Search

Serological tests are beneficial for recognizing the immune response against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). To identify protective immunity, optimization of the chemiluminescent reduction neutralizing test (CRNT) is critical. Whether commercial antibody tests have comparable accuracy is unknown. Serum samples were obtained from COVID-19 patients (n = 74), SARS-CoV-2 PCR-negative (n = 179), and suspected healthy individuals (n = 229) before SARS-CoV-2 variants had been detected locally. The convalescent phase was defined as the period after day 10 from disease onset or the episode of close contact. The CRNT using pseudotyped viruses displaying the wild-type (WT) spike protein and a commercial anti-receptor-binding domain (RBD) antibody test were assayed. Serology for the B.1.1.7 and B.1.351 variants was also assayed. Both tests concurred for symptomatic COVID-19 patients in the convalescent phase. They clearly differentiated between patients and suspected healthy individuals (sensitivity: 95.8% and 100%, respectively; specificity: 99.1% and 100%, respectively). Anti-RBD antibody test results correlated with neutralizing titers (r = 0.31, 95% confidence interval [CI] 0.22–0.38). Compared with the WT, lower CRNT values were observed for the variants. Of the samples with ≥100 U/mL by the anti-RBD antibody test, 77.8% and 88.9% showed ≥50% neutralization against the B.1.1.7 and the B.1.351 variants, respectively. Exceeding 100 U/mL in the anti-RBD antibody test was associated with neutralization of variants (P < 0.01). The CRNT and commercial anti-RBD antibody test effectively classified convalescent COVID-19 patients. Strong positive results with the anti-RBD antibody test can reflect neutralizing activity against emerging variants. IMPORTANCE This study provides a diagnostic evidence of test validity, which can lead to vaccine efficacy and proof of recovery after COVID-19. It is not easy to know neutralization against SARS-CoV-2 in the clinical laboratory because of technical and biohazard issues. The correlation of the quantitative anti-receptor-binding domain antibody test, which is widely available, with neutralizing test indicates that we can know indirectly the state of acquisition of functional immunity against wild and variant-type viruses in the clinical laboratory.

Primary effusion-based lymphoma (EBL) presents as a malignant effusion in a body cavity. The clinicopathologic features and prognosis of primary human herpesvirus 8 (HHV8)–negative EBL remain unclear. We therefore conducted a retrospective study of 95 patients with EBL, regardless of HHV8 status, in Japan. Of 69 patients with EBL tested for HHV8, a total of 64 were negative. The median age of patients with primary HHV8-negative EBL at diagnosis was 77 years (range, 57-98 years); all 58 tested patients were negative for HIV. Primary HHV8-negative EBL was most commonly diagnosed in pleural effusion (77%). Expression of at least 1 pan B-cell antigen (CD19, CD20, or CD79a) was observed in all cases. According to the Hans algorithm, 30 of the 38 evaluated patients had nongerminal center B-cell (non-GCB) tumors. Epstein-Barr virus–encoded small RNA was positive in 6 of 45 patients. In 56 of 64 HHV8-negative patients, systemic therapy was initiated within 3 months after diagnosis. Cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) or CHOP-like regimens with or without rituximab (n = 48) were the most common primary treatments. The overall response and complete response rates were 95% and 73%, respectively. Three patients did not progress without systemic treatment for a median of 24 months. With a median 25-month follow-up, the 2-year overall survival and progression-free survival rates were 84.7% and 73.8%. Sixteen patients died; 12 were lymphoma-related deaths. Thus, most EBL cases in Japan are HHV8-negative and affect elderly patients. The non-GCB subtype is predominant. Overall, primary HHV8-negative EBL exhibits a favorable prognosis after anthracycline-based chemotherapy.

