Richard Champlin, M.D., Chair, Dept. of Stem Cell Transplantation and Cellular Therapy, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center - Newest Modalities in Bone Marrow Transplantation
Presented at New Frontiers in the Management of Solid and Liquid Tumors hosted by the John Theurer Cancer Center at Hackensack University Medical Center. jtcancercenter.org/CME
Allogeneic hematopoietic stem cell transplantation (allo HSCT) from an HLA-matched related donor provides the most potent anti-leukemic effect of any post-remission therapy in AML, as demonstrated by the lowest rates of relapse.
Graft vs leukemia plays and important role here.
Provides the best chance of long-term survival
Transplant in pediatrics in Acute lymphoblastic Luekemia in CR1Dr. Liza Bulsara
to transplant or not to transplant pediatric luekemia in CR1 Has also been a controversial topic . here we give clear recommendation to transplant in difeerent biology group
Allogeneic hematopoietic stem cell transplantation (allo HSCT) from an HLA-matched related donor provides the most potent anti-leukemic effect of any post-remission therapy in AML, as demonstrated by the lowest rates of relapse.
Graft vs leukemia plays and important role here.
Provides the best chance of long-term survival
Transplant in pediatrics in Acute lymphoblastic Luekemia in CR1Dr. Liza Bulsara
to transplant or not to transplant pediatric luekemia in CR1 Has also been a controversial topic . here we give clear recommendation to transplant in difeerent biology group
Linda Cendales Composite Tissue Graft Summary Banff 2013 Meeting in BrazilKim Solez ,
Composite tissue graft summary from 12th Banff Conference on Transplant Pathology from the meeting in Comandatuba-Bahia, Brazil on August 23rd, 2013 http://cybernephrology.ualberta.ca/banff/2013
Present and Future Impact of Cytogenetics on Acute Myeloid Leukemialarriva
Cytogenetics is an advancement in which clinicians can look for specific genetic mutations of chromosomal DNA and use that information to determine patient prognosis and individualize therapy. In this presentation I cover what cytogenetics are, how they impact patient risk, what therapies to use based on risk, and how genetically targeted agents may be used in the future.
Linda Cendales Composite Tissue Graft Summary Banff 2013 Meeting in BrazilKim Solez ,
Composite tissue graft summary from 12th Banff Conference on Transplant Pathology from the meeting in Comandatuba-Bahia, Brazil on August 23rd, 2013 http://cybernephrology.ualberta.ca/banff/2013
Present and Future Impact of Cytogenetics on Acute Myeloid Leukemialarriva
Cytogenetics is an advancement in which clinicians can look for specific genetic mutations of chromosomal DNA and use that information to determine patient prognosis and individualize therapy. In this presentation I cover what cytogenetics are, how they impact patient risk, what therapies to use based on risk, and how genetically targeted agents may be used in the future.
Bone marrow transplantation for thalassemia in lower resource settings - The Cure2Children Foundation experience in Pakistan. By Dr Naila Yaqub, Assistant Professor, Bone Marrow Transplant unit, The Children hospital, PIMS, Pakistan
Get the bone marrow transplant treatment in Delhi by best doctor / surgeon in world class hospital. We ensure you get the best medical care and even stay in touch for more assistance. website :- http://www.transplantsurgeryindia.com/bone-marrow-transplants/
Christopher Azzoli, M.D., Assistant Member, Thoracic Oncology Service, Memorial Sloan-Kettering Cancer Center: Current Modalities in the Treatment of Lung Cancer
Presented at New Frontiers in the Management of Solid and Liquid Tumors hosted by the John Theurer Cancer Center at Hackensack University Medical Center. jtcancercenter.org/CME
Part of the MaRS Entrepreneurship 101 Event Series
"Hey buddy, can you spare a $100 million?"
OR: How to convince successful financiers to give you millions of dollars in a project doomed to fail!
