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Rituximab-based chemo-immunotherapy is currently the standard first-line treatment for Waldenstrom macroglobulinaemia (WM), while ibrutinib has emerged as an alternative. In the absence of randomised trials (RCTs) comparing these regimens, the optimal first-line treatment for WM remains uncertain. In this systematic review and meta-analysis, we sought to assess the efficacy and safety of first-line treatment regimens for WM. We searched key databases from January 2007 to March 2023, including phase II and III trials, including treatment-naïve WM patients treated with rituximab-based regimens or ibrutinib. Response rates, progression-free survival (PFS), overall survival (OS), and toxicities were evaluated. Four phase III and seven phase II trials were included among 736 unique records. Pooled response rates from all comparative and non-comparative trials were 46%, 33% and 26% for bendamustine rituximab (BR), bortezomib-dexamethasone, cyclophosphamide, rituximab (BDRC) and ibrutinib rituximab (IR), respectively. Two-year pooled PFS was 89%, 81% and 82% with BR, BDRC and IR, respectively. Neuropathy was more frequent with bortezomib, while haematologic and cardiac toxicities were more common with chemo-immunotherapy and ibrutinib-based regimens respectively. Our findings suggest that BR yields higher response rates than bortezomib or ibrutinib-based combinations. RCTs comparing BR against emerging therapies, including novel Bruton Tyrosine Kinase Inhibitors, are warranted., (© 2023. Springer Nature Limited.)

Cancers often overexpress multiple clinically relevant oncogenes, but it is not known if combinations of oncogenes in cellular subpopulations within a cancer influence clinical outcomes. Using quantitative multispectral imaging of the prognostically relevant oncogenes MYC, BCL2, and BCL6 in diffuse large B-cell lymphoma (DLBCL), we show that the percentage of cells with a unique combination MYC+BCL2+BCL6- (M+2+6-) consistently predicts survival across four independent cohorts (n = 449), an effect not observed with other combinations including M+2+6+. We show that the M+2+6- percentage can be mathematically derived from quantitative measurements of the individual oncogenes and correlates with survival in IHC (n = 316) and gene expression (n = 2,521) datasets. Comparative bulk/single-cell transcriptomic analyses of DLBCL samples and MYC/BCL2/BCL6-transformed primary B cells identify molecular features, including cyclin D2 and PI3K/AKT as candidate regulators of M+2+6- unfavorable biology. Similar analyses evaluating oncogenic combinations at single-cell resolution in other cancers may facilitate an understanding of cancer evolution and therapy resistance., Significance: Using single-cell-resolved multiplexed imaging, we show that selected subpopulations of cells expressing specific combinations of oncogenes influence clinical outcomes in lymphoma. We describe a probabilistic metric for the estimation of cellular oncogenic coexpression from IHC or bulk transcriptomes, with possible implications for prognostication and therapeutic target discovery in cancer. This article is highlighted in the In This Issue feature, p. 1027., (©2023 The Authors; Published by the American Association for Cancer Research.)

Background: There is currently no clinically validated biomarker to predict respiratory compromise in sudden acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Cycle threshold time (Ct), absolute lymphocyte count (AL) and neutrophil:lymphocyte ratio (NLR) have been previously evaluated for this purpose. We hypothesized that the combination of these parameters at presentation may be predictive of hypoxia (oxygen saturation <92%)., Methods: Data were collected on 118 patients with SARS-CoV-2 infection between May 2020 and April 2021. Demographics, clinical parameters and laboratory and radiological investigation results were recorded. Respiratory compromise (RC) was defined based on symptoms and signs, hypoxia and chest X-ray abnormalities., Results: RC occurred in 61 (51.7%) of patients. The Ct, AL and NLR at median day 3 of illness were significantly different between patients with and without RC (Ct, RC vs not: 19.46±2.64 vs 22.62±3.37, p=0.0001; AL, RC vs not: 531.49±289.09 vs 764.69±481.79, p=0.0001; NLR, RC vs not: 3.42±0.75 vs 2.59±0.55, p=0.0001). Receiver operating characteristics analysis showed that a Ct <19.9, AL <630.8×103/μL and NLR >3.12 at median day 3 of symptoms was predictive of hypoxia on day 7 of illness (area under the curve 0.805, sensitivity 96.7%, specificity 69.1%). The predictive value for the parameters combined was significantly superior to their individual predictive power., Conclusions: Ct, AL and NLR used in combination on day 3 of symptoms are predictive of hypoxia on day 7 of SARS-CoV-2 illness., (© The Author(s) 2021. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.)

