Perspectives: Why are we so stubborn?
By John Wingard, MD
I have a shirt that I really love. That surprises me since I am totally not into clothes, and I hate shopping for myself. The shirt is plaid and contains my college's colors in subtle ways. It fits me well. I can wear it to work, parties, and sports events. Colleagues, friends, casual acquaintances, and even my patients compliment me on my shirt. Total strangers stop me on the street and ask me where I got it so they can get one just like mine. I feel good when I wear the shirt.
There is only one problem with my shirt: It is so old, the collar and sleeves are frayed. My wife keeps saying: "John, you need to throw it away." Of course, I ignore her advice and hide it in the back of the closet so she does not throw it away herself. I understand her point, but I have my reasons.
I thought about my shirt when we planned the ASTCT / CIBMTR / EBMT Plenary Session at the 2022 Tandem Meetings addressing "The Challenge of Translating Evidence into Action in HCT," and I thought about it even more during the August BMT CTN Steering Committee meeting.
We spend a lot of time and money designing and conducting trials to test new interventions to improve outcomes and change practice. Yet, sometimes successful trials do not convince clinicians to adopt the new practice.
Why is this? Sometimes, there are valid reasons to resist change: It takes too much time to adopt the new thing, it is too hard to get everyone in my center to agree, the data are not believable, the findings are in patients that are very different from my patients, or it is too expensive. One of the often-cited problems is that the rigid eligibility criteria for trials exclude most of the patients we care for, and we are not sure how generalizable the findings are. Maybe, we changed our minds that the new intervention is not as great as we thought.
Even when we agree that the new intervention is better, change is still hard. Studies across all medical disciplines show this to be true. Some centers are better at adopting new practices than others. It is good to know that there are enablers to change: Your institution may be supportive of innovation, payers may insist on change, accreditation bodies may expect the adoption of "standards," and patients may expect you to adopt "breakthroughs" that they have heard about through their lay sources of information. A local champion to push a new practice forward can often make all the difference. Certainly, the local culture of a transplant team is crucial in adopting new practices.
Kudos to Linda Burns, MD, and Nandita Khera, MD, MPH, who are chairing a BMT CTN task force to try to improve the translation of evidence into practice in BMT. The task force recommended developing a committee to incorporate dissemination and implementation considerations into each BMT CTN trial. They described the importance of taking action even before the trial, the value of identifying the key stakeholders, the need to identify local champions, and the importance of identifying the impact of change on patients and non-transplant providers.
The coin of the realm for evaluating the quality of research is its impact. It would be a shame to do a trial that shows something that truly works, and we are slow or uneven to adopt it or do not adopt it at all. As Drs. Burns and Khera emphasized, it is time for us to consider implementation when we are designing trials.
Perhaps, my wife is also right: It is past time to throw away my beloved shirt. I need to go shopping this weekend.
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Current Committee Leadership
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Nina Shah, MD, University of California
San Francisco Medical Center, Chair |
Muzaffar Qazilbash, MD, MD Anderson, Chair |
Heather Landau, MD, Memorial
Sloan Kettering Cancer Center, Chair |
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Ruta Brazauskas, PhD, PhD Statistician |
Temitope Oloyede, MD, MPH, MS Statistician |
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Committee Leadership
Co-Chairs:
- Nina Shah, MD, University of California San Francisco Medical Center, San Francisco, CA
- Muzaffar Qazilbash, MD, MD Anderson Cancer Center, Houston, TX
- Heather Landau, MD, Memorial Sloan Kettering Cancer Center, New York, NY
Scientific Director:
Statistical Director:
Statistician:
Multiple myeloma is the most common indication for HCT in the US. The Plasma Cell Disorders Working Committee collaborates with investigators from around the world to define the optimal utilization of transplantation for not only multiple myeloma but also other plasma cell disorders, such as light chain amyloidosis, Waldenstrom macroglobulinemia, POEMS syndrome, and plasma cell leukemia.
We have five ongoing projects, including outcomes of autologous HCT in light chain deposition disease patients, differences in outcomes of myeloma treatment worldwide, secondary primary malignancies after cell transplantation for multiple myeloma patients, and bortezomib-based versus lenalidomide maintenance therapy for high-risk multiple myeloma patients. Noteworthy accomplishments from this committee in 2021-2022 include four peer-reviewed publications, two presentations at the American Society of Clinical Oncology (ASCO) Annual Meeting, one presentation at the ASH Annual Meeting, one presentation at the EBMT Annual Meeting, and one presentation at the Tandem Meetings.