Background: Novel agents capable of inducing deeper responses dramatically improve the prognosis of patients with multiple myeloma (MM). Innovative technologies such as multiparameter flow cytometry (MFC) and next-generation sequencing (NGS) are utilized to assess minimal residual disease (MRD) for further stratification of patients who achieve a complete response (CR). EuroFlow-next-generation flow (EuroFlow-NGF) is one of the gold standard MFC methods. Recently, both NGF and NGS have been used in many clinical trials to assess MRD levels associated with progression-free survival (PFS) and overall survival (OS). The present study prospectively assessed MRD levels by both NGF and NGS to elucidate the prognostic impact of both methods and clarify their characteristics in MM patients in an autologous stem cell transplantation (ASCT) setting. Methods: We prospectively assessed the response in Japanese patients with newly diagnosed MM who underwent ASCT and lenalidomide-based maintenance therapy at multiple Japanese medical centers between September 2016 and July 2021. The diagnosis of MM and patients' responses to therapy were assessed using the IMWG criteria. Only patients with CR or stringent CR on days 100-365 post-ASCT were included, and bone marrow (BM) samples were obtained to assess MRD. Four milliliters of BM was divided equally. Cells derived from 2 mL BM were analyzed by the NGF method (Flores-Montero et al., Leukemia 2017) at Kanazawa University, and DNA extracted from the remaining 2 mL BM cells was processed by Adaptive Biotechnologies' standardized NGS-MRD assay (Seattle, WA) (Ching et al., BMC Cancer 2020) to assess MRD levels. MRD levels in BM were also monitored at 1-year (± 20 days) and 2-year (± 20 days) post-ASCT. The prognostic value of MRD levels in BM was assessed, and their correlation between NGF and NGS was compared at a cut-off value of 1×10 -5. Sustained MRD negativity was defined as the maintenance of MRD negativity in the BM for more than 6 months. BM cells were analyzed for high-risk cytogenetics (del(17p), t(4;14), and t(14;16)) by FISH. Results: A total of 60 patients (male = 29, female = 31) underwent bortezomib-based induction therapy, ASCT conditioned with high-dose melphalan, and lenalidomide-based maintenance. The median age was 62 years at the ASCT (range 36-71; ISS 1 [n = 13], 2 [n = 24], and 3 [n = 23]). Thirty-three percent of patients showed high-risk chromosomal abnormalities (del17p (n=11), t(4;14) (n=10), t(14;16) (n=2)), 3 patients had double hit diseases, and five patients had extramedullary diseases. With a median follow-up of 3 years, the 3-year progression-free survival (PFS) and 3-year overall survival (OS) rates were 69.2% and 94.2%, respectively. In total, 148 samples were analyzed using NGF and 138 were analyzed using NGS. The rates of MRD negativity at least once using NGF and NGS were 80% and 61%, respectively. The patients who achieved at least one MRD negativity exhibited significantly better 3-year PFS (82.9% by NGF; 84.8% by NGS) than those who did not (P < 0.0001, 0% by NGF; P = 0.005, 49.1% by NGS). Patients who sustained MRD negativity for more than 6 months also showed significantly better 3-year PFS (96.7% by NGF; 92.3% by NGS) compared with those without sustained MRD negativity (Figure; P < 0.0001, 37.1% by NGF; P < 0.01, 50.9% by NGS). The MRD levels between the NGF and NGS methods were significantly correlated with each other (r = 0.9295, P < 0.0001). Among the 17 patients who developed PD after ASCT, seven cases showed discrepancies in the MRD results and two cases in which one case was MRD-positive and the other was MRD-negative by both methods progressed with extramedullary diseases. Five of the seven cases were MRD-positive by NGS and MRD-negative by NGF. Conclusions: In this prospective comparison study of MRD assessment in BM cells using EuroFlow-NGF and NGS approaches, MRD levels highly correlated with each other, and MRD negativity and sustained MRD negativity were significantly associated with prolonged PFS. Multiple MRD assessments by NGF or NGS are essential for predicting durable remission and prolonged clinical outcomes. Figure 1 Figure 1. Disclosures Takamatsu: Bristol-Myers Squibb: Honoraria, Research Funding; Adaptive Biotechnologies, Eisai: Honoraria; SRL: Consultancy; Janssen: Consultancy, Honoraria, Research Funding. Yoshihara: Bristol-Myers Squibb: Honoraria; Janssen: Honoraria; Novartis: Honoraria. Matsumoto: Sanofi: Honoraria; Janssen: Honoraria; Ono: Honoraria; Bristol-Myers Squibb: Honoraria. Yamashita: Janssen: Honoraria; Bristol-Myers Squibb: Honoraria; celgene: Honoraria; Takeda: Honoraria. Fuchida: Takeda Pharmaceutical Co., Ltd.: Honoraria; Ono Pharmaceutical Co., Ltd.: Honoraria; Janssen Pharmaceutical K.K.: Honoraria; Sanofi: Honoraria; Bristol-Myers Squibb Co., Ltd.: Honoraria; Celgene Co., Ltd.: Honoraria. Hiragori: BML: Current Employment. Suzuki: Amgen: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria; ONO: Honoraria; Novartis: Honoraria; Sanofi: Honoraria; Abie: Honoraria; Janssen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Research Funding; Bristol-Myers Squibb: Honoraria, Research Funding. Nakao: Symbio: Consultancy; Kyowa Kirin: Honoraria; Novartis Pharma: Honoraria; Alexion Pharma: Research Funding. Durie: Amgen: Other: fees from non-CME/CE services ; Amgen, Celgene/Bristol-Myers Squibb, Janssen, and Takeda: Consultancy.

Background Most patients with multiple myeloma (MM) are considered to be incurable, and relapse owing to minimal residual disease (MRD) is the main cause of death among these patients. Therefore, new technologies to assess deeper response are required. Patients and methods We retrospectively analyzed 125 patients with MM who underwent high-dose melphalan plus autologous stem-cell transplantation (ASCT) to detect MRD in autograft/bone marrow (BM) cells using a next-generation sequencing (NGS)-based method and allele-specific oligonucleotide-polymerase chain reaction (ASO-PCR). Results NGS-based method was applicable to 90% and this method had at least one to two logs greater sensitivity compared to ASO-PCR. MRD negative by NGS [MRDNGS(−)] (defined as

Vitamin B12 deficiency is associated with mucocutaneous symptoms, such as glossitis and hyperpigmentation, as well as megaloblastic anemia and neuropathy. These are reversible conditions, and the symptoms improve with early detection and treatment. Whenever anemia is encountered in routine practice, vitamin B12 deficiency should be considered and the presence of skin symptoms should be investigated.

An increasing number of patients with lung cancer are undergoing outpatient chemotherapy, and thus, it is very important to maintain the quality of life(QOL)of these patients. Ninjin-Youei-To(TJ-108), a Japanese traditional medicine, has been reported to improve the QOL of patients with advanced cancer. However, the effect of TJ-108 in patients with lung cancer undergoing outpatient chemotherapy is unknown. Therefore, we conducted this study. To investigate factors influencing the QOL of these patients, we administered a QOL questionnaire,"The QOL Questionnaire for Cancer Patients Treated with Anticancer Drugs"(QOL-ACD)to 15 patients with non-small cell lung cancer. Factors related to the overall QOL scores and other categories indicating"activity","physical condition","psychological condition","social relationship", and"face scale" were analyzed. No significant decrease in each of the evaluated factors was observed in this study.

Cases of low-grade B-cell lymphoma presenting primarily in the bone marrow are rare, and its clinicopathology remains unclear. We retrospectively examined patients with low-grade B-cell lymphoma presenting primarily in the bone marrow. Fourteen patients met the inclusion criteria, including 5 with lymphoplasmacytic lymphoma (LPL), 3 with chronic lymphocytic leukemia/small lymphocytic lymphoma, 2 with follicular lymphoma (FL), and 4 with low-grade B-cell lymphoma not otherwise specified (LGBCL-NOS). The median age was 69.5 years (range, 42-89 years), and a slight male predominance was noted (9 men and 5 women, 1.8: 1). Immunohistochemically, all cases were positive for CD20. One case was positive for CD138. Both cases of FL were positive for CD10 and B-cell lymphoma 2 (BCL-2), and immunoglobulin heavy locus (IgH)/B-cell lymphoma 2 rearrangement was observed by fluorescence in situ hybridization. The myeloid differentiation primary response gene (88) leucine to proline mutation was observed in 3 of 5 LPL, 1 of 2 FL, and 2 of 4 LGBCL-NOS patients. Paraproteinemia was observed in 10 patients; IgM and IgG paraproteinemia were observed in 6 and 3 patients, respectively. In this patient series, 3 patients had died at a median follow-up of 36.5 months; the cause of death of 1 LPL patient was malignant lymphoma itself. Thus, low-grade B-cell lymphoma presenting primarily in the bone marrow has various subtypes, and approximately one-third of the patients had LGBCL-NOS. The immunophenotypic features and myeloid differentiation primary response gene (88) leucine to proline mutation data of LGBCL-NOS suggested that some cases present with characteristics similar to those of LPL or marginal zone lymphoma.

