Search

Although chimeric antigen receptor T-cell (CAR-T) therapies have dramatically improved the outcomes of relapsed/refractory B-cell malignancies, recipients suffer from severe humoral immunodeficiencies. Furthermore, patients with coronavirus disease 2019 (COVID-19) have a poor prognosis, as noted in several case reports of recipients who had COVID-19 before the infusion. We report the case of a 70-year-old woman who developed COVID-19 immediately before CAR-T therapy for high-grade B-cell lymphoma. She received Tixagevimab−Cilgavimab chemotherapy and radiation therapy but never achieved remission. She was transferred to our hospital for CAR-T therapy, but developed COVID-19. Her symptoms were mild and she was treated with long-term molnupiravir. On day 28 post-infection, lymphodepleting chemotherapy was restarted after a negative polymerase chain reaction (PCR) test was confirmed. The patient did not experience recurrence of COVID-19 symptoms or severe cytokine release syndrome. Based on the analysis and comparison of the previous reports with this case, we believe that CAR-T therapy should be postponed until a negative PCR test is confirmed. In addition, Tixagevimab−Cilgavimab and long term direct-acting antiviral agent treatment can be effective prophylaxis for severe COVID-19 and shortening the duration of infection. [ABSTRACT FROM AUTHOR]

Although magnetic resonance imaging (MRI) data of patients with multiple myeloma (MM) are used to predict prognosis, few reports have applied artificial intelligence (AI) techniques for this purpose. We aimed to analyze whole-body diffusion-weighted MRI data using three-dimensional (3D) convolutional neural networks (CNNs) and Gradient-weighted Class Activation Mapping (Grad-CAM), an explainable AI, to predict prognosis and explore the factors involved in prediction. We retrospectively analyzed the MRI data of a total of 142 patients with MM obtained from two medical centers. We defined the occurrence of progressive disease after MRI evaluation within 12 months as a poor prognosis and constructed a 3D CNN-based deep learning model to predict prognosis. Images from 111 cases were used as the training and internal validation data; images from 31 cases were used as the external validation data. Internal validation of the AI model with stratified 5-fold cross-validation resulted in a significant difference in progression-free survival (PFS) between good and poor prognostic cases (2-year PFS, 91.2% versus [vs.] 61.1%, P = 0.0002). The AI model clearly stratified good and poor prognostic cases in the external validation cohort (2-year PFS, 92.9% vs. 55.6%, P = 0.004), with an area under the receiver operating characteristic curve of 0.804. According to Grad-CAM, the MRI signals of the spleen and bones of the vertebrae and pelvis contributed to prognosis prediction. This study is the first to show that image analysis of whole-body MRI using a 3D CNN without any other clinical data is effective in predicting the prognosis of patients with MM. [ABSTRACT FROM AUTHOR]

Objectives To demonstrate the clinical features and prognostic impact of cyclin D1 positivity in patients with amyloid light chain amyloidosis (AL). Methods We consecutively included 71 patients diagnosed with AL with cyclin D1 positivity between February 2008 and January 2022. t(11;14) was examined through interphase fluorescence in situ hybridization using bone marrow cells. Results The median age of the patients was 73 years, and 53.5% were male. The underlying diseases included symptomatic multiple myeloma, smoldering multiple myeloma, Waldenström macroglobulinemia, and monoclonal gammopathy of undetermined significance, representing 33.8%, 26.8%, 2.8%, and 36.6%, respectively. The prevalence of cyclin D1 and t(11;14) was 38.0% and 34.7%, respectively. Higher frequency of light chain paraprotein type was seen in cyclin D1–positive patients with AL than in cyclin D1–negative patients (70.4% vs 18.2%). The median overall survival (OS) of patients with AL with and without cyclin D1 expression was 18.9 months and 73.1 months, respectively (P =.019). Early death occurred in 44.4% of cyclin D1–positive patients and 31.8% of cyclin D1–negative patients. Moreover, 83.3% of cyclin D1–positive patients and 21.4% of cyclin D1–negative patients died of cardiac causes. Conclusions Cyclin D1 immunohistochemistry accurately identified patients with t(11;14). Cyclin D1–positive patients had significantly inferior OS compared with cyclin D1–negative patients. [ABSTRACT FROM AUTHOR]

Summary: Antibody titres in 462 patients with haematological malignancies after the second (D2) and third (D3) SARS‐CoV‐2 vaccine were compared with those of healthy controls (HCs). Significant decay of antibody titre was observed pre D3, but titre surged post D3. The number of seronegative patients decreased from 79 (17.1%) to 44 (9.5%) from post D2 to post D3, and patients with adequate antibody titre increased from 204 (44.2%) to 358 (77.5%). Of the patients who received B‐cell‐targeted therapy, 80% were seronegative and 71% remained seronegative after D3. CD19+, CD4+, CD8+ cell counts, and immunoglobulin G (IgG) levels were identified as independent predictors for adequate serologic response. [ABSTRACT FROM AUTHOR]

