West Immunotherapy, Vaccines for Lung Cancer Mage-A3, Stimuvax, and LucanixH. Jack West
Update of results and current clinical trials of vaccines for lung cancer, including MAGE-A3, Stimuvax, and Lucanix for stage I-III non-small cell lung cancer. @JackWestMD, @CancerGRACE cancerGRACE.org
Characterizing the Microbiome of Neonates and Infants to explore associations...QIAGEN
This webinar slidedeck will focus on the acquisition and development of the preterm gut microbiome from birth and following discharge from intensive care. Specifically, the discussion will be around the association of the gut microbiome with necrotizing enterocolitis (NEC) and late onset sepsis (LOS), as well as the impact of birth mode. The other discussion points will be the analysis of multi-omic datasets, including the analysis of the airway microbiome and metabolome in infants hospitalized with bronchiolitis.
Dr. David Mooney - Simposio Internacional 'Terapias oncológicas avanzadas'Fundación Ramón Areces
Los días 15 y 16 de octubre de 2014, la Fundación Ramón Areces y la Real Academia Nacional de Farmacia, en colaboración con la Fundación de la Innovación Bankinter, reunieron en Madrid a algunos de los mayores expertos mundiales en nuevas terapias contra el cáncer. El Simposio Internacional, coordinado por la profesora y académica María José Alonso, analizó el momento actual de la lucha contra esta enfermedad. También fue un punto de encuentro para científicos de los más innovadores institutos de investigación en oncología, quienes debatieron sobre tres grandes temas: la Medicina Personalizada contra el cáncer, los nanomedicamentos en la terapia del cáncer y las terapias basadas en la inmunomodulación.
West Immunotherapy, Vaccines for Lung Cancer Mage-A3, Stimuvax, and LucanixH. Jack West
Update of results and current clinical trials of vaccines for lung cancer, including MAGE-A3, Stimuvax, and Lucanix for stage I-III non-small cell lung cancer. @JackWestMD, @CancerGRACE cancerGRACE.org
Characterizing the Microbiome of Neonates and Infants to explore associations...QIAGEN
This webinar slidedeck will focus on the acquisition and development of the preterm gut microbiome from birth and following discharge from intensive care. Specifically, the discussion will be around the association of the gut microbiome with necrotizing enterocolitis (NEC) and late onset sepsis (LOS), as well as the impact of birth mode. The other discussion points will be the analysis of multi-omic datasets, including the analysis of the airway microbiome and metabolome in infants hospitalized with bronchiolitis.
Dr. David Mooney - Simposio Internacional 'Terapias oncológicas avanzadas'Fundación Ramón Areces
Los días 15 y 16 de octubre de 2014, la Fundación Ramón Areces y la Real Academia Nacional de Farmacia, en colaboración con la Fundación de la Innovación Bankinter, reunieron en Madrid a algunos de los mayores expertos mundiales en nuevas terapias contra el cáncer. El Simposio Internacional, coordinado por la profesora y académica María José Alonso, analizó el momento actual de la lucha contra esta enfermedad. También fue un punto de encuentro para científicos de los más innovadores institutos de investigación en oncología, quienes debatieron sobre tres grandes temas: la Medicina Personalizada contra el cáncer, los nanomedicamentos en la terapia del cáncer y las terapias basadas en la inmunomodulación.
Pathways and targets how might these affect my treatment decisions gail eckh...Fight Colorectal Cancer
Dr. Gail Eckhardt
Professor and Head of the Division of Medical Oncology at the University of Colorado Denver and Health Sciences Center.
Join us for an exciting webinar about pathways and targets. Dr. Eckhardt will discuss the basic of pathways within a cancer cell, and how (and why) they can affect treatment options for patients. She'll explain how we learn about how new pathways are discovered, and how this information tell us what drugs may work in certain patients and why some drugs don’t.
Dr. Eckhardt will discuss the idea of targeted therapies, and the difference between them and regular chemotherapy. She'll talk about the relationship between pathways and targeted drugs, and how this may impact drug development in the future.
Innovación en terapia sistémica de cáncer de pulmónMauricio Lema
Para evento de cirugía de tórax, Hotel Intercontinental, Medellín, 22.05.2018 (se complementa con las otras dos presentaciones de hoy: qué hay de nuevo en diagnóstico molecular, pronóstico y seguimiento, y células tumorales circulantes en NSCLC).