An increasing number of patients with lung cancer are undergoing outpatient chemotherapy.It is very important to retain the quality of life (QOL) of these patients.Japanese traditional medicine, TJ-48, has been reported to improve the QOL of patients with advanced cancer. However, the effect of TJ-48 in patients with lung cancer undergoing outpatient chemotherapy is unknown. The present study was conducted to investigate the factors influencing the QOL of these patients. We used "The QOL questionnaire for cancer patients treated with anticancer drugs" (QOL-ACD) with 16 patients with non-small cell lung cancer. The medical factors related to the overall QOL scores and other variables indicating "activity," "physical condition, "psychological condition,""social relationships," "psychological condition," and "face scale" were analyzed. Significant improvement was observed in the total QOL score, mainly owing to the improvement in the patients "physical condition."

Primary effusion lymphoma (PEL) is a rare type of non-Hodgkin lymphoma usually confined to the body cavities of predominantly immunosuppressed patients infected with human herpes virus-8 (HHV-8). In PEL, malignant cells are usually negative for B-cell markers, such as CD19, CD20, and CD79a, but are positive for activation and plasma cell-related markers, such as CD30, CD38, and CD138. It has been reported that HHV-8-unrelated PEL shows high expression of B-cell markers, which is referred to as PEL-like lymphoma. Here, we report two cases of HHV-8-unrelated HIV-negative PEL-like lymphoma in which malignant cells regressed spontaneously after effusion drainage alone. These cells expressed B-cell markers, such as CD20. No chemotherapy was given to either patient, as they were of an advanced age, and both achieved a complete response by effusion drainage alone. One showed a complete response for 16 months after effusion drainage, and the other has survived for 11 months with a complete response. This suggests that sufficient drainage of serous effusion may induce and maintain a complete response in some patients with HHV-8-unrelated HIV-negative PEL-like lymphoma, which represents an excellent treatment option for elderly patients with this disease.

A 48-year-old woman was admitted to our hospital for sixth-line chemotherapy. A chest X-ray film and computed tomographic (CT) scan revealed a right-sided massive tumor with multiple lung tumors. Repeated treatment with carboplatin (AUC 6) on day 1 and nab-paclitaxel (100mg/m2) on days 1, 8, and 15, every 28 days were effective in this patient. Chemotherapy with nab-paclitaxel may be effective for patients with multi-recurrent adenocarcinoma.

Venous stasis is generally accepted to be a predisposing factor for venous thrombosis. However, benign causes of inferior vena cava (IVC) obstruction with associated thrombus formation have not been well described. We herein present a case of IVC compression caused by a distended ileal neobladder measuring 2,000 mL in capacity that led to IVC thrombosis. Following transurethral drainage for six weeks and anticoagulation therapy with warfarin for six months, the thrombus completely disappeared. The patient was considered to have a hypercoagulable state resulting from an acute urinary tract infection, a condition that may be associated with an increased risk of thrombosis.

Objective The telomere in mature myeloid cells derived from abnormal progenitor cells of myeloproliferative diseases (MPDs) may shorten more rapidly than that in T lymphocytes, which are considered to be derived from normal clones. To test this hypothesis, we measured telomere lengths in granulocytes and T lymphocytes from patients with MPDs and compared them with those from normal individuals. Materials and Methods Granulocytes and T lymphocytes were separated from the peripheral blood of 65 patients with MPDs (25 chronic myelogenous leukemia [CML], 16 polycythemia vera, 19 essential thrombocythemia, 5 chronic idiopathic myelofibrosis) and 35 normal individuals. Genomic DNA from each cell fraction was subjected to Southern blot hybridization to determine the mean telomere length. Results Telomere lengths in granulocytes from patients with MPDs were significantly shorter than those from normal individuals (vs CML, p=0.002; vs other MPDs, p Conclusions The results support the disease theory that MPDs result from extensive proliferation of myeloid progenitor cells, leading to accelerated telomere length shortening in mature granulocytes. An increase in ΔTRF over the standard value (>1.74 kb) may be useful for discriminating leukocytosis due to MPDs from reactive leukocytosis.

Increasing number of patients with advanced non-small cell lung cancer are receiving outpatient maintenance chemotherapy. It is very important to maintain these patients' quality of life(QOL). Pemetrexed has been reported to be an effective maintenance chemotherapy. However, its effects on the QOL of patients with non-small cell lung cancer who are undergoing outpatient maintenance chemotherapy are unknown; therefore, we conducted this study. To investigate factors that influence the QOL of these patients, we provided a QOL questionnaire,"The QOL Questionnaire for Cancer Patients Treated with Anticancer Drugs(QOL-ACD)"to 7 patients with non-small cell lung cancer. The medical factors related to the overall QOL scores, as well as other categories indicating"activity","physical condition","psychological condition","social relationship", and"face scale", were analyzed. No significant reductions in any of the factors were observed in this study.

We report a 55-year-old postmenopausal woman with occult breast carcinoma with multiple bone metastases and myelophthisis in whom complete response (CR) was achieved with chemo-endocrine therapy. At the time of admission, she had anemia and left axillary lymph node enlargement, with extremely high levels of serum tumor markers and no breast mass on physical examination or on a mammogram. Roentgenograms and bone scintigrams showed multiple bone, lung, and pleural metastases. Bone marrow biopsy and aspiration cytology from the left axillary lymph node revealed an invasion of adenocarcinoma cells. On immunohistochemical staining, the cancer cells were positive for estrogen receptor (ER), progesterone receptor (PgR), and gross cystic disease fluid protein-15 (GCDFP-15). CR was induced with a combination chemotherapy of doxorubicin, cyclophosphamide, and 5-fluorouracil (CAF), and has been maintained with sequential docetaxel administration with endocrine therapy. Her performance status (Eastern Cooperative Oncology Group) improved from 4 to 0. This patient represents a very specific and rare case in whom a primary tumor could not be detected despite severe advanced breast carcinoma, and in whom CR was achieved by chemo-endocrine therapy.