To evaluate the efficacy of high-dose methotrexate (HD-MTX, ≥1 g/m2) for the prevention of central nervous system (CNS) recurrence in patients with intravascular large B-cell lymphoma (IVLBCL), we reviewed 51 patients with pathologically diagnosed untreated IVLBCL. In total, there were five cases of CNS relapse (9.8%), and the 12-month CNS relapse rate was 9.2%. No statistical difference in CNS relapse rate (p = 0.86) was observed between patients with and without HD-MTX (n = 20 and 31, respectively). Furthermore, the composite endpoint defined as either CNS and/or neurolymphomatosis relapse was not significant in terms of the administration of HD-MTX (p = 0.25). No significant predictor of CNS relapse was found. In conclusion, patients with IVLBCL are at high risk of CNS recurrence; however, HD-MTX administration may not be effective for CNS recurrence prophylaxis. The administration of HD-MTX for patients with untreated IVLBCL may not be effective for preventing CNS relapse. [ABSTRACT FROM AUTHOR]

Chylous effusion is associated with lymphatic obstruction or leakage in mediastinal or abdominal lymph nodes, and is a rare but troublesome complication in patients with malignant lymphomas. Although there is no standard of care, it is often treated with simultaneous chemotherapeutic and non-chemotherapeutic interventions. Here, we describe the cases of five patients with lymphoma-associated chylothorax with the aim of clarifying an effective treatment strategy. All patients achieved a partial response or better for lymphoma. All patients underwent interventional radiology (IVR) procedures, including lymphangiography (LAG) and thoracic duct embolization (TDE). Complete resolution of chylothorax was eventually achieved by IVR procedures or pleurodesis in all patients. No patients experienced serious adverse events related to LAG/TDE. Treatment of chylous effusion required months for most patients (range: 0.2-4.8 months). Our data suggest that a combination of chemotherapy and LAG/TDE is effective for refractory lymphoma-related chylous effusion. [ABSTRACT FROM AUTHOR]

Variable causes such as veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS), liver graft-versus-host disease (GVHD), and drug-induced liver injury contribute to development of ascites in allo-HSCT [[1]]. Refractory ascites after allogenic hematopoietic stem cell transplantation (allo-HSCT) is a rare and potentially fatal complication. In conclusion, our case highlights that HS after allo-HSCT should be kept as a differential diagnosis when refractory portal hypertensive ascites and liver atrophy rapidly develop in late-phase allo-HSCT. The largest series of 40 patients with portal hypertensive ascites after allo-HSCT without any known cause demonstrated a cumulative incidence of non-relapse mortality of 63%, and a median survival duration after the development of ascites of 7 months [[4]]. [Extracted from the article]

Multiple myeloma (MM) is an incurable hematological malignancy, but treatment advances made in the last two decades have markedly improved its prognosis. Imaging has played a particularly important role in the management of myeloma. Whole-body low-dose computed tomography (WBLDCT) is replacing conventional skeletal survey by whole-body X-rays. In addition, magnetic resonance imaging (MRI) and positron-emission tomography/computed tomography (PET/CT) have become important imaging modalities not only for MM diagnosis but also for assessment of myeloma cell infiltration, extramedullary disease, treatment efficacy, and prognosis. However, there is room to improve their accuracy and specificity for assessment of treatment response, tumor volume, and residual disease. This review introduces novel diagnostic techniques, such as WBLDCT, MRI, and PET/CT, discusses their contribution to MM care, and lists areas for future research. [ABSTRACT FROM AUTHOR]

Summary: This study reports the relationship between CD38+ regulatory T cells (Tregs) and messenger RNA coronavirus disease 2019 (mRNA‐COVID‐19) vaccination in 60 patients with plasma cell dyscrasia. Patients treated with anti‐CD38 monoclonal antibodies (mAbs) had significantly lower CD38+ Tregs than those not treated (0.9 vs. 13.2/μl). Late‐responders, whose antibody titres increased from weeks 4–12 after the second vaccination, had significantly lower CD38+ Treg counts than non‐late‐responders (2.5 vs. 10.3/μl). Antibody titres in patients with lower CD38+ Treg levels were maintained from weeks 4–12 but decreased in those with higher CD38+ Treg levels. Therefore, depletion of CD38+ Tregs by anti‐CD38 mAbs may induce a durable response to mRNA‐COVID‐19 vaccination. [ABSTRACT FROM AUTHOR]

