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In high-pressure die casting, attention has been paid to the J factor, which is defined by the speed of the metal injected at the gate and the shape of the gate. In casting experiments using a piston die, the porosity of the product can be reduced by increasing the J factor such that the metal flow passing through the gate forms an atomized flow. To clarify the underlying mechanisms, we developed a system for simulating a two-phase flow of air and aluminum by large-scale calculations of turbulent flow. During the development of the system, we injected metal into an open space and performed imaging to confirm the state of the atomized flow. The system was then verified by reproducing the atomized flow. The analysis results visualized the many small turbulent vortices generated in the thick part far from the gate. We demonstrated that the change from small to longitudinal vortices promoted entrainment of air into the aluminum and increased the efficiency of air expulsion outside the die through an increase in the J factor.

Clarifying the mechanism of particle removal by megasonic cleaning and multiple-bubble dynamics in megasonic fields is essential for removing contaminant particles during nanodevice cleaning without pattern damage. In particular, the effect of the interaction of multiple bubbles on bubble-collapse behaviour and impulsive pressure induced by bubble collapse should also be discussed. In this study, a compressible locally homogeneous model of a gas–liquid two-phase medium is used to numerically analyse the multiple-bubble behaviour in a megasonic field. The numerical results indicate that, for bubbles with the same equilibrium radius, the natural frequency of the bubble decreases, and bubbles with smaller equilibrium radii resonate with the megasonic wave as the number of bubbles increases. Therefore, the equilibrium radius of bubbles showing maximum wall pressure decreases with an increasing number of bubbles. The increase in bubble number also results in chain collapse, inducing high wall pressure. The effect of the configuration of bubbles is discussed, and the bubble–bubble interaction in the concentric distribution makes a greater contribution to the decrease in the natural frequency of bubbles than the interaction in the straight distribution.

Understanding multiple-bubble behavior in a megasonic field is essential for efficient megasonic nanodevice cleaning without pattern damage. In this study, we numerically studied the effects of equilibrium radius and initial void fraction on multiple-bubble behavior and induced pressure. We analyzed the nonspherical collapse, coalescence, and breakup of bubbles in a megasonic field using a compressible, locally homogeneous model of a gas-liquid two-phase medium. Bubbles were simulated with a uniform equilibrium radius or with a bubble size distribution. Our results indicate that the bubble behavior and induced pressure depended mainly on the initial void fraction. For the case of bubbles with uniform equilibrium radius, small bubbles generated high wall pressure at large initial void fractions. When there was a size distribution, bubbles with small equilibrium radii contributed little to the wall pressure because of the damping effect of the oscillation of larger bubbles. Furthermore, the addition of a large bubble suppressed the resonant behavior of the bubbles that induced high wall pressure.

The fundamental characteristics of the cryogenic single-component micro-nano solid nitrogen (SN2) particle production using super adiabatic Laval nozzle and its application to the physical photo resist removal-cleaning technology are investigated by a new type of integrated measurement coupled computational technique. As a result of present computation, it is found that high-speed ultra-fine SN2 particles are continuously generated due to the freezing of liquid nitrogen (LN2) droplets induced by rapid adiabatic expansion of transonic subcooled two-phase nitrogen flow passing through the Laval nozzle. Furthermore, the effect of SN2 particle diameter, injection velocity, and attack angle to the wafer substrate on resist removal-cleaning performance is investigated in detail by integrated measurement coupled computational technique.

The fundamental characteristics of a thermomechanical resist removal-cleaning system using cryogenic micro-nano solid nitrogen spray flow was investigated using a new type of integrated measurement coupled numerical technique. The effect of ultra-high heat flux cooling on the resist removal performance due to the thermal contraction of resist material was clarified. It was numerically predicted that resist removal performance could be improved by the scraping effect of impinging micro-solid nitrogen particle with plastic deformation in the narrow region between the resist. Furthermore, it was numerically and experimentally found that the hybrid interactive effects of fluid mechanical force by impingement of micro-solid particles and the thermomechanical effect due to