It has been reported that trisomy 14 is associated with myeloid malignancies, but a case with increased platelet count has also been reported. However, the clinical significance of trisomy 14 is still uncertain. We report a patient with trisomy 14 with thrombocytosis and a gradual increase in monocytosis. He was treated with hydroxyurea, cytarabine and aclarubicin in low doses and his quality of life was maintained for a period of about 1 year from blastic crisis. Hydroxyurea, cytarabine or aclarubicin in low doses may be the treatment of choice for trisomy 14 patients with respect to the patients’ quality of life.

The authors examined the survival rates of 60 patients with breast cancer who underwent parasternal lymph node biopsy during surgery with axillary lymph node dissection and had histologically confirmed axillary node metastasis followed by adjuvant doxorubicin- or mitoxantrone-containing combination chemotherapy to ascertain whether administration of anthracycline or its analogue improved the prognosis of both axillary and parasternal node-positive patients. The overall survival rate (OS) for the parasternal node-positive patients (n=13, 21.7%) was 30.6%, and relapse-free survival rate (RFS) fell to 0% at the 104-month follow-up. Although the survival rate for all axillary node-positive patients was similar to those in previous reports, the OS and RFS for both axillary and parasternal node-positive patients were significantly worse than that for axillary node-positive and parasternal node-negative patients, despite treatment with adjuvant doxorubicin- or mitoxantrone-containing combination chemotherapy. Other intensive adjuvant treatment strategies are needed to reduce distant metastases for high-risk breast cancer patients having both axillary and parasternal nodes positive.

Post-autologous stem cell transplantation (ASCT) consolidation and maintenance therapies in multiple myeloma (MM) have recently been the central focus of studies. However, there have been no reports of Japanese patients with MM treated with post-ASCT consolidation/maintenance therapies.We retrospectively evaluated eight Japanese patients with newly-diagnosed symptomatic MM who received ASCT after high-dose melphalan, and three to four courses of bortezomib-plus-dexamethasone and two courses of lenalidomide-plus-dexamethasone followed by maintenance lenalidomide for 6-24 months.Four patients achieved complete response (CR) after ASCT, and five patients (63%) achieved stringent CR after the consolidation and maintenance therapy; two out of these five were in molecular CR. At the median follow-up of 38 months, all patients were alive and only one patient had disease progression following post-ASCT therapy.Post-ASCT consolidation and maintenance therapy using lenalidomide may be effective in the treatment of Japanese patients with MM.

An increasing number of patients with lung cancer are undergoing outpatient chemotherapy. It is very important to maintain good quality of life(QOL)for these patients, and Japanese traditional medicine, TJ-41, has been reported to improve the QOL of patients with advanced cancer. However, the effect of TJ-41 on patients with lung cancer undergoing outpatient chemotherapy is unknown. Therefore, we conducted this study. To investigate the factors influencing the QOL of these patients, we distributed a QOL questionaire,"The QOL Questionnaire for Cancer Patients Treated with Anticancer Drugs"(QOL-ACD)to 11 patients with non-small cell lung cancer. The medical factors related to the overall QOL scores and other categories, indicating"activity","physical condition","psychological condition","social relationships","psychological condition"and"face scale"were analyzed. A significant decrease in each of the factors was not observed in this study.

Malignant lymphomas may originate from any area of the body and cause a variety of symptoms. However, a malignant lymphoma causing urinary symptoms is uncommon. We report a unique case of a 77-year-old woman who presented with a persistent pollakiuria. Radiographic imaging showed a large pelvic mass ( cm) remarkably compressing and invading the bladder wall and accompanied with bilateral hydronephrosis. Urinary cytology revealed malignant lymphoma, and a final diagnosis of malignant lymphoma was made on the basis of transvaginal needle biopsy. Urinary cytology facilitated the definite diagnosis, following which we initiated a rapid and successful treatment with cyclophosphamide, doxorubicin, vincristine, and prednisone with rituximab.

Polymerase chain reaction (PCR)-negative molecular complete remission (mCR) can be induced by stem cell transplantation in some patients with multiple myeloma (MM) and is associated with long-term progression-free survival (PFS). The detection of molecular minimal residual disease (MRD), however, requires fresh or frozen materials for designing clone-specific primers, which are not always readily available. In this study, we used DNA extracted from archival bone marrow (BM) slides for PCR to detect MRD in 50 patients with MM who received various induction therapies and autologous peripheral blood stem cell transplantation (ASCT). Clonotype-specific immunoglobulin (Ig) H PCR primers were prepared for 32 of 50 cases (64%) using BM slides, and for 9 of 14 cases (64%) using fresh BM cells. DNA in peripheral blood stem cell autografts of the 22 patients who achieved at least a partial response after ASCT was subjected to PCR to amplify clonotype-specific rearranged IgH gene sequences. The median PFS of the eight patients with MRD-positive autografts was 18 months, whereas that of 14 patients with MRD-negative autografts was not reached at a median follow-up of 27 months (p = 0.012). Post-ASCT PFS of the four patients who achieved mCR was 100% at a median follow-up of 47 months. These results indicate that archival BM slides can serve as a source of DNA for preparing clonotype-specific primers for MRD monitoring in patients with MM whose cryopreserved myeloma cells are not available for DNA preparation. Our results also suggest that patients with MM who received MRD-negative autografts and achieved mCR have a long PFS.

Imatinib was the first BCR-ABL tyrosine kinase inhibitor to become clinically available. In this study, we retrospectively evaluated the long-term efficacy of low-dose imatinib (final maintenance dose

A 64-year-old man was admitted to our hospital for 6th-line chemotherapy. Chest X-ray film and computed tomographic (CT) scan showed right-sided pleural thickening with multiple lung tumors. Repeated treatment with carboplatin (AUC 6), paclitaxel (200 mg/m(2)) and bevacizumab (150 mg/kg) on day 1 every 21 days was effective for this patient. Chemotherapy with bevacizumab may be effective for patients with multi-recurrent adenocarcinoma.