Background: There is a paucity of predictive factors for early recovery from thrombocytopenia related to dengue. The immature platelet fraction (IPF%) is reflective of megakaryopoiesis and may correlate with recovery from dengue-related thrombocytopenia. Our objective was to assess the predictive value of IPF% on days 2 and 3 of illness for recovery from dengue-related thrombocytopenia., Methods: A prospective study was conducted among patients with dengue admitted to our institution (Nawaloka Hospital PLC) from December 2019 to October 2020. Dengue was diagnosed based on positive non-structural antigen 1 or IgM. IPF% data were extracted from the Sysmex-XN-1000 automated hematology analyzer. Clinical data were obtained from electronic medical records. Statistical analyses were performed using SPSS version 20., Results: We included 240 patients. An IPF% on day 2 of illness of >7.15% had a sensitivity of 80.0% and specificity of 70.4% for prediction of platelet recovery (defined as platelet count ≥60×109/L) on day 7 of illness. An IPF% of >7.25% on day 3 of illness had a sensitivity of 88.9% and specificity of 47.1% for predicting platelet recovery >60×109/L on day 8 of illness. The IPF% was significantly lower in patients with severe dengue. Platelet recovery was observed within 48 h after the peak IPF% was reached, regardless of severity., Conclusion: We propose that IPF% values on days 2 and 3 of illness are a promising predictive tool for early recovery from dengue-related thrombocytopenia., (© The Author(s) 2021. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.)

CNS prophylaxis is commonly used in Diffuse Large B-Cell Lymphoma (DLBCL) patients with risk features for CNS relapse. This systematic review and meta-analysis compares CNS relapse rates with and without CNS prophylaxis, for patients at intermediate to high CNS relapse risk. Studies reporting CNS relapse risk category and CNS outcomes with and without CNS prophylaxis for antiCD20-CHOP treated DLBCL patients were included. 10 studies with 3770 patients at intermediate to high CNS relapse risk were analyzed. No significant difference in the pooled Absolute Risk Difference (ARD 0.01, 95 % CI -0.01 to 0.02, P = 0.61) or Risk (RR 1.22, 95 % CI 0.81-1.83, P = 0.34) was noted in patients with and without CNS prophylaxis. There were also no differences within pre-specified subgroups of IV Methotrexate or IT chemotherapy. However, the quality of evidence supporting these observations was low. A meta-analysis of individual patient data will help evaluate the benefit of CNS prophylaxis strategies., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The role of central nervous system (CNS) prophylaxis with high-dose methotrexate (HDMTX) in DLBCL is controversial. In this retrospective study, we evaluated the efficacy of prophylactic HDMTX on isolated CNS relapse, concomitant CNS and systemic relapse, systemic relapse, and survival outcomes in 226 patients with newly diagnosed DLBCL and high-risk CNS International Prognostic Index (CNS-IPI) score treated with RCHOP. The three-year risk of isolated CNS relapse was significantly lower in patients who received HDMTX, at 3.1% compared to 14.6% (P = 0.032) in those who did not. However, neither concomitant CNS-systemic relapse rates, systemic relapse rates, nor three-year PFS and OS were significantly different between treatment groups in multivariable analysis. Among propensity score-matched patients (N = 102), HDMTX was also associated with significantly lower isolated CNS relapse rates (HR 0.06, 95% CI 0.004-0.946, P = 0.046). HDMTX was well tolerated with manageable toxicities when given at a dose of 3 g/m 2 by day 3 of RCHOP chemotherapy. Using propensity score matching and multivariable regression to yield treatment groups with well-balanced covariates, we showed that prophylactic HDMTX improved isolated CNS relapse rates but did not decrease concomitant CNS-systemic relapse rates, systemic relapse rates, or improve survival outcomes., (© 2021. The Author(s).)