The clarification of the mechanism and the control of a megasonic cleaning are necessary for the megasonic cleaning without pattern damage. In the present study, the numerical analysis of the bubble behavior in a megasonic field is performed to clarify the mechanism of the particle removal of megasonic cleaning. The bubble behavior in the standing wave of a megasonic wave is analysed using a compressible locally homogeneous model of a gas-liquid two-phase medium. The results show that the present numerical method is found to can simulate the characteristic of the bubble translational motion in a standing wave that the direction of the movement due to the primary Bjerknes force changes at the resonant radius. And the calculated wall pressure is higher than the exposed megasonic pressure, and the cavitation is confirmed to influence the particle removal of megasonic cleaning.

The innovative characteristics of the cryogenic single-component micro-nano solid nitrogen (SN2) particle production using super adiabatic Laval nozzle and its application to the physical resist removal-cleaning process are investigated by a new type of integrated measurement coupled computational technique. The originality to be noted in the present study is that the continuous production of micro-nano SN2 particle is achieved by using single component gas-liquid two-phase flow of subcooled nitrogen through a Laval nozzle (converging-diverging nozzle). As a result of present computation, it is found that high-speed ultra-fine SN2 particle is continuously generated due to the freezing of liquid nitrogen (LN2) droplet induced by rapid adiabatic expansion of subsonic subcooled two-phase subcooled nitrogen flow passing through the Laval nozzle. Furthermore, the effect of SN2 particle diameter, injection velocity, and attack angle to the wafer substrate on resist removal-cleaning performance is investigated in detail by integrated measurement coupled computational technique.

Cavitation often involves an abrupt phase change phenomenon. This phenomenon causes cavitation erosion on the material surface. In particular, violent bubble collapse near the material surface causes severe erosion. Numerical simulation is a powerful approach by which to clarify the high-speed, complex bubble collapse behavior near the wall boundary. In the present study, numerical analysis of nonspherical bubble collapse behavior and induced impulsive pressure at several initial standoff distance from the wall boundary is performed using a locally homogeneous model of a gas-liquid two-phase medium. The second collapse is confirmed to be more violent than the first collapse, and a circular erosion pattern is predicted owing to a toroidal bubble collapse attached to the wall boundary at a certain standoff distance. The influence of the symmetry breaking of the initial spherical bubble shape on the collapse behavior is investigated, and the asymmetry is found to influence the second bubble collapse, especially the generation of the high impulsive pressure in the central area.

Summary In the present work, we established a rapid, cost-effective and high-throughput method for genotyping using a multiplexed microsphere-based suspension array platform – Luminex® × MAP™, which enabled us to analyse two SNPs in the promoter of IL-6 gene, determining haplotypes associated with different levels of expression. Using this system, IL-6 diversity in four different ethnic groups – East Asians, Caucasians, Hispanic and African Americans – was assessed. Results showed a significant variability in terms of allele, genotype and haplotype distribution. Considering the important immunoregulatory role of this cytokine and as a clinically relevant marker, this genotyping approach will provide a powerful tool for disease association or transplant outcome studies.

A numerical prediction method of cavitation erosion is proposed. In this method, the analysis of bubbles in cavitating flows is performed and the intensity of cavitation erosion is evaluated by the impact pressure induced by spherical bubble collapse. In the present study, two-dimensional cavitating flow around the Clark Y 11.7 % hydrofoil is used to examine the proposed numerical prediction method. The proposed numerical method predicts that the intensities of cavitation erosion in noncavitating, attached cavitating and pseudo-supercavitating flows are far weaker than the intensity of cavitation erosion in a transient cavitating flow, and the intensity in the vicinity of the sheet cavity termination is high. These results correspond well to experimental results, and it is confirmed that systematic erosion characteristics are generally captured by this method. Furthermore, the velocity dependence of cavitation erosion is examined, and it is found that the exponent n in the relation between the intensity I and main flow velocity Uin (I ∝ Uinn) becomes large when the bubble radius is large and ranges between 4.3 and 7.0 in the present study. According to the bubble dynamics, the ambient pressure and the rate of increases in pressure increase as the main flow velocity, and the maximum internal pressure increase. Therefore, it is thought that smaller bubbles cause cavitation erosion when the main flow velocity is large.