Carfilzomib (Cfz) is widely used to treat multiple myeloma. However, real-world data of the incidence of thrombotic microangiopathy (TMA) caused by Cfz is inconsistent (<1–5%). We evaluated 96 consecutive patients who received Cfz to evaluate the incidence of TMA in clinical practice. TMA developed in five patients (5.2%) who were mainly receiving high-dose Cfz (≥56 mg/m2). Based on a literature review, precaution should be taken for Cfz-induced TMA in male patients receiving high-dose Cfz irrespective of the combination therapy, Cfz administration period, and complement level. In conclusion, Cfz-induced TMA might be underestimated in clinical practice, and early intervention should be considered. [ABSTRACT FROM AUTHOR]

We evaluated anti-spike protein antibody (anti-S) production in 130 hematopoietic stem cell transplant (HSCT) recipients who received the coronavirus disease-2019 vaccine. Sixty-five received allo-HSCT and 65 received auto-HSCT. Disease-specific treatments were being administered to 43.1% of allo-HSCT and 69.2% of auto-HSCT patients. Seropositivity was observed in 87.7% of allo-HSCT and 89.2% in auto-HSCT patients. Anti-S antibody production was significantly impaired in auto-HSCT patients compared with controls (178U/mL [0.4–4990.0] vs. 669 U/mL [40.3–4377.0], p < 0.001), but not in allo-HSCT patients (900 U/mL [0.4–12,893.0] vs. 860 U/mL [40.3–8988.0], P = 0.659). Clinically relevant anti-S antibody levels (> 264 U/mL) were achieved in 59.2% of patients (76.9% in allo-HSCT and 41.5% in auto-HSCT). The main factors influencing the protective level of the antibody response were the CD19 + cell count and serum immunoglobulin G levels, and these were significant in both allo-HSCT and auto-HSCT patients. Other factors included time since HSCT, complete remission status, use of immunosuppressive drugs, and levels of lymphocyte subsets including CD4, CD8 and CD56 positive cells, but these were only significant in allo-HSCT patients. Allo-HSCT patients had a relatively favorable antibody response, while auto-HSCT patients had poorer results. [ABSTRACT FROM AUTHOR]

Patients with lymphoma are at increased risk for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); therefore, evaluation of SARS-CoV-2 vaccination efficacy is essential. We conducted a prospective observational study to monitor the antibody response in 500 patients with lymphoma after SARS-CoV-2 vaccination. Antibody levels increased in a stepwise manner after the first and second dose of the vaccine. After completion of the two-dose series, anti-S antibody was negative in 109 patients (21.8%), and below clinically protective levels (anti-S ≥ 264 U/mL) in 236 patients (47.2%). The median anti-S titers at 0–6 months, 7–12 months, 13–24 months, and 24 months after treatment completion were 0.4 U/mL, 3.8 U/mL, 270 U/mL, and 650 U/mL, respectively. Multivariate analysis showed that receiving the vaccine < 6 months since completing treatment, white blood cell count < 5050/μL, percentage of CD19 + cells < 10%, CD4 + cells < 27%, immunoglobulin (Ig) A < 195 mg/dL, IgM < 50 mg/dL, serum soluble interleukin 2 receptor > 600 U/mL, and presence of lymphoma cells in the peripheral blood were significantly correlated with anti-S < 264 U/mL. Lymphoma patients had variably impaired antibody response to the SARS-CoV-2 vaccine. We identified various factors to predict COVID-19 vaccine effectiveness in lymphoma patients that may help tailoring possible vaccine boosters. [ABSTRACT FROM AUTHOR]

We conducted a prospective, three-center, observational study in Japan to evaluate the prevalence of seropositivity and clinically protective titer after coronavirus disease 2019 vaccination in patients with plasma cell dyscrasia(PCD). Two-hundred sixty-nine patients with PCD [206 symptomatic multiple myeloma (MM)] were evaluated. Seropositivity was observed in 88.7% and a clinically protective titer in 38.3% of MM patients, both of which were significantly lower than those of healthy controls. Patients receiving anti-CD38 antibodies had much lower antibody titers, but antibody titers recovered in those who underwent a wash-out period before vaccine administration. Older age (≥65), anti-CD38 antibody administration, immunomodulatory drugs use, lymphopenia (<1000/μL), and lower polyclonal IgG (<550 mg/dL) had a negative impact for the sufficient antibody production according to multivariate analysis. Patients with clinically protective titer had a significantly higher number of CD19+ lymphocytes than those with lower antibody responses (114 vs. 35/μL, p = 0.016). Our results suggested that patients with PCD should be vaccinated, and that the ideal protocol is to temporarily interrupt anti-CD38 antibody therapy for a "wash-out" period of a few months, followed by a (booster) vaccine after the B-cells have recovery. [ABSTRACT FROM AUTHOR]