HIV Alert- Novel Strategies and Agents for HIV Management.2016hivlifeinfo
In this downloadable slideset, Daniel R. Kuritzkes, MD, and Paul E. Sax, MD, review potential future HIV treatment strategies—including long-acting ART, dual-therapy regimens, and investigational agents—and discuss where these strategies might fit into the current therapeutic landscape.
Format: Microsoft PowerPoint (.ppt)
File size: 926 KB
Date posted: 6/21/2016
Robert Anders, MD, PhD, Robert L. Ferris, MD, PhD, and Lauren L. Ritterhouse, MD, PhD, prepared useful Practice Aids pertaining to biomarker testing for this CME/MOC activity titled "The Central Role of Biomarker Testing in Piecing Together the Immuno-Oncology Puzzle: Essential Guidance for Pathologists to Maximize the Potential of Cancer Immunotherapies." For the full presentation, monograph, complete CME/MOC information, and to apply for credit, please visit us at http://bit.ly/2QAudYX. CME/MOC credit will be available until December 26, 2019.
NSCLC: diagnóstico molecular, pronóstico y seguimiento; CTCMauricio Lema
Lo nuevo en diagnóstico molecular, pronóstico y seguimiento en NSCLC, y el impacto pronóstico de las Células Tumorales Circulantes. Para evento de cirugía de tórax, Hotel Intercontinental, Medellín, 22.05.2018 (se complementa con las la presentación de lo nuevo en terapia sistémica en NSCLC).
Hepatitis B infection in Stem cell transplant patients and role of lamivudine...Alok Gupta
The presentation describes Hepatitis B infection in Stem cell transplant patients and role of lamivudine prophylaxis in prevention.
The presentation was made at annual meeting of Mumbai Hematology Group held at ACTREC, Mumbai in 2014.
Roy H. Decker, MD, PhD; Kristin Higgins, MD; and Jyoti D. Patel, MD, prepared useful practice aids pertaining to immunotherapies in lung cancer for this CME/MOC activity titled “NSCLC Tumor Board: Navigating the Evolving Role of Immunotherapy in Multimodal Management of Locally Advanced and Early-Stage Lung Cancer.” For the full presentation, monograph, complete CME/MOC information, and to apply for credit, please visit us at http://bit.ly/2mFfEWE. CME/MOC credit will be available until October 22, 2020.
Sipuleucel_T Immunotherapy for Metastatic Prostate Cancer after Failing Hormo...mjavan2001
This PowerPoint presentation demonstrates findings on a clinical trial of sipuleucel-T in HRPC patients to evaluate overall survival in this group. The FDA approval of Provenge was based on the results of IMPACT study.
Pathways and targets how might these affect my treatment decisions gail eckh...Fight Colorectal Cancer
Dr. Gail Eckhardt
Professor and Head of the Division of Medical Oncology at the University of Colorado Denver and Health Sciences Center.
Join us for an exciting webinar about pathways and targets. Dr. Eckhardt will discuss the basic of pathways within a cancer cell, and how (and why) they can affect treatment options for patients. She'll explain how we learn about how new pathways are discovered, and how this information tell us what drugs may work in certain patients and why some drugs don’t.
Dr. Eckhardt will discuss the idea of targeted therapies, and the difference between them and regular chemotherapy. She'll talk about the relationship between pathways and targeted drugs, and how this may impact drug development in the future.
Innovación en terapia sistémica de cáncer de pulmónMauricio Lema
Para evento de cirugía de tórax, Hotel Intercontinental, Medellín, 22.05.2018 (se complementa con las otras dos presentaciones de hoy: qué hay de nuevo en diagnóstico molecular, pronóstico y seguimiento, y células tumorales circulantes en NSCLC).
HIV Alert- Novel Strategies and Agents for HIV Management.2016hivlifeinfo
In this downloadable slideset, Daniel R. Kuritzkes, MD, and Paul E. Sax, MD, review potential future HIV treatment strategies—including long-acting ART, dual-therapy regimens, and investigational agents—and discuss where these strategies might fit into the current therapeutic landscape.