Clarification of the mechanism of particle removal by megasonic cleaning and control of cavitation bubbles in the megasonic field are essential for cleaning of nanodevices without pattern damage. Multiple bubble interactions complicate the mechanism of particle removal. Therefore, it is important to understand multiple bubble dynamics to clarify the mechanism of particle removal by megasonic cleaning. In the present study, the dynamics of two bubbles in a megasonic field with several initial radii and initial separation distances were simulated by numerical analysis using a compressible locally homogeneous model of a gas-liquid two-phase medium. The present numerical method simulated the various complex behaviors of two bubbles, which are repulsive motion, coalescence, periodic and stable motion of the separation distance, and bubble breakup. The initial separation distance strongly affected the behavior of the two bubbles because the effect of the secondary pressure induced by the oscillation of one bubble on the other bubble depends on the separation distance. In particular, when the equilibrium radii are larger than the resonant radius and the radius of one or both bubbles is close to the resonant radius, the bubbles can show characteristic behaviors, such as periodic and stable motion of the separation distance.

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.

A 16 year-old male with B-cell non-Hodgkin's 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.

RAS gene mutations occur in 30 - 40% of multiple myeloma (MM) patients. Farnesylation is the first step in the post-translational modification of RAS proteins. Tipifarnib is a potent farnesyl transferase inhibitor, and incadronate prevents post-translational prenylation of GTP-binding proteins such as RAS proteins. We examined the effect of tipifarnib in combination with incadronate on the growth of fresh and cloned myeloma cells in vitro. Tipifarnib inhibited the growth of myeloma cells, and this inhibition was intensified when tipifarnib was combined with incadronate. Tipifarnib, in combination with incadronate, may have some benefits in MM patients.

Ras gene mutations occur in 30% to 40% of patients with multiple myeloma (MM), and farnesylation is the first and most important step in the posttranslational modification of Ras proteins. R115777 is a newly synthesized potent farnesyl transferase inhibitor (FTI) and has recently demonstrated significant antitumor activities in vitro and in vivo. Therefore, we examined the effect of R115777 on the growth of fresh and cloned myeloma cells in vitro. R115777 inhibited the growth of fresh and cloned myeloma cells dose dependently, and effects were not dependent on the status of N-Ras mutation in fresh myeloma cells. Flow cytometric analysis using annexin V and 7-aminoactinomycin D (7AAD) showed that R115777 induced apoptosis of 2 of 3 myeloma cell lines at a concentration of 1.0 × 10-8 M. R115777 appears to be a potent inducer of apoptosis, and its effects depend on the status of Ras mutation in cloned myeloma cells but not on the status of N-Ras mutation in fresh myeloma cells. This is the first report that demonstrates the relationship between the N-Ras mutation in fresh myeloma cells and the effect of R115777. R115777 might have some benefit in the treatment of myeloma patients.

A 17-year-old male with chronic myelogenous leukemia in blast crisis received a non-T cell-depleted (TCD) HLA haplo-identical three-loci mismatched hematopoietic stem cell transplant (HSCT) from his mother. Long-term feto-maternal microchimerism was detected by nested polymerase chain reaction with sequence-specific primer typing. The post-transplantation prophylaxis against graft-versus-host disease (GVHD) was tacrolimus with minidose methotrexate. Sustained engraftment was obtained. Acute GVHD (grade 2) developed, but improved rapidly. Bone marrow aspiration on day 120 showed complete remission. Non-TCD HLA haplo-identical HSCT based on feto-maternal microchimerism might be feasible and has important implications in the selection of alternative family donors in HSCT.