This study investigated the clinical significance of loss of spleen visualization (LSV) on whole-body diffusion-weighted imaging (WB-DWI) in patients with multiple myeloma (MM). The WB-DWI of 96 patients with newly diagnosed MM (NDMM) and 15 patients with smoldering MM (sMM) were retrospectively reviewed. LSV was observed in 56 patients with NDMM (58.3%) and 1 patient with sMM (6.7%). Patients with NDMM with LSV had a higher median infiltration of bone marrow plasma cells (80.0% vs. 50.0%, p < 0.001) and median total diffusion volume (median; 540.2 vs. 137.0 mL, p = 0.003) than patients without LSV. Patients with LSV had a lower spleen-to-spinal cord ratio (0.36 vs. 0.96, p < 0.001) and worse 2-year overall survival (OS) (84.6% vs. 100%, p = 0.032). Patients who did not recover spleen visualization during treatment had a worse prognosis, even when they obtained very good partial response (median progression-free survival: 13.2 months). Spleen histopathological findings revealed higher cellularity and diffuse myeloma cell infiltration in a patient with LSV and splenic amyloidosis without extramedullary hematopoiesis in a patient without LSV. Therefore, LSV indicates worse prognosis for patients with MM, even when the patient responds to treatment. Further studies are warranted to clarify the immunological role of spleen in MM. [ABSTRACT FROM AUTHOR]

In the surface treated inorganic particles with silane coupling agent (SCA), chemisorbed and physisorbed molecules are present in the treated layer. Increasing the amount of chemisorption by increasing the molecular weight of SCAs was investigated. Oligomers formed via self‐condensation during storage more than 10 days at room temperature for 3‐methacryloxypropyltrimethoxysilane‐treated silica particles. Monomeric SCA evaporates easily by heating. The oligomers restrict evaporation, and heating increases the chemisorption. The influence of molecular weight of SCA was investigated. In the case of amino group, the amount of chemisorbed was greater for aminoethylaminooctyltrimethoxysilane with high molecular weight than for 3‐aminopropyltriethoxysilane. For SCAs with hydrocarbon chains, the amount of chemisorption was lower for both low molecular weight molecules and decyltrimethoxysilane (D) with a high molecular weight. For fluorocarbon chains, the amount of chemisorption was lower for low molecular weight molecules, whereas it increased significantly by heating for high molecular weight type of 1H,1H,2H,2H‐heptadecafluorodecyltriethoxysilane (F). Wide‐angle X‐ray diffraction analysis of F‐treated silica particles showed that the fluorocarbon chains formed an ordered structure. There was no such indication for the D‐treated system. This ordered structure seems to influence on higher chemisorption for F‐treated systems. [ABSTRACT FROM AUTHOR]

CD38 expression on myeloma cells is a critical factor affecting the early response to the anti‐CD38 antibody daratumumab. However, factors affecting CD38 expression in untreated multiple myeloma are not fully elucidated. In this study, we found that CD38 expression was significantly lower in myeloma patients with the translocation t(11;14)‐associated immature plasma cell phenotype, and particularly in those expressing B–cell‐associated genes such as PAX5 and CD79A. CD138, a representative marker of plasmacytic differentiation, was also significantly lower in these patients, suggesting that CD38 expression may be associated with the differentiation and maturation stages of myeloma cells. Furthermore, the BCL2/BCL2L1 ratio, a response marker of the BCL2 inhibitor venetoclax, was significantly higher in patients with the immature phenotype expressing B–cell‐associated genes. The BCL2/BCL2L1 ratio and CD38 expression were significantly negatively correlated. We also confirmed that patients with translocation t(11;14) expressing B–cell‐associated genes were indeed less sensitive to daratumumab‐mediated direct cytotoxicity but highly sensitive to venetoclax treatment in ex vivo assays. Moreover, all‐trans‐retinoic acid, which enhances CD38 expression and induces cell differentiation in myeloma cells, reduced B‐cell marker expression and the BCL2/BCL2L1 ratio in myeloma cell lines, leading to reduced efficacy of venetoclax. Venetoclax specifically induces cell death in myeloma with t(11;14), although why patients with translocation t(11;14) show BCL2 dependence is unclear. These results suggest that BCL2 dependence, as well as CD38 expression, are deeply associated with the differentiation and maturation stages of myeloma cells. This study highlights the importance of examining t(11;14) and considering cell maturity in myeloma treatment strategies. [ABSTRACT FROM AUTHOR]