Format: Microsoft PowerPoint (.ppt)
File size: 926 KB
Date posted: 6/21/2016
Robert Anders, MD, PhD, Robert L. Ferris, MD, PhD, and Lauren L. Ritterhouse, MD, PhD, prepared useful Practice Aids pertaining to biomarker testing for this CME/MOC activity titled "The Central Role of Biomarker Testing in Piecing Together the Immuno-Oncology Puzzle: Essential Guidance for Pathologists to Maximize the Potential of Cancer Immunotherapies." For the full presentation, monograph, complete CME/MOC information, and to apply for credit, please visit us at http://bit.ly/2QAudYX. CME/MOC credit will be available until December 26, 2019.
NSCLC: diagnóstico molecular, pronóstico y seguimiento; CTCMauricio Lema
Lo nuevo en diagnóstico molecular, pronóstico y seguimiento en NSCLC, y el impacto pronóstico de las Células Tumorales Circulantes. Para evento de cirugía de tórax, Hotel Intercontinental, Medellín, 22.05.2018 (se complementa con las la presentación de lo nuevo en terapia sistémica en NSCLC).
Hepatitis B infection in Stem cell transplant patients and role of lamivudine...Alok Gupta
The presentation describes Hepatitis B infection in Stem cell transplant patients and role of lamivudine prophylaxis in prevention.
The presentation was made at annual meeting of Mumbai Hematology Group held at ACTREC, Mumbai in 2014.
Roy H. Decker, MD, PhD; Kristin Higgins, MD; and Jyoti D. Patel, MD, prepared useful practice aids pertaining to immunotherapies in lung cancer for this CME/MOC activity titled “NSCLC Tumor Board: Navigating the Evolving Role of Immunotherapy in Multimodal Management of Locally Advanced and Early-Stage Lung Cancer.” For the full presentation, monograph, complete CME/MOC information, and to apply for credit, please visit us at http://bit.ly/2mFfEWE. CME/MOC credit will be available until October 22, 2020.
Sipuleucel_T Immunotherapy for Metastatic Prostate Cancer after Failing Hormo...mjavan2001
This PowerPoint presentation demonstrates findings on a clinical trial of sipuleucel-T in HRPC patients to evaluate overall survival in this group. The FDA approval of Provenge was based on the results of IMPACT study.
In placental mammals, the umbilical cord (also called the navel string, birth cord or funiculus umbilicalis) is a conduit between the developing embryo or fetus and the placenta. During prenatal development, the umbilical cord is physiologically and genetically part of the fetus and, (in humans), normally contains two arteries (the umbilical arteries) and one vein (the umbilical vein), buried within Wharton's jelly. The umbilical vein supplies the fetus with oxygenated, nutrient-rich blood from the placenta. Conversely, the fetal heart pumps deoxygenated, nutrient-depleted blood through the umbilical arteries back to the placenta.
The blood within the umbilical cord, known as cord blood, is a rich and readily available source of primitive, undifferentiated stem cells (of type CD34-positive and CD38-negative). These cord blood cells can be used for bone marrow transplant.
Some parents choose to have this blood diverted from the baby's umbilical blood transfer through early cord clamping and cutting, to freeze for long-term storage at a cord blood bank should the child ever require the cord blood stem cells (for example, to replace bone marrow destroyed when treating leukemia).
In the future, cord blood-derived embryonic-like stem cells (CBEs) may be banked and matched with other patients, much like blood and transplanted tissues. The use of CBEs could potentially eliminate the ethical difficulties associated with embryonic stem cells (ESCs).
Современное лечение ВИЧ.Обобщённые данные с конференции CROI 2020 / Contempor...hivlifeinfo
Современное лечение ВИЧ.Обобощенные данные с конференции CROI 2020 / Contemporary Management of HIV.Integrating New Data From CROI 2020
Широкий спектр вопросов, включая стратегии АРТ на поздних стадихя заболевания, менеджмент ожирения, метаболические исходы АРТ, данные по АРТ во время беременности и пр
Format: Microsoft PowerPoint (.ppt)
File Size: 554 KB
Released: April 14, 2020
HIV Alert:Emerging Updates on Dual Therapy.2018hivlifeinfo
In this downloadable slideset, Joseph J. Eron, Jr., MD, and Babafemi Taiwo, MBBS, provide expert insight into the use of a recently-approved dual-therapy regimen and review data surrounding investigational two-drug regimens.
