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Pure white cell aplasia (PWCA) is a rare neutropenic disorder caused by absence of neutrophil-lineage cells. A 49-year-old man was diagnosed with scleroderma renal crisis 2 months prior to admission to Ohta-Nishinouchi Hospital after experiencing a fever and abdominal pain. Blood tests revealed severe neutropenia, and bone marrow aspirate showed the absence of neutrophil-lineage cells. He was diagnosed with PWCA. Steroids alone were not effective, but adding cyclosporine A and high-dose immunoglobulin recovered his neutropenia and improved his condition. Cyclosporine A and high-dose immunoglobulin are thus considered effective for treating PWCA in autoimmune diseases.

Summary Background Standard treatment for untreated advanced-stage follicular lymphoma is rituximab plus chemotherapy. The incidence of histological transformation of follicular lymphoma has been reported only in heterogeneously treated populations and rarely with long-term follow-up. Additionally, the incidence of secondary malignancies after treatment, without high-dose therapy for follicular lymphoma, is largely unknown. The aim of our study was to assess progression-free survival, overall survival, incidence of secondary malignancies, and incidence of histological transformation in a 10-year follow-up analysis of the JCOG0203 trial. Methods In the phase 2–3 randomised JCOG0203 trial, previously untreated patients with stage III or IV indolent B-cell lymphoma, including grades 1–3 follicular lymphoma, from 44 hospital centres in Japan, were randomly assigned (1:1) by use of a minimisation method to receive six cycles of R-CHOP (rituximab [375 mg/m2], given on day 1, plus cyclophosphamide [750 mg/m2], doxorubicin [50 mg/m2], vincristine [1·4 mg/m2, capped at 2·0 mg] given intravenously on day 3, and oral prednisone [100 mg once daily on days 3–7]) every 3 weeks (R-CHOP-21) or every 2 weeks (enabled by mandatory granulocyte-colony stimulating factor administration once daily for 6 days, starting on day 8; R-CHOP-14) without rituximab maintenance. Age, bulky disease (nodal or extranodal mass ≥10 cm in diameter on CT), and institution were used as adjustment factors. Investigators enrolled participants, and assignment to trial groups was done with a computer-assisted randomisation allocation sequence that took place centrally at the Japan Clinical Oncology Group Data Center, without the intervention of investigators. Interventions were not masked for patients or investigators. Data were collected 10 years after enrolment of the last patient. The primary endpoint of the phase 3 part of the study was progression-free survival, and the primary endpoint of the phase 2 part of the study was the proportion of patients who achieved a complete response. Accrual was 4·5 years, and follow-up was 3 years after registration was closed. Data were updated on the cutoff date of Feb 28, 2017. Intention-to-treat analyses (ie, progression-free survival, overall survival, and incidence of secondary malignancies) were predefined, to be done at 10 years after the last patient was enrolled. An additional analysis of the incidence of histological transformation was defined 15 years after the protocol, on May 8, 2017, in a supplementary analysis plan, and assessed at 10 years after the last patient was enrolled. Follow-up is ongoing. This trial is registered with ClinicalTrials.gov, number NCT00147121. Findings Between Sept 1, 2002, and Feb 28, 2007, 300 patients were enrolled, and 149 (50%) were assigned to the R-CHOP-21 group and 151 (50%) were assigned to the R-CHOP-14 group. After eligibility was assessed, one patient was excluded from the R-CHOP-21 group. 10-year progression-free survival was not different between groups (R-CHOP-21 33%, 95% CI 25–41; R-CHOP-14 39%, 31–47; hazard ratio 0·89, 95% CI 0·67–1·17). In 248 patients with grade 1–3a follicular lymphoma, progression-free survival was 39% (33–45) at 8 years and 36% (30–42) at 10 years. The cumulative incidence of histological transformation was 3·2% (95% CI 1·5–6·0) at 5 years, 8·5% (5·4–12·4) at 8 years, and 9·3% (6·1–13·4) at 10 years after enrolment. At 10 years, the cumulative incidence of secondary malignancies was 8·1% (5·1–12·0) and the cumulative incidence of haematological secondary malignancies was 2·9% (1·3–5·5). Interpretation R-CHOP is a viable option for first-line treatment in patients with newly diagnosed advanced follicular lymphoma. Clinicians choosing a first-line treatment for patients with follicular lymphoma should be cautious of secondary malignancies caused by immunochemotherapy and severe complications of infectious diseases in the long-term follow-up—both of which could lead to death. Funding National Cancer Center and Ministry of Health, Labour and Welfare of Japan.

A 49-year-old man was hospitalized with infectious mononucleosis-like symptoms, hepatosplenomegaly, and circulating abnormal lymphocytes. Hepatosplenic T-cell lymphoma was suspected, and bone marrow aspiration and liver biopsy were performed. The pathological diagnosis was T-cell lymphoma. When explaining malignant lymphoma to the patient, he disclosed his Men Who Have Sex with Men (MSM) status. HIV RNA test showed a markedly high viral load, and TCR gene rearrangement was negative. In view of these results, the patient was diagnosed with acute HIV infection. The previous lack of information concerning his MSM status led to a misdiagnosis, highlighting the relevance of this case to raise awareness of the importance of previously interviewing the patient.

Niemann-Pick disease type C (NP-C) is an autosomal recessive lysosomal lipid storage disorder characterized with accumulation of cholesterol in endosomes and lysosomes. The diagnosis of NP-C is difficult due to its heterogeneous group of diseases. Biochemical diagnosis of NP-C is conducted by cholesterol staining with cultured skin fibroblasts and confirmed by the analysis of genetic mutations of NPC1 or NPC2 gene. Here, we report an easier biochemical diagnostic method with blood smear by filipin staining.

