Ryo Uchida

Hyperbaric oxygen in addition to antibiotic therapy is effective for bisphosphonate-induced osteonecrosis of the jaw in a patient with multiple myeloma

A 60-year-old man with multiple myeloma (MM) (IgG-κ, stage IIIA) had been treated with minodronate at 6 mg orally as a phase 1 clinical trial for myeloma bone disease for 13 months (total dose, 4032 mg). Then he received incadronate at 10mg intravenously every 1 to 4 weeks (total dose, 350 mg). In July 2005, he complained of mild right mandibular pain, and bone scintigram showed a hot spot at the right side of the mandible. Panoramic radiograph showed osteonecrosis of the jaw (ONJ) and axial and 3-dimensional computed tomography confirmed ONJ. Oral examination showed massive gingival swelling of the right side of the mandible without exposed necrotic bone. He was given clarithromycin in addition to levofloxacin, followed by hyperbaric oxygen (HBO) therapy, which resulted in the complete disappearance of the pain. This is a first reported case of ONJ induced by incadronate. The present case suggests that early detection of ONJ by regular dental check-ups is important in the management of patients with MM who have received bisphosphonate therapy, and HBO in combination with antibiotic therapy is effective in the early stage of ONJ.

Disseminated Infection Due to Scedosporium apiospermum in a Patient with Acute Myelogenous Leukemia

A 62-year-old man diagnosed with acute myelogenous leukemia which had developed from myelodysplastic syndrome received cytarabine and idarubicine as on induction therapy. The patient developed pneumonia and bacterial sepsis during profound neutropenia. Fever and sepsis improved by using many anti-bacterials and anti-fungals but he became febrile again and complained of severe lumbar pain. 67 Ga scintigram showed abnormal uptake in the lumbar vertebra and left sternoclavicular joint, suggesting a diagnosis of discitis and osteomyelitis in the lumbar vertebra and sternoclavicular arthritis. We biopsied the site several times but culture of the biopsy specimen could not isolate any pathogens, and high fever persisted for about 10 months despite administration of various anti-bacterials and anti-fungals. Finally we inserted a catheter into the abscess at the iliopsoas muscle and Scedosporium apiospermum was isolated in the bloody pus obtained from the catheter. Itraconazole and amphotericin B were restarted, and the high fever and lumbar pain improved rapidly. The findings of S. apiospermum infection in this patient emphasizes the importance of being aware of this pathogen in patients with hematologic malignancy during the neutropenic phase.

Non-T-cell-depleted HLA-haploidentical stem cell transplantation after reduced-intensity conditioning in advanced haematological malignancies based on feto-maternal microchimerism

Long-term feto-maternal microchimerism suggests that immune tolerance exists between mother and child. Based on this hypothesis, we have previously demonstrated that haploidentical stem cell transplantation (SCT) is possible without Tcell depletion (TCD) between non-inherited maternal antigen (NIMA)-mismatched family members (Shimazaki et al, 2003). Recently, reduced-intensity conditioning stem cell transplantation (RIST) has been developed and was applicable for patients who could not undergo conventional high-dose chemoradiotherapy because of their age or organ dysfunction (Giralt et al, 2001). However, the issue of whether RIST from a human leucocyte antigen (HLA)-haploidentical related donor is feasible remains unknown. We therefore examined whether RIST could be performed without TCD in HLA-haploidentical SCT between NIMA-mismatched family members. Six patients with haematological malignancies were included in this study (Table I). There were two males and four females, whose ages ranged from 24 to 62 years. All patients but one were in a refractory stage. The mother served as donor in one patient, a child was the donor in two and NIMA-mismatched siblings were donors in three cases. HLA disparity in both graft-versus-host (GVH) and host-versus-graft directions (HVG) included two loci mismatches in one patient, and three loci mismatches in five patients. Microchimerism was detected by HLA-nested polymerase chain reaction (PCR) with a single specific primer in the donor for all patients. The conditioning regimen consisted of fludarabine 25 mg/m 2 i.v. for 5 d (days ) 6t o)2) and melphalan 80 mg/m 2 i.v. on day )3. GVH disease (GVHD) prophylaxis consisted of tacrolimus 0AE02 mg/kg/d i.v., with methotrexate 5 mg/m 2 i.v. on days 1, 3,

Combination Therapy with Thalidomide, Incadronate, and Dexamethasone for Relapsed or Refractory Multiple Myeloma

The feasibility and efficacy of a combination of thalidomide, incadronate, and dexamethasone (TID) were studied in 12 patients with relapsed or refractory multiple myeloma. The protocol, consisting of 300 mg/day of thalidomide administered orally, intravenous incadronate (10 mg/day) administered weekly, and 12 mg/day dexamethasone for 4 days, was repeated every 3 weeks. Evaluations of efficacy and toxicity were carried out every 3 weeks and were continued for 3 cycles. Three patients were excluded during the study because of apnea, severe somnolence, and pancytopenia. Of 9 evaluated patients, the partial responses achieved in 3 patients and the minor responses achieved in 4 patients corresponded to a response rate of 78% according to the criteria of the European Group for Blood and Marrow Transplantation. In addition, painful osteolytic symptoms improved rapidly after 1 cycle of TID therapy in the 10 patients evaluated. These data suggest that TID is a feasible and promising therapeutic approach for refractory and relapsed multiple myeloma.