Format: Microsoft PowerPoint (.ppt)
File size: 375 KB
Date posted: 1/5/2018
HIV Alert:Новые стратегии и агенты в лечении ВИЧ/Novel Strategies and Agents ...hivlifeinfo
HIV Alert-Новые стратегии и агенты в лечении ВИЧ/Novel Strategies and Agents for HIV Management.2017
In this downloadable slideset, Daniel R. Kuritzkes, MD, and Paul E. Sax, MD, review potential future HIV treatment strategies—including dual-therapy regimens, long-acting ART, and investigational agents—and discuss where these might fit into the current therapeutic landscape.
Format: Microsoft PowerPoint (.ppt)
File size: 570 KB
Date posted: 9/27/2017
Современное лечение ВИЧ: новые подходы к оптимизации АРТ/Contemporary Managem...hivlifeinfo
Вопросы, связанные с АРТ первого ряда, смена арв-стратегии для пациентов с вирусной супрессией, акцентом на возрастающую роль новыхантиретровирусных стратегий.
Circulating Tumor Cells (CTC) and pathological Complete Response (pCR) are strong independent prognostic factors in Inflammatory Breast Cancer (IBC) in a pooled analysis of two multicentre phase II trials (BEVERLY 1 & 2) of neoadjuvant chemotherapy combined with bevacizumab
Every summer, the American Society for Clinical Oncology (ASCO) brings together internationally renowned cancer researchers, doctors and medical professionals to discover and discuss the latest in cancer research and patient care. This webinar, scheduled for June 19 2013 is presented by Dr. John Marshall, and will highlight the key colorectal cancer findings from the 2013 meeting and what these advances mean for you.
Report Back from San Antonio Breast Cancer Symposium (SABCS 2022)bkling
Curious about the latest developments in Early-Stage Breast Cancer and Metastatic Breast Cancer Research? Join us as Dr. Anne Blaes, the Division Director of Hematology/Oncology/Transplantation and Professor in Hematology/Oncology at the University of Minnesota, breaks down the most recent developments released at the annual San Antonio Breast Cancer Symposium regarding early-stage and metastatic breast cancer research.
Современное лечение и профилактика ВИЧ : передовые стратегии лечения у пациен...hivlifeinfo
Стратегии смены АРТ у пациентов с вирусной супрессией, включая смену АРТ при резистентности, рекомендации по инъекционным препаратам длительного действия , смена АРТ до или во время беременности
Similar to Double Unit Cord Blood Transplantation for Acute Leukemia (20)
Report Back from SGO 2024: What’s the Latest in Cervical Cancer?bkling
Are you curious about what’s new in cervical cancer research or unsure what the findings mean? Join Dr. Emily Ko, a gynecologic oncologist at Penn Medicine, to learn about the latest updates from the Society of Gynecologic Oncology (SGO) 2024 Annual Meeting on Women’s Cancer. Dr. Ko will discuss what the research presented at the conference means for you and answer your questions about the new developments.
Pulmonary Thromboembolism - etilogy, types, medical- Surgical and nursing man...VarunMahajani
Disruption of blood supply to lung alveoli due to blockage of one or more pulmonary blood vessels is called as Pulmonary thromboembolism. In this presentation we will discuss its causes, types and its management in depth.
Knee anatomy and clinical tests 2024.pdfvimalpl1234
This includes all relevant anatomy and clinical tests compiled from standard textbooks, Campbell,netter etc..It is comprehensive and best suited for orthopaedicians and orthopaedic residents.
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
Acute scrotum is a general term referring to an emergency condition affecting the contents or the wall of the scrotum.
There are a number of conditions that present acutely, predominantly with pain and/or swelling
A careful and detailed history and examination, and in some cases, investigations allow differentiation between these diagnoses. A prompt diagnosis is essential as the patient may require urgent surgical intervention
Testicular torsion refers to twisting of the spermatic cord, causing ischaemia of the testicle.
Testicular torsion results from inadequate fixation of the testis to the tunica vaginalis producing ischemia from reduced arterial inflow and venous outflow obstruction.