Although cladribine has been reported to be an active purine analog against indolent B-cell non-Hodgkin lymphoma (B-NHL), there are few reports of combination use of cladribine and rituximab. This multicenter phase II study evaluated the efficacy and toxicity of cladribine with rituximab (R-2-CdA) therapy in relapsed or refractory indolent B-NHL. Twenty patients with the median age of 58.5 yrs (range, 42-72) were enrolled and received R-2-CdA therapy from April 2005 to July 2007. The median number of prior regimens was 2 (range, 1-3), and fifteen patients (75%) were previously treated with rituximab-containing regimens. Disease histology included follicular lymphoma in 16 patients, MALT lymphoma in two patients, nodal marginal B-cell lymphoma in one patient, and lymphoplasmacytic lymphoma in one patient. The overall response rate (ORR) was 90%, with a complete response rate (CRR) of 70%. Estimated median progression-free survival (PFS) time was 22.4 months (95%CI, 10.9-32.6 months) at a median follow-up time of 27 months (range, 12-43). Two-year PFS and 2-yr overall survival (OS) were 52.6% (95%CI, 31.0-73.2%) and 89.5% (95%CI, 66.1-97.3%), respectively. Grade 3 or grade 4 toxicities were neutropenia in 74% and thrombocytopenia in 11%. R-2-CdA therapy was demonstrated to have a high activity with durable PFS and acceptable toxicity in relapsed or refractory indolent B-NHL mostly pretreated with rituximab-containing therapy. Although a large-scale trial is needed for confirmation, R-2-CdA therapy could be a good salvage therapy option in relapsed or refractory indolent B-NHL.

We prospectively compared allogeneic hematopoietic stem cell transplantation (allo-HSCT) with chemotherapy as a post-remission therapy in a multicenter trial (JALSG AML97) of adult patients with intermediate or poor risk acute myeloid leukemia (AML). Of 503 patients aged 15-50 years old registered between December 1997 and July 2001, 392 achieved complete remission (CR). CR patients classified in the intermediate or poor risk group using a new scoring system were tissue typed. Seventy-three with and 92 without an HLA-identical sibling were assigned to the donor and no-donor groups. Of 73 patients in the donor group, 38 (52%) received allo-HSCT during CR1 and 17 (23%) after relapse. Intention-to-treat analysis revealed that the relapse incidence was reduced in the donor group (52 vs. 77%; p = 0.008), and the disease-free survival (DFS) improved (39 vs. 19%; p = 0.016), but overall survival (OS) was not significantly different (46 vs. 29%; p = 0.088). The OS benefit was seen in the patients aged 36-50 years old (49 vs. 24%; p = 0.031), suggesting an advantage of allo-HSCT among older patients with leukemia that is more resistant to chemotherapy than that among younger patients.

A micro-scale catalytic combustor fueled by butane was investigated. High-precision ceramic tape-casting technology was adopted for developing a three-dimensional structure of the combustor with embedded heat exchange channels. Nano-porous alumina fabricated through anodic oxidation of aluminum layers was employed for the support of Pd catalyst. Combustion experiments were carried out in a solder bath to keep the catalyst temperature constant. Complete fuel conversion for a n-butane flow rate of 5.0 sccm has been achieved at 390 °C corresponding to 100 MW m−3 heat generation. Reaction constants for catalytic combustion on the Pd/nano-porous alumina were determined with the aid of a 1D plug flow model. Those parameters were successfully combined with a CFD analysis to investigate the detailed transport phenomena and to predict the performance of the combustor at higher temperature. It was also shown in a preliminary experiment in air that the reaction can be self-sustained at 425 °C with the n-butane flow rate of 15 sccm.

BACKGROUND A major concern in the treatment of patients with acute myeloid leukemia (AML) is how to prevent disease recurrences. Although intensive consolidation therapy has proven useful, the effectiveness of maintenance therapy remains controversial. METHODS Seven hundred eighty-nine patients ages 15–64 (median: 45 yrs) with de novo AML received induction therapy, which consisted of cytosine arabinoside (at a dose of 100 mg/m2 on Days 1–7) and idarubicin (at a dose of 12 mg/m2 on Days 1–3). The patients who achieved complete remission (CR) were then randomized into groups that received either four courses of standard-dose consolidation therapy without maintenance (Arm A) or three courses of standard-dose consolidation and six courses of maintenance therapy (Arm B). RESULTS In total, 78.7% of patients achieved CR. The 5-year overall survival (OS) rate for the 789 eligible patients was 46.9%, and the disease-free survival (DFS) rate for the 621 patients who achieved CR was 32.9%. The 5-year OS rate for Arm A was 52.4%, and 58.4% for Arm B (P = 0.599). The 5-year DFS rate for the patients who achieved CR was 35.8% in Arm A and 30.4% in Arm B (P = 0.543). In analyzing the data according to the risk groups, no statistical difference was observed either in the 5-year OS rate or in the 5-year DFS rate between the 2 arms. CONCLUSIONS In the current study, the Japan Adult Leukemia Study Group's conventional postremission therapy (three courses of standard-dose consolidation and six courses of maintenance therapy) was replaced successfully by a shorter duration of four courses of standard-dose consolidation therapy without the need for additional maintenance therapy. Cancer 2005. © 2005 American Cancer Society.

Purpose Despite the effectiveness of cardiac rehabilitation (CR), the participation percentage is low in Japan. Therefore, we investigated factors associated with enrollment and adherence in outpatient cardiac rehabilitation (OCR) in Japan. Methods This was a single-hospital, case-controlled study. During a 2-year study period, 544 patients were hospitalized for ischemic heart disease, heart failure, or open heart surgery, and recommended for in-hospital CR. Among them, 78 OCR participants and 179 randomly selected nonparticipants were included in the study. These 2 groups were compared to examine factors associated with OCR enrollment. In addition, OCR participants were divided into those who continued OCR for 3 months (adherence group) and those who did not (nonadherence group), and these 2 groups were compared to examine factors associated with OCR adherence. Univariate and multivariate logistic regression analyses were conducted for both objectives and included sociodemographic, clinical, and OCR-related variables. Results OCR enrollment was significantly associated with younger age (OR, 0.96; 95% CI, 0.93-0.98) and shorter distance to the hospital (OR, 0.97; 95% CI, 0.95-0.99). OCR adherence was significantly associated with a history of ischemic heart disease (OR, 6.03; 95% CI, 1.62-22.5) and prescription of antidepressants and/or sleeping pills (OR, 4.14; 95% CI, 1.07-16.0). Conclusions The main factors associated with OCR enrollment and adherence were sociodemographic factors related to easier hospital access and clinical conditions that reflected high disease awareness, respectively.

