1) The document summarizes research on donor selection for haploidentical hematopoietic stem cell transplantation (HSCT). It finds that donor-specific anti-HLA antibodies were associated with primary graft failure after unmanipulated haploidentical HSCT.
2) Specifically, the research studied 345 HSCT recipients and found that 25.2% had donor-specific anti-HLA antibodies, and those with higher antibody levels had higher rates of graft rejection and poor graft function.
3) Patients who experienced primary graft failure due to these antibodies had inferior survival outcomes compared to those without graft failure. The results suggest donor-specific antibodies should be considered when selecting a haploidentical donor.
HCT and Gene Therapy for Thalassemia Major
Mark Walters, M.D.
January 18, 2014
Thalassemia Patient and Family Conference
Northern California Comprehensive Thalassemia Center
Children's Hospital Oakland
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
HCT and Gene Therapy for Thalassemia Major
Mark Walters, M.D.
January 18, 2014
Thalassemia Patient and Family Conference
Northern California Comprehensive Thalassemia Center
Children's Hospital Oakland
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
Expert Guidance on Current Standards and New Directions in Newly Diagnosed Mu...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
Presented by leading expert Urvi Shah, MD, Assistant Attending in the Myeloma Service at Memorial Sloan Kettering Cancer Center, this slide deck will explore guidance on current standards and new directions in newly diagnosed multiple myeloma.
STATEMENT OF NEED
An estimated 35,730 new cases of multiple myeloma are diagnosed in the United States annually, and 12,590 people die of the disease (Siegel et al, 2023). Characterized by clonal proliferation of malignant plasma cells in the bone marrow, multiple myeloma is associated with anemia, renal insufficiency, bone destruction, and hypercalcemia, all of which significantly impact patients’ quality of life. The development of novel therapies and combinations in recent years, including anti-CD38 antibodies, has provided numerous therapeutic options for newly diagnosed multiple myeloma. However, the optimal selection of induction therapy and subsequent treatment sequencing for individual patients remains a challenge. Additionally, factors including age, frailty, comorbidities, transplant eligibility, treatment-related toxicities, and supportive care needs complicate treatment decisions (Costello et al, 2022). This hematology/oncology fellows lecture series will explore expert guidance on current standards and new directions in newly diagnosed multiple myeloma.
TARGET AUDIENCE
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with multiple myeloma.
LEARNING OBJECTIVES
Upon completion of this activity, participants should be able to:
Assess guideline-recommended treatment combination and sequencing strategies in NDMM
Evaluate the role of minimal residual disease (MRD) assessment in NDMM treatment
Review the mechanism of action, efficacy, and safety of anti-CD38 monoclonal antibodies in the treatment of NDMM
Discuss strategies to monitor and manage treatment-related toxicities and optimize survivorship care
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Cancer patients are at an increased risk of venous thromboembolism. There have been several guidelines published on the topic from the American College of Chest Physicians (ACCP), the American Society of Clinical Oncology (ASCO), and the National Comprehensive Cancer Network (NCCN). Although they agree on some issues regarding prophylaxis and treatment there are several areas that vary. This presentation covers the varying recommendations and the areas of consensus (yellow boxes) among the guidelines while using a patient case to guide their interpretation.
Lab Diagnosis of Chronic lymphoproliferative disorders (CLPD); Flowcytometric...Dr Siddartha
Lab Diagnosis of Chronic lymphoproliferative disorders (CLPD); Flowcytometric Evaluation
Basavatarakam Indo-American Cancer Hospital and Research Institute
Leveraging BCMA-Directed Therapies for Improved Patient Outcomes in Relapsed/...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Rahul Banerjee, Assistant Professor at the University of Washington and Fred Hutchinson Cancer Center, will provide a case-based discussion on leveraging BCMA-directed antibody-drug conjugates, CAR T-cell therapies, and bispecific T-cell engagers to improve outcomes for patients with multiple myeloma in need of additional treatment options.
STATEMENT OF NEED
Multiple myeloma is a disease that remains incurable for most patients, many of whom become refractory to the majority of available treatments (Kumar et al, 2022). It is estimated that 35,730 new cases of multiple myeloma are diagnosed in the United States annually, and 12,590 people die of the disease (Siegel et al, 2023). Agents targeting B-cell maturation antigen (BCMA), including antibody-drug conjugates (ADCs), chimeric antigen receptor (CAR) T-cell therapies, and bispecific T-cell engagers, represent a promising therapy class for patients in need of additional treatment options, including those with higher genetic risk and heterogeneity (Kumar et al, 2022). This activity led by Rahul Banerjee, MD, FACP, Assistant Professor in the Division of Medical Oncology at the University of Washington and Fred Hutchinson Cancer Center, will provide strategies for leveraging BCMA-directed therapies for improved patient outcomes in relapsed/refractory multiple myeloma.