Summary. This study aimed to identify which graft product subset of cells might be the most predictive of late haematopoietic recovery (three to 12 months) following autologous peripheral blood stem cell transplantation (PBSCT). The relationships between the numbers of reinfused CD34+ cells and their immature subsets such as CD34+/CD90+, CD34+/AC133+, CD34+/CD38– and CD34+/HLA-DR– cells, and haemoglobin, white blood cell (WBC) and platelet counts at 3, 6, 9 and 12 months after PBSCT, were studied in 25 patients with haematological and solid malignancies. The total CD34+ cell number, as well as CD34+/CD90+ and CD34+/AC133+ cell numbers, correlated with platelet counts at 3, 6, 9 and 12 months after PBSCT, but the CD34+/CD90+ cells infused best predicted platelet recovery during the first 12 months after PBSCT (P

The ultra-high heat flux cooling characteristics and impingement behavior of cryogenic micro-solid nitrogen (SN2) particles in relation to a heated wafer substrate were investigated for application to next generation semiconductor wafer cleaning technology. The fundamental characteristics of cooling heat transfer and photoresist removal-cleaning performance using micro-solid nitrogen particulate spray impinging on a heated substrate were numerically investigated and experimentally measured by a new type of integrated computational-experimental technique. This study contributes not only advanced cryogenic cooling technology for high thermal emission devices, but also to the field of nano device engineering including the semiconductor wafer cleaning technology.

Four patients (three males and one female) were diagnosed as myeloid/natural killer (NK) cell precursor acute leukemia in our department. Two patients showed the extramedullary involvement at initial presentation. Leukemic cells expressed CD7, CD33, CD45 and CD56 in all patients. Additionally, CD13, CD34, HLA-DR, cytoplasmic CD3 and myeloperoxidase were expressed in some patients. Trisomy 10 was found in two patients, which has not been reported in this disease. Therefore, myeloid/NK cell precursor acute leukemia might be rather heterogeneous especially in chromosomal abnormality though it seemed to constitute the distinct clinical entity among acute myeloid leukemia of M0 subtype.

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.

Feto-maternal microchimerism suggests that immunologic tolerance exists between mother and fetus. Based on this hypothesis, we performed haploidentical stem cell transplantation (SCT) without T-cell depletion (TCD) in 5 patients with advanced hematologic malignancies. HLA incompatibilities for graft-versus-host disease (GVHD) direction included 3-loci mismatches in 4 patients, and 2-loci mismatches in one patient. Recipient chimeric cells were detected in all patients. The prophylaxis against GVHD was tacrolimus with minidose methotrexate. Engraftment was obtained in all patients. An acute GVHD of less than or equal to grade 2 developed in all patients except one who developed tacrolimus encephalopathy. Two patients died, 1 from fungal pneumonia and 1 from disease progression. The other 3 patients survived, with one patient in complete remission. These observations suggest that haploidentical SCT based on the feto-maternal microchimerism without TCD is possible.

Cavitation erosion is a material damage phenomenon caused by the repeated application of impulsive pressure on a material surface induced by bubble collapse, and the establishment of a method by which to numerically predict cavitation erosion is desired. In the present study, a numerical quantitative prediction method of cavitation erosion in a cavitating flow is proposed. In the present method, a one-way coupled analysis of a cavitating flow field based on a gas-liquid two-phase Navier–Stokes equation (Eulerian) and bubbles in the cavitating flow by bubble dynamics (Lagrangian) is used to treat temporally and spatially different scale phenomena, such as the macroscopic phenomenon of a cavitating flow and the microscopic phenomenon of bubble collapse. Impulsive pressures acting on a material surface are evaluated based on the bubble collapse position, time, and intensity, and the erosion rate is quantitatively predicted using an existing material-dependent relationship between the impulsive energy (square of the impulsive force) and the maximum erosion rate. The erosion rate on a NACA0015 hydrofoil surface in an unsteady transient cavitating flow is predicted by the proposed method. The distribution of the predicted erosion rate corresponds qualitatively to the distribution of an experimental surface roughness increment of the same hydrofoil. Furthermore, the predicted erosion rate considering the bubble nuclei distribution is found to be of the same order of magnitude as the actual erosion rate, which indicates that considering bubble nuclei distribution is important for the prediction of cavitation erosion and that the present prediction method is valid to some degree.