In this study, we reported five cases of CD5+ diffuse large B-cell lymphoma (DLBCL) which initially presented as bone marrow involvement without lymphadenopathy. The cases involved two males and three females, with an average age of 73.8 years. The patients had fever and showed general fatigue. Three of the five cases presented hepatosplenomegaly. Laboratory examination highlighted anemia, thrombocytopenia, presence or absence of leukopenia, hypoalbuminemia as well as a considerable elevation of serum lactate dehydrogenase, soluble IL-2R and ferritin. Bone marrow aspiration smears showed large-sized lymphoma cells, which were found to aggregate, and clot sections showed many clusters of lymphoma cells, which had a large and round or indented nucleus with vesicular chromatin and occasional small nucleoli. Mitotic rate was high. In the bone marrow clot section, whereas three cases exhibited a diffuse infiltration of the lymphoma cells (diffuse type), two cases exhibited a sinusoidal proliferation (intravascular type). Cytogenetic analysis showed many and complex abnormalities in all 3 cases examined. The lymphoma cells were positive for CD5, CD19, CD20, CD38, IgM, bcl-2 and bcl-6, while they were negative for CD3, CD10, CD23, CD30, cyclin D1 and TdT. In four cases, after a semi-nested PCR amplification of the immunoglobulin heavy chain (IgH) gene, a discrete band could be detected. All the cases exhibited an in-frame sequence and the frequency of somatic mutations ranged from 2.1 to 11.1% with no intraclonal diversity. These DLBCL may have derived from the same counterpart as CD5+ B-CLL. There were no differences in laboratory, immunological and molecular examination between the diffuse type and the intravascular type. Recurrences in the bone marrow and an aggressive clinical course were also observed in both types.

PURPOSE To determine whether macrophage colony-stimulating factor (M-CSF) reduces the incidence and duration of febrile neutropenia during three courses of intensive consolidation therapy and whether it shortens time to complete consolidation therapy. PATIENTS AND METHODS In 198 adult patients with acute myeloid leukemia (AML) in complete remission (CR), M-CSF (8 x 10(6) U/d) or placebo was administered from 1 day after the end of each consolidation chemotherapy for 14 days. RESULTS The duration and incidence of febrile neutropenia was significantly reduced by 34% (P = .00285) and 17% (P = .02065), respectively, in 88 assessable patients in the M-CSF group compared with those in 94 assessable patients in the placebo group. Patients in the M-CSF group had 565 days and 133 episodes of febrile neutropenia during 7,901 days at risk, while patients in the placebo group had 977 days and 185 episodes during 9,077 days at risk. The median period required to finish the three courses of consolidation therapy was 93 days in the M-CSF group, which was significantly shorter than 110 days in placebo group (P = .0050). In the M-CSF group, the recovery of neutrophils and platelets was significantly faster (P = .0348 and P = 0.0364, respectively), the administration of systemic antimicrobial agents tended to be less (P = .0839), and the frequency of platelet transfusion (P = .0259) and the total volume of transfused platelets (P = .0292) were significantly less. However, there was no significant difference in the disease-free survival. CONCLUSION M-CSF significantly reduced the incidence and duration of febrile neutropenia during the intensive consolidation therapy, and shortened the time to complete consolidation chemotherapy in AML.

Although cladribine has been reported to be an active purine analog against indolent B-cell non-Hodgkin lymphoma (B-NHL), there are few reports of combination use of cladribine and rituximab. This multicenter phase II study evaluated the efficacy and toxicity of cladribine with rituximab (R-2-CdA) therapy in relapsed or refractory indolent B-NHL. Twenty patients with the median age of 58.5 yrs (range, 42-72) were enrolled and received R-2-CdA therapy from April 2005 to July 2007. The median number of prior regimens was 2 (range, 1-3), and fifteen patients (75%) were previously treated with rituximab-containing regimens. Disease histology included follicular lymphoma in 16 patients, MALT lymphoma in two patients, nodal marginal B-cell lymphoma in one patient, and lymphoplasmacytic lymphoma in one patient. The overall response rate (ORR) was 90%, with a complete response rate (CRR) of 70%. Estimated median progression-free survival (PFS) time was 22.4 months (95%CI, 10.9-32.6 months) at a median follow-up time of 27 months (range, 12-43). Two-year PFS and 2-yr overall survival (OS) were 52.6% (95%CI, 31.0-73.2%) and 89.5% (95%CI, 66.1-97.3%), respectively. Grade 3 or grade 4 toxicities were neutropenia in 74% and thrombocytopenia in 11%. R-2-CdA therapy was demonstrated to have a high activity with durable PFS and acceptable toxicity in relapsed or refractory indolent B-NHL mostly pretreated with rituximab-containing therapy. Although a large-scale trial is needed for confirmation, R-2-CdA therapy could be a good salvage therapy option in relapsed or refractory indolent B-NHL.

A multicenter, prospective, randomized study was conducted to compare a response-oriented individualized remission induction therapy with a standard fixed-schedule induction therapy, using idarubicin (IDR) and cytarabine (Ara-C), in adult patients with acute myeloid leukemia (AML). Newly diagnosed patients with AML of age less than 65 were randomly assigned to receive either of the two schedules. Both groups received IDR (12 mg/m2) for 3 days and Ara-C (100 mg/m2) for 7 days. In the individualized group, if the bone marrow on day 8 did not become hypocellular with less than 15% blasts, patients received additional IDR for one more day and Ara-C for 2 or 3 more days. Patients achieving complete remission (CR) received the same post-remission therapy. The CR rate was 79.4% for the individualized group (n = 209) and 81.9% for the fixed group (n = 221) (p = 0.598). At a median follow-up of 81 months, 7-year predicted overall survival was 37% for the individualized group and 39% for the fixed group (p = 0.496), and 7-year predicted event-free survival was 22% for the individualized group and 23% for the fixed group (p = 0.546). Thus, the present study could not demonstrate any advantage of a response-oriented individualized induction therapy over a fixed-schedule induction therapy in this protocol setting.