Current prognostic scoring systems based on clinicopathologic variables are inadequate in predicting the survival and treatment response of extranodal natural killer/T-cell lymphoma (ENKTL) patients undergoing nonanthracyline-based treatment. We aimed to construct a classifier based on single-nucleotide polymorphisms (SNPs) for improving predictive accuracy and guiding clinical decision making. Data from 722 patients with ENKTL from international centers were analyzed. A 7-SNP-based classifier was constructed using LASSO Cox regression in the training cohort (n = 336) and further validated in the internal testing cohort (n = 144) and in 2 external validation cohorts (n = 142 and n = 100). The 7-SNP-based classifier showed good prognostic predictive efficacy in the training cohort and the 3 validation cohorts. Patients with high- and low-risk scores calculated by the classifier exhibited significantly different progression-free survival (PFS) and overall survival (OS) (all P < .001). The 7-SNP-based classifier was further proved to be an independent prognostic factor by multivariate analysis, and its predictive accuracy was significantly better than clinicopathological risk variables. Application of the 7-SNP-based classifier was not affected by sample types. Notably, chemotherapy combined with radiotherapy significantly improved PFS and OS vs radiotherapy alone in high-risk Ann Arbor stage I patients, whereas there was no statistical difference between the 2 therapeutic modalities among low-risk patients. A nomogram was constructed comprising the classifier and clinicopathological variables; it showed remarkably better predictive accuracy than either variable alone. The 7-SNP-based classifier is a complement to existing risk-stratification systems in ENKTL, which could have significant implications for clinical decision making for patients with ENKTL., (© 2021 by The American Society of Hematology.)

This study aims to evaluate the efficacy and safety of Daratumumab-based induction therapy (DBI) in newly diagnosed multiple myeloma (MM). We identified four eligible RCTs including 2735 patients. The primary outcomes of RCTs involving transplant eligible (TEMM) and non-transplant eligible MM (NTEMM) were stringent complete response (sCR) and progression-free survival (PFS) respectively. Meta-analysis was performed using random-effects models. DBI improved sCR rates for standard risk (SR) (OR 1.86, 95 % CI 1.41-2.46) but not HiR (high risk) (OR 0.78, 95 % CI 0.41-1.48) (interaction P = 0.01) TEMM. In NTEMM, DBI improved PFS in SR (HR 0.44, 95 % CI 0.35-0.55) but not HiR patients. (HR 0.81, 95 % CI 0.52-1.27) (interaction P = 0.02). In conclusion, while DBI is efficacious in SR patients, there is insufficient data to support a benefit in HiR-MM., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Multiple myeloma (MM) is an aggressive plasma cell neoplasm characterized by genomic heterogeneity. Superenhancers (SEs) are defined as large clusters of enhancers in close genomic proximity, which regulate genes for maintaining cellular identity and promote oncogenic transcription to which cancer cells highly addicted. Here, we analyzed cis-regulatory elements in MM samples with H3K27ac ChIP-seq, to identify novel SE-associated genes involved in the myeloma pathogenesis. SEs and their associated genes in cancerous tissue were compared with the control samples, and we found SE analysis alone uncovered cell-lineage-specific transcription factors and well-known oncogenes ST3GAL6 and ADM. Using a transcriptional CDK7 inhibitor, THZ1, coupled with H3K27ac ChlP-seq, we identified MAGI2 as a novel SE-associated gene of myeloma cells. Elevated MAGI2 was related to myelomagenesis with gradual increased expression from MGUS, SMM to newly diagnosed and relapsed MM. High prevalence of MAGI2 was also associated with poor survival of MM patients. Importantly, inhibition of the SE activity associated with MAGI2 decreased MAGI2 expression, inhibited cell growth and induced cell apoptosis. Mechanistically, we revealed that the oncogenic transcription factor, MAF, directly bound to the SE region and activated gene transcription. In summary, the discoveries of these acquired SEs-associated genes and the novel mechanism by which they are regulated provide new insights into MM biology and MAGI2-MAF-SE regulatory circuit offer potential novel targets for disease treatment.

