Wearable EMG Measurement Device Using Polyurethane Foam for Motion Artifact Suppression.

We propose the use of a specially designed polyurethane foam with a plateau region in its mechanical characteristics-where stress remains nearly constant during deformation-between the electromyography (EMG) electrode and clothing to suppress motion artifacts in EMG measurement. Wearable EMG devices are receiving attention for monitoring muscle weakening due to aging. However, daily EMG measurement has been challenging due to motion artifacts caused by changes in the contact pressure between the bioelectrode and the skin. Therefore, this study aims to measure EMG signals in daily movement environments by controlling the contact pressure using polyurethane foam between the bioelectrode on the clothing and the skin. Through mechanical calculations and finite element method simulations of the polyurethane foam's effect, we clarified that the characteristics of the polyurethane foam significantly influence contact pressure control and that the contact pressure is adjustable through the polyurethane foam thickness. The optimization of the design successfully controlled the contact pressure between the bioelectrode and skin from 1.0 kPa to 2.0 kPa, effectively suppressing the motion artifact in EMG measurement.

Leukemic-phase mucosa-associated lymphoid tissue lymphoma.

A 78-year-old man presenting with leukocytosis was admitted to our hospital. The patient was asymptomatic and showed no lymphadenopathy. Peripheral blood flow cytometry revealed a leukemic-phase B-cell lymphoma with medium-to-large abnormal cells with reticulum. Positron emission tomography/computed tomography revealed abnormal uptake in the right orbit, bone marrow, and spleen. We performed immunological staining and fluorescence in situ hybridization on tissues extracted from the right orbit and bone marrow, which led to the diagnosis of mucosa-associated lymphoid tissue (MALT) lymphoma. Polymerase chain reaction analysis of immunoglobulin heavy chain rearrangements in the right orbital mass and bone marrow suggested that they were identical clones. Based on these collective findings, the diagnosis of leukemic-phase MALT lymphoma was confirmed, with sites of involvement including the bone marrow, peripheral blood, right orbit, and spleen. This is a highly rare case of leukemic MALT lymphoma.

Biopsy remains indispensable for evaluating bone marrow involvement in DLBCL patients despite the use of positron emission tomography.

Initial staging by positron emission tomography/computed tomography (PET/CT) scanning is recommended for patients with diffuse large B-cell lymphoma (DLBCL). Whether both PET/CT and bone marrow biopsy (BMB) are required remains unclear. This study examined whether staging by PET/CT is sufficient. Participants with untreated DLBCL assessed using both PET/CT and BMB were included. Patients received independent diagnostic assessments from a radiologist and a hematopathologist. Both hematoxylin-eosin staining and CD20 immunostaining were performed to determine the bone marrow involvement in BMB. A total of 84 patients were included. The number of patients with positive bone marrow involvement identified by PET/CT and BMB was 16 (19%) and 22 (26%), respectively. Eight (10%) patients showed positive results in both tests. When considering BMB as a reference, PET/CT showed 36% sensitivity and 87% specificity, with positive and negative predictive values of 50% and 79%, respectively. BMB-positive patients had shorter progression-free (PFS) and overall (OS) survival than their BMB-negative counterparts. Compared to PET/CT-negative patients, patients with positive results did not show any significant differences in PFS and OS. However, among 16 PET/CT-positive patients, poor PFS and OS were observed among patients who were also BMB positive. BMB remains a mandatory step in staging of untreated DLBCL patients.

Dose-adjusted EPOCH with or without rituximab for aggressive lymphoma patients: real world data.

CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) -/+ rituximab (R) is the standard chemotherapeutic regimen for aggressive lymphoma, but is insufficient for aggressive lymphoma with adverse prognostic factors. Dose-adjusted (DA)-EPOCH (etoposide, doxorubicin, cyclophosphamide, vincristine, and prednisolone) -/+ R demonstrates excellent efficacy against some aggressive lymphoma. Thus, we conducted a retrospective study to evaluate the feasibility and efficacy of this therapy in clinical practice. We enrolled 149 patients from 17 institutions diagnosed between 2007 and 2015. The median follow-up period for survivors was 27 months (range 0.2-123). The complete response (CR) rate of newly diagnosed patients was 79% (95% CI 68-87%). All patients were hospitalized to receive this therapy and 94% of patients also received granulocyte-colony-stimulating factor support. There were no treatment-related deaths. Febrile neutropenia (FN) and grade 3 or 4 infection occurred in 55% and 28% of patients, respectively. There were no significant differences in FN or infection between young (≤ 65 years) and elderly patients (> 65 years). In newly diagnosed diffuse large B-cell lymphoma-not otherwise specified patients (n = 46), the CR rate was 80% (95% CI 64-91%) and the 2-year OS rate was 81% (95% CI 66-90%). In the present study, DA-EPOCH -/+ R exhibited excellent efficacy and feasibility for aggressive lymphoma.

[Leukemic cell kinetics of APL with a novel complex variant t (12;17;15)(p13;q21;q22)].

A 69-year-old woman with leukocytopenia and thrombocytopenia was referred to our hospital. Her bone marrow comprised 70.5% abnormal promyelocytes that were positive for myeloperoxidase/CD33/CD117 and CD13 (dim) and negative for CD2/CD34/CD56 and HLA-DR. Chromosome analysis of the bone marrow showed t (12;17;15) (p13;q21;q22), and fluorescence in situ hybridization revealed the PML-RARA fusion signal only on the derivative chromosome 15. The patient was diagnosed with acute promyelocytic leukemia (APL) with PML-RARA and was treated using all-trans retinoic acid (ATRA). In peripheral blood (PB), PML-RARA-positive polymorphonuclear cells (PMNs) appeared on the second week and became negative on the sixth week after treatment, whereas PML-RARA-negative PMNs started to increase in number on the sixth week. Molecular remission was confirmed on the 10th week. Quantitative evaluation of the differentiated leukemic cells of APL and recovered cells from normal hematopoiesis in PB can provide useful information for a safer induction therapy. No significant difference was noted in the kinetics of the leukemic cells under ATRA treatment as well as in the clinical features between our patient without RARA-PML and those with t (15;17), which is a cytogenetic evidence for the critical role of PML-RARA in the pathogenesis of APL.

Improved prognosis of extranodal NK/T cell lymphoma, nasal type of nasal origin but not extranasal origin.

Extranodal NK/T cell lymphoma (NKTCL), nasal type (ENKL) that shows no apparent nasal involvement, is termed extranasal NKTCL or non-nasal NKTCL. In this study, we aimed to explore therapeutic approaches and outcomes in patients with extranasal NKTCL in current clinical practice. A data set of patients with newly diagnosed NKTCL who were diagnosed at 31 institutes in Japan between 2000 and 2013 was used for analysis. The patients' fitness for steroid, methotrexate, ifosfamide, L-asparaginase, and etoposide (SMILE) chemotherapy was assessed using the major inclusion criteria of the SMILE phase 2 study. Of 358 patients, 47 (13%) had extranasal NKTCL. The most frequent extranodal sites of involvement in extranasal NKTCL were skin/subcutaneous tissue (n = 18). Six (13%) of the patients with extranasal NKTCL had localized disease and were diagnosed before 2010. With a median follow-up of 5.8 years, the 2-year overall survival (OS) in patients with nasal and extranasal NKTCL was 70% (95% confidence interval [CI], 65-75%) and 34% (95% CI, 21-47%), respectively. OS in patients with nasal NKTCL had a trend toward better according to treatment era (P = 0.063). In contrast, no obvious improvement of OS was observed in extranasal NKTCL (P = 0.43). The major inclusion criteria of the SMILE-P2 were met in 21% (10/47) of patients with extranasal NKTCL and 60% (188/311) of those with nasal NKTCL (P < 0.001). Despite the advent of new treatments for ENKL, OS remains unfavorable in extranasal NKTCL. A more effective therapy is needed for extranasal NKTCL.

Light-chain plasma cell myeloma caused by 14q32/IGH translocation and loss of the other allele.