The primary objective of this study was to investigate the tolerability, efficacy and pharmacokinetic profile of gemtuzumab ozogamicin (GO) in patients with relapsed and/or refractory CD33-positive acute myeloid leukemia (AML). Patients received 2-h infusions of GO twice with an interval of approximately 14 days. Tolerability was assessed using the National Cancer Institute Common Toxicity Criteria Version 2.0. Samples for pharmacokinetics were taken on day 1 and day 8 of the first treatment cycle. The dose was increased stepwise and, in each cohort, patients were treated at the same dose. Forty patients, median age 58 years (range 28–68) were treated; 20 and 20 patients were enrolled to the phase I and II parts, respectively. In the phase I part, dose-limiting toxicities (DLTs) were hepatotoxicities, and the recommended dose was established as 9 mg/m2 given as two intravenous infusions separated by approximately 14 days. The pharmacokinetic study revealed that Cmax and AUC were equivalent to those of non-Japanese patients. In the phase II part, complete remission was observed in 5 patients, and one patient had complete remission without platelet recovery. Four of these 6 in remission and one in the phase I are long-term survivors (alive for at least 44 months). GO is safe and effective as a single agent among Japanese CD33-positive AML patients. Remission lasted longer in a subset of patients than in non-Japanese patients in earlier studies. Further studies of this agent are warranted to establish standard therapy.

To investigate whether combination chemotherapy with vincristine, cyclophosphamide, prednisolone, and melphalan (COP/ MP) with the addition of ranimustine (MCNU) (MCNU-COP/MP) is superior to the slightly modified COP/MP (mCOP/MP) regimen in multiple myeloma (MM), a multicenter randomized study was performed. Two hundred ten patients with newly diagnosed, overt MM not treated with chemotherapy were enrolled from 32 institutions of the Lymphoma Study Group of the Japan Clinical Oncology Group and were randomized to receive either MCNU-COP/MP or mCOP/MP. The response rate (RR) to mCOP/MP was 43.7% (95% confidence interval [CI], 33.9%–53.8%] and to MCNU-COP/MP was 56.1 % (95% CI, 46.1 %–65.7%) (P = .097). The progression-free survival (PFS) was significantly longer for patients treated with MCNU-COP/MP than for patients treated with mCOP/MP (median, 23.0 months [95% CI, 18.9–25.8] versus 15.8 months [95% CI, 14.1–19.4]) (P = .014). However, no significant difference in overall survival rate (OS) was observed between the groups (median, 49.9 months [95% CI, 40.4-59.1] versus 44.0 months [95% CI, 32.8–59.8]) ( P = .75). Grades 3 and 4 hematological toxicities were more frequently observed with MCNU-COP/MP than with mCOP/MP, but the incidence of grades 3 and 4 nonhematological toxicities was low in both groups. In conclusion, MCNU-COP/MP in comparison with mCOP/MP improved RR and PFS in overt MM; however, this outcome did not contribute to prolonging OS, indicating that addition of MCNU to mCOP/MP has no benefit on survival.

Myeloid/natural killer (NK) cell precursor acute leukemia is an entity of acute leukemia characterized by poor prognosis and a CD7+CD56+ myeloid antigen+ phenotype without light-microscopic myeloperoxidase reactivity. This disease shares several clinical characteristics with acute myeloid leukemia (AML) M0. To clarify the relationship between these 2 leukemias, we analyzed 105 cases of AML M0. Among them, 17 were CD7+ and CD56+, 77 were negative for either antigen, and 11 could not be determined. CD7+CD56+ AML M0 showed onset at significantly lower patient age (median 46 versus 63 years, P = .004). The disease localization and the hematological manifestations were significantly different: CD7+CD56+ AML showed more frequent extramedullary involvement, fewer circulating leukemic blasts, less anemia, and less thrombocytopenia than did AML M0. The cytogenetic aberrations were also unique, because no 5q abnormalities were found in CD7+CD56+ M0. The prognosis of CD7+CD56+ M0 was poor in patients younger than 46 years (P = .03). Multivariate analysis showed that the CD7+CD56+ phenotype was a significant prognostic factor for AML M0, as well as age, circulating blast percentage, and chromosome 5 abnormalities These findings suggest that AML M0 consists of heterogeneous subgroups to be managed separately, and CD7+CD56+ M0 constitutes a distinct subtype of AML M0.

Chip Scale Package (CSP) adaptation has been drastically increasing as the key component to facilitate miniaturization for portable electronic devices such as Cellular phone, Camcorder, PDA, etc. which are mainly consumer electronics devices. In addition, high I/O count CSP are predicted to support high performance IC devices for Workstation and Mainframe, and high reliability CSP is also demanded for broadening the application for high-end market such as satellite communication application. Ceramic has been a leading material for the rigid interposer style of CSP. Ceramic technology has many advantages such as design flexibility with fine design rule, buried and blind via holes, high thermal conductivity, and stability of material properties at high temperature and harsh environment. Ceramic technology is considered to be the most suitable for CSP application where high performance and high reliability are required. Kyocera has been developing Snap Array CSP/sup TM/ technologies utilizing ceramic technology and optimized assembly materials. Productivity at assembly process has been drastically improved by using an array format carrier. Specification of an array format carrier is optimized for utilizing current assembly equipment designed for PBGA and PQFP. Through continued development and optimization, a wide variety of Snap Array CSP/sup TM/ have been realized.

All-trans-retinoic acid (ATRA) has been incorporated in front-line therapy for newly diagnosed acute promyelocytic leukemia (APL). We conducted a multicenter study of differentiation therapy with ATRA alone or in combination with chemotherapy followed by intensive postremission chemotherapy in patients with APL (the JALSG APL92 study), and analyzed prognostic factors to increase the cure rate in our subsequent trial. From 1992 to 1997, adult patients with newly diagnosed APL received oral ATRA 45 mg/m2 daily alone until complete remission (CR) if initial leukocyte counts were3.0x10(9)/l, and ATRA daily plus daunorubicin (DNR) 40 mg/m2x3 days plus enocitabine (BHAC) 200 mg/m2x5 days if leukocyte counts wereor =3.0 x 10(9)/l. If peripheral blasts exceeded 1.0x10(9)/l during therapy, DNRx3 days plus BHACx5 days was added. After CR was achieved, three courses of consolidation and six courses of maintenance/intensification chemotherapy were administered. Of 376 patients enrolled, 369 were evaluable (median age 46 years, range 15-86 years; median leukocyte counts 2.0x10(9)/l), and 333 (90%) achieved CR (94% of patients treated with ATRA alone, 88% with ATRA plus later chemotherapy, 89% with ATRA plus initial chemotherapy, and 86% with ATRA plus initial and later chemotherapy). At a median follow-up of 45 months, the predicted 6-year overall and event-free survival (EFS) rates for all patients were 65% and 52%, respectively. Favorable prognostic factors for CR were younger age, no or mild purpura, high serum total protein level, low lactate dehydrogenase level, and no or mild disseminated intravascular coagulation (DIC). Favorable prognostic factors for EFS were leukocyte counts10.0x10(9)/l, mild DIC, and no sepsis during induction therapy. In the JALSG APL97 study, we intensified chemotherapy for patients with leukocyte countsor =3.0x10(9)/l, and are randomly testing whether further chemotherapy is required for APL patients with negative PCR for PML/retinoic acid receptor alpha in the maintenance phase.