Mantle cell lymphoma (MCL) is a rare subtype of B-celllymphoma characterized by amplification of cyclin D1.The effect of chemotherapies, such as CHOP (cyclophos-phamide, doxorubicin, vincristine, and prednisone), is oftentransient, and most patients die at median 3–5 years fromdiagnosis [1]. Before the rituximab era, a number of smallstudies evaluated the efficacy of high-dose chemotherapy(HDC) supported with autologous stem cell transplantation(ASCT), but did not find an evident contribution to survivalbenefit [2, 3]. Consequently, no single standard treatmentfor MCL has been established to date [4]. We thereforeconducted a nation-wide multicenter retrospective analysisof newly diagnosed patients with MCL in order to inves-tigate the efficacy and clinical outcome of each initialtreatments and HDC/ASCT in the rituximab era.Clinical data of 64 newly diagnosed MCL cases treated in12 institutions participating in the Lymphoma TreatmentStudyGroupinJapanbetween2001and2008werecollectedand analyzed by the end of April 2009. The data includedpatient characteristics [age, sex, performance status definedby European Cooperative Oncology Group (ECOG PS),clinical stage according to the Ann Arbor staging system,complete blood count, and serum lactate dehydrogenaselevel], as well as details of treatment and clinical outcome.Positivity of cyclin D1 and/or chromosomal abnormalityt(11;14)(q13;q32) in the biopsy specimen were required forthe diagnosis of MCL following the World Health Organi-zation classification system. This study was approved by theinstitutional review board in Nihon University ItabashiHospital, where the analysis was performed.Table 1 shows the clinical characteristics of all patientsand risk factors that might influence overall survival,including MCL international prognostic index (MIPI) [5].The median age of patients and median observation periodwere 64 years (range 47–80 years) and 34 months (range2–91 months), respectively. Most of patients were treatedwith rituximab-combined CHOP (R-CHOP)-based che-motherapy for a median 6 (range 2–8) cycles or R-Hyper-CVAD/MA regimen (rituximab, hyperfractionatedcyclophosphamide, vincristine, doxorubicin, and dexameth-asone alternating with high-dose methotrexate and cytara-bine), as initial treatment. As a result, 5-year overallsurvival (OS) and progression-free survival (PFS) for allpatients were 62 and 34%, respectively (Fig. 1a). Thecomplete response rate of the R-CHOP group was lowerthan that of the R-Hyper-CVAD/MA group (49 vs. 80%,P = 0.031), but there was no significant difference in OSor PFS (Fig. 1b, c). Sixteen patients (25%) received vari-ous combinations of HDC followed by ASCT. Amongthese patients, nine underwent HDC/ASCT in their firstcomplete remission, six were in a refractory phase of thedisease, and one was in a second remission. The clinicaloutcome of this group was quite encouraging, withouttreatment-related mortality or secondary malignancy dur-ing the observation period (93% of 5 year OS) (Fig. 1d).In this study, the majority of patients were treated withR-CHOP-based chemotherapy. After rituximab becameclinically available for treating B-cell lymphomas, theclinical outcome of MCL appeared to be improved.

An increasing number of patients with lung cancer are undergoing outpatient chemotherapy as an alternative to inpatient therapy. To investigate the factors influencing the quality of life (QOL) for these patients, we administered a QOL questionnaire, The QOL Questionnaire for Cancer Patients Treated with Anticancer Drugs (QOL-ACD) to 8 older adult patients with non-small cell lung cancer. The medical factors related to the overall QOL scores and other categories indicating activity, physical condition, psychological condition, social relationship, psychological condition and face scale were analyzed. No significant decrease in each factor was observed in this study.

The present patient was diagnosed as having human herpes virus-8 (HHV-8)/Kaposi sarcoma herpes virus (KSHV)-negative and CD20-positive primary effusion lymphoma (PEL) of the right-sided pleural effusion. After pleural drainage, malignant cells disappeared spontaneously in a small amount of the remaining pleural effusion without chemotherapy. The patient was treated with six cycles of chemotherapy consisting of rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone. He has been in complete remission for more than 22 months. It is suggested that effusion drainage followed by chemotherapy containing rituximab is a potential treatment strategy for patients with HHV-8/KSHV-negative and CD20-positive PEL.

A 77-year-old man was admitted to our hospital complaining of general malaise, loss of appetite and hemoptysis. Chest X-ray film and computed tomography (CT) scan showed right-sided pleural effusion with lung tumor. Succeeding upper gastro-intestinal fiberscopy and cystoscopy revealed poorly-differentiated adenocarcinoma of the stomach and urothelial carcinoma of the bladder. Repeated treatment with 100 mg/body of S-1 on day 1 followed by 60 mg/m(2) of cisplatin on day 8 was effective in this patient.

A 64-year-old woman visited our hospital in December 2005 because of general malaise. Her hemoglobin level was 9.0 g/dl. Gastrointestinal fiberscopy detected a hemorrhagic gastric ulcer, which was considered as etiology of anemia. Abdominal ultrasonography showed bilateral hydronephroses and hydroureters. A urine test revealed pyuria and macroscopic hematuria, and urine culture revealed 10(8) colony-forming units of Escherichia coli per ml. Pelvic MRI showed thickening of the posterior wall and trigone of the urinary bladder. Transurethral resection was peformed, and biopsy of the mucous of the bladder gave a diagnosis of primary mucosa-associated lymphoid tissue (MALT) lymphoma of the urinary bladder. Ann Arbor clinical stage was IEA. It was planned to administer irradiation at a total dose of 36 Gy to the whole bladder and part of the tumor; however, radiotherapy was discontinued at a dose of 26 Gy because of the development of pollakisuria. Pelvic MRI and pathologic examination of the urinary bladder after radiotherapy showed that the lymphoma was in complete remission; however, she received retuximab therapy at a dose of 375 mg/m2/week, 8 times additionally, because of the reduced radiotherapy. The patient has remained in complete remission for 14 months.

A 78-year-old woman was admitted to our hospital because for pancytopenia and splenomegaly. The bone marrow examination revealed hairy cells in 11.6% of all nucleated bone marrow cells. Hairy cells were positive for tartaricresistance acid phosphatase (TRAP) staining, CD2, CD11c, CD19, CD20, sIgD, CD25, CD103 and k chain. In addition, abdominal enhanced computed tomography (CT) demonstrated splenomegaly and multiple nodular early stains in the spleen. She was diagnosed as having typical hairy cell leukemia (HCL). The patient was treated with cladribine infused continuously for 7 days at a dose of 0.09 mg/kg/day, which induced partial remission without severe adverse effects. Purine analogs such as cladribine and pentostatine are considered first-line agents for patients with HCL. Treatment with cladribine achieved a high overall response rate for patients with HCL and was safe even in elderly patients like ours. It is necessary to observe carefully the complications of severe infections, second malignancies and relapse of HCL after treatment with cladribine.