TARGET AUDIENCE
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with multiple myeloma (MM).
LEARNING OBJECTIVES
Upon completion of this activity, participants should be able to:
Evaluate the mechanisms of action, efficacy, and safety of BCMA-directed therapies in relapsed/refractory MM
Assess guideline-recommended combination and sequential treatment strategies for relapsed/refractory MM
Identify risk factors for the development of treatment-specific adverse events with different classes of BCMA-directed therapies
Describe mechanisms of drug resistance/loss of response to BCMA-directed therapies
Examine the roles of gene expression profiling, soluble BCMA, and measurable residual disease (MRD) in clinical practice.
Ohio State's 2016 ASH Review Blood and Marrow Trasplantation (with Turning Po...OSUCCC - James
Ohio State’s 2016 ASH Review
Blood and Marrow Transplantation
Basem M. William, MD, MRCP(UK), FACP
Assistant Professor of Internal Medicine
Blood and Marrow Transplant Program
Expert Guidance on Current Standards and New Directions in Newly Diagnosed Mu...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
Presented by leading expert Urvi Shah, MD, Assistant Attending in the Myeloma Service at Memorial Sloan Kettering Cancer Center, this slide deck will explore guidance on current standards and new directions in newly diagnosed multiple myeloma.
STATEMENT OF NEED
An estimated 35,730 new cases of multiple myeloma are diagnosed in the United States annually, and 12,590 people die of the disease (Siegel et al, 2023). Characterized by clonal proliferation of malignant plasma cells in the bone marrow, multiple myeloma is associated with anemia, renal insufficiency, bone destruction, and hypercalcemia, all of which significantly impact patients’ quality of life. The development of novel therapies and combinations in recent years, including anti-CD38 antibodies, has provided numerous therapeutic options for newly diagnosed multiple myeloma. However, the optimal selection of induction therapy and subsequent treatment sequencing for individual patients remains a challenge. Additionally, factors including age, frailty, comorbidities, transplant eligibility, treatment-related toxicities, and supportive care needs complicate treatment decisions (Costello et al, 2022). This hematology/oncology fellows lecture series will explore expert guidance on current standards and new directions in newly diagnosed multiple myeloma.
TARGET AUDIENCE
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with multiple myeloma.
LEARNING OBJECTIVES
Upon completion of this activity, participants should be able to:
Assess guideline-recommended treatment combination and sequencing strategies in NDMM
Evaluate the role of minimal residual disease (MRD) assessment in NDMM treatment
Review the mechanism of action, efficacy, and safety of anti-CD38 monoclonal antibodies in the treatment of NDMM
Discuss strategies to monitor and manage treatment-related toxicities and optimize survivorship care
Venous Thromboembolism in the Cancer Patientlarriva
Cancer patients are at an increased risk of venous thromboembolism. There have been several guidelines published on the topic from the American College of Chest Physicians (ACCP), the American Society of Clinical Oncology (ASCO), and the National Comprehensive Cancer Network (NCCN). Although they agree on some issues regarding prophylaxis and treatment there are several areas that vary. This presentation covers the varying recommendations and the areas of consensus (yellow boxes) among the guidelines while using a patient case to guide their interpretation.
Lab Diagnosis of Chronic lymphoproliferative disorders (CLPD); Flowcytometric...Dr Siddartha
Lab Diagnosis of Chronic lymphoproliferative disorders (CLPD); Flowcytometric Evaluation
Basavatarakam Indo-American Cancer Hospital and Research Institute
Leveraging BCMA-Directed Therapies for Improved Patient Outcomes in Relapsed/...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Rahul Banerjee, Assistant Professor at the University of Washington and Fred Hutchinson Cancer Center, will provide a case-based discussion on leveraging BCMA-directed antibody-drug conjugates, CAR T-cell therapies, and bispecific T-cell engagers to improve outcomes for patients with multiple myeloma in need of additional treatment options.