The significantly increasing transmission capacity in the subscriber system are accelerating demands for higher data transmission speed, low cost, and system miniaturization in the millennium approaches. The key solution for the demands, smaller, lower cost, and high performance package, is surface technology. OptoBGA package has been developed to meet this challenge, a surface mountable type optical package that is designed for high frequency transmission speeds. OptoBGA package has a BGA structure to bring forth effectively size and cost reduction for the packaging. OptoBGA consists of ceramic material, a robust material, which has many advantages such as design flexibility with fine design rule, ease of process technology, high performance, and high reliability. The design of OptoBGA was made possible by improvement in the physical structure. The results of this research produced an OptoBGA with a return loss of about -20dB at 10GHz. Furthermore, reliability test evaluations have been conducted to demonstrate that the OptoBGA can withstand harsh environments.© (2000) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

PURPOSE We conducted a multicenter study of differentiation therapy with all-trans retinoic acid (ATRA) followed by intensive chemotherapy in patients with newly diagnosed acute promyelocytic leukemia (APL) and analyzed the prognostic factors for predicting complete remission (CR), event-free survival (EFS), and disease-free survival (DFS). PATIENTS AND METHODS All patients received ATRA until CR. If patients had an initial leukocyte count greater than 3.0 x 10(9)/L, they received daunorubicin (DNR) and behenoyl cytarabine (BHAC). During therapy, if patients showed blast and promyelocyte counts greater than 1.0 x 10(9)/L, they received additional DNR and BHAC. After achieving CR, patients received three courses of consolidation and six courses of maintenance/intensification chemotherapy. RESULTS Of 198 registered, 196 were assessable (age range, 15 to 86 years; median, 46) and 173 (88%) achieved CR. Multivariate analysis showed that no or minor purpura at diagnosis (P = .0046) and age less than 30 years (P = .0076) were favorable factors for achievement of CR. Predicted 4-year overall survival and EFS rates were 74% and 54%, respectively, and the 4-year predicted DFS rate for 173 CR patients was 62%. Multivariate analysis showed that age less than 30 years (P = .0003) and initial leukocyte count less than 10 x 10(9)/L (P = .0296) were prognostic factors for longer EFS, and initial leukocyte count less than 10.0 x 10(9)/L was a sole significant prognostic factor for longer DFS (P = .0001). CONCLUSION Our results show that age, hemorrhagic diathesis, and initial leukocyte count are prognostic factors for APL treated with ATRA followed by intensive chemotherapy.

Allogeneic hematopoietic stem cell transplantation (allo-SCT) is considered to be the most intensive post remission treatment consisting of high-dose chemoradiotherapy and allo-immune mechanisms. However, the powerful anti-leukemic effects of this treatment are counterbalanced by a high incidence of treatment-related mortality (TRM), thus allo- SCT has not always been considered superior to chemotherapy. The aim of this study was to investigate the efficacy of allo-SCT as a postremission treatment in patients with intermediate/poor risk AML in first CR. Previously untreated patients aged 15 – 50 years were eligible. Patients received standard induction therapy consisting of cytarabine (100 mg/ m2 d1–7) and idarubicin (12 mg/m2 d1- 3). If the patients did not achieve remission after the first induction therapy, then the same induction therapy was given again. The patients who achieved CR were randomized into an intensified short-course postremission chemotherapy group (arm A) or conventional JALSG postremission chemotherapy group (arm B). Patients were also categorized into good, intermediate or poor risk groups by risk factors selected from previous JALSG AML trials using univariate and multivariate analyses. Intermediate or poor risk patients with living siblings were tissue typed. If an HLA matched sibling was found it was assumed that the patient would receive allo-SCT during CR1 (donor group). Those without living or HLA matched siblings were assigned to the no-donor group that continued receiving chemotherapy. The disease-free survival (DFS) rates, the relapse incidence rates (RI), TRM and the overall survival (OS) rates of the patients of the donor group were compared with those of the no-donor group on the basis of the intention to treat. Result: Of 503 patients aged 15 – 50 years old registered between December 1997 and July 2001, 397 achieved complete remission (CR). The 5-year OS rate of the CR patients with good, intermediate and poor risk was 68%, 43% and 29%, respectively (p Conclusions: Our study showed that allo-SCT reduced the risk of relapse and contributed to the survival advantage of AML patients aged from 36 to 50 years old with intermediate or poor risk.

A new cell structure has been developed to realize very high darkroom contrast ratio. Crystal Emissive Layer (CEL) is added on the phosphor layers, in addition to that on the MgO layer. As this structure enables stable and very low luminance reset discharge, high contrast ratio over 20000:1 has been achieved in new Pioneer's PDP “KURO”.

50-inch diagonal Full HD PDPs (1920 × 1080 pixels) have been developed and introduced in the market place. In the development, manufacturing of the fine cell structure has been obtained by the optimization of cell design, materials and process conditions. T & Waffle structure has been employed and shows sufficiently high luminous efficacy. Most important issue of high speed addressing has been solved by CEL structure and its improvement. CEL technology has opened new aspect in higher resolution PDP technology. We expect that it will open new technology area in PDP field.