Light-chain plasma cell myeloma (LC-PCM) is a PCM subtype in which only immunoglobulin light-chain is secreted. However, the absence of immunoglobulin heavy-chain (IGH) production in this condition has not been fully elucidated. To address this issue, we retrospectively analyzed patients at our center with LC-PCM and found a group who had only split signals of IGH gene derived from 14q32/IGH translocations by fluorescence in situ hybridization (FISH). Six patients were identified with only split signals of the IGH gene derived from 14q32/IGH translocations. Five of these patients were newly diagnosed, while one had IgG-λ PCM at presentation, which transformed to λ LC-PCM after treatment. The translocation partners were identified in four patients: two cases of (11;14)(q13;q32) and two cases of (4;14)(p16;q32). The development of LC-PCM appears to be explained by the application of allelic exclusion in these patients, such that 14q32/IGH translocation in one allele contributes to the pathogenesis of PCM and the subsequent loss of the other allele is responsible for the loss of IGH production. These findings suggest that a FISH pattern of IGH with "split and loss" may constitute a unique subgroup of LC-PCM.

Septicemia from Lactobacillus rhamnosus GG, from a Probiotic Enriched Yogurt, in a Patient with Autologous Stem Cell Transplantation.

Probiotic-rich foods are consumed without much restriction. We report here, a case of septic shock caused by yogurt derived Lactobacillus species in a 54-year-old male patient with acute promyelocytic leukemia, in second complete remission, and who was an autologous stem cell transplantation recipient. He received high dose chemotherapy and autologous peripheral blood stem cell transplantation. He ingested commercially available probiotic-enriched yogurt because of severe diarrhea. One week later, he developed septic shock, and the pathogen was determined by strain-specific PCR analysis as Lactobacillus rhamnosus GG (ATCC 53103), which was found to be identical with the strain in the yogurt he consumed. Thus, because even low virulent Lactobacilli in the probiotic products can be pathogenic in the compromised hosts, ingestion of such products should be considered with caution in neutropenic patients with severe diarrhea, such as stem cell transplantation recipients.

Correction to: Cell dynamics during differentiation therapy with all-trans retinoic acid in acute promyelocytic leukemia.

In the original publication of the article, Table 2 was published incorrectly. The column names were swapped under the column heading "Prom (%)". The correct column names are PB and BM.

Cell dynamics during differentiation therapy with all-trans retinoic acid in acute promyelocytic leukemia.

The introduction of all-trans retinoic acid (ATRA) has made acute promyelocytic leukemia (APL) a curable disease; however, early death prior to the completion of treatment remains a problem. In quantitative evaluation of response to ATRA treatment, lymphocytes must be excluded as they do not originally have t(15;17). We categorized peripheral blood leukocytes by nuclear morphology into polymorphonuclear cells (PMNs) comprising segmented granulocytes, and non-polymorphonuclear cells (NPMs) which includes lymphocytes, monocytes, band cells, and immature myeloid cells. We consecutively evaluated the ratio of t(15;17)-positive cells using fluorescence in situ hybridization in eight newly diagnosed patients with APL. We confirmed the differentiation of APL cells until cytogenetic complete remission; the association of a decrease of t(15;17)-positive NPMs and an increase of t(15;17)-positive PMNs was followed by a decrease of t(15;17)-positive PMNs. The kinetic pattern of t(15;17)-positive NPMs and PMNs was consistent in most patients, irrespective of leukocyte counts at diagnosis, additional chromosomal changes, and ATRA with or without chemotherapies. Kinetic analysis enables us to evaluate treatment response and the recovery of normal hematopoiesis in individuals.

[MALT lymphoma with t (X;14) (p11.2;q32) developing during the course of cutaneous leukocytoclastic angitis].