Objective: This study compared the tumor burden and prognostic impact of total diffusion volume (tDV) and total lesion glycolysis (TLG) in the same patients with newly diagnosed multiple myeloma (NDMM) simultaneously. We also examined the relationship between these imaging tumor volumes (TVs) and plasma cell (PC) TV in bone marrow (BM) specimens. Methods: We retrospectively reviewed the data of 63 patients with newly diagnosed multiple myeloma (NDMM) from April 2016 to March 2018. tDV was calculated from whole-body diffusion-weighted imaging and TLG was calculated from the average standard uptake value and the metabolic tumor volume, respectively. Cellularity of BM hematopoietic tissue and the percentage of BM PCs were used as a reference of PC volume in the BM. Results: The Spearman correlation coefficient between tDV and TLG was moderate (ɤs = 0.588, p < 0.001) when PET false-negative patients were excluded. There were positive correlations between the BM plasma cell volume (BMPCV) and the imaging TVs (ɤs = 0.505, vs. tDV; and 0.464, vs. TLG). Patients with high tDV and high TLG, as determined by the receiver operating characteristic curve, had worse survival; moreover, patients with both high tDV and high TLG showed the worst prognosis (median progression-free and overall survival: 13.2 and 28.9 months, respectively). Conclusions: Although tDV and TLG each reflected the total TV, in several cases, tDV and TLG were discrepant due to the biological features of each MM. It is important to use both modalities for complementary assessment of total tumor burden and biological characteristics in MM. Key Points: • Total diffusion volume (tDV) and total lesion glycolysis (TLG) reflect the total tumor volume and have prognostic value in patients with multiple myeloma (MM). • tDV and TLG could assess MM from different biological perspectives and should be considered for each patient individually. [ABSTRACT FROM AUTHOR]

Stringent complete response (sCR) is defined as a deeper response than complete response (CR) in multiple myeloma. Whether achieving sCR correlates with better survival remains controversial. We evaluated the outcomes in patients with intact immunoglobulin multiple myeloma (IIMM) and light chain multiple myeloma (LCMM) who achieved a very good partial response (VGPR) or better. Multicolour flow cytometry was used to assess the depth of response. LCMM patients with sCR had significantly lower measurable residual disease (MRD) levels than those with CR (median MRD: 7.9 × 10–4 vs. 5.6 × 10–5, P < 0.01). Nonetheless, no significant difference was observed in MRD levels across the responses in groups of patients with IIMM (VGPR vs. CR: 3.5 × 10–4 vs. 7.0 × 10–5, P = 0.07; CR vs. sCR: 7.0 × 10–5 vs. 5.4 × 10–5, P = 0.81. In accordance with MRD levels, the median overall survival of patients with sCR was significantly longer (sCR, CR, VGPR; not reached, 41 months, and 58 months, respectively; VGPR vs. CR, P = 0.83; CR vs. sCR, P = 0.04) in LCMM, but not in IIMM (sCR, CR, VGPR; not reached, 41 months, and not reached, respectively; VGPR vs. CR, P = 0.59; CR vs. sCR; P = 0.10). Our results show that sCR represents a deeper response that correlates with longer survival in patients with LCMM, but not IIMM. [ABSTRACT FROM AUTHOR]

Here, we describe the case of a male patient with Epstein-Barr virus post-transplantation lymphoproliferative disorder (EBV-PTLD), which developed 18 months after a haploidentical hematopoietic stem cell transplantation (haplo-HSCT) and the administration of post-transplant cyclophosphamide (PTCy). Of note, no anti-thymoglobulin was used in the entire clinical course. Prior to the onset of EBV-PTLD, the patient had pulmonary chronic graft-versus-host disease and was treated with prednisolone and tacrolimus. After stopping immunosuppressive therapy, he was diagnosed with EBV-positive infectious mononucleosis PTLD, and EBV-associated hemophagocytic syndrome; therefore, dexamethasone and rituximab monotherapies were administered. After four courses of rituximab, EBV-DNA was no longer detected in the peripheral blood, and the patient's laboratory data improved. Overall, this study highlights the need to predict the risk factors associated with the development of EBV-PTLD in transplanted patients after haplo-HSCT with PTCy. [ABSTRACT FROM AUTHOR]

IFLC levels just before the first daratumumab administration are as follows: Patient number (no.) 1, 68-4 mg/l; no. 2, 20-8 mg/dl; no. 3, 66-4 mg/l; no. 4, 447 mg/l; no. 5, 33900 mg/l; no. 6; 23-8 mg/l; no. 7, 598 mg/l; no. 8, 2435-3 mg/l; no. 9, 401 mg/l; no. 10, 283 mg/l; no. 11, 12 700 mg/l; no. 12, 664f0 mg/l. gl The most common adverse event (in four patients) was Grade 1/2 infusion reaction after the first dose. Pre-treatment CD38-positive regulatory T cells affect the durable response to daratumumab in relapsed/refractory multiple myeloma patients. In general, adverse events of daratumumab in patients with severe RI are similar to those in patients without RI. There has been considerable improvement in the treatment of multiple myeloma (MM), but severe renal impairment (RI) owing to cast nephropathy (CN) is still one of the frequent complications requiring prompt treatment. [Extracted from the article]