Background: Translocation (8;21) is one of the most common structural aberrations found in AMLand good response rates and a better DFS have been described in pts possessing it. Especially, the DFS rate may exceed 60–70% in younger pts given repetitive courses of HDAra-C. However, it was recently reported that a subtype of AML with t(8;21) showed a poor prognosis and this case also had the KIT mutation. As a result, we retrospectively analyzed the prognosis of AML pts with t(8;21) prospectively enrolled in the JALSG AML97 study. Patients and Methods: Between 1997 and 2001, JALSG AML97 enrolled 809 pts previously untreated for AML and pts with M3 were excluded. From the 789 eligible pts, we selected the subjects with t(8;21) for this study. Induction therapy consisted of cytarabine and idarubicin. All CR pts were randomized to receive either four courses of standard dose consolidation therapy without maintenance therapy or three courses of standard dose consolidation with 6 courses of maintenance therapy. HDAra-C was not administered in the JALSG AML97 study. Peripheral blood and bone marrow smears and karyotypes were reevaluated by the central review committees. Any patients who underwent SCT were censored at the date of SCT. The Kaplan-Meier method was used to estimate OS and DFS. For comparisons of OS or DFS, the log rank test was used. Result: Cytogenetic studies were performed in 783 patients (99.2%) and only 15 studies resulted in failure. One hundred forty-two (18.5%) of those pts showed t(8;21). The median age was 43 yrs (15–64). The male: female ratio was 95: 47. The distribution of FAB types was as follows: AMLM2, 130; M4, 6; M1, 5; and M5, 1. A total of 69 (48.6%) pts had a sole t(8;21), 46 (32.4%) had a loss of a sex chromosome, and 27 (19.0%) had other cytogenetic abnormalities. The CR rate was 90.0%. Thirty-two pts underwent two courses of induction therapy. The early death (< one month) rate was 1.4% (2/142). Only a high WBC count (>=10x109/L) was found to be a marginally significant prognostic factor (p=0.0517). The estimated OS rate at 5yrs was 53.6%, and the DFS of the CR pts was 41.2%. We found no relationship between OS or DFS and the following factors: age, gender, karyotypic abnormality, performance status, the percentage of MPO positive blasts, the presence or absence of Auer rods, the platelet count, the number of induction therapies for CR and the type of postremisson therapy. However, two factors, the WBC count and the percentage of blasts in bone marrow were found to be strongly predictive factors for the outcome. For the pts with a WBC count >=10x109/L, the DFS rate at 5yrs was 30.8%, while for the pts with less than 10x109/L, it was 48.8% (p=0.0215). For the pts with blast >=50% and less than 50%, the DFS rates at 5yrs were 32.2% and 56.7% (p=0.0087), respectively. According to these two factors, a poor risk group (N=30, 21.0%) was thus identified. They had a WBC count >=10x109/L and blast >=50%. The DFS rate at 5yrs was only 22.3 % in the poor risk group while that of the other pts was 48.9% (P=0.0003). Conclusion: This study confirmed that all AML pts with t(8;21) shows a high response rate and a good prognosis, thus indicating that this favorable AML group includes a poor risk group which can be identified based on the WBC count and the blast percent in the bone marrow.

The aim of this study was to investigate the efficacy of allo-SCT as a postremission treatment in patients (pts) with intermediate/poor risk AML in first CR. Previously untreated pts aged15–64 years were eligible. Pts received standard induction therapy consisting of cytarabine (100 mg/m2 d1–7) and idarubicin (12 mg/m2 d1- 3). If the pts did not achieve remission after the first induction therapy, the same induction therapy was given once more. The pts who achieved CR were randomized into an intensified short-course postremission regimen group (arm A) and conventional JALSG postremission regimen group (arm B). Pts were also categorized into good, intermediate or poor risk groups by risk factors based on previous JALSG AML trials using univariate and multivariate analyses. The intermediate or poor risk pts Result: 809 pts were registered between December 1997 and July 2001. 789 pts were evaluable (median age: 45 years). 621 pts achieved CR (78.7%) after one or two courses of induction therapy. Os of 789 evaluable pts at five years and DFS of CR pts at five years were 40.8% and 35.5%, respectively. Of the 75 pts who were assigned to the allo-SCT group, 56 pts underwent allo-SCT (38 during CR1 and 18 after relapse). For the allo-SCT group, OS and DFS at 5 years were 51.8% and 43.1%, respectively. For the non-transplant group (n=95), OS and DSF at 5 years were 32.2% and 18.3%, respectively. DFS was significantly better in the allo-SCT group compared to the non-transplant group (p=0.005). OS was marginally better in the allo-SCT group (p=0.06). In conclusion, our study showed that allo-SCT for pts with intermediate or poor risk is effective as a postremission treatment in adult AML.

