganization of F-actin induced by initial cell-substrate interaction.

The linking of integrin to cytoskeleton is a critical event for an effective cell migration. Previously, we have reported that a novel integrin-linked kinase (ILK)-binding protein, affixin, is closely involved in the linkage between integrin and cytoskeleton in combination with ILK. In the present work, we demonstrated that the second calponin homology domain of affixin directly interacts with alpha-actinin in an ILK kinase activity-dependent manner, suggesting that integrin-ILK signaling evoked by substrate adhesion induces affixin-alpha-actinin interaction. The overexpression of a peptide corresponding to the alpha-actinin-binding site of affixin as well as the knockdown of endogenous affixin by small interference RNA resulted in the blockade of cell spreading. Time-lapse observation revealed that in both experiments cells were round with small peripheral blebs and failed to develop lamellipodia, suggesting that the ILK-affixin complex serves as an integrin-anchoring site for alpha-actinin and thereby mediates integrin signaling to alpha-actinin, which has been shown to play a critical role in actin polymerization at focal adhesions.

Actinin↗

Epstein-Barr virus-associated extranodal NK/T-cell lymphoma following mosquito bites in an elderly patient without prior hypersensitivity.

We describe a 73-year-old woman who developed fever and inflammation with ulceration at the site of mosquito bites in the lower thigh. Soon she developed disseminated skin lesions characterized by redness, induration, and local heat. Some lesions showed necrosis and ulceration, including those located in the nasal cavity. She had no history of hypersensitivity to mosquito bites, and the serum IgE concentration was within the reference range. A skin biopsy specimen from the lower thigh adjoining the mosquito bites was diagnosed pathologically as showing extranodal NK/T cell lymphoma, nasal type. Southern analysis of the biopsy specimen showed an oligoclonal band representing Epstein-Barr virus (EBV) DNA. Bone marrow examination revealed infiltration by lymphoma cells and marked hemophagocytosis. The patient underwent three cycles of chemotherapy with carboplatin, etoposide, ifosfamide, and dexamethasone (DeVIC), but died of lymphoma progression during treatment. We speculate that, rather than an allergic reaction, this late-life occurrence of hypersensitivity to mosquito bites might represent lymphoproliferative disease induced by a direct action of mosquito salivary gland secretions on EBV- infected NK cells.

Aged↗

Long-term cytogenetic remission with ubenimex monotherapy in a case of chronic myeloid leukemia.

A 65-year-old man was diagnosed with chronic myeloid leukemia (CML) in February 1990, and was treated with busulfan and ubenimex. Cytogenetic analysis of the bone marrow revealed the Philadelphia (Ph) chromosome in 100% of cells of analyzed at diagnosis. Treatment with busulfan was stopped in March 1993 due to bone marrow suppression. The Ph chromosome was seen in 80% of cells in June 1993. He received ubenimex monotherapy after cessation of busulfan. Complete disappearance of the Ph chromosome was confirmed in May 1995 and has continued to date. This suggests that ubenimex might specifically affect the Ph chromosome and be useful as maintenance therapy for CML.

Aged↗