Thymoma is a common primary epithelial tumor in the anterior mediastinum; thymoma with polyclonal T-cell lymphocytosis has rarely been reported as a consequence of thymic T-cell overproduction [[1]]. In conclusion, the development of thymoma-associated polyclonal T-cell lymphocytosis and subsequently I BCR-ABL1 i -positive T-cell leukemia after thymoma treatment was presented for the first time. Although the relationship between the thymoma and T-cell lymphocytosis remains partially unclear, clonality and molecular assays in the context of both the thymoma and T-cell lymphocytosis may contribute to the development of new treatment strategies for refractory thymoma cases complicated by T-cell lymphocytosis. To clarify the relationship between thymoma and T-cell leukemia, pleural needle re-biopsy was performed; diffuse CD3-positive and TdT-negative T-cell infiltration was observed (Figure 1(g-j)). [Extracted from the article]

The prevention of chronic graft- versus -host disease (cGVHD) is important for recipients of hematopoietic stem-cell transplantation (HSCT). As one of the etiologies, the relationship between early T-cell recovery and subsequent cGVHD development has been the focus of attention. Recently, letermovir (LTV) was approved for preventing cytomegalovirus (CMV) reactivation in the early transplantation phase. Although CMV affects the immune reconstitution after HSCT, the impacts of LTV to prevent CMV reactivation on early T-cell recovery and cGVHD have not been fully investigated. We aimed to identify early T-cell recovery under LTV at day 30 in 15 and 33 recipients from matched related donors (MRDs) and haploidentical donors with post-transplant cyclophosphamide (PTCy-haplo), respectively. Early increases in the levels of total lymphocytes and HLA-DR+ activated T-cells at day 30 were observed under CMV prophylaxis by LTV only in PTCy-haplo recipients and not in MRD recipients. Moreover, PTCy-haplo recipients with LTV showed a significantly higher incidence of cGVHD, but not acute GVHD. Our observations suggest that an early increase in the levels of HLA-DR+ activated T-cells may be implicated in the development of cGVHD in patients treated with PTCy who received LTV. Further studies are warranted to validate our results and elucidate the detailed mechanisms of our new insights. [ABSTRACT FROM AUTHOR]

Background: IgD multiple myeloma (MM) is a rare subtype of MM and light chain deposition disease (LCDD) outside the kidney is also a rare and has scarcely been reported. We report herein the details of the first reported case of LCDD involving the kidney and liver co-occurring with IgD myeloma.Case Presentation: A 66-year-old female with IgD MM presented with rapidly progressive acute renal failure, ascites and pleural effusion. Immunofluorescent study of revealed the characteristic linear deposition of Igκ light chain along the glomerular and tubular basement membrane in kidney. Electron microscopy showed the powdery electron-dense deposits along the tubular and glomerular basement membrane consistent with the diagnosis of LCDD. Laser microdissection followed by mass spectrometry identified only Igκ light chain with more than 95% probability confirm the diagnosis of κ-LCDD but not heavy/light chain deposition disease. Liver biopsy with immunofluorescence study revealed the linear deposition of Igκ chain along the perisinusoidal space indicating the hepatic involvement of κ-LCDD. The patient was successfully treated with combination therapy with bortezomib, cyclophosphamide, dexamethasone, and daratumumab.Conclusions: This report emphasizes that prompt biopsy of affected organs and initiation of clone directed therapy led to the correct diagnosis and favorable outcome in patient with LCDD who has extrarenal involvement. [ABSTRACT FROM AUTHOR]

We evaluated the immune response to SARS-CoV-2 vaccination among dialysis patients and kidney transplant recipients, and compared them with a control group. Keywords: COVID-19; SARS-CoV-2; Vaccine; Hemodialysis; Peritoneal dialysis; Kidney transplantation EN COVID-19 SARS-CoV-2 Vaccine Hemodialysis Peritoneal dialysis Kidney transplantation 305 307 3 02/16/22 20220301 NES 220301 I To the Editor i Generally, immune response to vaccination is less robust in chronic kidney disease (CKD) patients than in healthy patients. After the second vaccination, anti-SARS-CoV-2-S (Spike) IgG levels were found to be positive (> 0.8 U/ml) in all 38 controls (100%), 77 of 78 HD patients (98.7%), and 26 of 27 PD patients (96.2%), but only 10 of 21 KTx recipients (47.6%). [Extracted from the article]