Between 1997 and 2001, JALSG conducted a randomized study to assess the optimal post remission therapy for adult AML in the first CR. The JALSG AML97 enrolled 809 previously untreated AML patients (pts) aged 15–64 yrs. Induction therapy consisted of cytarabine (100mg/m2 day1–7) and idarubicin (IDR 12mg/m2 day1– 3). If the patients did not achieve remission after the first induction therapy, the same therapy was given once more. Pts were categorized into good, intermediate or poor risk groups by risk factors based on the previous JALSG AML studies. All CR pts were randomized to receive either the intensified short course post remission regimen (arm A) or the conventional JALSG’s post remission regimen for AML including maintenance therapy (arm B). Arm A: 1) AraC 200mg/m2 day1–5+ Mitoxantrone (MTZ) 7mg/m2 day1–3, 2) AraC 200mg/m2 day1–5+Daunorubicin (DNR) 50mg/m2 day1–3, 3) AraC 200mg/ m2 day1–5+ Aclacinomycin (ACR) 20mg/m2 day1–5, 4) AraC 200mg/m2 day1–5+ Etoposide (ETP) 100mg/m2 day1–5 + Vincristine (VCR) 0.8mg/m2 day 8 + Vindesine (VDS) 2 mg/m2 day10. Arm B: 1) AraC 200mg/m2 day1–5 + MTZ 7mg/m2 day1–3, 2) Behenoyl AraC (BHAC) 200mg/m2 day1–7 + ETP 100mg/m2 day1–5 + DNR 50mg/m2 day1–3 + 6 mercptopurine (6MP) day1–7, 3) BHAC 200mg/m2 day1–7 + ACR 14mg/m2 day1–7, and then 6 courses maintenance therapy: 1) BHAC 170mg/m2 day1–5 + DNR 50mg/m2 day1,4+6MP day1–7, 2) BHAC 170mg/m2 day1–5 + MTZ 5mg/m2 day1–3, 3) BHAC 170mg/m2day1–5 + ETP 80mg/m2 day1,5,7 + VDS 2mg/m2 day1,8, 4) BHAC 170mg/m2 day1–5 + ACR 14mg/m2 day1–4 + 6MP day1–7, 5) BHAC 170mg/m2 day1–5 + DNR 50mg/m2 day1–4 + 6MP day1–7, 6) BHAC 170mg/m2 day1–5 + ETP 80mg/m2 day1,5,7 + VDS 2mg/m2 day1,8. Result: Of the 809 pts registered, 789 pts (median age: 45 years) were evaluable. 621 pts (78.7%) achieved CR after one or two courses of induction therapy. The 5-year OS rate of arm A was 45.6% and of arm B 53.2% (p=0.3259). The 5-year DFS rate of CR patients was 34.8% in arm A and 28.9% in arm B (p=0.4978). Among the good risk group, the 5-year OS rate of arm A was 62.1% and of arm B 70.2% (p=0.5068), and the 5-year DFS rate of arm A was 53.4% and of arm B 42.0% (p=0.3719). Among the intermediate risk group, the 5-year OS rate of arm A was 35.6% and of arm B 45.5% (p=0.4776), and the 5-year DFS rate of arm A was 26.0% and of arm B 26.1% (p=0.9653). Among the poor risk group, the 5-year OS rate of arm A was 29.7% and of arm B was 33.4% (p=0.6523), and the 5-year DFS rate of arm A was 20.4% and of arm B was 13.5% (p=0.6339). In conclusion: JALSG’s conventional post remission therapy consisting of 3 courses of consolidation and 6 courses of maintenance therapy could be replaced by a shorter duration of intensified consolidation therapy.

A case-control study of leukemia and diagnostic X-ray exposure was conducted by a multi-institution co-operative study group. The subjects were 134 patients with acute myelogenous leukemia, 57 with chronic myelogenous leukemia, 56 with acute lymphocytic leukemia and 50 with myelodysplasia syndrome, who were between 15 and 79 years old, and diagnosed at one of 27 hospitals between September 1993 and August 1995. The controls were 479 first-visit patients seen at eight of these 27 hospitals. History of diagnostic X-ray tests between 1982 and 1991 was determined by an anonymous self-administered questionnaire. The total relative dose of radiation exposure was calculated by summing the products of given weights and frequencies of each test. The relative risk was 0.83 (95% confidence interval (C.I.), 0.58-1.19) for relative dose of 10-30 (equivalent to 4-11 times of UGI series), 0.76 (0.48-1.20) for relative dose of 30 or more (more than 12 times of UGI series), when compared with relative dose of 0-10 (0-3 times of UGI series). Analysis according to type of leukemia revealed that only acute myelogenous leukemia had an estimated relative risk above unity (1.08, 95% C.I. 0.69-1.69, for relative dose 10-30). This study did not support the hypothesis that diagnostic X-ray tests increases leukemia risk.

A circadian rhythm was demonstrated in 10 males and 10 females with respective mean decreases in plasma iron concentration at 18 hr of 62% and 47% of morning values. Ferrokinetic studies performed on 5 normal males and 5 normal females showed a more rapid disappearance rate and lower plasma iron turnover in the evening. Parallel studies were done on 6 normal males in the morning and 4 normal males in the evening of the release of reticuloendothelial iron at 8 and 18 hr after intravenous injection of 59Fe chondroitin ferrous sulfate. The 6-hr release in the morning was 54.1% and in the evening 25.9%. Composite data from morning and evening showed a correlation between plasma iron level and plasma iron turnover (r = 0.76, p less than 0.001). A similar correlation existed between the plasma iron level and the percent of radioiron released from the reticuloendothelial system (r = 0.67, 0.02 less than p less than 0.05). These data are consistent with a fluctuating iron release from the reticuloendothelial cell in normal subjects, which would account for the diurnal variation in plasma iron.

Pyroglobulin血症を有し,多彩な臨床症状で経過して死亡したIgG(κ)型多発性骨髄腫を報告する.症例は, 54才主婦.全身倦怠感,動悸などを主訴に入院, IgG(κ)型多発性骨髄腫と,血清補体結合反応のさいの56°C30分の血清非働化で白濁凝固するpyroglobulinの存在が見出された.入院7ヵ月でmelphalan, prednisolone治療により自覚症状は軽減して,外来にて経過を観察したが, 14カ月目に貧血,鼻出血,耳鳴をきたして再入院,そのさい肝脾腫が認められた. melphalan, prednisolone治療の後より,頭痛,項部硬直,髄液の細胞増多など髄膜炎症状をきたし, 15ヵ月目に後遺症なく回復した. 18ヵ月目に患者は腰痛と下肢の脱力感をきたし, paraplegia,尿失禁,など脊髄横断症状を呈し,化学療法,放射線照射にも反応しなかつた. 17ヵ月目に肝脾腫が著明となり, 18ヵ月には,末梢血形質細胞は10000以上に増加,気管支肺炎のため死亡した.骨髄は全経過を通じてdry tapであった.剖検で,肋骨,脊椎の腫瘤形成と骨髄腫細胞の浸潤が著明で,これは肝,脾,腎などにもみられた,骨はosteolyticな変化よりosteoclasticな変化が目立つた. pyroglobulin血症は,それ自体,特有の臨床症状を発現することは少ないとされるが,本症例は,髄膜炎症状を経過し,腫瘤形成とそれによる脊髄横断症状を呈し,末期に白血化をきたして死亡した. pyroglobulin血症を有する症例で,これらの多彩な症状で経過したものは文献上見当らず,希なものと思われる.

