Advancing Clinical Trials Endeavoring to Improve Odds Against Pancreatic Cancer

<h1>Advancing Clinical Trials Endeavoring to Improve Odds Against Pancreatic Cancer</h1>

Advancing Clinical Trials Endeavoring to Improve Odds Against Pancreatic Cancer

PALM BEACH, Florida, November 28, 2018 /PRNewswire/ — Positive results from clinical trials are headlining the current market for pancreatic cancer treatments in the active biotech industry. Pancreatic cancer is one of the deadliest cancers in the world, but…

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Quote: from: Mr Ken on December 14, 2018, 01:17:16 PM
Being on the transplant list is a privilege. Not everyone gets that privilege. I would not be so quick to blow it. Transplant centers are busy and they do not have time to play around with people. They will simply go on to the next person.
I have no idea what the experience is for a transplant but i have seen several people who had it done and within six weeks they were out and about like they nothing done…
You say you do not want to be on dialysis forever. If you do not have the surgery then you will be on dialysis forever. That answers that question / concern cut and dry.
Sounds like the person who put in the PD tube does not know what he /she is doing. There should be no pain with the tube in. Placement is very important and the person putting it in should know exactly where to go with its placement. Not everyone could do PD but if that option is available it does have advantages… Disadvantage is it is a longer process than hemo though it is done mostly at bed time
Mr Ken, you’re absolutely right. It’s a privilege that so many others deserve more than me, because at this point, I’m still very angry at all of this, and probably (definitely) in a state of denial. I’m angry that all of this happened to me, and even though I know that if my kidneys failing is anyone’s fault, it’s mine (I did not take care of my diabetes very well as a child,) I subconsciously look for anyone and everyone else to blame for this. I want to blame my nephrologist. I want to blame all the doctors and nurses in the hospital. I want to blame the dialysis center. I am so full of anger that all of this is happening to me that I don’t know what to do with it, and the only way I’ve been able to deal with it is to rationalize it. I think I am so blinded by this anger and this frustration and this depression/anxiety that I can’t see what a gift it is to have the opportunity to be able to have what so many people wish they could have so badly. If I could give it away to someone more deserving of it than myself, I would, but unfortunately, I don’t think it works that way. And that makes me feel awful.
Thanks everyone- your input and information is really helpful. (Even if I sound like I’m just complaining!)
Charlie B53- I do love reading, so I appreciate the book! I didn’t know you could pretty much eat anything on PD. I’ve been diabetic T1 since I was 10 or so, and have eaten very healthy since I was a child, but I do like a lot of things that I’m told we as kidney patients are not supposed to eat. (Potatoes are my FAVORITE. I love squash, pumpkin, oranges, avocado…) My levels were never bad, so I eat whatever I want. However, the dietitian at the dialysis center is constantly lecturing me about what I have to limit and what I have to eat lots of. (Granted, I’m 100lb soaking wet, and I don’t eat much to begin with, so I don’t know if I even eat enough to HAVE high levels of anything! Did your dialysis center tell you that you had more freedom to eat what you wanted when you were on PD, or was that something you just discovered on your own? Because I feel as though my clinic is always telling me I need to limit everything! Also, like you, my legs were swellling very badly. Not to the point where they were leaking, but they were bad. If I can take one good thing away from going on dialysis, it’s that my legs are back to a normal(ish) size.
UkranianTracksuit- Wow, I can completely relate. I feel like, since I have been diabetic since I was very young, I’m so used to health care routines, that having to maintain another chronic illness isn’t a big deal. The dialysis team slotted me for two weeks training for the manuals/cycler, and I picked up both in four. They were shocked at how quick I could do it, and I told them I’d been diabetic and messing with medical equipment for more years than I haven’t, this is a piece of cake. I think I’ve taken care of my medical issues for so long that I can’t even fathom what it’s like to NOT have anything to take care of. And I’m ABSOLUTELY gun shy. One of the things that was so horrifying to me when I was in the coma was that people were touching and doing things to me, and I didn’t know it. I’m the kind of person that would rather pop stitches and be sewn back up just to give myself a bath rather than have someone help me with it! As far as the scar goes, I am ABSOLUTELY not worried about the scar. I think they’re pretty cool. What I’m worried about is getting a weird belly. I’m VERY thin. As in, stick thin. I always have been. A scar I could care less about, but if the surgery is going to give me a belly, I’m gonna be wicked pissed. I actually do have a few neuropathy issues. Nothing huge, but I’m told they will clear up with the KPx. Thanks so much for your story, very helpful. I’m really glad to hear you’re doing well, that’s super encouraging!
Cupcake- Thanks! (It’s actually a Dodge Challenger, but I know what you meant. Thank you much! He’s my baby!) Would you say that book is worth a read? What do they recommend? PTSD sounds exactly like what I have, in addition to not being able to sleep due to the discomfort of the fluid being in me. I keep having dreams that I’m in the hospital again and I can hear the machines alarming, and I can’t tell if I’m dreaming or not. It feels exactly like it did when I woke up in the hospital, and I can’t tell if I’m dreaming, of if it’s happened again. It’s TERRIFYING. I hope you are recovering well from your transplant and are feeling like a new person!
MooseMom- You sound like my mom. Don’t take that the wrong way, I mean that as the highest of compliments. My mom is very sensible and wise! You are right. I don’t need to worry about choices I don’t need to make yet. and I DO do that. I take medication for my anxiety, but am looking for something that either works better, or something I can do, as far as behavior modification, to help. I’m even looking into CBD oil. (My PD nurse says she has a couple of patients that this works wonders for, but for different issues than mine.) Thanks for your help, and your support! It means a lot.
Simon Dog- Chicks absolutely dig scars. At least I do. It’s not the scar that I’m worried about, though! It’s getting that weird misshapen stomach! Do you know how hard I work for these abs?! … Ok, not very, but I don’t want them to go away! When I went to my consultation, they told me I would probably have to go home with the foley. Right then I was like NOPE NOPE NOPE. If protocol is 72 hours, I don’t know why they would tell me I would have to go home with it. Is it different with women than men? I’ve also heard that they keep the stent in for a very long time, and that the stent is very uncomfortable. Constant pressure up near your kidneys or something. A coworker had one, and he said he was miserable. Who knows if I’ll need the pain killers, though. For some reason I can handle straight up pain, but discomfort…. I’m an absolute grump. Glad you are doing well with your transplant!
Sahern- I am sorry you are having such a difficult time with receiving another transplant. I can’t imagine how frustrating that has to be. Like I said to Mr Ken, if only I could trade places with someone who truly wanted a tx, because I am certainly not ready! Hopefully something will change that will allow you another chance at a kidney. I am talking to my coordinator about prednisone, because I cannot take it. They gave me a list of medications they use, and prednisone is not on it. I took a small dose of it some time ago and it made me AWFUL sick, so I have to make sure to stress it to them that it isn’t an option for me. 22 years us a long time! Can I ask you, though, did knowing that the tx kidney had an expiration date have any bearing on getting a transplant or not? Do you feel kind of… betrayed that it failed on you? If that’s an intrusive question, I apologize. These are just things I think about. sometimes I think, why bother go through all of this, when I am just going to end up needing another transplant later on in life, and by then, I probably won’t be able to get one? And then I have to remind myself of why I’m doing it.
Thanks EVERYONE for taking the time to give me useful and helpful information and stories. I can’t tell you how much I appreciate each and every one of you!

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<h1>buckle and long billet on each end.</h1>

buckle and long billet on each end.

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New DARZALEX® (daratumumab) Phase 3 Study Shows Efficacy and Safety Data of Anti-CD38 Monoclonal Antibody in Patients with Newly Diagnosed Multiple Myeloma

New DARZALEX® (daratumumab) Phase 3 Study Shows Efficacy and Safety Data of Anti-CD38 Monoclonal Antibody in Patients with Newly Diagnosed Multiple Myeloma

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Takeda Receives Positive CHMP Opinion for ADCETRIS® (brentuximab vedotin) for the Treatment of Adult Patients with Previously Untreated CD30+ Stage IV Hodgkin Lymphoma in Combination with AVD

<h1>Takeda Receives Positive CHMP Opinion for ADCETRIS® (brentuximab vedotin) for the Treatment of Adult Patients with Previously Untreated CD30+ Stage IV Hodgkin Lymphoma in Combination with AVD</h1>

Takeda Receives Positive CHMP Opinion for ADCETRIS® (brentuximab vedotin) for the Treatment of Adult Patients with Previously Untreated CD30+ Stage IV Hodgkin Lymphoma in Combination with AVD

CAMBRIDGE, Mass. & OSAKA, Japan–(BUSINESS WIRE)–Takeda Pharmaceutical Company Limited (TSE: 4502) today announced that the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion for the extension o…

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Leukemia Lymphoma Myelodysplastic Syndromes (MDS) Myeloma Myeloproliferative Neoplasms (MPNs)

<h1>Leukemia Lymphoma Myelodysplastic Syndromes (MDS) Myeloma Myeloproliferative Neoplasms (MPNs)</h1>