STATEMENT OF NEED
Multiple myeloma is a disease that remains incurable for most patients, many of whom become refractory to the majority of available treatments (Kumar et al, 2022). It is estimated that 35,730 new cases of multiple myeloma are diagnosed in the United States annually, and 12,590 people die of the disease (Siegel et al, 2023). Agents targeting B-cell maturation antigen (BCMA), including antibody-drug conjugates (ADCs), chimeric antigen receptor (CAR) T-cell therapies, and bispecific T-cell engagers, represent a promising therapy class for patients in need of additional treatment options, including those with higher genetic risk and heterogeneity (Kumar et al, 2022). This activity led by Rahul Banerjee, MD, FACP, Assistant Professor in the Division of Medical Oncology at the University of Washington and Fred Hutchinson Cancer Center, will provide strategies for leveraging BCMA-directed therapies for improved patient outcomes in relapsed/refractory multiple myeloma.
TARGET AUDIENCE
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with multiple myeloma (MM).
LEARNING OBJECTIVES
Upon completion of this activity, participants should be able to:
Evaluate the mechanisms of action, efficacy, and safety of BCMA-directed therapies in relapsed/refractory MM
Assess guideline-recommended combination and sequential treatment strategies for relapsed/refractory MM
Identify risk factors for the development of treatment-specific adverse events with different classes of BCMA-directed therapies
Describe mechanisms of drug resistance/loss of response to BCMA-directed therapies
Examine the roles of gene expression profiling, soluble BCMA, and measurable residual disease (MRD) in clinical practice.
Ohio State's 2016 ASH Review Blood and Marrow Trasplantation (with Turning Po...OSUCCC - James
Ohio State’s 2016 ASH Review
Blood and Marrow Transplantation
Basem M. William, MD, MRCP(UK), FACP
Assistant Professor of Internal Medicine
Blood and Marrow Transplant Program
This presentation discusses the latest evidence for blood transfusion triggers in the intensive care unit of various clinical condition including severe sepsis, GI bleed, post surgical cases, and post cardiac surgery among other cnditions
Instructions for Submissions thorugh G- Classroom.pptxJheel Barad
This presentation provides a briefing on how to upload submissions and documents in Google Classroom. It was prepared as part of an orientation for new Sainik School in-service teacher trainees. As a training officer, my goal is to ensure that you are comfortable and proficient with this essential tool for managing assignments and fostering student engagement.
Embracing GenAI - A Strategic ImperativePeter Windle
Artificial Intelligence (AI) technologies such as Generative AI, Image Generators and Large Language Models have had a dramatic impact on teaching, learning and assessment over the past 18 months. The most immediate threat AI posed was to Academic Integrity with Higher Education Institutes (HEIs) focusing their efforts on combating the use of GenAI in assessment. Guidelines were developed for staff and students, policies put in place too. Innovative educators have forged paths in the use of Generative AI for teaching, learning and assessments leading to pockets of transformation springing up across HEIs, often with little or no top-down guidance, support or direction.
This Gasta posits a strategic approach to integrating AI into HEIs to prepare staff, students and the curriculum for an evolving world and workplace. We will highlight the advantages of working with these technologies beyond the realm of teaching, learning and assessment by considering prompt engineering skills, industry impact, curriculum changes, and the need for staff upskilling. In contrast, not engaging strategically with Generative AI poses risks, including falling behind peers, missed opportunities and failing to ensure our graduates remain employable. The rapid evolution of AI technologies necessitates a proactive and strategic approach if we are to remain relevant.
Operation “Blue Star” is the only event in the history of Independent India where the state went into war with its own people. Even after about 40 years it is not clear if it was culmination of states anger over people of the region, a political game of power or start of dictatorial chapter in the democratic setup.
The people of Punjab felt alienated from main stream due to denial of their just demands during a long democratic struggle since independence. As it happen all over the word, it led to militant struggle with great loss of lives of military, police and civilian personnel. Killing of Indira Gandhi and massacre of innocent Sikhs in Delhi and other India cities was also associated with this movement.
Acetabularia Information For Class 9 .docxvaibhavrinwa19
Acetabularia acetabulum is a single-celled green alga that in its vegetative state is morphologically differentiated into a basal rhizoid and an axially elongated stalk, which bears whorls of branching hairs. The single diploid nucleus resides in the rhizoid.