Speaker: Mike Polonsky, Senior Vice President, The Equicom Group
Download the audio presentation and post questions on the MaRS blog:
http://blog.marsdd.com/2007/04/11/entrepreneurship-101-who-should-pitch/
Identifying Tumor Permeability Heterogeneity with MRI Contrast AgentsMike Aref
We tested the hypothesis that macromolecular agents will have a greater sensitivity in identifying areas of high regional mammary tumor permeability-surface area products than low molecular weight agents. New modalities such as ultrasound, MRI, and nuclear medicine may improve breast cancer diagnosis(1). MRI can detect small tumors, 1 mm, with nearly 100% sensitivity(2) and can differentiate benign from malignant tumors with an accuracy of only 30 to 40%(3). A need exists for more accurately characterizing tumor specificity with MR mammography. Dynamic contrast enhanced MR mammography shows promise, and is based on differences in capillary density. Only a subset of tumor cells acquire angiogenic activity and this results in heterogeneous capillary density and surface area(4). High regional capillary density indicates poor prognosis(5). Tumor secreted factors induce angiogenesis, including vascular endothelial growth factor (VEGF), which is necessary for metastasis and regions high in VEGF exhibit hyperpermeability(6). Some of the physiological byproducts of angiogenesis regulate the extraction of an agent by a tumor from the blood. This extraction depends on (a) capillary surface area, S, (b) capillary permeability, P, (c) capillary blood flow, F, (d) transit time of the agent through the tumor interstitium, and (e) the plasma half-life, T1/2 DIST(7, 8). By imaging the time evolution of a contrast agent in the lesion, one can model agent extraction. Knowing the plasma half-life of an agent and regional blood flow provides a measure of the capillary surface area and permeability. Such knowledge may provide a means of differentiating benign from malignant tumors.
A Clinical Trial of CCR5 Inhibition in Treated HIV Infection: Highlighting Mu...CTSI at UCSF
A presentation by Peter W. Hunt, M.D., Assistant Professor in Residence at the University of California, San Francisco (UCSF), conducted at the San Francisco General Hospital (SFGH) and supported by CTSI's Clinical Research Services. Learn more about the service at http://ctsi.ucsf.edu/our-work/clinical-research-services
Epistemic Interaction - tuning interfaces to provide information for AI supportAlan Dix
Paper presented at SYNERGY workshop at AVI 2024, Genoa, Italy. 3rd June 2024
https://alandix.com/academic/papers/synergy2024-epistemic/
As machine learning integrates deeper into human-computer interactions, the concept of epistemic interaction emerges, aiming to refine these interactions to enhance system adaptability. This approach encourages minor, intentional adjustments in user behaviour to enrich the data available for system learning. This paper introduces epistemic interaction within the context of human-system communication, illustrating how deliberate interaction design can improve system understanding and adaptation. Through concrete examples, we demonstrate the potential of epistemic interaction to significantly advance human-computer interaction by leveraging intuitive human communication strategies to inform system design and functionality, offering a novel pathway for enriching user-system engagements.
Accelerate your Kubernetes clusters with Varnish CachingThijs Feryn
A presentation about the usage and availability of Varnish on Kubernetes. This talk explores the capabilities of Varnish caching and shows how to use the Varnish Helm chart to deploy it to Kubernetes.
This presentation was delivered at K8SUG Singapore. See https://feryn.eu/presentations/accelerate-your-kubernetes-clusters-with-varnish-caching-k8sug-singapore-28-2024 for more details.
A tale of scale & speed: How the US Navy is enabling software delivery from l...sonjaschweigert1
Rapid and secure feature delivery is a goal across every application team and every branch of the DoD. The Navy’s DevSecOps platform, Party Barge, has achieved:
- Reduction in onboarding time from 5 weeks to 1 day
- Improved developer experience and productivity through actionable findings and reduction of false positives
- Maintenance of superior security standards and inherent policy enforcement with Authorization to Operate (ATO)
Development teams can ship efficiently and ensure applications are cyber ready for Navy Authorizing Officials (AOs). In this webinar, Sigma Defense and Anchore will give attendees a look behind the scenes and demo secure pipeline automation and security artifacts that speed up application ATO and time to production.
We will cover:
- How to remove silos in DevSecOps
- How to build efficient development pipeline roles and component templates
- How to deliver security artifacts that matter for ATO’s (SBOMs, vulnerability reports, and policy evidence)
- How to streamline operations with automated policy checks on container images
Transcript: Selling digital books in 2024: Insights from industry leaders - T...BookNet Canada
The publishing industry has been selling digital audiobooks and ebooks for over a decade and has found its groove. What’s changed? What has stayed the same? Where do we go from here? Join a group of leading sales peers from across the industry for a conversation about the lessons learned since the popularization of digital books, best practices, digital book supply chain management, and more.
Link to video recording: https://bnctechforum.ca/sessions/selling-digital-books-in-2024-insights-from-industry-leaders/
Presented by BookNet Canada on May 28, 2024, with support from the Department of Canadian Heritage.
Le nuove frontiere dell'AI nell'RPA con UiPath Autopilot™UiPathCommunity
In questo evento online gratuito, organizzato dalla Community Italiana di UiPath, potrai esplorare le nuove funzionalità di Autopilot, il tool che integra l'Intelligenza Artificiale nei processi di sviluppo e utilizzo delle Automazioni.