Leukemia Lymphoma Myelodysplastic Syndromes (MDS) Myeloma Myeloproliferative Neoplasms (MPNs)

Πέμπτη, 13 Δεκεμβρίου 2018 Leukemia Lymphoma Myelodysplastic Syndromes (MDS) Myeloma Myeloproliferative Neoplasms (MPNs) http://www.bloodjournal.org/content/132/Suppl_1/1457 Nov 21st, 2018 – Background: Older patients (pts) with AML unfit for intense induction chemotherapy have a poor prognosis with a 5 year survival of <10%. 225Ac-lintuzumab is composed of 225Ac linked to a humanized anti-CD33 monoclonal antibody. Data were previously presented on the initial 13 pts who received 2.0 µCi/kg/dose on Days 1 and 8 (ASH, 2017, Abstract 616). Although that dose resulted in a high respon… http://www.bloodjournal.org/content/132/Suppl_1/2747 Nov 21st, 2018 – Introduction: Acute myeloid leukemia (AML) is a highly aggressive form of leukemia that results a poor survival outcome. Currently, diagnosis and prognosis are based on invasive single-point bone marrow biopsies (iliac crest). Although non-invasive positron emission tomography (PET) imaging has been developed for almost all solid tumors and some hematological malignancies, there is currently no… http://www.bloodjournal.org/content/132/Suppl_1/3895 Nov 21st, 2018 – Genome-wide transcriptome profiling detected an increased splicing alterations in MM and AML. While these malignancies are derived from different cell linages, their tumor cells acquire similar aberrant splicing (AbSp), mostly intron retentions. To delineate AbSp mechanism in MM/AML, we focused on PTBPs (1/2/3) that play a critical role in intron excision. We have previously reported deregulate… http://www.bloodjournal.org/content/132/Suppl_1/3126 Nov 21st, 2018 – INTRODUCTION: Cardiac involvement is common in both wild-type transthyretin (wATTR) and AL amyloidosis and these entities can have overlapping clinical features (Banypersad et al, JAHA 2012). Accurate diagnosis is vital given differences in spectrum of disease, management, and prognosis. We examined the presenting clinical features and survival outcome of patients diagnosed with cardiac wATTR a… http://www.bloodjournal.org/content/132/Suppl_1/3316 Nov 21st, 2018 – Background. Allogeneic bone marrow transplant (BMT) is a potentially curative approach in patients with refractory or high risk hematologic malignancies, such as acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). Prior to transplant, patients are prepared with non-specific, high dose chemotherapy alone or in combination with total body irradiation, which are associated with early… http://www.bloodjournal.org/content/132/Suppl_1/5428 Nov 21st, 2018 – Background Extracellular Vesicles (EVs) compose a naturally occurring, heterogeneous group of membrane-bound, nano-sized particles shed by all cells. Depending on cellular type, physiological state, and mode of secretion some harbor potent regenerative properties while others have the propensity to induce disease. Human bone marrow mesenchymal stem cell (MSC)-derived EVs harbor regenerative pot… http://www.bloodjournal.org/content/132/Suppl_1/5915 Nov 21st, 2018 – Introduction Survival outcomes for patients with lymphoid, myeloid and plasma cell malignancies, have improved with the use of oral small molecule inhibitory agents. Oral anti-cancer therapies are often administered continuously and can have significant side-effects, which can adversely impact adherence, quality of life (QoL) and survival outcomes. In order to improve tolerability, non-standard… http://www.bloodjournal.org/content/132/Suppl_1/5911 Nov 21st, 2018 – Background: Based on cohort studies and a limited number of prospective studies, physical activity (PA) can improve quality of life (QoL) in non-Hodgkin lymphoma (NHL), multiple myeloma (MM), and patients (pts) undergoing autologous stem cell transplant (ASCT). There are also data to suggest that survival (Pophali et al, ASH 2017) is improved with increased PA in NHL pts. After ASCT, it is know… http://www.bloodjournal.org/content/132/Suppl_1/5905 Nov 21st, 2018 – Aims: The objective of this study was to compare the efficacy and safety of pegfilgrastim in patients affected by heavily pretreated MM, treated with pomalidomide-dexamethasone, in order to determine whether a single subcutaneous injection of pegfilgrastim is as effective as daily injections of standard filgrastim, in terms of haematological toxicity, febrile neutropenic episodes, antibiotic us… http://www.bloodjournal.org/content/132/Suppl_1/5268 Nov 21st, 2018 – Acute myeloid leukemia (AML) is a genetically and phenotypically heterogeneous disorder. Precision therapies for AML have been developed that target specific driver mutations. The efficacies of these therapies are variable, making it critical to determine successful therapies prior to patient relapse. For patients achieving a first complete remission, minimum residual disease (MRD) is an import… http://www.bloodjournal.org/content/132/Suppl_1/5914 Nov 21st, 2018 – Introduction. Cancer-related cognitive impairment is a distressing symptom that affects numerous patients after cancer therapy, including those treated for hematological malignancy. The lack of effective interventions has driven interest in determining underlying mechanisms. Accumulating evidence in the context of solid tumours suggests inflammatory processes are involved in the development of … http://www.bloodjournal.org/content/132/Suppl_1/5903 Nov 21st, 2018 – Objective: To investigate the clinical features of 2nd hematological malignancies post to the initial cancer treatment. METHODS: A retrospective study was performed to analyze the available clinical data of 116 patients diagnosed with 2nd hematologic malignancies after treatment of various malignant tumors from June 1998 to June 2018 at Sun Yat-sen University cancer center. RESULTS: The charact… http://www.bloodjournal.org/content/132/Suppl_1/4098 Nov 21st, 2018 – Background: Resistance to apoptosis is one of the hallmarks in hematological neoplasms, most typically via dysregulation of the intrinsic mitochondrial pathway. The most important antiapoptotic/pro-survival proteins in this pathway are BCL2, BCL2L1 and MCL1. Molecules targeting each of these proteins are in various stages of preclinical and clinical development. The BCL2 inhibitor venetoclax is… http://www.bloodjournal.org/content/132/Suppl_1/1610 Nov 21st, 2018 – Introduction: As in multiple myeloma, Waldenström macroglobulinemia (WM) is preceded by an asymptomatic phase, mainly as monoclonal gammopathy of undetermined significance (MGUS) or by a smoldering WM (SWM) phase. It has recently been reported that patients with IgM MGUS have a higher risk of progression in comparison to those with other MGUS isotypes. Moreover, it has been described that if th… http://www.bloodjournal.org/content/132/Suppl_1/4178 Nov 21st, 2018 – While monoclonal antibodies (MoAb) are already well established for the treatment of B cell-derived malignancies and usually show a good safety profile, not all patients benefit and relapses may be a problem. In order to identify novel surface structures suitable for antibody-based therapies and to improve killing mechanisms, 'EBU-141 Tetra' was developed. The parental MoAb EBU-141 is of mouse … http://www.bloodjournal.org/content/132/Suppl_1/5320 Nov 21st, 2018 – Background: We recently reported that the International Prognostic Scoring System for Waldenström macroglobulinemia (ISSWM), which is widely used to predict the prognosis of WM patients, might not be applicable to Japanese patients, and evidence of pleural effusion might be a novel adverse prognostic factor for symptomatic WM in the rituximab era. Further studies with a large number of patients… http://www.bloodjournal.org/content/132/Suppl_1/4604 Nov 21st, 2018 – BACKGROUND: High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is now standard of care for newly diagnosed patients with multiple myeloma (MM) and is used for some forms of non-Hodgkin lymphoma, providing improved outcomes. ASCT has been associated with a high incidence of engraftment syndrome (ES), which clinically presents as skin rashes, diarrhea, non-infectious f… http://www.bloodjournal.org/content/132/Suppl_1/5383 Nov 21st, 2018 – Histone deacetylase 6 (HDAC6) is a protein modifier that is an increasingly attractive pharmacological target. Interestingly, the observation that the HDAC6 knock-out mouse is not lethal, in contrast to those undergoing complete loss of class I, II and III HDACs, suggests that specific HDAC6 inhibitors may be better tolerated than pan-HDAC inhibitors or drugs that target the other HDAC classes…. http://www.bloodjournal.org/content/132/Suppl_1/5300 Nov 21st, 2018 – Primary effusion lymphoma (PEL) is a rare, aggressive form of B-cell lymphoma. With a median survival time of around six months the prognosis for PEL patients is poor. Therefore, there is a medical need for novel therapeutic strategies. We performed expression array analysis to find potential targets for antibody-based therapy. Unsupervised clustering analysis revealed that PEL cell lines group… http://www.bloodjournal.org/content/132/Suppl_1/4382 Nov 21st, 2018 – Introduction Myelodysplastic syndromes (MDS) are heterogeneous myeloid disorders characterized by dysplasia in one or more hematopoietic cell lines, peripheral cytopenia(s), and distinct cytogenetic abnormalities. The presence of certain cytogenetic abnormalities [e.g. 7/del(7q), -5/del(5q), 13/del(13q), i(17p)], in the setting of unexplained persistent cytopenia, has been considered presumptiv… http://www.bloodjournal.org/content/132/Suppl_1/1908 Nov 21st, 2018 – A proliferation-inducing ligand (APRIL) is produced by multiple accessory and myeloid cells in the bone marrow niche. Through binding to its receptors B-cell maturation antigen (BCMA) and transmembrane activator and CAML interactor (TACI), APRIL plays an important role in the development and maintenance of cells derived from the B cell lineage. Both APRIL and its receptors have been identified … http://www.bloodjournal.org/content/132/Suppl_1/3039 Nov 21st, 2018 – Background: Polycythemia vera (PV) and essential thrombocythemia (ET) are myeloproliferative neoplasms (MPN) that can progress to post-PV (PPV) myelofibrosis (MF) and post-ET (PET) MF, from now on referred to as secondary myelofibrosis (SMF). Recent studies have shown an increased risk of developing solid tumors (ST) in MPN patients in comparison to the general population. Information on develo… http://www.bloodjournal.org/content/132/Suppl_1/4483 Nov 21st, 2018 – Purpose : This study evaluated the prognostic role of 18F-FDG PET/CT at baseline in patients with newly diagnosed multiple myeloa (MM) and evaluated the prognostic relevance of 18F-FDG PET/CT for each stage according to the Revised International Staging System (R-ISS). Method: We retrospectively analyzed the records of 167 patients with newly diagnosed MM. 18F-FDG PET/CT was performed prior to … http://www.bloodjournal.org/content/132/Suppl_1/1975 Nov 21st, 2018 – Introduction: The median progression free survival (PFS) and overall survival (OS) of multiple myeloma (MM) patients have been prolonged due to novel agents combined with ASCT but the median OS in MM is still 7-8 years. Thus, the feasibility of new combinations and dosing of available agents must be investigated. The first proteasome inhibitor (PI), bortezomib (B), combined with elotuzumab and … http://www.bloodjournal.org/content/132/Suppl_1/3254 Nov 21st, 2018 – Introduction: In the ASPIRE and ENDEAVOR trials, multiple myeloma (MM) patients treated with carfilzomib (K) had significantly improved progression‐free survival and overall survival compared with standard of care. The incidence of all-grade adverse cardiovascular events (ACVE) was 26.6% and 24.5% in the K treated groups in ASPIRE and ENDEAVOR respectively. The atherosclerotic cardiovascular di… http://www.bloodjournal.org/content/132/Suppl_1/1981 Nov 21st, 2018 – Introduction: Patients (pts) with newly diagnosed multiple myeloma (MM) are commonly treated with the standard of care combination of lenalidomide (Len), bortezomib (Bz), and dexamethasone (Dex), also known as RVD. A recent randomized phase 3 study found that the addition of Bz to Len and Dex significantly increased median overall and progression free survival as well as response rate (Durie et… http://www.bloodjournal.org/content/132/Suppl_1/3203 Nov 21st, 2018 – Background: The oncogenic drivers and progression factors in multiple myeloma (MM) are heterogeneous and difficult to target therapeutically. As a result, personalized medicine approaches have not yet been realized. However, clinical availability of numerous anti-myeloma drugs and readily obtainable bone marrow (BM) aspirates raises the possibility to benefit patients by profiling the drug sens… http://www.bloodjournal.org/content/132/Suppl_1/1008 Nov 21st, 2018 – Multiple myeloma is the second most common hematological malignancy in the U.S. with an estimated 30,700 new diagnoses in 2018. It is a clonal disease of plasma cells that, despite recent therapeutic advances, remains incurable. Myeloma cells retain numerous characteristics of normal plasma cells including reliance on survival signals in the bone marrow for long term viability. However, maligna… http://www.bloodjournal.org/content/132/Suppl_1/56 Nov 21st, 2018 – Introduction: Multiple Myeloma (MM) is consistently preceded by pre-malignant asymptomatic monoclonal gammopathies (AMG). To date, our understanding of the pathogenesis of progression to MM remains incomplete. Genetic analyses of AMG cells compared to MM-derived plasma cells (PCs) have found few differences, suggesting that progression may be mediated in part by tumour-extrinsic mechanisms. To … http://www.bloodjournal.org/content/132/Suppl_1/799 Nov 21st, 2018 – Introduction: Triplet regimens incorporating a proteasome inhibitor and immunomodulatory drug are standards of care for the treatment of patients with newly diagnosed multiple myeloma (NDMM). The combinations of carfilzomib-lenalidomide-dexamethasone (KRd) and bortezomib-lenalidomide-dexamethasone (VRd) are recommended regimens for the treatment of NDMM by the National Comprehensive Care Networ… http://www.bloodjournal.org/content/132/Suppl_1/3308 Nov 21st, 2018 – Introduction The first two trials to test the activity of daratumumab (DARA) in relapsed/refractory multiple myeloma (MM) were GEN501 (DARA monotherapy) and GEN503 (DARA in combination with lenalidomide [LEN] and dexamethasone [DEX]). GEN501 enrolled 104 participants from 2008 and GEN503 enrolled 45 participants from 2012. GEN501 has been completed; GEN503 is active but has finished accrual. We… http://www.bloodjournal.org/content/132/Suppl_1/406 Nov 21st, 2018 – Introduction: Multiple myeloma, a malignant proliferation of differentiated plasma cells, is the second most commonly diagnosed hematologic malignancy, and the number of cases may grow by almost 60% between 2010 and 2030. Recent therapeutic advances, including the use of proteasome inhibitors (PIs), have contributed to a doubling of the median overall survival in myeloma patients. This has been… http://www.bloodjournal.org/content/132/Suppl_1/110 Nov 21st, 2018 – Introduction: The study of multiple myeloma (MM) genomics has identified many abnormalities that are associated with poor progression free survival (PFS) and overall survival (OS). Copy number abnormalities have been extensively studied in many datasets with long follow-up, however, the prognostic impact of mutations have not been extensively studied and available datasets have generally had a … http://www.bloodjournal.org/content/132/Suppl_1/473 Nov 21st, 2018 – Background Ixazomib, the first oral proteasome inhibitor, is approved in combination with lenalidomide-dexamethasone (Rd) for pts with MM who have received at least 1 prior therapy. Approval was based on the phase 3 TOURMALINE-MM1 study (NCT01564537), in which ixazomib showed a consistent progression-free survival (PFS) benefit in combination with Rd (IRd) in the ITT population as well as in pr… http://www.bloodjournal.org/content/132/Suppl_1/1912 Nov 21st, 2018 – Background The survival of patients with multiple myeloma (MM) has improved significantly over the past two decades with the introduction of novel treatment agents. However, MM is still largely considered an incurable malignancy with a relapsing-remitting course. A follow-up of at least 10 years from active disease is required to determine whether a plateau in progression-free survival has been… http://www.bloodjournal.org/content/132/Suppl_1/3261 Nov 21st, 2018 – Chimeric Antigen Receptors (CARs) are engineered transmembrane proteins consisting of an antibody-derived antigen recognition domain linked to intracellular cell signaling domains. CAR engineered autologous T cells have been successful in the treatment of a variety of hematologic malignancies. However, several major caveats, including lack of universal donors, long manufacturing times, and abse… http://www.bloodjournal.org/content/132/Suppl_1/187 Nov 21st, 2018 – INTRODUCTION. Systemic light chain amyloidosis (AL) is caused by accumulation of plasma cells producing misfolded monoclonal light chains depositing as amyloid fibrils in different organs, most frequently heart and kidney. AIM of our study is first assessing the molecular characteristics of malignant plasma cells from AL-patients in relation to those from MGUS, asymptomatic, and symptomatic mye… http://www.bloodjournal.org/content/132/Suppl_1/3224 Nov 21st, 2018 – Daratumumab targets the cell surface protein CD38 and is the only FDA approved monoclonal antibody that has demonstrated single agent efficacy in relapsed refractory myeloma. CD38 is broadly expressed in the immune system, and its high expression on multiple myeloma cells allows for effective targeting by daratumumab. Daratumumab induces myeloma cell death through multiple mechanisms, including… http://www.bloodjournal.org/content/132/Suppl_1/2024 Nov 21st, 2018 – Introduction: Multiple Myeloma (MM) is a hematologic cancer caused by malignant plasma cells. Daratumumab is an immunoglobin G1 kappa human monoclonal antibody that targets CD38 antigen which is a cell surface glycoprotein highly expressed on myeloma cells. Daratumumab is FDA approved as monotherapy and in combination with dexamethasone and lenalidomide, bortezomib or pomalidomide in relapsed/r… http://www.bloodjournal.org/content/132/Suppl_1/152 Nov 21st, 2018 – Background: Dara, a human IgGκ monoclonal antibody that targets CD38, is approved in combination with bortezomib, melphalan, and prednisone (VMP) for the treatment of newly diagnosed (ND) MM. CyBorD is another commonly used immunomodulatory drug-sparing regimen for MM. We evaluated the safety and efficacy of dara-CyBorD