An increasing number of patients with lung cancer are undergoing outpatient chemotherapy as an alternative inpatient therapy. To investigate the factors influencing the quality of life (QOL) for these patients,we used a QOL questionnaire, "The QOL Questionnaire for Cancer Patients Treated with Anticancer Drugs" (QOL-ACD) for 8 patients with non-small cell lung cancer. The medical factors related to the overall QOL scores and other categories indicating "activity," "physical condition," "psychological condition," "social relationship" and "face scale" were analyzed. Significant improvements in the factors indicating "psychological condition" were observed in this study.

A 63-year-old woman was diagnosed as having multiple myeloma (MM), IgG-kappa type, stage IIIA, in October 2003. She achieved partial response after receiving three courses of VAD therapy and one course of high dose dexamethasone therapy (HDD); maintenance therapy consisted of melphalan and prednisolone. In November 2004, the patient developed spinal canal stenosis that required surgery. At the end of December 2004, the patient developed renal dysfunction that progressed to anuria. A CT scan showed multiple retroperitoneal masses that impinged on and obstructed both ureters and caused bilateral hydronephroses. Renal function improved after a right percutaneous nephrostomy and chemotherapy consisting of HDD, cyclophosphamide, vincristine, and doxorubicin. Nevertheless, the patient died due to MM in February 2005. On autopsy, multiple retroperitoneal and pelvic plasmacytomas with 13q- and t(4;14) (p16;q32) were found. Our patient is a rare case that, in the terminal stage of MM, developed aggressive phase multiple myeloma with extramedullary plasmacytomas that caused acute renal failure due to compression on both ureters.

Background: Autologous stem cell transplantation (ASCT) in conjunction with therapeutic drugs such as bortezomib, thalidomide, and lenalidomide can dramatically improve response rates and the prognosis of patients with multiple myeloma (MM). However, most patients with MM are considered to be incurable, and relapse owing to minimal residual disease (MRD) is the main cause of death among these patients. Here we utilized a next-generation sequencing (NGS) approach for MRD assessment, which offers at least 1 to 2 logs greater sensitivity (10-6) compared to allele-specific oligonucleotide PCR (ASO-PCR) and flow cytometry, respectively (Faham et al Blood 2012). Previous studies have shown that NGS-based MRD assessment 90 days post-ASCT has prognostic value (Martinez-Lopez et al Blood 2014). In this study, we compared the prognostic value of MRD assessment in autografts and bone marrow (BM) samples from MM patients in the ASCT setting. Methods: One hundred and twenty-three Japanese patients with newly diagnosed MM who received various induction regimens prior to ASCT were retrospectively analyzed. All patients received ASCT and were followed between June 15, 2004 and April 25, 2015. All patients had achieved a partial response (PR) or better after ASCT. Analyzed samples included: (1) BM slides from 96 MM patients at diagnosis, (2) fresh/frozen BM cells from 27 MM patients at diagnosis, (3) autografts and/or (4) post-ASCT BM cells obtained at the time of best response based on serum and urine tests. IGH-based ASO-PCR was performed as described previously (Methods Mol Biol 2009). NGS-based MRD assessment was performed using the immunosequencing platform (Adaptive Biotechnologies, South San Francisco, CA) (Martinez-Lopez et al Blood 2014). Results: We compared MRD results in 51 samples assessed by ASO-PCR and NGS. We observed a high correlation between NGS and ASO-PCR results at MRD levels of 10-5 or higher (r=0.86, P Conclusions: In this study, we show the prognostic value of NGS-based MRD assessment in autografts of patients with MM. The NGS platform has improved sensitivity compared with ASO-qPCR in detecting MRD in autografts. Importantly, this retrospective study suggests that therapeutic intervention based on NGS-based MRD positivity has a significant effect on patient outcome in the post-ASCT setting. Disclosures Zheng: Adaptive Biotechnologies Corp.: Employment, Equity Ownership. Moorhead:Adaptive Biotechnologies Corp.: Employment, Equity Ownership. Faham:Adaptive Biotechnologies Corp.: Employment, Other: Stockholder.

Background: Most patients with multiple myeloma (MM) are considered to be incurable, and relapse, due to minimal residual disease (MRD), is the main cause of death among these patients. Even though allele-specific oligonucleotide real-time quantitative PCR (ASO-qPCR) of immunoglobulin heavy chain gene rearrangement has been used to assess the MRD in MM due to its excellent sensitivity and specificity, ASO-qPCR has a major limitation in its relative quantification method because it needs a reference standard curve, which is usually made with dilutions of diagnostic myeloma DNA or from plasmids containing the target IgH rearrangement gene. Recently, droplet digital PCR (ddPCR) was developed to perform reliable absolute quantification of target genes. Based on the principle of single target gene detection, the sensitivity can be increased when the larger amount of DNA is analyzed. Here we assessed the prognostic value of MRD assessment in autografts from MM patients in the autologous stem cell transplantation (ASCT) setting using ASO-qPCR, ddPCR and next-generation sequencing (NGS) approaches. Methods: Twenty-three Japanese patients with newly diagnosed MM who received various induction regimens prior to ASCT without any post-ASCT therapy were retrospectively analyzed. Median age 57 (range 39-67); males 11, females 12; ISS 1 (n=7), 2 (n=12), 3 (n=3), not assessed (n=1). 11 patients were analyzed by G-banding and FISH (t(4;14), del17p, t(14;16)) and 4 patients showed high-risk chromosomal abnormalities (t(4;14) (n=2), t(14;16) (n=1), -13 by G-banding (n=1)). All patients had achieved a very good partial response (VGPR) or better after ASCT. Analyzed samples included: (1) BM slides from 20 MM patients at diagnosis, (2) fresh/frozen BM cells from 3 MM patients at diagnosis, and (3) obtained autografts. IGH-based ASO-qPCR was performed as described previously (Methods Mol Biol 2009). ddPCR was performed by the QX200 Droplet Digital PCR system (Bio-RAD Inc.) with a total 6000 ng of genomic DNA combined with the same ASO-primers and TaqMan-probes used in the ASO-qPCR. Droplets were generated by the QX200 droplet generator. End-point PCR (40 cycles) was performed on a C1000 Touch Thermal cycler (Bio-RAD Inc). The PCR product was loaded in the QX200 droplet reader and analyzed by QuantaSoft 1.7.4 (Bio-Rad Inc). NGS-based MRD assessment was performed using the immunosequencing platform (Adaptive Biotechnologies, South San Francisco, CA) (Martinez-Lopez et al Blood 2014). Results: Nineteen patients could be analyzed by ASO-qPCR and ddPCR, while all 23 patients could be analyzed by NGS. We compared MRD results in autografts between ddPCR and NGS. We observed a high correlation between ddPCR and NGS results of MRD (r=0.82, P Conclusions: In this study, we showed the prognostic value of ddPCR and NGS-based MRD assessment in autografts of patients with MM. Although the ddPCR had improved sensitivity in detecting MRD in autografts and demonstrated higher prognostic value compared with ASO-qPCR, the NGS platform showed the highest sensitivity and prognostic value among these methods. Disclosures Zheng: Adaptive Biotechnologies Corp: Employment, Equity Ownership. Moorhead:Adaptive Biotechnologies Corp: Employment, Equity Ownership. Faham:Adaptive Biotechnologies Corp.: Employment, Other: Stockholder.