📕 Vedremo insieme alcuni esempi dell'utilizzo di Autopilot in diversi tool della Suite UiPath:
Autopilot per Studio Web
Autopilot per Studio
Autopilot per Apps
Clipboard AI
GenAI applicata alla Document Understanding
👨🏫👨💻 Speakers:
Stefano Negro, UiPath MVPx3, RPA Tech Lead @ BSP Consultant
Flavio Martinelli, UiPath MVP 2023, Technical Account Manager @UiPath
Andrei Tasca, RPA Solutions Team Lead @NTT Data
Securing your Kubernetes cluster_ a step-by-step guide to success !KatiaHIMEUR1
Today, after several years of existence, an extremely active community and an ultra-dynamic ecosystem, Kubernetes has established itself as the de facto standard in container orchestration. Thanks to a wide range of managed services, it has never been so easy to set up a ready-to-use Kubernetes cluster.
However, this ease of use means that the subject of security in Kubernetes is often left for later, or even neglected. This exposes companies to significant risks.
In this talk, I'll show you step-by-step how to secure your Kubernetes cluster for greater peace of mind and reliability.
State of ICS and IoT Cyber Threat Landscape Report 2024 previewPrayukth K V
The IoT and OT threat landscape report has been prepared by the Threat Research Team at Sectrio using data from Sectrio, cyber threat intelligence farming facilities spread across over 85 cities around the world. In addition, Sectrio also runs AI-based advanced threat and payload engagement facilities that serve as sinks to attract and engage sophisticated threat actors, and newer malware including new variants and latent threats that are at an earlier stage of development.
The latest edition of the OT/ICS and IoT security Threat Landscape Report 2024 also covers:
State of global ICS asset and network exposure
Sectoral targets and attacks as well as the cost of ransom
Global APT activity, AI usage, actor and tactic profiles, and implications
Rise in volumes of AI-powered cyberattacks
Major cyber events in 2024
Malware and malicious payload trends
Cyberattack types and targets
Vulnerability exploit attempts on CVEs
Attacks on counties – USA
Expansion of bot farms – how, where, and why
In-depth analysis of the cyber threat landscape across North America, South America, Europe, APAC, and the Middle East
Why are attacks on smart factories rising?
Cyber risk predictions
Axis of attacks – Europe
Systemic attacks in the Middle East
Download the full report from here:
https://sectrio.com/resources/ot-threat-landscape-reports/sectrio-releases-ot-ics-and-iot-security-threat-landscape-report-2024/
GraphRAG is All You need? LLM & Knowledge GraphGuy Korland
Guy Korland, CEO and Co-founder of FalkorDB, will review two articles on the integration of language models with knowledge graphs.
1. Unifying Large Language Models and Knowledge Graphs: A Roadmap.
https://arxiv.org/abs/2306.08302
2. Microsoft Research's GraphRAG paper and a review paper on various uses of knowledge graphs:
https://www.microsoft.com/en-us/research/blog/graphrag-unlocking-llm-discovery-on-narrative-private-data/
SAP Sapphire 2024 - ASUG301 building better apps with SAP Fiori.pdfPeter Spielvogel
Building better applications for business users with SAP Fiori.
• What is SAP Fiori and why it matters to you
• How a better user experience drives measurable business benefits
• How to get started with SAP Fiori today
• How SAP Fiori elements accelerates application development
• How SAP Build Code includes SAP Fiori tools and other generative artificial intelligence capabilities
• How SAP Fiori paves the way for using AI in SAP apps
Encryption in Microsoft 365 - ExpertsLive Netherlands 2024Albert Hoitingh
In this session I delve into the encryption technology used in Microsoft 365 and Microsoft Purview. Including the concepts of Customer Key and Double Key Encryption.
The Art of the Pitch: WordPress Relationships and SalesLaura Byrne
Clients don’t know what they don’t know. What web solutions are right for them? How does WordPress come into the picture? How do you make sure you understand scope and timeline? What do you do if sometime changes?
All these questions and more will be explored as we talk about matching clients’ needs with what your agency offers without pulling teeth or pulling your hair out. Practical tips, and strategies for successful relationship building that leads to closing the deal.