and administered the first dara infusion as a split dose over 2 days in pts… http://www.bloodjournal.org/content/132/Suppl_1/1942 Nov 21st, 2018 – Multiple myeloma (MM) is an incurable cancer of plasma cells (PC), with a median survival of 5-7 years. Osteolytic bone disease and skeletal complications occur in more than 80% of MM patients and significantly contribute to the morbidity and mortality of these patients. Glycosphingolipid (GSL), an essential constituent of the outer leaflet of the cellular membrane, is altered in MM and other h… http://www.bloodjournal.org/content/132/Suppl_1/4477 Nov 21st, 2018 – Background:In 2015, the International Myeloma Working Group (IMWG) developed the Revised International Staging System (R-ISS), which combined the ISS with the status of high-risk cytogenetic abnormalities (CAs) and serum levels of lactate dehydrogenase to identify three multiple myeloma (MM) entities with clearly different outcomes. However, although MM tends to affect older adults, the origina… http://www.bloodjournal.org/content/132/Suppl_1/4489 Nov 21st, 2018 – Introduction Chromosome instability (CIN) is a driver of copy number aberrations (CNAs) in cancer, and is a major factor leading to tumor heterogeneity and resistance to therapy. By definition, CIN is an increased rate or ongoing acquisition and accumulation of CNAs and not simply the existence of structurally and numerically abnormal aneuploid clones. In multiple myeloma (MM), the most common … http://www.bloodjournal.org/content/132/Suppl_1/802 Nov 21st, 2018 – Background The benefit of single agent maintenance is largely established from studies in newly diagnosed patients, while extended therapy combination regimens are more commonly used in relapsed disease. Extended therapy on combination protocols may be limited by tolerability and safety, as well as patient compliance. Fixed duration combination treatment followed by single agent maintenance may… http://www.bloodjournal.org/content/132/Suppl_1/58 Nov 21st, 2018 – Background Loss of immune surveillance is thought to contribute to disease progression and treatment resistance in a range of malignancies including multiple myeloma (MM). Understanding the degree and pattern of immunological abnormality present within the bone marrow microenvironment at the time of MM diagnosis is vital if we are to utilize emerging immunological therapeutic strategies success… http://www.bloodjournal.org/content/132/Suppl_1/3173 Nov 21st, 2018 – The B-cell maturation antigen (BCMA) is selectively expressed by cells of the B-lineage, including multiple myeloma (MM) cells, and constitutes a promising target for immunotherapeutic approaches. At present, BCMA is being evaluated as target for immunotherapeutic approaches, such as CAR T cells and bispecific antibodies, which have demonstrated promising results in phase I clinical trials. The… http://www.bloodjournal.org/content/132/Suppl_1/3209 Nov 21st, 2018 – A proliferation inducing ligand (APRIL) is a natural ligand with higher affinity than BAFF for both B cell maturation antigen (BCMA) and transmembrane activator and CAML interactor (TACI), which are overexpressed on multiple myeloma (MM) cells. APRIL, which is abundantly secreted by myeloma-supporting osteoclasts and macrophages, promotes MM cell progression in vivo and further induces regulato… http://www.bloodjournal.org/content/132/Suppl_1/3280 Nov 21st, 2018 – Background: The depth of response both pre- and post- autologous stem cell transplant (ASCT) has been shown to correlate with clinical outcome for myeloma patients. Maximizing response can be achieved by modifying therapy either at induction, transplant, consolidation or during maintenance. In this work we explore the role of pre-transplant induction therapy in the UK NCRI Myeloma XI clinical t… http://www.bloodjournal.org/content/132/Suppl_1/1916 Nov 21st, 2018 – Introduction: Despite recent advances in treatment, multiple myeloma (MM) is still considered incurable. Several novel therapies with different mechanisms of action are currently being studied for use in MM. These include targeted therapies such as pathway inhibitors and BCL-2 homology domain 3 (BH3) mimetics. BH3-mimetics overcome apoptosis resistance by binding and inhibiting select pro-survi… http://www.bloodjournal.org/content/132/Suppl_1/1984 Nov 21st, 2018 – Background: Carfilzomib, a second generation proteosome inhibitor, is effective in the treatment of relapsed and refractory multiple myeloma (RRMM). Recent phase II and phase III trials have demonstrated the efficacy of weekly dosing strategies. The aim of this study was to examine high dose once weekly carfilzomib in combination with weekly dexamethasone and low dose weekly cyclophosphamide (w… http://www.bloodjournal.org/content/132/Suppl_1/3287 Nov 21st, 2018 – Background: Multiple myeloma (MM) is a disease of older adults with a median age of onset of 70 years. Approximately 20% of the incident cases are diagnosed in patients 85 years and older. There is significant heterogeneity among older adults with regards to the tolerability of myeloma directed therapy. In newly diagnosed transplant ineligible patients with MM, available evidence indicates that… http://www.bloodjournal.org/content/132/Suppl_1/1882 Nov 21st, 2018 – Introduction The multiple myeloma (MM) tumor microenvironment (TME) strongly influences patient outcomes as evidenced by the success of immunomodulatory therapies. To develop precision immunotherapeutic approaches, it is essential to identify and enumerate TME cell types and understand their dynamics. Methods We estimated the population of immune and other non-tumor cell types during the course… http://www.bloodjournal.org/content/132/Suppl_1/959 Nov 21st, 2018 – Introduction: BCMA targeted CAR T cell therapy has shown promising results in patients with relapsed/refractory multiple myeloma (MM). Herein, we report on the safety and efficacy of MCARH171, a second generation, human derived BCMA targeted autologous 4-1BB containing CAR T cell therapy, including a truncated epidermal growth factor receptor safety system (Smith EL. Mol Ther 2018). Methods: Th… http://www.bloodjournal.org/content/132/Suppl_1/1891 Nov 21st, 2018 – Introduction: Drivers that underlie the progression of MGUS (Monoclonal gammopathy of undetermined significance) to multiple myeloma are yet largely unknown. Because of the vast number of potential players, these drivers may not necessarily aimed to transform plasma cell or the bone marrow niche, but rather remodel a supporting microenvironment. Metabolic alterations have been linked to cancer … http://www.bloodjournal.org/content/132/Suppl_1/1011 Nov 21st, 2018 – Background: Despite advances in the treatment of multiple myeloma (MM) almost all patients relapse and high risk features continue to portend a short median survival. The adoptive transfer of B-Cell Maturation Antigen (BCMA) chimeric antigen receptor (CAR) T cells is demonstrating early promise in MM, but the durability of response has not been established. The infusion of genetically modified … http://www.bloodjournal.org/content/132/Suppl_1/3223 Nov 21st, 2018 – Background: Histone deacetylases (HDACs) are potential novel therapeutic targets for multiple myeloma (MM) treatment. A pan-HDAC inhibitor (HDI) panobinostat was approved by the FDA in 2015 to treat relapsed/refractory MM patients, and several other HDIs are currently in different phases of clinical trials. However, unfavorable side-effects of the non-selective HDIs necessitate further dissecti… http://www.bloodjournal.org/content/132/Suppl_1/3222 Nov 21st, 2018 – Introduction: MM is characterized by the accumulation of aberrant BM plasma cells (aPCs). The use of novel agents for anti-MM treatment has enabled the achievement of deeper responses and prolonged progression free survival (PFS) and overall survival (OS). These advances have created the need for sensitive means to detect residual PCs. MFC allows aPC detection with high sensitivity and is used … http://www.bloodjournal.org/content/132/Suppl_1/1968 Nov 21st, 2018 – Advances in the management of multiple myeloma (MM) led to a significant prolongation of overall survival (OS), mainly of the younger patients; almost 10% of them experience more than 10-year OS. Although long progression-free survival (PFS) correlates with extended OS, there is very limited information for the characteristics of patients who manage to be progression-free for a long period afte… http://www.bloodjournal.org/content/132/Suppl_1/4461 Nov 21st, 2018 – INTRODUCTION: Progression from precursor states, MGUS and smoldering multiple myeloma (SMM), to multiple myeloma (MM) is dependent upon adaptive and innate immune contexture shaped by cross-talk between malignant plasma cells and bone marrow (BM) milieu. The complexity and heterogeneity of interactions between the immune system and plasma cells in BM triggers alterations in peripheral blood (PB… http://www.bloodjournal.org/content/132/Suppl_1/3210 Nov 21st, 2018 – Introduction Regardless of significant advances in the therapy of multiple myeloma (MM) there is still a lack of effective treatment options for patients with high-risk disease. In this context, we recently developed a network of high-risk disease based on more than 30 000 genomic and clinical variables from 645 patients of the CoMMpass dataset (Gruber et al., ASH 