Biological screening of herbal drugs: Introduction and Need for
Phyto-Pharmacological Screening, New Strategies for evaluating
Natural Products, In vitro evaluation techniques for Antioxidants, Antimicrobial and Anticancer drugs. In vivo evaluation techniques
for Anti-inflammatory, Antiulcer, Anticancer, Wound healing, Antidiabetic, Hepatoprotective, Cardio protective, Diuretics and
Antifertility, Toxicity studies as per OECD guidelines
The Roman Empire A Historical Colossus.pdfkaushalkr1407
The Roman Empire, a vast and enduring power, stands as one of history's most remarkable civilizations, leaving an indelible imprint on the world. It emerged from the Roman Republic, transitioning into an imperial powerhouse under the leadership of Augustus Caesar in 27 BCE. This transformation marked the beginning of an era defined by unprecedented territorial expansion, architectural marvels, and profound cultural influence.
The empire's roots lie in the city of Rome, founded, according to legend, by Romulus in 753 BCE. Over centuries, Rome evolved from a small settlement to a formidable republic, characterized by a complex political system with elected officials and checks on power. However, internal strife, class conflicts, and military ambitions paved the way for the end of the Republic. Julius Caesar’s dictatorship and subsequent assassination in 44 BCE created a power vacuum, leading to a civil war. Octavian, later Augustus, emerged victorious, heralding the Roman Empire’s birth.
Under Augustus, the empire experienced the Pax Romana, a 200-year period of relative peace and stability. Augustus reformed the military, established efficient administrative systems, and initiated grand construction projects. The empire's borders expanded, encompassing territories from Britain to Egypt and from Spain to the Euphrates. Roman legions, renowned for their discipline and engineering prowess, secured and maintained these vast territories, building roads, fortifications, and cities that facilitated control and integration.
The Roman Empire’s society was hierarchical, with a rigid class system. At the top were the patricians, wealthy elites who held significant political power. Below them were the plebeians, free citizens with limited political influence, and the vast numbers of slaves who formed the backbone of the economy. The family unit was central, governed by the paterfamilias, the male head who held absolute authority.
Culturally, the Romans were eclectic, absorbing and adapting elements from the civilizations they encountered, particularly the Greeks. Roman art, literature, and philosophy reflected this synthesis, creating a rich cultural tapestry. Latin, the Roman language, became the lingua franca of the Western world, influencing numerous modern languages.
Roman architecture and engineering achievements were monumental. They perfected the arch, vault, and dome, constructing enduring structures like the Colosseum, Pantheon, and aqueducts. These engineering marvels not only showcased Roman ingenuity but also served practical purposes, from public entertainment to water supply.
Introduction to AI for Nonprofits with Tapp NetworkTechSoup
Dive into the world of AI! Experts Jon Hill and Tareq Monaur will guide you through AI's role in enhancing nonprofit websites and basic marketing strategies, making it easy to understand and apply.
Francesca Gottschalk - How can education support child empowerment.pptxEduSkills OECD
Francesca Gottschalk from the OECD’s Centre for Educational Research and Innovation presents at the Ask an Expert Webinar: How can education support child empowerment?
June 3, 2024 Anti-Semitism Letter Sent to MIT President Kornbluth and MIT Cor...Levi Shapiro
Letter from the Congress of the United States regarding Anti-Semitism sent June 3rd to MIT President Sally Kornbluth, MIT Corp Chair, Mark Gorenberg
Dear Dr. Kornbluth and Mr. Gorenberg,
The US House of Representatives is deeply concerned by ongoing and pervasive acts of antisemitic
harassment and intimidation at the Massachusetts Institute of Technology (MIT). Failing to act decisively to ensure a safe learning environment for all students would be a grave dereliction of your responsibilities as President of MIT and Chair of the MIT Corporation.
This Congress will not stand idly by and allow an environment hostile to Jewish students to persist. The House believes that your institution is in violation of Title VI of the Civil Rights Act, and the inability or
unwillingness to rectify this violation through action requires accountability.
Postsecondary education is a unique opportunity for students to learn and have their ideas and beliefs challenged. However, universities receiving hundreds of millions of federal funds annually have denied
students that opportunity and have been hijacked to become venues for the promotion of terrorism, antisemitic harassment and intimidation, unlawful encampments, and in some cases, assaults and riots.
The House of Representatives will not countenance the use of federal funds to indoctrinate students into hateful, antisemitic, anti-American supporters of terrorism. Investigations into campus antisemitism by the Committee on Education and the Workforce and the Committee on Ways and Means have been expanded into a Congress-wide probe across all relevant jurisdictions to address this national crisis. The undersigned Committees will conduct oversight into the use of federal funds at MIT and its learning environment under authorities granted to each Committee.