A 73-year-old man was admitted to our hospital complaining of general malaise, loss of appetite and body weight loss. Chest X-ray film showed left-sided pleural effusion. Computed tomographic (CT) scan of the chest also demonstrated left-sided pleural effusion with lung tumor and lymphnode swelling. Repeated treatment with 60 mg/m(2) of cisplatin on day 1 followed by 80 mg/m(2) of irinotecan on days 1 and 8 were effective in this patient.

Background: Although molecular complete remission (mCR) in multiple myeloma (MM) can be assessed by allele-specific oligonucleotide (ASO)-PCR, this technique requires preparation of clonotype-specific primers for each individual, which is laborious and time-consuming. We utilized the LymphoSIGHTTM platform, which employs consensus primers and next-generation sequencing (NGS) to amplify and sequence all rearranged immunoglobulin gene segments present in a myeloma clone, to assess mCR. This technique has been shown to have 1-2 logs greater sensitivity compared to ASO-PCR and flow cytometry, respectively (Faham et al, Blood 2012). Usage of the sequencing method for minimal residual disease (MRD) detection in MM may provide increased sensitivity and specificity, while overcoming the challenges associated with ASO-PCR. We compared the LymphoSIGHTTM method with ASO-qPCR for MRD detection in autografts and bone marrow (BM) in the autologous peripheral blood stem cell (PBSC) transplantation (ASCT) setting. Methods: One hundred and nine Japanese patients with newly diagnosed MM who received various induction regimens prior to ASCT were retrospectively analyzed. All patients had achieved a partial response (PR) or better after ASCT. BM slides from 84 MM patients and fresh/frozen BM cells from 25 MM patients at diagnosis, as well as autografts/post-ASCT BM cells from each patient, were obtained for DNA extraction. IGH-based ASO-qPCR was performed as described previously (Methods Mol Biol 2009). Using universal primer sets, we amplified IGH variable (V), diversity (D), and joining (J) gene segments, IGH-DJ, and IGK from genomic DNA. Amplified products were subjected to deep sequencing using NGS. Reads were analyzed using standardized algorithms for clonotype determination. Myeloma-specific clonotypes were identified for each patient based on their high frequency in BM samples. Results : Myeloma clonotypes could be identified in autografts/post-ASCT BM cells in 98 of 109 patients (90%) and by ASO-qPCR in 63 of 101 patients (62%). MRD by NGS was assessed in autografts of 89 patients. 70 of 89 patients (79%) were positive by NGS; 28 of 62 patients (45%) were positive by ASO-qPCR. Although we observed a high correlation between NGS and PCR MRD results at MRD levels of 10-5 or higher, the sensitivity of ASO-PCR was 10-4-10-5, whereas that of NGS was 10-6 or lower when a sufficient amount of DNA was available for analysis. Eight cases where MRD was not detected in the autograft by NGS (MRDNGS(-)) and 38 MRDNGS(+) cases received post-ASCT therapy using novel agents such as bortezomib/lenalidomide/thalidomide, while 11 MRDNGS(-) cases and 32 MRDNGS(+) cases were followed without post-ASCT therapy. The MRDNGS(-) cases without post-ASCT therapy showed significantly better progression-free survival (PFS) than the MRDNGS(+) cases without post-ASCT therapy (P = 0.012) (Figure 1A) although overall survival rates were comparable between these groups. To investigate the value of sensitive detection by NGS, we compared PFS in 11 MRDNGS(-) cases (Group 1) with the 12 MRDNGS(+) cases where MRD was not detected by ASO-qPCR (MRDASO(-)) (Group 2). The patients in both groups did not receive any post-ASCT therapy. Group 1 showed significantly better PFS than Group 2 (P = 0.027) (Figure 1B). Furthermore, 9 MRDNGS(-) in post-ASCT BM cases tended to show a better PFS than 18 MRDNGS(+) in post-ASCT BM cases (P = 0.075) (Figure 1C). In a multivariate analysis, post-ASCT therapy using novel agents (P Conclusions: In this study, we showed the prognostic value of MRD detection using the NGS-based LymphoSIGHT platform in autografts of patients with MM who received and in those who did not receive post-ASCT therapy with novel agents. The NGS platform has improved sensitivity compared with ASO-qPCR in detecting MRD in autografts. Patients with low level MRD detected by NGS but not by ASO-qPCR have worse prognosis compared to patients who are MRD negative by sequencing, which underscores the need for sensitive detection. Figure 1 Figure 1. Disclosures Zheng: Sequenta, Inc.: Employment. Moorhead:Sequenta, Inc.: Employment. Faham:Sequenta, Inc.: Employment, Equity Ownership, Membership on an entity's Board of Directors or advisory committees.