2016). Validation of these fin… http://www.bloodjournal.org/content/132/Suppl_1/4496 Nov 21st, 2018 – Introduction Monoclonal gammopathy of undetermined significance (MGUS) is a prevalent hematological condition among elderly population with incidence rates of 3% and 5% over the age of 50 and 70 years, respectively (Kyle et al., 2018). It is considered a premalignant state of multiple myeloma with a risk of progression of 1% per year. It has also been shown that MGUS patients have a shorter sur… http://www.bloodjournal.org/content/132/Suppl_1/1898 Nov 21st, 2018 – Introduction: Gene fusions are the result of genomic rearrangements that create hybrid protein products or bring the regulatory elements of one gene into close proximity of another. Fusions often dysregulate gene function or expression through oncogene overexpression or tumor suppressor underexpression (Gao, Liang, Foltz, et al. Cell Rep 2018). Some fusions such as EML4–ALK in lung adenocarcin… http://www.bloodjournal.org/content/132/Suppl_1/4458 Nov 21st, 2018 – Monoclonal gammopathies, including multiple myeloma (MM), represent a group of plasma cell (PC) disorders that comprise of mostly incurable hematopoietic malignancies with an increasing incidence in the US. Previous epidemiological studies demonstrated a 2-3 fold higher incidence of monoclonal gammopathy of undetermined significance (MGUS) and a similarly higher incidence of MM along with a ~4-… http://www.bloodjournal.org/content/132/Suppl_1/3279 Nov 21st, 2018 – Background Data from the Australian and New Zealand (ANZ) Myeloma and Related Diseases Registry (MRDR) shows that 85% of newly diagnosed multiple myeloma (NDMM) patients (pts) in ANZ are induced with bortezomib(V)-containing therapies, predominantly triplets of V-cyclophosphamide-dexamethasone (VCD). Of these, 15% demonstrate treatment failure – either a sub-optimal response ( http://www.bloodjournal.org/content/132/Suppl_1/3197 Nov 21st, 2018 – CRISPR/Cas9-based gene editing has become a powerful tool for loss-of-function (LOF) studies and has allowed us to systematically interrogate the function of genes regulating the survival and proliferation of multiple myeloma (MM) cells in vitro, in vivo and in the context of treatment resistance (e.g. De Matos Simoes et al., Shirasaki et al., and Gandolfi et al. ASH 2017). We reasoned, however… http://www.bloodjournal.org/content/132/Suppl_1/595 Nov 21st, 2018 – Background: Isatuximab (ISA) is an anti-CD38 monoclonal antibody with multiple modes of action for killing tumor cells via direct tumor targeting and immune cell engagement. ISA, combined with bortezomib, has demonstrated strong potentiation in a multiple myeloma (MM) xenograft model (Clin Cancer Res 2014:20:4754). This supported evaluation of ISA with bortezomib combinations in pts with newly … http://www.bloodjournal.org/content/132/Suppl_1/3170 Nov 21st, 2018 – Background: Since survival in AL mainly depends on the extent of organ involvement of patients at presentation, early diagnosis and risk stratification are key to improve patients' outcome. Therefore, together with surrogates of organ involvement, biomarkers identifying patients with MGUS or MM at greater risk of developing AL would be highly valuable to prevent organ damage, to maximize therap… http://www.bloodjournal.org/content/132/Suppl_1/1907 Nov 21st, 2018 – Introduction Multiple myeloma (MM) is a plasma cell malignancy that manifests continuous cell dissemination to multiple bone marrow (BM) niches and extramedullary (EM) sites. However, the molecular mechanisms behind this phenomenon remain elusive. CD45, a receptor tyrosine phosphatase, is an important regulator for T-cell and B-cell signaling pathways. In MM, the loss of CD45 expression has bee… http://www.bloodjournal.org/content/132/Suppl_1/3904 Nov 21st, 2018 – Introduction: Multiple myeloma (MM) is characterized by the over-expression of D-cyclin genes and the expression is tightly linked to cytogenetic subgroups. For instance, overexpression of CCND1 in the t(11;14) and CCND3 in the t(6;14) is direct through IgH super-enhancer translocation, and CCND2 overexpression in t(4;14), t(14;16) and t(14;20) indirectly, presumably as a result of transcriptio… http://www.bloodjournal.org/content/132/Suppl_1/4462 Nov 21st, 2018 – The APOBEC family of cytidine deaminases include AID (activity induced deaminase) and 10 related APOBEC enzymes (A1,A2,A3A,A3B,A3C,A3D,A3F,A3G,A3H and A4). AID is well studied for its role in somatic hyper mutation and class switch recombination of immunoglobulin genes. APOBECs (apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like) have been shown to have roles in mRNA editing and i… http://www.bloodjournal.org/content/132/Suppl_1/4486 Nov 21st, 2018 – Seventy percent of all patients with light chain amyloidosis (AL) have cardiac involvement, and most of those patients ultimately die from complications related to their heart disease. While consensus guidelines outline criteria for grading hematologic response to chemotherapy for AL, there are no currently validated criteria for grading cardiac response to therapy. Recently, Muchtar et al. cre… http://www.bloodjournal.org/content/132/Suppl_1/3242 Nov 21st, 2018 – Introduction: Daratumumab (DARA), a human IgG1k monoclonal antibody with single activity in multiple myeloma (MM) shows strong synergy in combination with other anti-MM agents, including immunomodulatory drug (IMiDs) and proteasome inhibitors (PI). This has led to the exploration of DARA in combination with front line regimens. Triplets including a PI and an IMiD are considered an ideal backbon… http://www.bloodjournal.org/content/132/Suppl_1/593 Nov 21st, 2018 – Background: Deletion (del) of 17p involving the p53 tumor suppressor (TP53) remains an adverse prognostic factor in multiple myeloma (MM) despite the use of novel agents as well as high-dose chemotherapy with autologous stem cell rescue. Genomic TP53 deletion can cause haploinsufficiency of nearby genes, such as RNA polymerase II subunit A (POLR2A), which ia also located on 17p13.1. We therefor… http://www.bloodjournal.org/content/132/Suppl_1/3274 Nov 21st, 2018 – Background and aims Treatment of relapsed/refractory myeloma (RRMM) remains a challenge as most approved and commonly accessible doublet treatments induce responses (≥PR) in less than half of patients. The combination of the classical alkylator cyclophosphamide with thalidomide (CTD) or lenalidomide (CRD) is standard of care in early lines of therapy in the UK and elsewhere. Data on the clinica… http://www.bloodjournal.org/content/132/Suppl_1/951 Nov 21st, 2018 – Multiple myeloma is a malignancy of long-lived plasma cells of the bone marrow that is rarely curable. Thus, despite recent advances in the development of new therapies, additional approaches are required. We investigated potential molecular vulnerabilities in the BCL2 family. Using the MMRF CoMMpass (NCT0145429) study (IA13), we determined the frequency of nonsynonymous coding mutations in the… http://www.bloodjournal.org/content/132/Suppl_1/2004 Nov 21st, 2018 – Background: Hematogenous extramedullary multiple myeloma (HEMM), though rare, is mainly observed in MM patients at relapse. The current study assesses the characteristics and outcomes of patients with MM who develop HEMM in the novel agent era. Methods: Consecutive patients, treated in 16 participating centers and diagnosed with HEMM, were included. Patient characteristics at diagnosis and at H… http://www.bloodjournal.org/content/132/Suppl_1/55 Nov 21st, 2018 – Introduction: Multiple Myeloma (MM) is a genetically complex and evolutionary process with well defined precursor states, which offer a unique opportunity to study the sequential evolution of the disease. A small number of detectable pre-malignant clones are present in early stage and continue to acquire more genomic abnormalities leading to overt disease. The interaction between cancer cells a… http://www.bloodjournal.org/content/132/Suppl_1/122 Nov 21st, 2018 – Introduction Multi-agent induction chemotherapy followed by autologous stem cell transplant (ASCT) is a standard of care for younger patients with multiple myeloma, aimed at maximising the depth and duration of first response (PFS1). However, the duration of PFS1 is variable between patients. Improved understanding of how to identify high risk patients who relapse early and the ability to desig… http://www.bloodjournal.org/content/132/Suppl_1/3897 Nov 21st, 2018 – Introduction: Poor prognosis and drug resistance in multiple myeloma (MM) is associated with increased mutational load. APOBEC3B is a major contributor to mutagenesis, especially in myeloma patients with t(14;16) MAF subgroup. It was shown recently that presence of the APOBEC signature at diagnosis is an independent prognostic factor for progression free survival (PFS) and overall survival (OS)… http://www.bloodjournal.org/content/132/Suppl_1/243 Nov 21st, 2018 – Introduction The multistep progression of multiple myeloma from a normal plasma cell to a system with the features of invasive cancer provides a unique opportunity to understand the co-evolution of the malignant clone within its microenvironment. Understanding these changes is becoming increasingly important as we attempt to design early intervention strategies and to precisely leverage emergin… http://www.bloodjournal.org/content/132/Suppl_1/1929 