2. Major Innovations SCT-CT
• Nonmyeloablative Conditioning
• Alternative Donors
– Cord Blood
– Haploidentical Transplants
• Cell Therapy
– T-cells
– Chimeric Antigen Receptors
– NK Cells
3. Hematopoietic Stem Cell Transplantation
Preparative D D
Regimen D D
HSCT
D
R
R D
R D
RL D
RL D
Allogeneic hematopoietic is an effective, but toxic treatment for
hematologic malignancies, associated with a high risk of morbidity
and mortality (10->50%), restricting its use to young patients without
comorbidities
4. Goal of Conditioning Regimen
• Provide immune suppression to prevent
rejection and create “space” for
engraftment
• Eradicate the malignancy
– Most effective drugs/radiation treatments
for hematologic malignancies also kill
normal myeloid and lymphoid cells
– Kill malignant stem cells
5. Allogeneic BMT for CML
Importance of GVL
High Dose
Chemoradiotherapy
Donor Lymphocyte
Infusion
Remission
T-cell
depletion
Identical twin
Unmodified Limit of
Detection
BMT Time
6.
7. Graft-vs-Malignancy
Allogeneic SCT
• High dose therapy and allogeneic SCT is an
effective treatment for hematologic malignancies
• Much of the benefit of alloSCT is due to immune
GVL effect; therefore maximally ablative therapy
may not be needed.
• Lower dose nonmyeloablative preparative
regimens are sufficient to prevent rejection.
• We hypothesized that a reduced intensity,
nonmyeloablative allogeneic transplant could
reduce toxicity and allow successful treatment of
older patients and those with major comorbidities.
8.
9. Nonablative and Reduced
Intensity Regimens
Nonablative Reduced Intensity Ablative
TBI/CyT
F-TBI
2Gy BuF BuCy
MF
FCR
Myelosuppression
Champlin et al 2000
10. Nonmyeloablative Transplant
PreparativeDsc DT DT
Regimen D DT DT DT
HSCT +DLI
Dsc DT DB
R
R DNK Dsc
R DT DNK
RL R D
RL RL D
Recipient Donor Mixed Chimera Complete Chimera
11. Busulfan AUC Relative to Toxicity and aGVHD
0.8
Probability of Mucositis ≥ 3 Probability of GI Toxicity ≥ 3
0.8
0.6
0.6
Probability
Probability
0.4
0.4
0.2
0.2
0.0
0.0
800 1000 1200 1400 1600 1800 800 1000 1200 1400 1600 1800
AUC AUC
Probability of Hepatic Toxicity ≥ 2 Probability of GVHD ≥ 2
1.0
0.8
0.8
0.6
0.6
Probability
Probability
0.4
0.4
0.2
0.2
0.0
0.0
800 1000 1200 1400 1600 1800 800 1000 1200 1400 1600 1800
AUC AUC
Andersson et al 2002
13. Grade 2-4 Acute GVHD
1.00
A
C 0.75
U HR 3.1 (CI= 1.3-7.2)
T
E
0.50
G BUCY/FM
V
H
D 0.25
0.00 NMA
0 50 100
Days
14. Nonablative BMT
• Reduced toxicity
• Reduced GVHD
• Similar infections occur, but generally
respond to therapy
• Lower treatment related mortality
• Can extend the use of HSCT to patients
up to 75 years of age
15. Comparisons Albative vs. RIC SCT
• Lack of randomized controlled trials
• Non-randomized comparisons always
confounded by different patient populations
– Ablative- young, fit patients
– RIC- Older patients with comorbidities
• Conclusions
– RIC higher relapse, lower NRM, survival not
significantly different.
• Can one develop effective anti-tumor
preparative regimens, with acceptable (less)
toxicity?
16. IV Bu-Flu Overall Survival
and Event Free Survival
1.0
1.0
0.8
0.8
Event-free probability
Survival Probability
0.6
0.6
0.4
0.4
In remission, PB.blast=0
Active Disease, PB.blast=0
Active Disease, PB.blast>0
0.2
In remission, PB.blast=0 0.2
Active Disease, PB.blast=0 p<0.0001
Active Disease, PB.blast>0 p<0.0001
0.0
0.0
0 20 40 60 80 100 120 0 20 40 60 80 100 120
Time(weeks) Time(weeks)
20. Ablative Allo-BMT in
Indolent Lymphoma
100
Survival
DFS
Probability, %
80 Treatment-related mortality
Relapse
60
40
20
0
0 1 2 3 4 5 6
van Besien et al. Blood. 1998;92:1832-1836. Years
21. NON-MYELOABLATIVE ALLOGENEIC SCT
Conditioning Regimen
Rituximab Fludarabine 30 mg/m2 Rituximab
375 mg/m2 Cyclophosphamide 750 mg/m2 1000
mg/m2
ASCT
Days
-13 -6 -5 -4 -3 0 +1 +8
•ATG 15 mg/kg daily, was given days –5 to –3 for mismatched or unrelated SCT
•Tacrolimus and methotrexate were used for GVHD prophylaxis
22. FCR allo SCT for Low Grade
Lymphoma
Khouri et al Blood 2008
23. Rituximab: Mechanism of Action
Antibody-Dependent Cell-Mediated
Cytotoxicity (ADCC)
Macrophage,
Monocyte,
or Natural Killer
Cell
CD20
FcγRI, FcγRII, or
FcγRIII
CELL
LYSIS
Anderson DR, et al. Biochem Soc Trans. 1997;25:705-708,
Clynes RA, et al. Nat Med. 2000;6:443-446.