Background: The early identification of patients at risk of severe dengue infection (DI) is critical to guide clinical management. Non-structural antigen 1 (NS-1), immunoglobulin M (IgM) and immunoglobulin G (IgG) are used routinely for the diagnosis of DI., Objectives: We sought to evaluate whether positivity for NS-1, IgM and IgG individually or together is predictive of severe complications of DI., Methods & Materials: A prospective study was conducted among patients with DI admitted to our institution between 2014 and 2019. DI was diagnosed based on a positive NS1 or IgM. IgG was also tested on all the patients. Clinical data was obtained from electronic medical records at NH. Statistical analyses were performed using SPSS version 20., Results: We collected data on 3504 patients. Patients who were positive for NS1, IgM and IgG (triple positive: TP) were more likely to develop severe DI (63.8 %) in comparison to those who were only NS1 positive (single positive: SP) (3.0 %) and patients with positive NS1 and IgM (double positive: DP) (7.5 %). [p = 0.001]. Regression analysis confirmed that TP status on admission was predictive of severe complications. (p < 0.01). Receiver operator characteristic curve (ROC) analysis showed (AUC: 84.8; sensitivity = 90.7 and specificity = 83.2) that TP status on admission is predictive of thrombocytopenia on day 5. The predictive power of TP status was superior to that of NS1 and IgG positivity., Conclusions: We propose that TP status on admission is a novel predictive factor for severe DI. Further studies are required to explore the biological basis for this finding., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: The treatment landscape for multiple myeloma (MM) has progressed significantly, and over the past decade, bortezomib-based induction therapy has been a standard of care. However, the practice of antibacterial prophylaxis during induction therapy has been diverse. The aim of our study is to evaluate the proportion of patients with febrile episodes and bacteremia among patients with MM, during the first 12 weeks of bortezomib-based induction therapy, without routine fluoroquinolone prophylaxis, but with routine Pneumocystis Carinii prophylaxis (mostly with trimethoprim-sulfamethoxazole), in a region with high fluoroquinolone resistance rate. Of note, these patients have direct access to health care facilities and timely supportive care., Patients and Methods: We evaluated newly diagnosed MM patients from 2014 to 2018 receiving bortezomib-based induction therapy for the proportion of patients who had febrile episodes and bacteremia in the first 12 weeks of bortezomib-based induction therapy. We also evaluated if there were factors associated with increased febrile episodes including age, absolute neutrophil count, creatinine clearance, M-band level at diagnosis, nadir platelet count, International Staging System, and Revised International Staging System., Results: Of the 108 evaluable patients, there were a total of 25 (23.1%) patients who had febrile episodes, and 1 (0.9%) patient who had bacteremia during the first 12 weeks of bortezomib-based induction therapy. All patients recovered well. No deaths were seen. Febrile episodes were associated with lower absolute neutrophil count (P = .036), renal impairment (P = .013), and ISS stage (P = .026)., Conclusion: The proportion of patients with significant bacterial infection during the first 12 weeks of bortezomib-based induction therapy without routine fluoroquinolone prophylaxis, but with routine Pneumocystis Carinii prophylaxis (mostly with trimethoprim-sulfamethoxazole), is low in a population with adequate access to health care facilities and timely supportive care., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: The Revised International Staging System (R-ISS) has been widely adopted to prognosticate multiple myeloma. As a result, the continued utility of conventional metaphase karyotyping has been called into question., Patients and Methods: A multi-center study for newly diagnosed patients with multiple myeloma who received novel agent(s) at induction was conducted. Conventional metaphase karyotype information was categorized based on ploidy. We evaluated the impact of ploidy on overall survival (OS) including multivariate analysis, taking into account the R-ISS stages, transplant status, age, and novel agent(s) used at induction. We also