Nov 21st, 2018 – Introduction: Multiple myeloma (MM) cells from patients with smoldering MM (SMM) and low-risk (LR) MM harbor genetic alterations typically seen in patients with high-risk (HR) disease. To test whether the bone marrow (BM) microenvironment plays a role in controlling growth of LR MM cells, we established an experimental model that mimics a HR microenvironment by co-culturing normal mesenchymal s… http://www.bloodjournal.org/content/132/Suppl_1/4475 Nov 21st, 2018 – Introduction After therapy or stem cell transplantation, multiple myeloma patients achieving complete response (CR) or stringent complete response (sCR) can still have a significant risk of disease relapse, illustrating the importance of using highly sensitive methods for minimal residual disease (MRD) detection and prognostication. Two techniques used clinically for MRD detection include multi… http://www.bloodjournal.org/content/132/Suppl_1/1976 Nov 21st, 2018 – Chimeric antigen receptor T cells (CART) targeting CD19 have shown substantial activity against leukemia and lymphoma, which motivated developing CART cell therapy for Multiple myeloma (MM). B cell maturation antigen (BCMA) is the target molecule in MM. Several kinds of CART targeting BCMA have been created from 2016. Among these, the Bluebird Bio uses the humanized murine BCMA scFv to make CAR… http://www.bloodjournal.org/content/132/Suppl_1/4459 Nov 21st, 2018 – Background: A renewed interest in immune and cellular based therapeutics in multiple myeloma was recently fueled by the development of CD38 targeting monoclonal antibodies as well as the introduction of engineered CAR-T cells. Daratumumab treatment in myeloma patients was demonstrated to expand clonal CD8+T cells and T cell clonality was correlated with the depth of response consistent with a d… http://www.bloodjournal.org/content/132/Suppl_1/1945 Nov 21st, 2018 – Background: Multiple myeloma (MM) requires combination drug therapies to delay acquired drug resistance and clinical relapse. We co-developed CX-5461, a highly-selective inhibitor of RNA polymerase I-mediated rDNA transcription(1), currently in phase I trials for relapsed haematological malignancies (Peter Mac). CX-5461 produces a targeted nucleolar DNA damage response (DDR), triggering both a … http://www.bloodjournal.org/content/132/Suppl_1/403 Nov 21st, 2018 – Background Survival in multiple myeloma ranges from months to decades and the majority of patients remain incurable with current treatment approaches. Given this high variability, it would be clinically very useful to quantitatively predict survival on a continuous scale. Current risk prediction models attribute patients to 2-3 groups, i.e. high, intermediate, and low risk. Group size and survi… http://www.bloodjournal.org/content/132/Suppl_1/3201 Nov 21st, 2018 – Introduction: Daratumumab (Dara) is a human monoclonal antibody targeting the highly expressed multiple myeloma (MM) surface receptor CD38, with significant activity in relapsed MM. However, resistance to Dara develops in virtually all patients (pts). Thus, in order to maximize its clinical activity and prevent resistance, it is imperative to understand why pts stop responding. Our group recent… http://www.bloodjournal.org/content/132/Suppl_1/3255 Nov 21st, 2018 – Background: Carfilzomib (CFZ) is a potent, irreversible proteasome inhibitor (PI) licenced in patients with multiple myeloma (MM) demonstrating improved progression free and overall survival (OS) to standard of care therapies. However, CFZ is also associated with hypertension (HTN) and rarely cardiac toxicity. The exact mechanism is unclear but may be due to a disturbance of endothelial nitric … http://www.bloodjournal.org/content/132/Suppl_1/3257 Nov 21st, 2018 – Background: Daratumumab is one of the most effective new myeloma drugs recently approved for relapsed/refractory multiple myeloma (MM), first in monotherapy in heavily pretreated patients, later in triplet combinations from first relapse, based on the results of the SIRIUS, POLLUX and CASTOR trials that showed good tolerability and high effectivity of daratumumab both in monotherapy and combine… http://www.bloodjournal.org/content/132/Suppl_1/956 Nov 21st, 2018 – Background: Promising results are seen from several early phase clinical trials on the cellular immunotherapy based on chimeric antigen receptor (CAR)-engineered T (CAR-T) targeting B cell maturation antigen (BCMA) for the treatment of relapsed/refractory (RR) multiple myeloma (MM). We developed an anti-BCMA CAR-T cell product manufactured via gamma-retrovirus-mediated transduction of activated… http://www.bloodjournal.org/content/132/Suppl_1/405 Nov 21st, 2018 – Patients with the plasma cell malignancy multiple myeloma now benefit from treatments such as proteasome inhibitors, immunomodulatory imide drugs (IMiDs), autologous stem cell transplant, and monoclonal antibodies. However, 20% of patients still relapse or die within two years and are deemed 'high risk'. Current markers fail to identify all high-risk patients resulting in misdiagnoses, therefor… http://www.bloodjournal.org/content/132/Suppl_1/2008 Nov 21st, 2018 – Introduction: Bortezomib-containing regimens (BCRs) have been the standard frontline approach for the treatment of transplant ineligible multiple myeloma (TIMM) patients in Canada for many years. Based on recent randomized clinical trial results lenalidomide and dexamethasone (Ld) has become another provincially funded option in Canada in the same therapeutic space. We aimed to compare the effe… http://www.bloodjournal.org/content/132/Suppl_1/3235 Nov 21st, 2018 – Introduction Multiple myeloma (MM) can be associated with paraskeletal (PP) or extramedullary (EMP) plasmocytomas (PL). Although PLs are relatively frequent, even at diagnosis, our knowledge on the subject mainly relies on small case series or single center experiences. Remarkably, little is known regarding the role of new drugs on MM with PL. Aim To perform a meta-analysis of 8 EMN-GIMEMA stud… http://www.bloodjournal.org/content/132/Suppl_1/3216 Nov 21st, 2018 – Selinexor (KPT-330) is a selective inhibitor of nuclear export (SINE) which specifically targets XPO1 (Exportin 1)-mediated nuclear export, leading to increased nuclear retention of major tumor suppressor proteins and inducing selective apoptosis in cancer cells. Several phase I and II clinical trials demonstrate evidence of anti-cancer activity of Selinexor in solid tumors (i.e metastatic pros… http://www.bloodjournal.org/content/132/Suppl_1/840 Nov 21st, 2018 – Background: Multiple myeloma (MM) is the most common hematologic malignancy in blacks with more than twice the incidence of non-black populations in national registry data. Prior studies have shown that blacks present with MM at an earlier age and have improved survival compared to non-blacks, contrary to the pattern in most malignancies. These findings have been theorized due to the effects of… http://www.bloodjournal.org/content/132/Suppl_1/3283 Nov 21st, 2018 – BACKGROUND & METHODS Cfz/Dex is a standard of care in relapsed MM, and renal impairment is a poor prognostic factor. The ALLG MM16 trial was initiated to assess the feasibility of treating patients (pts) who have significant RI (eGFR 15 – 40 ml/min) with Cfz/Dex, and to determine whether an early reduction in serum free light chains (SFLC), with a short half-life, could predict renal outcome. A… http://www.bloodjournal.org/content/132/Suppl_1/3302 Nov 21st, 2018 – Background: The incorporation of modern day induction regimens, autotransplant and continuous maintenance has resulted in better long-term outcomes for myeloma patients. Experience and trials demonstrated that by prolonging 1st progression-free survival (PFS1) and pushing the relapse farther, we can gain the OS advantage (McCarthy et al NEJM 2012). Unfortunately, a subgroup of patients fail to … http://www.bloodjournal.org/content/132/Suppl_1/3162 Nov 21st, 2018 – Introduction: HIV infection and the resulting immunodeficiency predispose individuals to various plasma cell disorders including reactive plasmacytosis, monoclonal gammopathy of undetermined significance (MGUS), multiple myeloma (MM) and plamacytomas. Studies have demonstrated nearly 4.5-fold increased risk of MM in HIV-infected (HIV+) individuals. Limited evidence from case reports/small serie… http://www.bloodjournal.org/content/132/Suppl_1/4491 Nov 21st, 2018 – Introduction: Several studies have shown the role of the immune system in the development of MM, but there is no systematic description of normal B-cell regeneration during treatment points. Recently, EuroFlow consortium has developed NGF panel with high sensitivity to evaluated MRD and potentially, to assess of the normal B-cell compartment of patients with MM. Aims: Here we evaluated the B ce… http://www.bloodjournal.org/content/132/Suppl_1/3208 Nov 21st, 2018 – INTRODUCTION: Despite advances in therapy, patients with relapsed AL amyloidosis die of resistant disease. New therapies are needed. siRNA directed at the constant regions of Ig light chains (LC) reduces LC mRNA and protein from patient cells, from human myeloma and AL cell lines, and in a flank plasmacytoma model with in vivo electroporation (Blood 2014;123:3440; Gene Ther 2016;23:727). To del… Αναρτήθηκε από Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00306932607174,00302841026182 στις