Cavitation of a hydrofoil is observed in detail by using a high speed video camera. A paint removal test is also carried out in order to evaluate cavitation aggressiveness for erosion. 2D hydrofoil profile is Clark Y 11.7% and its angle of attack is seven degrees. Cavitation number is σ = 1.08. The experimental results are compared with cavitation CFD. Numerous features of unsteady cavitation are observed such as cyclic fluctuation of the sheet cavity, existence of the glassy cones on a sheet cavity, generation of the cloud cavitation from the sheet cavity and the isolated bubbles traveling over the suction surface of the blade. The isolated traveling bubbles and their collapses are thought to be one of the main causes of the severe paint removals. The isolated traveling bubbles are derived from the flowing cavitation nucleus or from abrupt onset at the leading edge of the blade. For computing these complicated phenomena, combination of grid scale bubbles (GSB) and sub grid scale bubble model (SGSB) are proposed. GSB shall be computed by using the computational scheme for the free surface with phase change model. SGSB can be computed with conventional cavitation model. The breakup of GSB generates SGSB, and the coalescence of SGSB makes GSB. Upper limit of void fraction of SGSB is estimated in the range of five or ten percent from the simple speculation of the structure of packed spheres. The two types of cavitation bubble inception model are also discussed based on the generation of the isolated bubbles observed in the experiments. To verify the proposed concepts of cavitation model, a traveling air bubble over a hydrofoil is computed by using the free surface flow scheme of Volume of Fluid (VOF) approach. Cavitation on the hydrofoil is also computed by VOF approach with boiling model concerning the heat transfer. Both the computed results show qualitatively similar characteristics of the bubble dynamics to those in experimental results.Copyright © 2010 by ASME

Summary Clinical reports have suggested the existence of immunological tolerance to noninherited maternal antigens (NIMA) in human leukocyte antigen (HLA) mismatched allogeneic stem cell transplantation (allo-SCT). We studied the T-cell reactivity using IFN-γ enzyme-linked immunospot (ELISPOT) assay in three HLA fully matched allo-SCT cases and one healthy volunteer family case. In HLA fully matched allo-SCT cases, ELISPOT assay could detect the hyporesponsiveness of T cells from donors to the B cells from recipients. Moreover, ELISPOT assay showed that the T cells from an individual responded to B cell from his mother significantly weakly than those from an unrelated HLA-haploidentical individual. These observations suggest that our IFN-γ ELISPOT assay-based method may predict the presence of immunological tolerance to NIMA.

In the present work we established a rapid, cost-effective and high-throughput method for genotyping using a multiplexed microsphere-based suspension array platform - Luminex xMAP which enabled us to analyze 3 SNPs in the MBL2 gene promoter and 5' UTR, and 3 coding SNPs exon 1 haplotypes, associated with different levels of MBL2 expression. Using this system MBL2 diversity in four different ethnic groups, namely, Asian (Japanese), Caucasian, Hispanic and African-American-assessed. Results showed significant variability in terms of allele, genotype, and haplotype distribution. Characteristic MBL haplotype patterns were defined for each ethnic group. A prevalence of haplotypes coding functional proteins capable of complement activation and pathogen opsonization was observed. Regardless of the significant diversity of individual haplotypes, a high, almost similar (25-28%) proportion of haplotypes associated with MBL deficiency was found in the four ethic groups. The proportion of individuals homozygous for the haplotypes resulting in complete MBL2 deficiency was also significant (2-10%). Considering the role of MBL2 in innate immunity and as a clinically relevant marker, the genotyping approach developed and the knowledge of the genetic variation in different ethnic groups will be relevant to future medical genetic studies.

A 42-year-old female underwent hysterectomy because of a huge uterine mass. Histologically, she was diagnosed as having intravascular lymphoma co-existing with myoma uteri. Lymphoma cells were large in size and were positive for CD5, CD20, CD45, CD79a, lambda light chain, and EBV but were negative for CD3 and cyclin D1. No other organs except for the adjoining bilateral ovaries seemed to be affected by the lymphoma cells. She received the combination chemotherapy (cyclophosphamide, doxorubicin, vincristine, and prednisolone) together with rituximab and has been well without definite disease progression. So far, this is the first case of CD5+ EBV+ intravascular large B-cell lymphoma (CD5+ EBV+ IVLBL) in the uterus of a patient who was incidentally diagnosed and successfully treated.