• The Committee on Education and the Workforce has been investigating your institution since December 7, 2023. The Committee has broad jurisdiction over postsecondary education, including its compliance with Title VI of the Civil Rights Act, campus safety concerns over disruptions to the learning environment, and the awarding of federal student aid under the Higher Education Act.
• The Committee on Oversight and Accountability is investigating the sources of funding and other support flowing to groups espousing pro-Hamas propaganda and engaged in antisemitic harassment and intimidation of students. The Committee on Oversight and Accountability is the principal oversight committee of the US House of Representatives and has broad authority to investigate “any matter” at “any time” under House Rule X.
• The Committee on Ways and Means has been investigating several universities since November 15, 2023, when the Committee held a hearing entitled From Ivory Towers to Dark Corners: Investigating the Nexus Between Antisemitism, Tax-Exempt Universities, and Terror Financing. The Committee followed the hearing with letters to those institutions on January 10, 202
CLASS 11 CBSE B.St Project AIDS TO TRADE - INSURANCE
donor selection in Haplo Transplant
1. Kaiyan LIU
Peking University People’s Hospital,
Peking University Institute of Hematology
2015-8
Donor selection in haplo
HSCT
北京大学血液病研究所
INSTITUTE OF HEMATOLOGY
2. Current status of HSCT in China
Donor selection in haploHSCT
Donor specific anti-HLA antibodies
(DSA) in haploHSCT
Outline
3. Overall HSCT activities
in 2007-2014.6
0
2000
4000
6000
8000
10000
12000
14000
16000
15970
2007 2008 2009 2010 2011 2012 2013 2014.6
Current HSCT in China
5. Overall HSCT types
in 2007 to 2014.6
Haploidentical,7851,
28%
HLA identical
sibling,9477, 33%
Auto,5888, 21%
Unrelated
PBSC,4192, 15%
Unrelated CB and
syngeneic,3%
6. China Registry 2013
Unrelated
18%
Auto
54%
Cord
Blood 4%
Related
Matched
24%
Related
Match
29%
Related
Haplo
32%
Unrelat
ed
14%
Cord
3%
auto
22%
CIBMTR2007-2010
More Haplo and Allo-HSCT in China
Distribution of Transplantation Type
7. Total number and relative proportions of indications
for HSCT from 2007-2014.6
AML, 4763, 32%
ALL, 3420, 23%
CML, 1510, 10%
MM, 898, 6%
MDS, 1081, 7%
AA, 1086, 7%
NHL, 849, 6%
HD, 81, 1%
thalassemia , 209, 1% others,
1026,
7%
8. Chinease haploidentical SCT
• The establishment of GIAC：
G granulocyte colony-stimulating factor mobilization
I aggressive prophylaxis immunosuppression
A antithymocyte globulin
C combination of bone marrow and peripheral blood
Blood. 2006;107:3065-3073.
9. Wang Y, Liu DH, Liu KY, et al.Cancer. 2013;119:978-985.
Long-term follow-up of haploidentical HSCT
without in vitro T cell depletion for the
treatment of leukemia: nine years of experience
at a single center.
High risk
Standard risk
CML
AML
ALL
10. Lu DP, et al. Blood,2006,107(8):3065-3073
Haplo-HSCT vs. MSD
Unmanipulated HBMT can achieve
comparable outcomes with matched
related donor transplant
11. T-cell-replete haploidentical HSCT compared with
matched sibling HSCT and unrelated HSCT.
Luo Y, Xiao H, Lai X,et al.Blood. 2014 Sep 11. pii: blood-2014-04-571570.
os
DFS
12.