evaluated if it is possible to identify high-risk (HR) patients with conventional karyotyping when a fluorescence in situ hybridization analysis is not available. Results were validated in an independent cohort., Results: There were 308 patients evaluable. Ploidy significantly affected the OS of patients with R-ISS stage II, with non-hyperdiploid patients doing the worst. In the multivariate analysis, ploidy was significantly associated with OS. R-ISS stage II patients with or without non-hyperdiploid karyotype had significantly different survival. We replaced HR fluorescence in situ hybridization abnormalities with HR metaphase karyotypic abnormalities (non-hyperdiploid karyotype). When compared with R-ISS, there was a high level of concordance in HR patients identified using HR karyotypic abnormalities. These results were validated with an independent cohort of 375 patients., Conclusion: Conventional metaphase karyotyping is an independent prognostic factor even in the setting of R-ISS., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Venous thromboembolism (VTE) of the lower limbs is an important complication post total knee arthroplasty (TKA). Current guidelines recommend routine chemical prophylaxis to all patients undergoing this procedure but this is rarely done in Asia as it is believed that Asians have a lower risk of VTE. However, recent evidence suggests otherwise., Aims: We evaluated the incidence of DVT after TKA in a multi-ethnic Asian population with and without pharmacological prophylaxis, as well as the management and outcome of patients with post-operative DVTs., Methods: We conducted a retrospective study of consecutive patients who underwent TKA in our hospital from 1st January 2004 to 30th December 2014. All patients were on mechanical thromboprophylaxis via calf pumps after TKA with a postoperative day 3 to 5 doppler ultrasound (DUS) of bilateral lower limbs. 2258 (80.7%) patients did not receive additional chemoprophylaxis, while 540 (19.3%) received chemoprophylaxis on top of mechanical thromboprophylaxis. All patients who received chemoprophylaxis were administered the drug until they were ambulating, with a median administration duration of 6 days. Patients were followed up for a period of 3 months for recurrence of DVTs and 24 months for postoperative outcome scores., Results: Two thousand nine hundred seventy-eight patients had DUS of the lower limbs with 134 diagnosed with DVT giving an incidence of 4.5%. Six of these patients had concurrent PEs. There were 26 (19.4%) proximal DVTs and 108 (80.6%) distal DVTs. After 3 months of follow up, no additional VTE occurred. None of the DVTs or PEs progressed.All DVTs with accompanying PE were proximal. 102 out of 2200 patients (4.6%) without chemoprophylaxis developed DVT as compared to 32 out of 540 patients (5.9%) with chemoprophylaxis, which was not statistically significant ( p  = 0.13). 19 (0.8%) proximal and 83 (3.8%) distal DVT developed in the patient group without chemoprophylaxis while 4 (0.7%) proximal and 28 (5.2%) distal DVT developed in the patient group with ( p  = 0.62). Comparison of the incidence of PEs between the two groups, revealed a similar incidence with 5 out of 2200 patients (0.2%) without chemoprophylaxis developing PE as compared to 1 out of 540 patients (0.2%) with chemoprophylaxis ( p  = 0.87).In addition, patients with chemoprophylaxis showed an association with higher post-operative outcome scores such as post op 6 months SF36 (PCS), post op 12 months SF36 (PCS), post op 12 months SF36 (MCS), post op 24 months SF36 (MCS) and post op 24 months WOMAC., Conclusion: In one of the largest Asian studies specifically investigating the incidence of DVT after TKA, we found that the incidence is low at 4.5%. This is in contrast to recent studies that showed higher post-operative VTE rates similar to Western populations. In addition, patients who were administered chemoprophylaxis did not have a statistically significant difference in incidence of VTE although it did show a correlation with higher post-operative outcome scores which may indicate better function. This was seen in functional outcome scores such as post op 6 months SF36 (PCS), post op 12 months SF36 (PCS), post op 12 months SF36 (MCS), post op 24 months SF36 (MCS) and post op 24 months WOMAC., Competing Interests: Competing interestsThe authors declare that they have no competing interests.