[Background] Body cavity-based lymphoma (BCBL) arises in body cavity effusion without mass formation. Although there have been several case reports on HHV8-negative BCBL and the term "primary effusion lymphoma (PEL)-like lymphoma" has been coined, it is very rare and not defined in the current lymphoma classification. In those reports, HHV8-negative BCBL usually expresses B-cell markers and the prognosis seems to be better than those with HHV8-positive PEL with a few reports describing spontaneous regression of effusion. However, its clinicopathological features and prognosis remain unclear due to lack of retrospective study with sufficient number. [Method] We collected data of BCBL diagnosed between 1990 and 2014 from 42 institutions in Japan and clinicopathological features were retrospectively analyzed. We focused on clinicopathological features and prognosis of HHV8-negative BCBL, which was defined as HHV8-negative lymphoma that developed in body cavity effusion (pleural effusion, pericardial effusion, and ascites) without mass formation or extra-cavitary lesions at diagnosis. HHV8 status was assessed with immunohistochemical staining with anti-LANA-1 antibody (n=34) and/or polymerase chain reaction for HHV8 (n=31) of body-cavity effusion sample.Overall survival (OS), progression free survival (PFS), and time to progression (TTP) were calculated using Kaplan-Meier method. In patients without any systemic treatment for 3 months from diagnosis, failure of the first systemic treatment was considered as an event for PFS or TTP. [Results] Case report form of 71 patients with BCBL was collected. With central review, 4 patients did not meet the criteria of BCBL (existence of tumor mass or no objective evidence of lymphoma by morphology or immunophenotype) and 67 patients with BCBL were identified. Out of them, 50 and 6 were compatible with the diagnosis of HHV8-negative BCBL and PEL, respectively. In another 11 cases, HHV8 status could not be evaluated. In the 50 patients with HHV8-negative BCBL, male to female ratio was 1.3 : 1, and median age at the diagnosis was 76 years (57-98), HIV was negative in all of the 46 patients who were tested. Twenty-four patients (47%) had an underlying medical condition leading to fluid overload such as cirrhosis, cardiac disease, and renal dysfunction. Involved sites were pleural effusion (76%) followed by pericardial effusion (60%), and ascites (12%). Multiple sites were involved in 21 cases. The other clinical characteristics at the time of diagnosis were as follows: ECOG PS 0-1 (50%); B symptoms (14%); and elevated LDH (68%). Tumor cells expressed CD10 in 11/45 and CD20 in 48/50. Immunoglobulin light chain restriction was detected in 28/34. EBER in situ hybridization was positive in 4/32 (13%). The most common first-line systemic therapy was CHOP or CHOP-like with or without rituximab (n=38) followed by rituximab alone (n=2), rituximab with etoposide (n=2), and hyperCVAD/MA (n=1). One patient died within a month before initiating treatment, and five more patients had no systemic treatment at diagnosis for reasons such as comorbidity or frailty. Of the 43 patients treated with systemic therapy, the overall response rate was 98% with 70% achieving a complete remission. With a median follow up of 22 (0-147) months, 2-year OS, PFS, TTP of HHV8-negative BCBL was 83.6%, 76.8%, and 90.5%, respectively (Figure 1-3). Fifteen patients relapsed after achieving response: the same body-cavity effusion alone (n=7), different body-cavity effusion with or without the same site (n=2), intra- or extra-cavitary tumor mass formation (n=6). Eleven patients died and the causes of death were lymphoma (n=8) and others (n=3). Of the 5 patients without systemic treatment at diagnosis, systemic treatment was initiated in only 1 patient at 30 months due to re-emergence of effusion. The remaining 4 patients had had no systemic treatment for a median of 24 (5-147) months and 3 patients were alive without disease without any systemic therapy at last follow-up. [Conclusion] To the best of our knowledge, this is the largest retrospective study on HHV8-negative BCBL. HHV8-negative BCBL had distinct clinicopathological features from PEL. It affected HIV-negative elderly and the lymphoma cell was positive for B cell markers in most cases. Almost all of the patients responded to systemic treatment and its prognosis was favorable. Figure 1 Figure 1. Figure 2 Figure 2. Figure 3 Figure 3. Disclosures No relevant conflicts of interest to declare.

8601 Background: Although molecular CR in multiple myeloma (MM) can be assessed by allele-specific oligonucleotide (ASO)-PCR, this technique requires preparation of clonotype-specific primers for each individual which is laborious and time-consuming. The usage of the LymphoSIGHT method, a next-generation sequencing (NGS)-based platform, may overcome these challenges and increase sensitivity and specificity. We compared the LymphoSIGHT approach with ASO-qPCR for minimal residual disease (MRD) detection in autografts in the autologous peripheral blood stem cell transplantation (ASCT) setting. Methods: Seventeen Japanese patients with newly diagnosed MM who received various induction regimens prior to ASCT were retrospectively analyzed. All patients had achieved a PR or CR after ASCT. Bone marrow (BM) slides from 13 MM patients and fresh BM cells from 4 MM patients at diagnosis as well as autografts were obtained for DNA extraction. Using universal primer sets, we amplified IGH variable (V), diversity (D), and joining (J) gene segments, IGH-DJ, and IGK from genomic DNA. Amplified products were subjected to deep sequencing using NGS. Reads were analyzed using standardized algorithms for clonotype determination. Myeloma-specific clonotypes were identified for each patient based on their high frequency in BM samples. The presence of the myeloma clonotype was then assessed in follow-up samples. Results: MRD in autografts was detected in 6 of 17 (35%) by ASO-qPCR and 13 of 17 (76%) by NGS. When MRD was assessed by NGS, 6 MRD (+) cases received post-ASCT therapy while 4 MRD (-) cases and 7 MRD (+) cases were followed without post-ASCT therapy. The MRD (-) cases tended to show a better PFS than the MRD (+) cases with post-ASCT therapy (P = 0.26) and those without post-ASCT therapy (P = 0.09) although overall survival rates were comparable among the three groups. There was no difference in PFS between MRD (-) and MRD (+) cases when MRD was assessed by ASO-qPCR (P = 0.6). These studies will be extended in 30 additional MM patients, and results will be presented. Conclusions: MRD-negativity in autografts revealed by NGS may be more closely associated with durable remission of MM than that revealed by ASO-qPCR.

An increasing number of patients with lung cancer are undergoing outpatient chemotherapy. It is very important to keep the quality of life (QOL) for these patients. Japanese traditional medicine, TJ-41, has been reported to improve the QOL of patients with advanced cancer. However, it has been unknown about the effect of TJ-41 in patients with lung cancer undergoing outpatient chemotherapy. So we conducted this study. To investigate the factors influencing the quality of life (QOL) for these patients, we answered using a QOL questionaire, ‘The QOL Questionnaire for Cancer Patients Treated with Anticancer Drugs’ (QOL-ACD) to 8 patients (5 males, 3 females, aged 57–90, mean age 71.5) with non-small-cell lung cancer. The medical factors related to the overall QOL scores and other categories indicating ‘activity’, ‘physical condition’, ‘psychological condition’, ‘social relationship’, ‘psychological condition’ and ‘face scale’ were analyzed. Significant decreasement in each factor was not observed in this study.