13. Acute GVHD (Donor sex and age)
P=0.007
male n=686 39%
female n=524 46% >30y n=965 48%
<30y n=245 25%
P<0.001
Donor sex
Donor age
14. female n=686 24%
male n=524 16%
p=0.005 p=0.04
>30y n=965 22%
<30y n=245 12%
NRM (Donor sex and age)
Donor ageDonor sex
15. Donor sex Donor age
female n=356 24%
male n=393 16%
p=0.01 p=0.04
>30y n=590 22%
<30y n=159 12%
female n=524 61%
male n=686 70%
>30y n=965 62%
<30y n=245 78%
OS (Donor sex and age)
Donor sex Donor age
16. Donor sex Donor age
male n=393 39%
>30y n=590 48%
<30y n=159 25%
P<0.001
<30y n=239 25%
>30y n=672 44%
0 20 40 60 80 100
0.00.20.40.60.81.0
days after transplantation
CumulativeIncidenceofgrade2-4acuteGVHD
female n=226 34%
p=0.84
male n=685 39%
Donor ageDonor sex
Acute GVHD (Donor sex and age-exclude mother)
17. HLA disparity 3 vs. 4-5/6
GVHD
P<0.001
GVHD2-4 p=0.23
GVHD3-4 p=0.91
OS p=0.74
LFS p=0.55
n=678,407,125
18. NIMA vs. NIPA(n=53)
Outcome and significant factors Hazard risk (95% CI) P
Ⅱ-ⅣaGVHD
NIMA/NIPA 3.109 (1.092-8.849) 0.034
NIMA vs. Mother to offspring (n=129)
Outcome and significant factors Hazard risk (95% CI) P
Ⅱ-ⅣaGVHD
NIMA/mother to offspring 2.700 (1.261-5.780) 0.011
Father to offspring vs. Mother to offspring vs. NIMA vs. NIPA (n=322)
Outcome and significant factors Hazard risk (95% CI) P
Ⅱ-ⅣaGVHD
Mother donor 1
NIMA 0.348(0.137-0.884) 0.026
NIPA 1.115(0.584-2.129) 0.742
Father donor 0.698(0.467-1.044) 0.080
NIMA 不合供者优于 NIPA不合供者和 母亲供者；NIPA不合供者有不如父亲供者的趋势
Multivariate analysis
19. Selection order Donor source
Most preferred Child,NIMA-mismatched
2nd choice Younger brother,NIMA-
mismatched
3ed choice Older sister,NIMA-
mismatched or Father
4th choice Older
The last choice Mother
Proposed Proposed algorithm for donor selection
in haploidentical HSCT
20. Donor-specific anti-HLA antibodies were
associated with primary graft failure after
unmanipulated haploidentical blood and
marrow transplantation
Chang et al. Journal of Hematology &
Oncology (2015) 8:84
21. Complications, such as graft failure, remain
serious problems after Haplo-SCT
1 Aversa F, et al. J Clin Oncol,2005,23:3447-3454 3 Luznik L, et al. BBMT,2008,14:641-650
2 Federmann B, et al. Haematologica,97:1523-1531 4 Wang Y, et al. Cancer,2013,113:978-985
Authors, Year Patient
No.
Allografts Conditioning
regimen
Graft failure
Aversa et al. 2005 1 104 CD34 seleted PBSC MA 9%
Federmann et al. 2012 2 61 CD3/CD19-depleted PBSC RIC 8%
Luznik et al.2008 3 68 Unmanipulated bone marrow RIC 13%
Wang et al. 2013 4 756
Unmanipulated marrow and
blood grafts
MA 1%
Primary Poor
graft function,
PGF
5.9% Patient without
PGF
Patient with
PGF
22. Donor specific antibody
Donor specific antibody (DSA): anti-HLA antibodies, when
the specificity corresponded to a mismatched antigen of
donor
★ The prevalence of HLA antibodies caused by alloimmunization
★ Prevalance of HLA antibodies:
• Male: transfused 1.7%; non-transfused 1.0%
• Female: 24.4%
1.7% (0)
11.2% (1)
22.5% (2)
27.5% (3)
32.2% (4 or more pregnancies)
Yoshihara S,et al. Bone Marrow
Transplant,2012;47:1499-506
23. Limitations of these studies:
1) most studies were retrospective;
2) Primary graft failure including graft rejection (GR) and PGF
3) there were no training and validation groups.
MFI: median fluorescent intensity
Association of donor specific antibody with
graft failure after haplo-SCT
Yoshihara S,et al. Bone Marrow
Transplant,2012;47:1499-506
24. Definition of primary graft failure
Thomas' HCT, 4th Edition. Edited by Appelbaum F. R. et al.
1. Primary GF included graft rejection (GR) and poor
graft function (PGF).
2. GR is the failure to engraft neutrophils (ANC ≤0.5 ×
109/L) by day +28 for 3 consecutive days and the absence
of donor hematopoiesis.