Summary: Metabolic tumour volume (MTV) and total lesion glycolysis (TLG) are positron‐emission tomography/computed tomography (PET/CT) variables for predicting multiple myeloma's (MM) outcome. We retrospectively investigated and compared the predictive value of MTV, TLG and high‐risk PET/CT variables in clinical practice in 185 patients with newly diagnosed symptomatic MM. High‐risk PET/CT findings were defined as the presence of at least one of the following: more than three focal lesions, maximum standardised uptake value (SUVmax) >4·2 and extramedullary disease. MTV was defined as the volume of myeloma lesions visualised on PET/CT with SUV ≥ 2·5. TLG was calculated as the sum of the product of the average SUV and MTV of all lesions. The mortality prediction optimal cut‐off values for MTV and TLG were 56·4 cm3 and 166·4 g, respectively. High‐burden MTV (≥56·4 cm3), TLG (≥166·4 g) and high‐risk PET/CT findings differed significantly in progression‐free survival (PFS) and overall survival (OS). High‐burden MTV and TLG findings also predicted survival outcomes in young patients (age <75 years) and patients with high‐risk chromosomal abnormalities. High‐burden MTV and TLG independently predicted both worse PFS and OS. Pre‐treatment MTV and TLG independently predicted survival outcomes in clinical practice and may be more useful than high‐risk PET/CT variables. [ABSTRACT FROM AUTHOR]

Background: Peripheral T‐cell lymphoma (PTCL) represents a heterogeneous and rare subgroup of aggressive lymphomas that generally demonstrate poor clinical outcomes with conventional treatment. Since the prognosis of PTCL is heterogeneous, more accurate risk assessment, and risk‐adapted treatment strategies are required. In this study, we examined whether interim positron emission tomography (iPET)‐computed tomography (PET/CT) results can be combined with baseline volume‐based metabolic assessments including total metabolic tumor volume (TMTV) and total lesion glycolysis (TLG) for risk stratification in PTCL. Methods: The data of 63 patients with nodal PTCL, who had analyzable baseline PET/CT and iPET, were retrospectively reviewed. We calculated the baseline TMTV and TLG values. All iPET responses were analyzed using the Deauville 5‐point scale. Results: On univariate analysis, a prognostic index for PTCL (PIT) higher than 2 (hazard ratio [HR], 2.03; P =.026), high TMTV (>389 cm3; HR, 2.24; P =.01), high TLG (>875; HR, 3.77; P =.0005), and positive iPET (HR, 2.18; P =.009) were significantly associated with poorer progression‐free survival (PFS). On multivariate analysis, only high TLG and positive iPET independently predicted both poorer overall survival (OS) and PFS. A model combining TLG and iPET showed that patients with low TLG and negative iPET had superior outcomes, with a 5‐year PFS and OS of 72% and 90%, respectively. Conversely, both 5‐year PFS and OS for those with high TLG and positive iPET were 0%. Conclusions: In summary, TLG combined with iPET predicted survival in PTCL more accurately. This information may help in the development of risk‐adapted treatment strategies for PTCL. [ABSTRACT FROM AUTHOR]

An efficient solution-based process for the fabrication of air-stable n-type thermoelectric films is reported. A nickel-ethenetetrathiolate complex was synthesized in dimethyl formamide and used to produce a dispersion in an aqueous medium. The film, fabricated via a simple drop-casting method with ethylene glycol, exhibited a remarkably high thermoelectric n-type power factor of 33 μW m−1 K−2. [ABSTRACT FROM AUTHOR]

Renal impairment (RI) is a common clinical presentation in patients with multiple myeloma (MM). Despite treatment with novel agents or management strategies that focus on the disease response, some patients develop irreversible RI. This study aimed to determine the influencing, clinical variables of renal reversibility in patients with RI treated with novel drugs. We analyzed 244 patients newly diagnosed with MM retrospectively. Maximum renal response was assessed according to the criteria for the definition of renal response proposed by the International Myeloma Working Group. Major renal response was defined as the occurrence of complete renal response or partial renal response. RI (a glomerular filtration rate < 50 mL/min/1.73 m2) was observed in 110 patients (45%). In total, 56 patients (51%) achieved a major renal response. Serum erythropoietin (EPO) levels >25 mIU/mL (P <.001) and a percentage of urinary albumin excretion ≤25% (P <.001) were both significant factors that influenced the occurrence of major renal responses. Both remained significant factors associated with renal reversibility in the multivariate analysis. Patients were assigned a score of 1 each for EPO >25 mIU/mL and urinary albumin ≤25%. The estimated 6‐month rates of major renal responses of patients with scores of 2, 1, and 0 were 78.6%, 30.6%, and 0%, respectively (P <.001). In conclusion, a serum EPO level >25 mIU/mL is an independent predictive factor for major renal response and may predict renal reversibility more accurately when urinary albumin level is congruently ≤25%. [ABSTRACT FROM AUTHOR]