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A Case of Hypereosinophilic Syndrome After Mepolizumab Treatment

<h1>A Case of Hypereosinophilic Syndrome After Mepolizumab Treatment</h1>

A Case of Hypereosinophilic Syndrome After Mepolizumab Treatment

A Case of Hypereosinophilic Syndrome After Mepolizumab Treatment DECEMBER 14, 2018 MD Magazine Staff The following case study was authored by K Jackson, S Bahna and D Kaufman, and presented at the American College of Asthma, Allergy and Immunology (ACAAI) annual meeting in Seattle, Washington. Introduction: Little is known about potential consequences of stopping mepolizumab therapy in asthmatic patients. This is a case of a 43-year-old female diagnosed with eosinophilic myocarditis six months after cessation of mepolizumab. Case Description: A 43-year-old female with severe eosinophilic asthma was started on mepolizumab. She remained compliant for 2 year with significant improvement of symptoms but due to a lapse of insurance coverage, therapy was interrupted. Six months later, she developed low grade fever, cough, and dyspnea with infiltrates on CXR. She was diagnosed with atypical pneumonia and treated with antibiotics without improvement. Within a few days, she developed hypoxic respiratory failure requiring noninvasive ventilation support. WBC was 26.2 K/uL with eosinophilia of 9.69 K/uL. She had elevated troponin (7.58); EKG had lateral ST elevation myocardial infarction, and echocardiogram showed pericardial effusion with EF of 20-25%. Infectious workup was unremarkable. Heart catheterization revealed normal coronaries. Pericardiocentesis cytology demonstrated 89% eosinophils. Cardiac MRI showed circumferential subendocardial hyperenhancement of left ventricle and global ventricular hypokinesis. Bone marrow biopsy and cytogenetic testing were negative. She was diagnosed with eosinophilic myocarditis and started on IV methylprednisolone with marked improvement in symptoms. The patient was discharged on high dose prednisone and heart failure therapy. Three months later, she resumed mepolizumab and has been tolerating a slow prednisone taper. Discussion: To our best knowledge, this is the first reported case of eosinophilic myocarditis and pneumonia after mepolizumab cessation. This patient may have had a rebound hypereosinophilia or an underlying hypereosinophilic syndrome which was masked by mepolizumab therapy. In one practitioner’s experience, adding mepolizumab to the treatment regimens of patients with severe eosinophilic asthma in his practice resulted in improved symptoms and quality of life, similar to those reported in controlled clinical trials with screened participants.”After extensive double-blind controlled studies, it is always reassuring to the physician in the field that the results of these studies are applicable in a private practice office setting,” Ronald Strauss, MD, Cleveland Allergy & Asthma Center and Case Western Reserve University Medical School, Cleveland, Ohio, told MD Magazine® . Moreover, data from the longest anti-interleukin 5 (IL-5) biologic therapy trial in severe eosinophilic asthma ever reported found that mepolizumab consistently improved exacerbation reduction and asthma control in patients with the condition. Data from the open-label COLUMBA study, presented at the 2018 American Thoracic Society (ATS) International Conference in San Diego, CA, reported the results of patients with severe eosinophilic asthma who were treated with mepolizumab for a mean 3.5 years and up to 4.5 years. Along with consistent clinical efficacy, patients treated with the drug reported safety profiles similar with previous studies. You May Also be Interested in Most Popular

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Dexamethasone versus prednisone for children receiving asthma treatment in the paediatric inpatient population: protocol for a feasibility randomised controlled trial

Dexamethasone versus prednisone for children receiving asthma treatment in the paediatric inpatient population: protocol for a feasibility randomised controlled trial

Introduction Asthma exacerbations are a leading cause of paediatric hospitalisations. Corticosteroids are key in the treatment of asthma exacerbations. Most current corticosteroids treatment regimens for children admitted with asthma exacerbation consist of a…

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Lymphoma in animals

<h1>Lymphoma in animals</h1>

This article is about lymphoma in animals. For the disease in humans, see lymphoma.
Lymphoma in a Golden Retriever

Lymphoma (lymposarcoma) in animals is a type of cancer defined by a proliferation of malignant lymphocytes within solid organs such as the lymph nodes, bone marrow, liver and spleen. The disease also may occur in the eye, skin, and gastrointestinal tract.

Contents

  • 1 Lymphoma in dogs
    • 1.1 Classification
    • 1.2 Signs and symptoms
    • 1.3 Diagnosis
    • 1.4 Treatment
    • 1.5 Prognosis
  • 2 Lymphoma in cats
    • 2.1 Classification
    • 2.2 Symptoms
    • 2.3 Treatment and prognosis
  • 3 Lymphoma in ferrets
  • 4 See also
  • 5 References

Lymphoma in dogs[edit]

Lymphoma is one of the most common malignant tumors to occur in dogs. The cause is genetic, but there are also suspected environmental factors involved,[1] including in one study an increased risk with the use of the herbicide 2,4-D.[2] This risk was not confirmed in another study.[3]

Breeds that are commonly affected include Boxer, Scottish Terrier, Basset Hound, Airedale Terrier, Chow Chow, German Shepherd, Poodle, St. Bernard, Bulldog, Beagle, Rottweiler[1] and Golden Retriever. The Golden Retriever is especially susceptible to developing lymphoma, with a lifetime risk of 1:8.[4]

Classification[edit]

The cancer is classified into low and high grade types. Classification is also based on location. The four location types are multicentric, mediastinal, gastrointestinal, and extranodal (involving the kidney, central nervous system, skin, heart, or eye). Multicentric lymphoma, the most common type (by greater than 80 percent),[5] is found in the lymph nodes, with or without involvement in the liver, spleen, or bone marrow. Mediastinal lymphoma occurs in the lymph nodes in the thorax and possibly the thymus. Gastrointestinal lymphoma occurs as either a solitary tumor or diffuse invasion of the stomach or intestines, with or without involvement in the surrounding lymph nodes, liver or spleen.[6] Classification is further based on involvement of B-lymphocytes or T-lymphocytes. Approximately 70 percent are B-cell lymphoma.[7] Cutaneous lymphoma can be classified as epitheliotropic (closely conforming to the epidermis) or non-epitheliotropic. The epitheliotropic form is typically of T-cell origin and is also called mycosis fungoides. The non-epitheliotropic form is typically of B-cell origin.[8]

Signs and symptoms[edit]

General signs and symptoms include depression, fever, weight loss, loss of appetite, loss of hair or fur and vomiting. Lymphoma is the most common cancerous cause of hypercalcemia (high blood calcium levels) in dogs.[9] It can lead to the above signs and symptoms plus increased water drinking, increased urination, and cardiac arrhythmias. Hypercalcemia in these cases is caused by secretion of parathyroid hormone-related protein.

Multicentric lymphoma presents as painless enlargement of the peripheral lymph nodes. This is seen in areas such as under the jaw, the armpits, the groin, and behind the knees. Enlargement of the liver and spleen causes the abdomen to distend. Mediastinal lymphoma can cause fluid to collect around the lungs, leading to coughing and difficulty breathing. Hypercalcemia is most commonly associated with this type.[10]

Gastrointestinal lymphoma causes vomiting, diarrhea, and melena (digested blood in the stool). Low serum albumin levels and hypercalcemia can also occur.[6]

Lymphoma of the skin is an uncommon occurrence. The epitheliotropic form typically appears as itchy inflammation of the skin progressing to nodules and plaques.
The non-epitheliotropic form can have a wide variety of appearances, from a single lump to large areas of bruised, ulcerated, hairless skin.[8] The epitheliotropic form must be differentiated from similar appearing conditions such as pemphigus vulgaris, bullous pemphigoid, and lupus erythematosus.[11]

Signs for lymphoma in other sites depend on the location. Central nervous system involvement can cause seizures or paralysis. Eye involvement, seen in 20 to 25 percent of cases,[12] can lead to glaucoma, uveitis, bleeding within the eye, retinal detachment, and blindness. Lymphoma in the bone marrow causes anemia, low platelet count, and low white blood cell count.

Diagnosis[edit]

Cytology of lymphoma in a dog

Biopsy of affected lymph nodes or organs confirms the diagnosis, although a needle aspiration of an affected lymph node can increase suspicion of the disease. X-rays, ultrasound and bone marrow biopsy reveal other locations of the cancer. There are now a range of blood tests that can be utilised to aid in the diagnosis of lymphoma. Flow cytometry detects antibodies linked to tumour cell surface antigens in fluid samples or cell suspensions.[13] Polymerase chain reaction (PCR) for antigen receptor rearrangements (PARR) identifies circulating tumour cells based on unique genetic sequences.[14] The canine Lymphoma Blood Test (cLBT) measures multiple circulating biomarkers and utilises a complex algorithm to diagnose lymphoma.[15] This test utilises the acute phase proteins (C-Reactive Protein and Haptoglobin). In combination with basic clinical symptoms, it gives in differential diagnosis the sensitivity 83.5% and specificity 77%.[16] The TK canine cancer panel is an indicator of general neoplastic disease.[17] The stage of the disease is important to treatment and prognosis. Certain blood tests have also been shown to be prognostic.

The stage of the disease is important to treatment and prognosis.