The prevalence of testicular torsion in adult patients hospitalized with acute scrotal pain is approximately 25 to 50 percent
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
The prostate is an exocrine gland of the male mammalian reproductive system
It is a walnut-sized gland that forms part of the male reproductive system and is located in front of the rectum and just below the urinary bladder
Function is to store and secrete a clear, slightly alkaline fluid that constitutes 10-30% of the volume of the seminal fluid that along with the spermatozoa, constitutes semen
A healthy human prostate measures (4cm-vertical, by 3cm-horizontal, 2cm ant-post ).
It surrounds the urethra just below the urinary bladder. It has anterior, median, posterior and two lateral lobes
It’s work is regulated by androgens which are responsible for male sex characteristics
Generalised disease of the prostate due to hormonal derangement which leads to non malignant enlargement of the gland (increase in the number of epithelial cells and stromal tissue)to cause compression of the urethra leading to symptoms (LUTS
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
Couples presenting to the infertility clinic- Do they really have infertility...Sujoy Dasgupta
Dr Sujoy Dasgupta presented the study on "Couples presenting to the infertility clinic- Do they really have infertility? – The unexplored stories of non-consummation" in the 13th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2024) at Manila on 24 May, 2024.
ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
Double Unit Cord Blood Transplantation for Acute Leukemia
1. Juliet N. Barker, MBBS (Hons), FRACP
Associate Attending
Director, Cord Blood Transplant Program
Memorial Sloan-Kettering Cancer Center
Double Unit Cord Blood
Transplantation for Acute Leukemia
CSA/ MMF
-3 -2 -1-4-6 -5 30 1000
2. Acknowledgements
U of Minnesota
John E. Wagner
NYBC
Pablo Rubinstein
Cladd Stevens
Machi Scaradavou
MSKCC
Staff of Adult & Pediatric
Transplant
Search: Courtney Byam, Rosanna Ferrante
Debbie Wells, Melissa Sideroff, Sinda Lee
Cell Therapy Lab
CB Research Staff: Marissa Lubin
Anne Marie Gonzales , Katie Evans
Cellular Immunology Lab: Kathy Smith
Pediatrics: Machi Scaradavou
Nancy Kernan & Richard O’Reilly
Adult BMT Service: Doris Ponce
Marcel van den Brink & Sergio Giralt
Funding
Gabrielle’s Angel Foundation for Cancer Research, the MSKCC Society,
MSKCC Translational and Integrative Medicine Research Grant,
P01 CA23766 NCI, NIH.
3. Original Reasons for Double Unit CB Grafts
• Platform for investigation of expansion or other
graft manipulation.
• Augment graft cell dose = improve engraftment,
reduce TRM, improve survival.
4. Reasons for Double Unit CB Grafts: Successful?
• Platform for investigation of expansion or other
graft manipulation?: YES
• Augment graft cell dose = improve engraftment,
reduce TRM, improve survival?: YES in adults,
children?
5. Sibling typing →
simultaneous URD & CB search
Suitable Sibling or URD:Suitable CB Graft:
4-6/6 A,B antigen, DRB1 allele
2 units: each > 2 x 107 NC/kg
Hi Dose Prep RIC or Mini
Children
(Young adults)
RIC/ Mini
+ 10/10 donor
Hi Dose +
TCD 9-10/10 donor
MSKCC Donor Algorithm: DCBT Extends Access
Donors identified for > 95% patients.
6. URD (n=465) CB (n=156) No Graft (n=36)
NW Europe Asian
Eastern Europe African
Southern Europe White Hispanic
Europe Mix Middle Eastern
Non-Europe Mix
Transplant Type by Patient Ancestry (n = 657)
> 50% CBTs
non-European
ancestry:
DCB extends
access.
2012 update from Barker et al 2010, BBMT
7. P = NS
Comparable 5-Yr LFS: DCBT, MRD, & URD
(U of Minnesota & Fred Hutchinson CRC, n = 536)
Brunstein & Delaney,
Blood 2010
DCBT: Lower risk of relapse compensated for higher
TRM = comparable LFS to sib & URD.
(Similar results: Ponce et al, BBMT 2011; Dana Farber).
8. MSKCC DCBT for Acute Leukemia in
Adults & Children
• 10/2005 - 5/2012.
• High risk acute leukemia in morphologic CR1-4 or
aplasia or MDS/ MPD < 5% blasts.
• High dose or RIC (both ablative).
• Follow-up: median 3.2 years.