A 22-year-old male presented with multiple bilateral nodular shadows in the lungs by chest radiograph. He had been asymptomatic and showed no significant abnormal findings in laboratory examinations. He underwent a diagnostic partial lobectomy, and was diagnosed as having primary pulmonary mucosa-associated lymphoid tissue (MALT) lymphoma; i.e. bronchus-associated lymphoid tissue (BALT) lymphoma/BALToma. Neither t(11;18)(q21;q21) chromosomal translocation nor API2-MALT1 chimeric transcript was found at diagnosis. Epstein-Barr virus (EBV) was also not detected in lymphoma cells. He had been a nonsmoker, and had also never shown any associated autoimmune disorders, chronic inflammatory lung diseases or human immunodeficiency virus (HIV) infection. However, he had suffered from moderate atopic dermatitis on his arms from childhood. It appears necessary to clarify whether atopy might play a role in the pathogenesis of API2-MALT1(-) BALT lymphoma for HIV( - ) young patients who do not exhibit any other antecedent chronic antigenic stimulations.

A 43-year-old woman was diagnosed as having stage IV follicular lymphoma. Phenotypically, the lymphoma cells were CD5(-), CD10(+), CD19(+), CD20(+), CD23(-), HLA-DR(+), and IgM-lambda(+). Conventional chromosomal analysis showed a three-way t(3;14;18)(q27;q32;q21) in the lymphoma cells, which was confirmed by spectral karyotyping (SKY) and fluorescence in situ hybridization (FISH). Immunohistochemistry revealed that both BCL2 and BCL6 proteins were expressed in the lymphoma cells, whereas only the BCL6 gene, and not the BCL2 gene, was rearranged by Southern blotting. The patient received combination chemotherapy and has been well for 3 years. This is the first reported case showing a three-way translocation involving 2 major lymphoma-specific abnormalities, 3q27 and t(14;18)(q32;q21).

A 62-year-old man diagnosed with acute myelogenous leukemia which had developed from myelodysplastic syndrome received cytarabine and idarubicine as an 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. 67Ga 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.

We treated seven refractory or relapsed myeloma patients resistant to conventional chemotherapy with thalidomide. We started thalidomide at 100 mg daily and the dose was increased up to 300 mg if the patient could tolerate it. The patients were evaluated at four weeks and 12 mg of dexamethasone was added for four days when the patient failed to respond to thalidomide treatment. One patient was excluded from the study because of general fatigue. Two of the six patients responded to thalidomide alone and three of the remaining four patients responded to the combination with dexamethasone. The most common adverse effect was sleepiness which was seen in three patients. Two patients showed pancytopenia (Grade 3), constipation and skin eruption. Of the six patients four needed reduction of the thalidomide dose to 200 mg because of adverse effects. Plasma levels of TNF-alpha, IL-6, bFGF and VEGF were measured before and after four weeks. High plasma bFGF levels were seen in responding patients. In conclusion, treatment with thalidomide alone or in combination with dexamethasone is feasible and effective in refractory or relapsed myeloma patients. Further study is required to clarify the role of thalidomide in the therapeutic strategy for multiple myeloma.

Vinorelbine (NVB) is a newly synthesized vinca alkaloid that has been used to treat advanced malignant diseases including lung adenocarcinoma and lymphoma. The effect of NVB on myeloma, however, is unknown. We therefore examined the effect of NVB on the growth of human myeloma cell lines (RPMI8226, U266 and KPMM2) using the trypan blue dye exclusion test and Alamar blue assay. NVB inhibited the growth of myeloma cells of all three cell lines dose-dependently and this effect was intensified when NVB was combined with dexamethasone at 1.0 x 10(-6)mol/l. Flow cytometric analysis using annexin V (AN) and 7-amino-actinomycin D (7AAD) showed that NVB-induced apoptosis of these myeloma cells in all the cell lines. NVB appears to be a potent inducer of apoptosis in myeloma cells, and might have some benefit in the treatment of myeloma patients.