A 73-year-old man with left parotid gland swelling over 2 months was referred to our hospital in March 201X. Purpura on the lower legs had been recurrent for >20 years. Biopsy of the parotid gland demonstrated diffuse infiltration of abnormal lymphocytes that were negative for CD10 and positive for CD19, CD20, and κ-chain. The Ki-67 positivity was <10%; lymphoepithelial lesions were observed. The patient was diagnosed with extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma). Chromosome analysis revealed t (X;14) (p11.2;q32), and fluorescence in situ hybridization (FISH) of metaphase spreads showed three signals of the immunoglobulin heavy chain (IGH) gene on the derivative chromosomes X and 14, besides the normal chromosome 14. CT findings of parotid glands were suggestive of Sjogren syndrome, and biopsy of the purpura on the leg demonstrated leukocytoclastic vasculitis. In the literature, only seven patients with lymphoma and t (X;14) translocation have been reported. Of these, five patients had MALT lymphoma, one had nodal marginal zone lymphoma, and one had diffuse large B-cell lymphoma. In all patients, lymphoma evolved from previous autoimmune diseases. It is suggested that MALT lymphoma with the t (X;14) translocation forms a new entity of lymphoma.

Clinicopathological and genomic analysis of double-hit follicular lymphoma: comparison with high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements.

Most high-grade B-cell lymphomas with MYC and BCL2 and/or BCL6 rearrangements are aggressive B-cell lymphomas. Occasional double-hit follicular lymphomas have been described but the clinicopathological features of these tumors are not well known. To clarify the characteristics of double-hit follicular lymphomas, we analyzed 10 cases of double-hit follicular lymphomas and 15 cases of high-grade B-cell lymphomas with MYC and BCL2 and/or BCL6 rearrangements for clinicopathological and genome-wide copy-number alterations and copy-neutral loss-of-heterozygosity profiles. For double-hit follicular lymphomas, the median age was 67.5 years (range: 48-82 years). The female/male ratio was 2.3. Eight patients presented with advanced clinical stage. The median follow-up time was 20 months (range: 1-132 months). At the end of the follow-up, 8 patients were alive, 2 patients were dead including 1 patient with diffuse large B-cell lymphoma transformation. Rearrangements of MYC/BCL2, MYC/BCL6, and MYC/BCL2/BCL6 were seen in 8, 1, and 1 cases, respectively. The partner of MYC was IGH in 6 cases. There were no cases of histological grade 1, 4 cases of grade 2, 5 cases of grade 3a, and 1 case of grade 3b. Two cases of grade 3a exhibited immunoblast-like morphology. Immunohistochemistry demonstrated 9 cases with ≥50% MYC-positive cells. There was significant difference in MYC intensity (P=0.00004) and MIB-1 positivity (P=0.001) between double-hit follicular lymphomas and high-grade B-cell lymphomas with MYC and BCL2 and/or BCL6 rearrangements. The genome profile of double-hit follicular lymphomas was comparable with conventional follicular lymphomas (GSE67385, n=198) with characteristic gains of 2p25.3-p11.1, 7p22.3-q36.3, 12q11-q24.33, and loss of 18q21.32-q23 (P<0.05). In comparison with high-grade B-cell lymphomas with MYC and BCL2 and/or BCL6 rearrangements, double-hit follicular lymphomas had fewer copy-number alterations and minimal common region of gain at 2p16.1 (70%), locus also significant against conventional follicular lymphomas (P=0.0001). In summary, double-hit follicular lymphomas tended to be high-grade histology, high MYC protein expression, high MYC/IGH fusion, and minimal common region of gain at 2p16.1. Double-hit follicular lymphomas seemed to be a different disease from high-grade B-cell lymphomas with MYC and BCL2 and/or BCL6 rearrangements and have an indolent clinical behavior similar to follicular lymphomas without MYC rearrangement.

The standard international prognostic index for predicting the risk of CNS involvement in DLBCL without specific prophylaxis.

Central nervous system (CNS) involvement is a serious complication in patients with diffuse large B-cell lymphoma (DLBCL) and evaluating CNS risk is an important issue. Using the standard international prognostic index (IPI) and CNS-IPI, a recently proposed model including IPI risk factors and adrenal/kidney involvement, we assessed CNS risk in 1220 untreated DLBCL patients who received R-CHOP without prophylaxis. According to the standard IPI, the cumulative incidences of CNS involvement at 2 years were 1.3, 4.6, 8.8, and 12.7% in the low-, low-intermediate-, high-intermediate-, and high-risk groups, respectively (p <.001). This result is comparable with that of the CNS-IPI. Patients with breast involvement tended to have lower risk according to the standard IPI but showed frequent CNS involvement, similar to patients with testis involvement. The standard IPI is also a useful predictor of CNS involvement. Patients with breast/testis involvement would be candidates for prophylaxis regardless of the standard IPI risk.