Megakaryocytopoiesis in polycythemia vera (PV) was characterized by in vitro growth of marrow megakaryocytic progenitors (CFU-Meg) and quantitation of megakaryocyte numbers in marrow biopsy specimens in 14 patients with PV. Megakaryocyte numbers and CFU-Meg numbers in the 14 patients were variable, with values from the control range to markedly increased numbers. Nine of the 14 patients showed spontaneous CFU-Meg growth, and the presence or absence of spontaneous CFU-Meg growth was found to be related to the degree of marrow megakaryocyte increase, i.e., those with spontaneous CFU-Meg had higher megakaryocyte numbers. None of the plasmas from the PV patients contained detectable levels of megakaryocyte colony-stimulating activity (Meg-CSA), assayed using the culture with nonadherent normal marrow cells and tested plasma without phytohemagglutinin-stimulated leukocyte-conditioned medium as an exogenous source of Meg-CSA. Increased megakaryocyte numbers and resultant thrombocytosis in PV are likely based on the abnormal population of CFU-Meg.

Chromosome studies of cells from megakaryocytic colonies (CFU-Meg) as evidenced by a megakaryocyte-specific monoclonal antibody, TP80, from a patient with chronic myelogenous leukemia (CML) in the blast crisis (BC) revealed the same aberrant karyotype, 52,XY,+9, +9, +18, +19, +21, +22, t(9;22)(q34;q11),t(9;22), as that having newly appeared in the peripheral blood. Cells from erythroid bursts (BFU-E) showed only the standard 46,XY,t(9;22) karyotype, and cells from granulocyte/macrophage colonies (CFU-GM) had either of these karyotypes. These results demonstrated that the whole megakaryocytic line and part of the granulocyte/macrophage line had been involved in the BC while the erythroid line totally belonged to the original clone. Chromosome analysis coupled with immunophenotyping of hemopoietic colonies was useful for a definite diagnosis of megakaryoblastic crisis of CML in this patient.

UCHIDA, T., IGARASHI, T., SUZUKI, T., KOKUBUN, K., MATSUDA, S. and KARIYONE, S. The Effect of Acute Inflammation on Iron Metabolism in Rats. Tohoku J. exp. Med., 1983, 139 (3), 293-298-Iron metabolism in rats with acute turpentine-induced inflammation was evaluated. In acute inflammation, reduced plasma iron and total iron-binding capacity values, shortened plasma iron disappearance time and lower plasma iron turnover were observed. The administration of 59Fe chondroitin ferrous sulfate in order to evaluate the reticuloendothelial (RE) function revealed a significantly increased 59Fe retention in the liver and lower incorporation into red blood cells. Radioactivity in hepatic RE cells was higher in acute inflammation than in control. These results suggest the possibility of a block in the transfer of iron from RE cells to the plasma iron pool during acute inflammation.

Iron metabolism in patients with rheumatoid arthritis was evaluated. In 42 patients, anemia was seen in 57.1%, in which normochromic anemia was 63%, hypochromic 24% and hyperchromic 13%, respectively. Serum iron concentration was lower in 66% and total iron binding capacity (TIBC) was lower or normal in 82%. Serum ferritin level was not lower in 83%. Ferrokinetic studies in 15 patients with rheumatoid arthritis revealed rapid PID T_??_, lower PIT and RIT, which were compatible with lower serum iron concentration, less in vitro erythroid colonies (CFU-E) and hypocellular erythroid bone marrow. The release of reticuloendothelial iron was evaluated after intravenous injection of 59Fe chondrotin ferrous sulfate (Radio-Colloid). Percent radioactivity 4 and 6 hours after the injection to the injected dose was 7.9% and 6.7%, respectively, in patients with rhematoid arthritis, which was significantly lower than normal. The amounts of released iron in 8 hours were also reduced. These findings might suggest a defect in the release of iron from the reticuloendothelial tissues to the plasma, resulting in hypoferremia and inadeguate supply of iron to bone marrow. On the other hand, hypocellular bone marrow in erythroid series and lower PIT would explain the primary genesis of the anemia.

A method for labeling leukemic cells in vitro with 111In-oxine is described. Intravascular survival data and organ distribution of 111In-oxine-labeled leukemic cells in patients with acute leukemia are presented. No evidence of diminished cell viability or significant elution of the label could be found by the in vitro studies. Disappearance curves of 111In-labeled leukemic cell radioactivity in the circulation were a single exponential with average T1/2 value of 15.3 +/- 2.5 hr (mean +/- SEM), which was found to be prolonged when compared with the results of 4 hematologically normal subjects (7.0 +/- 0.8) and those of previously reported DF32P studies. Migratory patterns of the labeled leukemic cells, obtained by a scintillation camera, demonstrated sequestration in the lungs 5 min after the infusion, and thereafter, the uptake into the spleen and liver gradually increased. We believe that the properties of 111In-oxine might overcome many of the difficulties of studying leukemic cell kinetics with cells labeled with tritiated thymidine.

We describe a case of acute myelogenous leukaemia presenting with remarkable eosinophilia in relapse. Since the patient had chromosomal abnormalities, haemopoietic as well as eosinophilic colonies grown in culture were cytogenetically analysed to determine the origin of the eosinophils. Eosinophilic colonies as well as erythroid bursts revealed a normal karyotype, while a short-term culture of peripheral blood cells in relapse revealed an abnormal karyotype which had been observed before treatment. These data clearly demonstrate that the eosinophilia in this case originated from a normal clone. The cytogenetic analysis of eosinophilic colonies is a useful technique for the definite diagnosis of eosinophilic leukaemia or reactive eosinophilia in patients having marker chromosomes.

A case of neuroblastoma in a 4-yr-old boy presenting with the nephrotic syndrome is reported. Neither thrombosis nor stenosis of the renal veins and the inferior vena cava was present. Electron microscopy revealed lumps of subepithelial deposits as well as thickening and tortuosity of the glomerular basement membrane compatible with membranous nephropathy. It is postulated that deposition of neuroblastoma-associated immune complexes on the glomerular basement membrane-was responsible for the development of the nephrotic syndrome in this patient. Five pediatric cases of nephrotic syndrome associated with extrarenal neoplasia were collected from the world literature and are briefly discussed.

The effect of daily oral administration of 50-100mg aspirin was evaluated in 8 patients (Table 1). Platelet aggregation and platelet malondialdehyde (MDA) production were significantly inhibited after administration of aspirin for a week. Plasma thromboxane-B2 (TXB2) levels showed a tendency to decrease (0.1