Preparation of functional domains with a spacing of 10 nm is a benchmark set to fabricate next‐generation electronic devices. Organic–inorganic block copolymers form well‐ordered microphase separations with very small domain sizes. The design and preparation of a novel block copolymer consisting of syndiotactic polymethyl methacrylate (st‐PMMA) and polyhedral oligomeric silsesquioxane (POSS)‐functionalized polymethacrylate, designated as st‐PMMA‐b‐PMAPOSS, which can recognize functional molecules, are reported. The st‐PMMA segments form a helical structure and encapsulate C60 in the helical nanocavity, leading to the formation of an inclusion complex. Although the ordering of the domains is not high, C60 domains that are in a quasi‐equilibrium state, with about 10‐nm domain spacings, are generated using st‐PMMA‐b‐PMAPOSS that can recognize functional molecules. © 2019 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2019, 57, 2181–2189 [ABSTRACT FROM AUTHOR]

Daratumumab-based therapy has been shown to have significant clinical efficacy in phase 3 trials of patients with relapse or refractory multiple myeloma. Outside of clinical trials, however, clinical data on daratumumab remain limited. We reviewed medical records of patients who received daratumumab combination therapy at our institute (median age 74 years; median lines of prior therapy 4). The overall response rate was 69.4%, and 36.7% of patients achieved complete response (CR) or better. The proportion of patients who attained CR or better was significantly higher among patients with < 4 prior therapies than those with ≥ 4 (56.5% vs 19.2%, P = 0.009). Estimated median progression-free survival (PFS) was 12.4 months (95% confidence interval 8.6-not reached). The median PFS was significantly worse in patients who were refractory to bortezomib and lenalidomide and had received ≥ 4 lines of prior therapy. Twelve of 49 patients attained negative minimal residual disease. Common adverse events included hematological toxicities including neutropenia and lymphopenia; however, the rate of febrile neutropenia was low (3.8%). Infusion-related reactions occurred in 32.1% of patients, but were grade 1 or 2. Daratumumab combination therapies therefore appear to be effective and safe as salvage regimens in clinical practice, especially when used in the early phase. [ABSTRACT FROM AUTHOR]

Mantle cell lymphoma (MCL) comprises about 3% of all newly diagnosed non-Hodgkin's lymphoma cases and is thought to be incurable with conventional chemotherapy [[1]]. After noting dyspnea 2 months later, pleural effusion was detected, and MCL infiltration was confirmed by IHC and flow cytometry (FCM); however, the lymphoma cells were negative for SOX11 (Figure 1(D-F)). SOX11 is positive in 90% of MCL cases, and SOX11 negative MCL clinically indolent unrelated to CCND1 or -D2 expression, suggesting that SOX11 may determine disease severity [[8]]. [Extracted from the article]

The article describes the case of a 63-year-old woman who was diagnosed with sarcoid myopathy and then treated successfully with prednisolone.

Gray zone lymphoma (GZL) is a rare type of B-cell lymphoma characterized by features of both diffuse large B-cell lymphoma and classical Hodgkin lymphoma (cHL). The prognosis of GZL is poorer than that of cHL and mediastinal large B-cell lymphoma. However, an optimal treatment strategy for relapsed/refractory (R/R) GZL has not been established in the clinical setting. The current study reported an excellent clinical response in a patient with R/R CD30-positive GZL who received brentuximab vedotin (BV) maintenance after autologous stem cell transplantation (ASCT). Although the patient was resistant to prior treatments, BV maintenance after ASCT achieved long-term remission. Hence, BV was determined to be a safe and effective therapeutic option for CD30-positive R/R GZL. [ABSTRACT FROM AUTHOR]

The Hedgehog (Hh) pathway, containing the Patched (PTCH) and Smoothened (SMO) multitransmembrane proteins, is the main regulator of vertebrate embryonic development. A non-canonical Hh pathway was recently observed in numerous types of solid cancers and hematological malignancies. Although acute myeloid leukemia (AML) is a common and lethal myeloid malignancy, the chemotherapy for AML has not changed in the last three decades. The Hh pathway and other intracellular signaling pathways are important for the tumor cells' cycle or therapeutic resistance of AML cells. In this article, we will review the current trends in Hh pathway inhibitors for treating AML. [ABSTRACT FROM AUTHOR]