Extranodal NK/T cell lymphoma, nasal type (ENKTL) is an aggressive malignancy with a dismal prognosis. Although L-asparaginase-based chemotherapy has resulted in improved response rates, relapse occurs in up to 50% of patients with disseminated disease. There is hence an urgent need for effective targeted therapy, especially for patients with relapsed or refractory disease. Novel insights gleaned from high-throughput molecular and genomic profiling studies in recent years have contributed significantly to the understanding of the molecular biology of ENKTL, which exemplifies many of the hallmarks of cancer. Deregulated pro-proliferative signaling pathways, such as the Janus-associated kinase/signal transducer and activator of transcription (JAK/STAT), platelet-derived growth factor (PDGF), Aurora kinase, MYC, and NF-κB, have been identified as potential therapeutic targets. The discovery of the non-canonical function of EZH2 as a pro-proliferative transcriptional co-activator has shed further light on the pathogenesis of ENKTL. Loss of key tumor suppressor genes located on chromosome 6q21 also plays an important role. The best-studied examples include PR domain zinc finger protein 1(PRDM1), protein tyrosine phosphatase kappa (PTPRK), and FOXO3. Promoter hypermethylation has been shown to result in the downregulation of other tumor suppressor genes in ENKTL, which may be potentially targeted through hypomethylating agents. Deregulation of apoptosis through p53 mutations and upregulation of the anti-apoptotic protein, survivin, may provide a further growth advantage to this tumor. A deranged DNA damage response as a result of the aberration of ataxia telangiectasia-related (ATR) kinases can lead to significant genomic instability and may contribute to chemoresistance of ENKTL. Recently, immune evasion has emerged as a critical pathway for survival in ENKTL and may be a consequence of HLA dysregulation or STAT3-driven upregulation of programmed cell death ligand 1 (PD-L1). Immunotherapy via inhibition of programmed cell death 1 (PD-1)/PD-L1 checkpoint signaling holds great promise as a novel therapeutic option. In this review, we present an overview of the key molecular and pathogenic pathways in ENKTL, organized using the framework of the "hallmarks of cancer" as described by Hanahan and Weinberg, with a focus on those with the greatest translational potential.

Background: High dose Cyclophosphamide (Cy) and Vinorelbine Cyclophosphamide (Vino-Cy) are stem cell (SC) mobilisation options for patients with multiple myeloma (MM). We present a comparison of mobilisation outcomes using these regimens., Patients and Methods: Vino-Cy patients received Vinorelbine 25 mg/m 2 on day 1, cyclophosphamide 1500 mg/m 2 on day 2, and pegylated GCSF on day 4 or GCSF 10 mcg/kg/day from day 4 onwards. Cy patients were given cyclophosphamide 4000 mg/m 2 on day 1 and GCSF10 mcg/kg/day from day 5 onwards. The target CD34 + SC collection was 5 × 10 6  per kg/BW., Results: 149 patients were included. SC collection was lower in the Vino-Cy group (8.20 × 10 6 /Kg BW) compared to the Cy group (11.43 × 10 6 /Kg BW), with adjusted geometric mean ratio of 0.59 (95% CI 0.41 to 0.86, p = 0.006). Time taken to achieve an adequate PB SC count was shorter for Vino-Cy (9 ± 1 day compared to 12 ± 2 days for Cy, adjusted absolute mean difference -3.95, 95% CI -4.85 to -3.06, P < .001). Mobilisation related toxicities (in particular, neutropaenic fever) were greater for Cy., Conclusion: Vino-Cy is a potential alternative to Cy given the need for effective mobilisation protocols with acceptable toxicity., (Copyright © 2018 King Faisal Specialist Hospital & Research Centre. Published by Elsevier Ltd. All rights reserved.)

DNA alterations have been extensively reported in multiple myeloma (MM); however, they cannot yet fully explain all the biological and molecular abnormalities in MM, which remains to this day an incurable disease with eventual emergence of refractory disease. Recent years have seen abnormalities at the RNA levels being reported to possess potential biological relevance in cancers. ADAR1-mediated A-to-I editing is an important posttranscriptional mechanism in human physiology, and the biological implication of its abnormality, especially at the global level, is underexplored in MM. In this study, we define the biological implications of A-to-I editing and how it contributes to MM pathogenesis. Here, we identified that the MM transcriptome is aberrantly hyperedited because of the overexpression of ADAR1. These events were associated with patients' survival independent of 1q21 amplifications and could affect patients' responsiveness to different treatment regimes. Our functional assays established ADAR1 to be oncogenic, driving cellular growth and proliferation in an editing-dependent manner. In addition, we identified NEIL1 (base-excision repair gene) as an essential and a ubiquitously edited ADAR1 target in MM. The recoded NEIL1 protein showed defective oxidative damage repair capacity and loss-of-function properties. Collectively, our data demonstrated that ADAR1-mediated A-to-I editing is both clinically and biologically relevant in MM. These data unraveled novel insights into MM molecular pathogenesis at the global RNA level., (© 2018 by The American Society of Hematology.)