  • Stage I – only one lymph node or lymphoid tissue in one organ involved.
  • Stage II – lymph nodes in only one area of the body involved.
  • Stage III – generalized lymph node involvement.
  • Stage IV – any of the above with liver or spleen involvement.
  • Stage V – any of the above with blood or bone marrow involvement.[1]

Each stage is divided into either substage a, those without systemic symptoms; or substage b, those with systemic symptoms such as fever, loss of appetite, weight loss, and fatigue.

Treatment[edit]

Due to the high risk of recurrence and ensuing problems, close monitoring of dogs undergoing chemotherapy is important. The same is true for dogs that have entered remission and ceased treatment. Monitoring for disease and remission/recurrence is usually performed by palpation of peripheral lymph nodes. This procedure detects gross changes in peripheral lymph nodes. Some of the blood tests used in diagnosing lymphoma also offer greater objectivity and provide an earlier warning of an animal coming out of remission.[15]

Complete cure is rare with lymphoma and treatment tends to be palliative, but long remission times are possible with chemotherapy. With effective protocols, average first remission times are 6 to 8 months. Second remissions are shorter and harder to accomplish. Average survival is 9 to 12 months. The most common treatment is a combination of cyclophosphamide, vincristine, prednisone, L-asparaginase, and doxorubicin.[1] Other chemotherapy drugs such as chlorambucil, lomustine (CCNU), cytosine arabinoside, and mitoxantrone are sometimes used in the treatment of lymphoma by themselves or in substitution for other drugs. In most cases, appropriate treatment protocols cause few side effects, but white blood cell counts must be monitored.

Allogeneic and autologous stem cell transplantations (as is commonly done in humans) have recently been shown to be a possible treatment option for dogs.[18] Most of the basic research on transplantation biology was generated in dogs. Current cure rates using stem cell therapy in dogs approximates that achieved in humans, 40-50%.

When cost is a factor, prednisone used alone can improve the symptoms dramatically, but it does not significantly affect the survival rate. The average survival times of dogs treated with prednisone and untreated dogs are both one to two months.[1] Using prednisone alone can cause the cancer to become resistant to other chemotherapy agents, so it should only be used if more aggressive treatment is not an option.

Isotretinoin can be used to treat cutaneous lymphoma.[8]

Prognosis[edit]

Untreated dogs have an average survival time of 60 days.[19] Lymphoma with a histologic high grade generally respond better to treatment but have shorter survival times than dogs with low grade lymphoma.[6] Dogs with B-lymphocyte tumors have a longer survival time than T-lymphocyte tumors.[1] Mediastinal lymphoma has a poorer prognosis than other types, especially those with hypercalcemia.[12] Clinical stage and substage have some prognostic value, with poorer prognosis associated with Stage V disease, and with substage b (clinical illness at time of presentation).[20]

Lymphoma in cats[edit]

Lymphoma is the most common malignancy diagnosed in cats.[21] Lymphoma in young cats occurs most frequently following infection with feline leukemia virus (FeLV) or to a lesser degree feline immunodeficiency virus (FIV). These cats tend to have involvement of lymph nodes, spine, or mediastinum. Cats with FeLV are 62 times more likely to develop lymphoma, and cats with both FeLV and FIV are 77 times more likely.[22] Younger cats tend to have T-cell lymphoma and older cats tend to have B-cell lymphoma.[23] Older cats tend to have gastrointestinal lymphoma without FeLV infection,[24] although tests more sensitive to low level FeLV infections and replication-defective FeLV have found that many of these cats have been previously exposed.[25] The same forms of lymphoma that are found in dogs also occur in cats, but gastrointestinal is the most common type. Lymphoma of the kidney is the most common kidney tumor in cats, and lymphoma is also the most common heart tumor.[1]

Classification[edit]

Gastrointestinal lymphoma is classified into low grade, intermediate grade, and high grade. Low grade types include lymphocytic and small cell lymphoma. High grade types include lymphoblastic, immunoblastic, and large cell lymphoma. Low grade lymphoma is only found in the small intestine, while high grade can commonly be found in the stomach.[26]

Symptoms[edit]

Cats that develop lymphoma are much more likely to develop more severe symptoms than dogs. Whereas dogs often appear healthy initially except for swollen lymph nodes, cats will often be physically ill. The symptoms correspond closely to the location of the lymphoma. The most common sites for alimentary (gastrointestinal) lymphoma are, in decreasing frequency, the small intestine, the stomach, the junction of the ileum, cecum, and colon. Cats with the alimentary form of lymphoma often present with weight loss, rough hair coat, loss of appetite, vomiting and diarrhea, although vomiting and diarrhea are commonly absent as symptoms.[27] The tumor can also cause life-threatening blockage of the intestine. Cats with the mediastinal form often have respiratory distress and fluid in the thoracic cavity. If lymphoma develops in the kidney, the cat may have increased water consumption and increased urination. Lymphoma of the kidney presents as bilateral kidney enlargement and failure. If the lymphoma is located in the nose, the cat may have discharge from the nose and facial swelling. Lymphoma of the heart causes congestive heart failure, pericardial effusion, and cardiac arrhythmias. Ocular lymphoma in cats often presents as anterior uveitis (inflammation of the inside of the eye).[28] Cats who are also infected with FeLV often present with pale mucous membranes due to anemia. Anemia is a common problem in all cats with lymphoma, but hypercalcemia is rare.

Diagnosis is similar to dogs, except cats should be tested for FeLV and FIV. It is important to differentiate the alimentary form of lymphoma from inflammatory bowel disease because the signs are so similar in cats. A biopsy is necessary to do this.[29] One approach to differentiate inflammatory bowel disease from is to test the infiltrating lymphocytes for their monoclonal origin in lymphomas.[30]

Treatment and prognosis[edit]

Chemotherapy is the mainstay of treatment for lymphoma in cats. Most of the drugs used in dogs are used in cats, but the most common protocol uses cyclophosphamide, vincristine, and prednisone.[21] Gastrointestinal lymphoma has also commonly been treated with a combination of prednisolone and high dose pulse chlorambucil with success.[26] The white blood cell count must be monitored. Remission and survival times are comparable to dogs. Lower stage lymphoma has a better prognosis. Multicentric lymphoma has a better response to treatment than the gastrointestinal form, but infection with FeLV worsens the prognosis.[1]

About 75% of cats treated with chemotherapy for lymphoma go into remission. Unfortunately, after an initial remission, most cats experience a relapse, after which they have a median survival of 6 months. However, about one-third of cats treated with chemotherapy will survive more than 2 years after diagnosis; a small number of these cats may be cured of their disease. Untreated, most cats with lymphoma die within 4–6 weeks. Most cats tolerate their chemotherapy well, and fewer than 5% have severe side effects. Cats do not lose their fur from chemotherapy, though loss of whiskers is possible. Other side effects include low white blood cell count, vomiting, loss of appetite, diarrhea, or fatigue. These can typically be controlled well, and most cats have a good quality of life during treatment. If a cat relapses after attaining remission, the cat can be treated with different chemotherapy drugs to try for a second remission. The chances of a second remission are much lower than the chances of obtaining a first, and the second remission is often shorter than the first.

Lymphoma in ferrets[edit]

Lymphoma is common in ferrets and is the most common cancer in young ferrets. There is some evidence that a retrovirus may play a role in the development of lymphoma like in cats.[31] The most commonly affected tissues are the lymph nodes, spleen, liver, intestine, mediastinum, bone marrow, lung, and kidney.

In young ferrets, the disease progresses rapidly. The most common symptom is difficulty breathing caused by enlargement of the thymus.[32] Other symptoms include loss of appetite, weight loss, weakness, depression, and coughing. It can also masquerade as a chronic disease such as an upper respiratory infection or gastrointestinal disease. In older ferrets, lymphoma is usually chronic and can exhibit no symptoms for years.[33] Symptoms seen are the same as in young ferrets, plus splenomegaly, abdominal masses, and peripheral lymph node enlargement.

Diagnosis is through biopsy and x-rays. There may also be an increased lymphocyte count. Treatment includes surgery for solitary tumors, splenectomy (when the spleen is very large), and chemotherapy. The most common protocol uses prednisone, vincristine, and cyclophosphamide.[34] Doxorubicin is used in some cases. Chemotherapy in relatively healthy ferrets is tolerated very well, but possible side effects include loss of appetite, depression, weakness, vomiting, and loss of whiskers. The white blood cell count must be monitored. Prednisone used alone can work very well for weeks to months, but it may cause resistance to other chemotherapy agents. Alternative treatments include vitamin C and Pau d’Arco (a bark extract).[34]

The prognosis for lymphoma in ferrets depends on their health and the location of the cancer. Lymphoma in the mediastinum, spleen, skin, and peripheral lymph nodes has the best prognosis, while lymphoma in the intestine, liver, abdominal lymph nodes, and bone marrow has the worst.[34]

See also[edit]

  • Lymphadenopathy

References[edit]

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  • Source: https://en.wikipedia.org/wiki/Lymphoma_in_animals