Barker et al, ASBMT 2013
9. High*:
Cy 120
Flu 75
TBI 1375
“Midi” is new prep alternative
Mini:
Cy 50
Flu 150
TBI 200
Midi**:
Cy 50
Thio 10
Flu 150
TBI 400
MSKCC Conditioning for Acute Leukemia/ MDS
* If no TBI: Clo/ Mel/ Thio ** Ponce et al, BBMT 2013
10. 2-Yr DFS in 92 DCBT if Acute Leuk, MDS/MPD
Adults (n = 65, median 47 yrs, 2.7 + 2.0):
65% (95%CI: 55-78)
0.00.20.40.60.81.0
Months Post-Transplant
Disease-FreeSurvival
0 6 12 18 24
Children (n = 27, median 7 yrs, 4.4 + 2.9):
73% (95%CI: 56-93)
High rates of 2-year DFS after DCBT-
esp. given median 2.1 TNC dose of winner in adults.
Median TNC winner: Peds 4.3, Adults 2.1
Barker et al, ASBMT 2013
11. Early analyses:
• No relationship: TNC or CD34+ dose.
Association with higher CD3+ dose.
• No relationship: HLA-match to patient.
Why Does One Unit Win?*
Barker et al, Blood 2005
12. % of Viable
CD34+ Cells
Winner
(n = 44)
Loser
(n = 44)
< 75%
(n = 16)
1 15
≥ 75%
(n = 72)
43 29
Engraftment in 44 Double Unit CBT Recipients
By Post-Thaw CD34+ Cell Viability (n = 88 Units)
Using threshold of 75% viable CD34+s (mean-2SD),
all but one (43/44) engrafting units had
CD34+ viability > 75% (p = 0.0006).
ie Only 1/16 poor viability units engrafted.
Poor CD34+ viability correlated with lower CFUs (p = 0.02).
Scaradavou, BBMT 2010
14. DCB with CD34pos
#1 #2
DCB
with MNC
MNC #1
MNC #2
CD34pos Selection
Sacrifice mice weeks 4-8
Correlate murine & patient engraftment.
Double Unit CBT in NSG Mice Using
Samples from Patient Grafts
Eldjerou et al, Blood, 2010
15. DCB with CD34pos
#1 #2
DCB
with MNC
MNC #1
MNC #2
CD34pos Selection
Unit dominance.
Clinical correlation.
Double Unit CBT in NSG Mice Using
Samples from Patient Grafts
Eldjerou et al, Blood, 2010
No unit dominance.
No clinical correlation.
16. DCB with
CD34pos
CD34neg #2
+Add-back
CD34neg #2
#1 #2MNC #1
MNC #2
CD34neg #1
+Add-back
CD34neg #1
CD34pos Selection
Added CD34 negs - clinically engrafting unit:
100% murine engraftment with that unit.
Added CD34 negs - clinically NON-engrafting unit:
100% murine engraftment with that unit.
Double Unit CBT in NSG Mice Using
Samples from Patient Grafts
Eldjerou et al, Blood, 2010
17. Double Unit CBT: NSG Murine Model
Eldjerou et al 2010, Blood
• Murine-patient correlation suggests host factors
not relevant.
• Unit dominance mediated by CD34- fraction.
If either unit has engraftment potential
(majority but not all),
unit dominance is immune mediated.
18. In 9/10 DCBT Recipients: Development of IFN-γ–
Secreting CD8+ T-cells Recognizing Allo-antigens
Expressed by Non-engrafting Unit
Gutman et al, Blood 2010
Unit
dominance
is mediated
by effector
CD8+
T-cells
developed
from naïve
precursors
in winner
19. In 9/10 DCBT Recipients: Development of IFN-γ–
Secreting CD8+ T-cells Recognizing Allo-antigens
Expressed by Non-engrafting Unit
Gutman et al, Blood 2010
Unit
dominance
correlated
with higher
naïve CD8+
T-cell
dose:
Milano et al,
BBMT 2012
20. Day
post-CBT
N (%) with loser detected
Unit-unit match:
1-6/10
Unit-unit match:
7-10/10
P
+21 (n = 83) 2/ 56 (4%) 14/ 27 (52%) < 0.0001
+28 (n = 79) 0/ 54 (0%) 14/ 25 (56%) < 0.0001
+60 (n = 72) 0/ 47 (0%) 8/ 25 (32%) < 0.0001
+100 (n = 68) 0/ 45 (0%) 3/ 23 (13%) 0.04
+365 (n = 43) 0/ 30 (0%) 1/ 13 (8%) 0.30
Serial Detection of Losing Unit
After DCBT by Unit-Unit HLA-match (n = 83)
Higher level of unit-unit HLA-match associated with
co-engraftment of both units.