3. Because delayed red cell engraftment may happen for
many months post-transplant and is more difficult to
evaluate in an unarguable manner, PGF was defined as the
presence of 3 cytopenic counts (ANC ≤0.5 × 109/L, platelet
≤20 × 109/L, or Hb≤80 g/L) beyond day +28 with a
transfusion requirement associated with hypoplastic-aplastic
bone marrow (BM), in the presence of complete donor
chimerism. Patients with evidence of severe GVHD or
hematologic relapse were excluded
26. Patients and methods
A total of 345 subjects
Unmanipulated haploidentical blood and marrow transplant protocol
DSA were analyzed with a Luminex200 flow analyzer
Lu DP, et al. Bloood,2006,107:3065 Huang XJ, et al.Clin Cancer Res,2009,14:4777
Chang YJ,Huang XJ. Curr Opin Hematol,2012,19:454-461
27. • A total of 342 patients (99.1%) achieved sustained myeloid
engraftment.
Neutrophil engraftment: 13 days (range: 8-28 days)
Platelet engraftment:18 days (range, 6-330 days)
• Grade 2 through 4 acute GVHD: 42.7%±3.1%.
• After a median follow-up of 384 days (range, 25-784 days)
Chronic GVHD was 43.3%±3.1%.
The 2 year probablity of relapse: 8.8%±1.8%
TRM: 18.4±2.8%
DFS: 75.1%±2.9%
OS: 76.2%±3.0%
Results
28. • Of the 345 cases tested 87 (25.2%) were anti-HLA
antibody positive, including 44 male and 43 female.
• Of the positive cases, 39 (11.3%) were DSA positive.
Female: 16%
Male: 8%
• The median fluorescent intensity (MFI )of was 4726
(range, 504-19948).
Results
29. MFI≤2000
Group A
2000＜MFI＜1000
Group B
MFI≥10000
Group C
P value
Patient No. 316 (100%) 19 (100%) 10 (100%) NS
GR 0 (0%) 1 (6.3%) 2 (20%) 0.000
PGF 10 (3.2%) 5 (26.3%) 4 (40%) 0.000
GR+PGF 10 (3.2%) 6 (32.6%) 6 (60%) 0.000
Results
Group A
Group B
Group C
Figure 1. Effects of DSA on neutrophil and platelet engraftment
30. Group A Group B Group C
Results
Figure 2. Effects of DSA on TRM and OS
32. HR 95% CI P value
Primary graft failure
DSA MFI≥10000 1
2000≤MFI﹤10000 0.940 0.284-3.177 0.919
MFI﹤2000 0.187 0.048-0.730 0.016
OS
Disease status 2.839 1.702-4.736 0.000
GR 1
PGF 0.271 0.074-1.000 0.050
No primary graft failure 0.068 0.020-0.229 0.000
DFS
Disease status 3.593 2.212-5.836 0.000
GR 1
PGF 0.284 0.077-1.044 0.058
No primary graft failure 0.084 0.025-0.279 0.000
Relaspe
Disease status 9.906 4.099-23.940 0.000
TRM
GR 1
PGF 0.209 0.056-0.790 0.021
No primary graft failure 0.031 0.0009-0.107 0.000
ANC
CD34 1.370 1.106-1.697 0.004
PLT
CD34 1.483 1.187-1.852 0.001
DSA MFI≥10000 1
2000≤MFI﹤10000 3.074 1.137-8.311 0.027
MFI﹤2000 3.301 1.358-8.022 0.008
Multivariate analysis of factors associated with transplant outcomes
33. • We demonstrated that DSA might contribute to the
primary GF, including GR and PGF, after unmanipulated
haploidentical blood and marrow transplant.
• The onset of primary GF leads to inferior survival.
• Our results add new evidence that suggest DSA must
be considered when choosing among several
haploidentical donor sources.
Conclusion
34. Acknowledgements
Stem cell collection center
Hai-Yin Zheng
Hong Xu
Qing Zhao
Su Wang
Department of bone marrow transplant
Xiao-Jun Huang
Kai-Yan Liu
Dai-Hong Liu Lan-Ping Xu
Huan Chen Wei Han
Xiao-Hui Zhang
Yu-Hong Chen Feng-Rong Wang
Jing-Zhi Wang Yu Wang
Chen-Hua Yan Yuan-Yuan Zhang
Yu Ji Yu-Qian Sun
Laboratory of PUIH
Dan Li
Ya-Zhen Qin
Yan-Rong Liu
Yue-Yun Lai