25. Efficacy of Nonablative HSCT
Highly Effective Dose Intensity
(better than ablative) Important
LGL, CLL CML
Mantle cell lymphoma AML /MDS
Myeloma (tandem)? LCL, Hodgkin’s disease
Renal Cell, Ovarian ALL
Breast CA-Promising
26. ATG with RIC SCT
CIBMTR-Soiffer Blood 2011
• Compare T-replete transplants with no
ATG, ATG, Alemtuzumab
• ATG- assoc with decreased cGVHD,
increased relapse, worse PFS and
survival
• Alemtuzumab- assoc with decreased
acute and cGVHD, increased relapse,
no change in survival
29. Cord Blood Transplantation
• Rich source of stem cells
• ~50,000 units banked, immediately available
for transplantation
• Immunologically immature- less prone to
produce GVHD
• Less risk of transmitting infection
• Can successfully transplant across HLA
mismatch
• Major concern- low stem cell dose, longer
time to engraftment- may be overcome by ex
vivo expansion
• Results comparable to MUD BMTs
30. Mesenchymal Stem Cells (MSC)
• MSC are a stromal component
of the hematopoietic
microenvironment.
• They provide cellular and
extracellular components of the
stem cell “niche”.
• When isolated and used in vitro
in combination with cytokines,
MSC markedly increase the
expansion of CB hematopoietic
progenitors.
31. Co-culture with MSC significantly enhances
ex vivo expansion of CB cells
Fold increase x13 x25 x7 x14 x200 x44
Day 14 hematopoietic output from liquid culture of CD133+ (solid bar) vs.
co-culture of non-selected CB cells with MSC (striped bar)
Robinson et al. Bone Marrow Transplantati
32. MSC-CB Expansion Trial Engraftment Data
Median time to engraftment (range)
Neutrophil (>500/µl) 15 days (range 9-42)
Platelet (>20,000/µl) 40 days (range 13-62)
Cumulative Incidence of Engraftment
Neutrophil (>500/µl) 97% (n=31)
Platelet (>20,000/µl) 81% (n=26)
- One patient died before engraftment
de Lima et al. Blood (ASH Annual Meeting Abstracts), 2010; 116: 362
39. Allo NK-based conditioning:
Ablation of recipient targets
Kill recipient APCs =
protection from GvHD
Donor DC
alloreactive
DC
NK cells
DC
NK
Lysis
NK
NK Lysis
leukemia
Lysis
Kill leukemia =
T TT T GvL effect
Kill recipient T cells =
improved engraftment
Ruggeri et al. Science 2002
40. Addition of NK cells to HSCT
Phase I/II study to determine toxicity and efficacy of addition of
alloreactive NK cells to high dose chemotherapy and allogeneic
stem cell transplantation for myeloid leukemias
Haploidentical
Allo reactive Allo match
Busulfan NK Cells PBPC
ATG
Fludarabine
Champlin et al
47. If We Can Prevent GVHD
• Dramatically expand use of allogeneic
SCT
• Bone marrow failure/immune deficiency/metabolic
diseases of hematopoietic cells
• Non malignant hematologic/metabolic/immune
mediated diseases
– Thalassemia, Hemoglobinapathies
– Autoimmune diseases
» Arthritis, Diabetes, Rheumatologic diseases, ……
• Tolerance for Organ Transplants
• Malignant Diseases
– Eliminates major toxicity of highly effective treatment
48. Ideal Nonablative Hematopoietic Transplant
Preparative D D D D D
Regimen D D Vaccine or
Immune
HSCT
Effector cells
R R R D D
D
R D D
R D D
RL R D
RL RL D
Recipient Donor Tolerant Complete Chimera
Mixed Chimera
No GVHD, Immune Reconstitution, GVL for malignancy