Avery et al, Blood 2011
21. Why does one unit win?*:
Hematopoietic potential of each unit.
Unit vs unit immune interactions
(T-cell mediated).
As important:
What attributes of graft determine
engraftment success,
GVHD & survival after DCBT?
22. Infused Doses of Winner & Neutrophil Engraftment
Avery S et al, Blood 2011
Infused viable CD34+ cell dose of winner determines engraftment
23. Inf. Total Doses (Both Units Combined) & Engraftment
Total TNC & CD3+ cell dose also have dose dependent effects.
Avery S et al, Blood 2011
24. Neutrophil Engraftment after 92 DCBT by
Infused Viable CD34+ Cell Dose x 105/kg of Winner*
0.00.20.40.60.81.0
Days Post-Transplant
CumulativeIncidence
0 10 20 30 40
< 0.50
(n = 23)
0.51-1.00 (n = 27)
1.01-1.50
(n = 19)
> 1.51
(n = 23)
100%
engraftment
success if
winning unit
had viable
CD34+ cell
dose > 1.0.
* Unit predominating in assessment of hematopoiesis in 1st month post DCBT
P < 0.001
Barker et al,
ASBMT 2013
25. Day 180 Platelet Engraftment to 20,000 (n = 92)
0.00.20.40.60.81.0
Days Post-Transplant
CumulativeIncidence
0 45 90 135 180
Children: 85% (95%CI: 63-95)
Median 50 days
(range 29-118)
Adults: 83% (95%CI: 71-90)
Median 48 days
(range 29-162)
High rates of platelet engraftment by CBT standards.
93% if winning unit
infused CD34+ cell
dose > 1.0 x 105/kg
(vs 78% if lower, p = 0.01)
Barker et al, ASBMT 2013
26. 20
40
60
80
100
0
4-6/6 Allele
1-3/6 Allele
Months Post-Transplant
0
100
80
60
40
20
0
1-7/10 Allele
8-9/10 Allele
1 2 3 4 5 6 0 1 2 3 4 5 6
Ponce, D., BBMT 2013
Gr. III-IV Acute GVHD after DCBT
by Winning Unit HLA-Allele Match to Patient (n = 115)
HLA-allele match of winning unit to patient is important.
27. Comparison 2-Yr DFS P Value
Age 0-15 years (n = 27)
> 16 years (n = 65)
73%
65%
0.32
Ancestry Europeans (n = 40)
Non-Europeans (n = 52)
69%
66%
0.86
Remission
Status
CR1 (n = 49)
All others (n = 43)
66%
69%
0.98
Conditioning
Intensity
High-dose (n = 54)
RIC (n = 38)
70%
64%
0.60
Recipient CMV
Sero-status
CMV+ (n = 51)
CMV- (n = 41)
54%
85%
0.01
2-Yr DFS after DCBT for Acute Leukemia
By Recipient Characteristics (n = 92)
• Comparable DFS in Europeans & non-Europeans.
• RIC (“midi”) promising alternative to high dose prep.
• Recipient CMV+ remains challenging.
Barker et al, ASBMT 2013
28. Comparison 2-Yr DFS P Value
HLA-match
Dominant Unit
2-5/10 (n = 34)
6-7/10 (n = 39)
8-9/10 (n = 19)
69%
65%
68%
0.84
Inf. CD34+ Dose
Dominant Unit
< 1.0 (n = 50)
> 1.0 (n = 52)
64%
72%
0.13
Inf. TNC
Dominant Unit
< 2.0 (n = 34)
2.0-2.85 (n = 27)
> 2.85 (n = 31)
62%
74%
68%
0.29
• Mismatch had no impact on DFS.
• Suggestion of improved DFS if winner had higher CD34+
dose.