Immunohistochemistry (IHC) provides clinically useful information on protein expression in cancer cells. However, quantification of colocalizing signals using conventional IHC and visual scores is challenging. Here we describe the application of quantitative immunofluorescence in angioimmunoblastic T-cell lymphoma (AITL), a peripheral T-cell lymphoma characterized by cellular heterogeneity that impedes IHC interpretation and quantification. A multiplexed immunofluorescence (IF) panel comprising T- and B-lymphocyte markers along with T-follicular helper (T FH ) markers was validated for appropriate cellular localization in sections of benign tonsillar tissue and tested in two samples of AITL, using a Vectra microscope for spectral imaging and InForm software for analysis. We measured the percentage positivity of the T FH markers, BCL6 and PD1, in AITL CD4-positive cells to be approximately 26% and 45%, with 12% coexpressing both markers. The pattern is similar to CD4 cells within the germinal center of normal tonsils and clearly distinct from extragerminal CD4 cells. This study demonstrates the feasibility of automated and quantitative imaging of a multiplexed panel of cellular markers in formalin-fixed, paraffin-embedded tissue sections of a cellularly heterogenous lymphoma. Multiplexed IF allows the simultaneous scoring of markers in malignant and immune cell populations and could potentially increase accuracy for establishment of diagnostic thresholds.

Background: The current standard of care for transplant-eligible myeloma patients is novel agent-based induction, followed by high-dose chemotherapy and autologous stem cell rescue. Chemo-mobilization of peripheral blood CD34 + stem cells (PBSCs) with pegylated filgrastim (pegfilgrastim), a sustained-duration formulation of filgrastim, has been used as an alternative to filgrastim in several studies involving heterogeneous cohorts of lymphoma and multiple myeloma (MM) patients and shown to be equivalent in PBSC yield and cost-effectiveness. The present study focused on the efficacy of pegfilgrastim in PBSC mobilization compared with filgrastim exclusively after novel agent-based induction in a homogeneous group of MM patients., Patients and Methods: We analyzed the data from 89 patients with MM treated at 2 transplant centers in Singapore who had received novel agent-based induction chemotherapy, PBSC mobilization with vinorelbine/cyclophosphamide, high-dose melphalan conditioning, and autologous stem cell rescue. Of the 89 patients, 61 were included in the pegfilgrastim group and 28 in the filgrastim group, with a similar median age and disease characteristics. PBSC harvesting was performed at a similar median time of 9.51 ± 0.84 days for both, and the peak peripheral blood CD34 + stem cell count was 19.90 × 10 6 /kg for pegfilgrastim and 32.50 × 10 6 /kg for filgrastim (95% confidence interval, -4.36 to 0.70 × 10 6 /kg)., Results: No significant difference was found in the median PBSC collection between the 2 groups (pegfilgrastim, 7.90 × 10 6 /kg vs. filgrastim, 10.10 × 10 6 /kg; P = .16)., Conclusion: The present study has demonstrated that a single dose of pegfilgrastim is comparable to filgrastim in terms of the timing and efficacy of PBSC harvest and could potentially spare the patient 6 days of filgrastim injections. In addition, ours is the first study to compare these growth factors using vinorelbine/cyclophosphamide as mobilization chemotherapy., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Introduction: Bone marrow aspirate and trephine (BMAT) biopsy is a commonly performed procedure in hematology-oncology practice. Although complications are uncommon, they can cause significant morbidity and mortality. Simulation models are an excellent tool to teach novice doctors basic procedural skills before performing the actual procedure on patients to improve patient safety and well-being., Methods: There are no commercial BMAT simulators, and this technical report describes the rationale, technical specifications, and construction of a low-cost, easily constructed, reusable BMAT simulator that reproduced the tactile properties of tissue layers for use as a teaching tool in our resident BMAT simulation course. Preliminary data of learner responses to the simulator were also collected., Results: From April 2013 to November 2013, 32 internal medicine residents underwent the BMAT simulation course. Eighteen (56%) completed the online survey, 11 residents with previous experience doing BMAT and 7 without experience. Despite the difference in operative experience, both experienced and novice residents all agreed or strongly agreed that the model aided their understanding of the BMAT procedure. All agreed or strongly agreed that this enhanced their knowledge of anatomy and 16 residents (89%) agreed or strongly agreed that this model was a realistic simulator., Conclusions: We present a novel, low-cost, easily constructed, realistic BMAT simulator for training novice doctors to perform BMAT.