Acute myeloid leukemia with t (3;8) (q26.2;q24), a simple variant of 3q26.2/EVI1 translocation.

A 70-year-old man with pancytopenia was referred to our hospital. His bone marrow comprised 75.4% leukemic blast cells and increased micromegakaryocytes. The leukemic cells were positive for myeloperoxidase and expressed CD2, CD13, CD33, CD34, CD56, CD117, HLA-DR, and MYC. Chromosomal analysis revealed 45,XY,t (3;8) (q26.2;q24),-7[6]/46,XY[14]. Fluorescence in situ hybridization revealed the rearrangement of the ecotropic viral integration site 1 (EVI1) gene. Thus, the patient was diagnosed as having acute myeloid leukemia (AML) with maturation, according to the WHO classification; he achieved complete cytogenetic remission after two courses of combination chemotherapy using anthracyclines and cytarabine. The t (3;8) translocation is a rare simple variant of the 3q26.2/EVI1 translocation, which is an adverse prognostic factor of AML. Clarifying the clinical features of leukemia in patients with simple variant translocations facilitates the development of therapies.

BCL2 expression in DLBCL: reappraisal of immunohistochemistry with new criteria for therapeutic biomarker evaluation.

Overexpression of the BCL2 is associated with a poor prognosis in diffuse large B-cell lymphoma (DLBCL). The assessment of MYC immunohistochemistry (IHC) is becoming optimized, whereas the criteria for BCL2 positivity are highly variable. Furthermore, data on the frequency and prognostic value of BCL2 positivity are conflicting. We aimed to evaluate BCL2 expression by IHC and assess the prognostic significance of the histopathologically scored BCL2 expression in 456 patients with DLBCL uniformly treated with standard immunochemotherapy (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone, R-CHOP). We initially designed 4-grade BCL2 scoring criteria, from 0 to 3+, and found that ∼40% of DLBCL showed strong BCL2 expression (score 3+). The scores from the pathologist's visual estimation were confirmed to be reliable using a digital image analysis. A retrospective survival analysis revealed that BCL2 score 3+ was a significant prognostic factor independent of the international prognostic index (IPI), the IHC-determined cell of origin, and the MYC protein/rearrangement status in a training set (n = 218). The adverse prognostic impact of BCL2 score 3+ was confirmed in a validation set (n = 238). We also developed a prognostic model consisting of 3 groups with a combined BCL2 score and MYC protein/rearrangement status. Patients with BCL2 score 3+ showed a higher treatment failure rate; therefore, alternative therapeutic strategies should be considered for these patients. A highly selective BCL2 inhibitor, venetoclax, was recently introduced as breakthrough therapy. Our BCL2 scoring system could readily be used by pathologists to evaluate patients with DLBCL who might benefit from BCL2-targeted therapies.

Acute myeloid leukemia with t(3;21)(q13;q22), a novel simple variant of the 21q22/RUNX1 translocation.

A 69-year-old man diagnosed with leukocytosis was referred to our hospital in July 201X. The patient was diagnosed as having a myelodysplastic/myeloproliferative neoplasm. However, he presented with leukemia 2 months later. Chromosomal analysis of a bone marrow sample documented that this patient had a normal karyotype. The patient was successfully treated with idarubicin and cytarabine, and he underwent three courses of consolidation therapy. However, he suffered a relapse in May of the following year. A cytogenetic analysis revealed the presence of a t (3;21) (q13;q22) translocation, and fluorescence in situ hybridization of metaphase spreads detected three signals corresponding to the runt related transcription factor 1 (RUNX1) on the derivative chromosomes 3 and 21, besides the normal chromosome 21. Chromosomal translocations in leukemia often involve genes encoding transcription factors, and the RUNX1 is a common target for such translocations. To the best of our knowledge, this is a novel variant of the RUNX1 translocation. Identifying genes associated with translocations in leukemia contributes to novel insights into the mechanisms of disease progression and chemotherapy resistance and also facilitates the development of molecularly targeted therapies.