2-Yr DFS after DCBT for Acute Leukemia By
Winning Unit Characteristics (n = 92)
Barker et al, ASBMT 2013
29. Due to unit
vs unit
interactions?
Verneris et al,
Blood 2009
Double CBT: Reduced Relapse?
Myeloablative DCBT for Acute Leukemia, U of MN
Supported by multiple other analyses: Brunstein, Blood 2007;
Rodrigues, JCO 2009; Brunstein, Blood 2010;
Kindwall-Keller BMT 2012; Rocha, ASH abs 2012.
30. 2-year DFS after RIC CBT in Adult Acute
Leukemia - CR1
P = 0.03
In multivariate
analysis,
double CBT
associated
with improved
DFS (p = 0.04).
Advantage
attributed
to reduced
relapse risk.
Double CBT (n = 136):
51 ± 5%
Single CBT (n = 76):
32 ± 3%
Slide courtesy of
V. Rocha, 2013
31. Overall Survival after Doubles (n = 303) &
Adequately Dosed Singles (n = 106, TNC > 2.5)
Scaradavou A et al. Blood 2013
• Myeloablative & RIC.
• Median inf. TNC: singles 2.8, doubles 3.7.
DCBT extends access to those without an adequate single.
32. 100
0
20
40
60
80
0
100
20
40
60
80
Probability,%
Months 0 3 6 9 12
Double CBT: 64% (54 – 72)
Single CBT: 68% (58 – 76)
BMT CTN 0501 Pediatric Ablative
Randomized Trial: 1-Yr Disease-free Survival
P = 0.22
Slide Courtesy of Dr J. Wagner, ASH 2012
No DFS advantage after myeloablative DCBT in children
Median cryo. TNC:
singles 4.8, doubles 8.9.
33. -7 0 +100
U of MN Changes to Prep & IS for DCBT
Cy 120/ Flu 75/ TBI 1320
CSA/ MP
CB
#2
CB
#1
-8 0 +100
Cy 120/ ATG/ TBI 1320
CB
#2
CB
#1
CSA/ MMF
Prep & IS changes contributed to DCBT benefit
Barker et al, Blood 2005
34. Unit Type N Units
Transplanted
(N = 26)
Median (Range) Cost
Per Unit
NMDP-International 4 (15%) $41,338 (38,233 – 46,418)
NMDP-Domestic
(excl. NYBC)
14 (54%) $38,570 (33,150 - 40,230)
NYBC-Direct 7 (27%) $42,500
NCBI NYBC via NMDP 1 (4%)* $48,725
Charges to MSKCC for CB Units Jan-April 2013
Approximate cost of double unit graft
with 6 units typed: $90,000.
* NCBI unit = must be purchased via NMDP.
• 13 DCBT (n = 26 units).
• Median 6 units typed per patient (range 4-13).
35. DFS After DCBT in Engrafting Adults by Speed of
Neutrophil Recovery: Day 45 Landmark (n = 61)
P = 0.02
0.00.20.40.60.81.0
Time Post-Transplant
DFS
45 days 6mo 12mo 18mo 24mo
Neut. recovery < 25 days (n = 32):
84% (95%CI: 72-98)
Neut. recovery > 25 days (n = 29):
54% (95%CI: 39-76)
Marked survival advantage if rapid engraftment:
need to speed engraftment for all.
36. -8 0 +1 +28 +100
Compare engraftment
(speed, success,
chimerism) to
DCB controls
Hi dose or midi
myeloablative
MSK Approach to Speed Neutrophil Recovery:
DCBT + Haplo
Graft > 100k-but earlier neutrophil recovery = less
resources + earlier discharge compensates.
34+ selected
PBSC
(Miltenyi)
Haplo-identical
family member
37. Double Unit CBT: Conclusions
• Extends access.
• Insurance policy against poor viability unit.
• Facilitates engraftment in low dose setting:
oImplies loser has biologic activity.
oWinner determines engraftment & GVHD.
oAs compared with singles, need to analyze doubles based on
characteristics of winner: is loser doing anything?
(or if better unit had been given alone??).
• High rates of DFS in acute leukemics.
• Preliminary data: Europeans & non-Europeans comparable DFS.
• Multiple series: DCBTs comparable DFS with URDs.
• Problems:
o2 un-manipulated units not enough.
oEscalating cost is a major problem.