Plasmacytoma of the Urinary Bladder in a Renal Transplant Recipient

A 28-year-old woman underwent renal transplantation in 1993. Eight years later, she experienced macroscopic hematuria, and Epstein-Barr virus-negative solitary extramedullary plasmacytoma (EMP) of the urinary bladder was diagnosed. After the reduction of immunosuppressive therapy, she received combined chemotherapy, resulting in complete tumor disappearance. However, 10 months later, she relapsed with aggressive multiple EMP and died of disease progression in 2003. This report is the first of a case of solitary EMP of the urinary bladder appearing as posttransplantation plasma cell dyscrasias after renal transplantation.

The effects of thalidomide on chemotactic migration of multiple myeloma cell lines

We examined the effect of thalidomide and dexamethasone on the migration of multiple myeloma (MM) cell lines, U266, RPMI8226, and NCI‐H929, using chemotaxis chamber plates. U266 underwent chemotactic migration in response to stromal‐cell derived factor‐1 alpha (SDF‐1α), and other cell lines underwent random migration in response to SDF‐1α or monocyte chemotactic protein‐1 alpha. Following preincubation with 1 μg/ml thalidomide, the cell lines showed reduced migratory capacity in response to SDF‐1α. Concerning the corresponding receptors, CXC chemokine receptor 4 was detected only on the surface of U266, by flow cytometry, whereas chemokine (C‐C motif) receptor 2 was not detected on all three cell lines. Moreover, decreased migration by thalidomide was not accompanied by altered expression of the corresponding receptors of each cell line. This is the first report to show the effects of thalidomide on the migration of MM cell lines. The results suggest that the inhibition of chemotactic migration might be one of the mechanisms of the success of thalidomide in controlling MM.

Expression and role of MHC class I-related chain in myeloma cells

BACKGROUND The molecular mechanism of natural killer (NK) cell cytotoxicity to myeloma cells remains unclear. We investigated whether MHC class I-related chain (MIC), a ligand of NKG2D that is an activating NK cell receptor, is involved in the cytotoxicity of NK cells toward myeloma cells, and examined the effects of various drugs on the cytotoxicity. METHODS Two human myeloma cell lines and fresh myeloma cells from 10 patients were used. MIC expression was examined by flow cytometry and reverse transcription (RT)-PCR. NK cell cytotoxicity was examined using a 51Cr-release assay. The effects of various drugs, including thalidomide, all-trans retinoic acid, dexamethasone, IFN-alpha and incadronate, on the MIC expression and NK cell cytotoxicity were examined. RESULTS MIC was highly expressed on the human myeloma cell lines U266 and RPMI-8226 and in myeloma cells of one of 10 patients examined. MIC expression on these cells was not changed by various drugs except IFN-alpha, by which MIC expression was down-regulated. Although MIC and HLA class I molecules were similarly expressed at high levels on both cell lines, U266 was sensitive to NK cells whereas RPMI-8226 was not. Furthermore, cytolysis by NK cells was not inhibited by the addition of anti-MIC Ab or decreased expression of MIC caused by IFN-alpha. DISCUSSION MIC plays a role in the cytolysis by NK cells in multiple myeloma.

Malignant lymphoma presenting as a cardiac tumor and superior vena caval syndrome successfully treated by haploidentical stem cell transplantation.

Summary A 16 year-old male with B-cell non-Hodgkins lymphoma presenting as a cardiac tumor and superior vena caval (SVC) syndrome received a haploidentical stem cell transplant (SCT) from his mother after conventional and salvage chemotherapy. He received additional radiation therapy for the residual tumor and is alive and well on day 640 after transplantation. Malignant lymphoma presenting as a cardiac tumor, including primary cardiac lymphoma, is rare. Although many reports have shown the poor prognosis of cardiac lymphoma, our case suggests that allogeneic haploidentical SCT might be useful for the treatment of aggressive cardiac lymphoma.

Successful non-T-cell-depleted HLA-haploidentical stem cell transplantation (SCT) with reduced-intensity conditioning from a second child for late graft failure after the first HLA-haploidentical SCT for MDS/overt leukemia based on feto-maternal microchimerism

Successful non-T-cell-depleted HLA-haploidentical stem cell transplantation (SCT) with reduced-intensity conditioning from a second child for late graft failure after the first HLA-haploidentical SCT for MDS/overt leukemia based on feto-maternal microchimerism