Treatments and Outcomes of Patients With Extranodal Natural Killer/T-Cell Lymphoma Diagnosed Between 2000 and 2013: A Cooperative Study in Japan.

Purpose To elucidate the management and outcomes of patients with extranodal natural killer/T-cell lymphoma, nasal type (ENKL), who were diagnosed between 2000 and 2013 in Japan. Patients and Methods Data from 358 patients with ENKL diagnosed between 2000 and 2013 from 31 institutes were retrospectively analyzed. Results Patients' median age was 58 years, and 257 (72%) had localized disease. The most common first-line treatment was radiotherapy with dexamethasone, etoposide, ifosfamide, and carboplatin (RT-DeVIC) (66%) for localized ENKL and L-asparaginase-containing chemotherapy (30%) for advanced ENKL. With a median follow-up of 5.8 years, overall survival (OS) rates at 5 years for localized and advanced ENKL were 68% and 24%, respectively. The prognostic index of natural killer lymphoma was validated in our study, although only 4% of patients with localized ENKL were classified as high risk. With a median follow-up of 5.6 years, OS and progression-free survival at 5 years in the 150 patients who received RT-DeVIC in clinical practice were 72% (95% CI, 63% to 78%) and 61% (95% CI, 52% to 69%), respectively. Toxicities of RT-DeVIC were comparable to those in a previous trial. Multivariate analysis in patients with localized ENKL who received RT-DeVIC identified elevated soluble interleukin-2 receptor as an independent predictive factor for worse OS and progression-free survival (adjusted hazard ratios, 2.28 and 2.46; 95% CI, 1.24 to 4.23 and 1.42 to 4.28; P = .008 and .0014, respectively). Conclusion Favorable OS in response to new treatments was demonstrated in a large number of patients. Improved treatment approaches are needed for localized ENKL exhibiting elevated pretreatment soluble interleukin-2 receptor.

Outcome and prognostic factors among patients who underwent a second transplantation for disease relapse post the first allogeneic cell transplantation.

The prognosis for disease relapse after first hematopoietic cell transplantation (HCT1) is poor. Here, we present a retrospective multicenter study to evaluate the clinical outcome and the prognostic factors for second hematopoietic cell transplantation (HCT2). The cohort in this study comprised 60 patients diagnosed with acute leukemia, who underwent HCT2 due to hematological relapse after HCT1. The overall survival (OS) at two years, non-relapse mortality (NRM), and relapse mortality (RM) were 30.3%, 40.9%, and 28.8%, respectively. Multivariate analysis for OS identified the use of a donor other than matched-related (MR) donor (hazard ratios [HR] = 4.10, 95% confidence intervals [CI]: 1.72-9.74, p = .001) and high disease status (HR = 2.90, 95% CI: 1.28-6.56, p = .011) as the adverse risk factors for HCT2. On analyzing the combination of factors during HCT1 and HCT2, MR donor, reduced intensity conditioning regimen, and standard status were found to be significant as favorable prognostic factors for OS. Therefore, evaluating these prognostic factors would be helpful in taking decisions regarding post-relapse management.

Autologous hematopoietic cell transplantation for acute promyelocytic leukemia in second complete remission: outcomes before and after the introduction of arsenic trioxide.

We conducted a retrospective registry-based study involving 198 patients with acute promyelocytic leukemia (APL) who underwent autologous hematopoietic cell transplantation (HCT) during second complete remission (CR2) from 1995 to 2012. Arsenic trioxide (ATO) became commercially available in Japan in December 2004, and a substantial increase in the annual numbers of transplantations has occurred since 2005. Patients transplanted after 2006 had significantly better relapse-free and overall survival than those transplanted before 2004 (p = .028 and p = .027, respectively). There was a significant difference in cumulative incidence of relapse in favor of those transplanted after 2006 (p = .008), whereas non-relapse mortality did not differ between the two groups (p = .683). Our findings suggest that the introduction of ATO may have reduced post-transplantation relapse without increasing non-relapse mortality, resulting in significant improvements in overall outcomes for relapsed APL patients undergoing autologous HCT during CR2.