In 2021, we received 50 proposals, 5 of which were presented at the 2022 Tandem Meetings; one was accepted as a study. The Plasma Cell Disorders Working Committee is always seeking interesting and novel ideas for study as well as encouraging the involvement of junior investigators and those wanting to break into the field of HCT and outcomes research. We believe early involvement encourages long-term participation of young investigators in committee activities.
Our committee provides a platform for consolidating ideas from oncologists across the country regarding the role of transplant in the management of multiple myeloma, light chain amyloidosis, Waldenstrom's macroglobulinemia, POEMS syndrome, and germ cell tumors. The CIBMTR houses the largest set of data related to transplantation outcomes for these disorders. By serving as a partner for researchers, we leverage the power of big data to undertake projects and answer questions that would be impossible for a single institution to accomplish. This is particularly relevant for the rare plasma cell disorders for which no institution would have adequate numbers to answer any critical questions related to treatment. As a byproduct of the collaborative process, stronger connections and commitment to the overall mission of the CIBMTR are achieved, and a positive feedback loop results. The vision of the committee is to keep the positive feedback loop alive and have it lead to greater national and international integration of transplant-related research that will accelerate the discovery of cures for patients afflicted by these diseases.
The success of the working committee depends on new ideas and testable hypotheses as well as the participation of individuals with diverse perspectives and scientific backgrounds. The Plasma Cell Disorders Working Committee encourages all investigators with an interest in these diseases to propose a study. Information on how to propose a study can be found on the CIBMTR's How to Propose a Study webpage.
To learn more or discuss your research ideas and proposals, contact one of the members of the working committee leadership team.
We encourage our 525 current working committee members to actively participate. We look forward to your participation next February at the 2023 Tandem Meetings.
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2023 Tandem Meetings
The Tandem Meetings | Transplantation & Cellular Therapy Meetings of ASTCT and CIBMTR (Tandem Meetings) are the combined annual meetings of the ASTCT and CIBMTR. Administrators, clinicians, data manager / clinical research professionals, fellows-in-training, investigators, laboratory technicians, MD / PhDs, nurses, nurse practitioners, pharmacists, physician assistants, and other allied health professional attendees benefit from a full scientific program that addresses the most pressing issues in HCT and cellular therapy.
We look forward to hosting the 2023 Tandem Meetings in person at the World Center Marriott in Orlando, Florida. The 2023 Tandem Meetings will feature in-person and virtual programming, so everyone can experience the premier event in the evolving HCT and cellular therapy field.
Scientific Program
2023 Scientific Organizing Chairs, Stefanie Sarantopoulos, MD, PhD, and Sumithira Vasu, MBBS, along with the entire scientific organizing committee and session chairs have assembled a comprehensive program. An outline of topics is listed below. Throughout the 2023 Tandem Meetings, global experts in the HCT and cellular therapy field will present the latest developments during a combination of plenary and concurrent sessions as well as via oral abstracts, posters, specialized tracks, and more.
Scientific Program Topics
- Novel cellular therapy for heme malignancies: CAR-T & beyond
- Tumor microenvironment and relapse after immunotherapy
- Severe chronic GVHD: Lung, sclerotic, and brain manifestations
- Mechanisms in acute GVHD prevention: Applying what we now know
- Novel antibody-based conditioning regimens
- Lessons from the pandemic: Are we stronger?
- Mechanisms of relapse after cellular therapy and measures to address them
- Modulating host immune reconstitution: Vaccines and more
- Cell therapy for solid tumors
- Accelerated physiological aging after HCT
- How CAR-Ts drive the cell therapy treatment landscape for lymphoma patients
- Update on the global data for HCT
- Alternative grafts and donor sources: How to successfully transplant with a mismatched donor
- Treatment of refractory GVHD
- Statistical topics in design and analysis of cellular therapy and transplant studies
Plus: Mortimer M. Bortin lecture, E. Donnall Thomas lecture, late-breaking abstracts, CIBMTR Working Committee meetings, ASTCT spotlight sessions, and Meet-the-Professor sessions as well as industry-supported satellite symposia, product and innovation theaters, and an exhibit hall.
Tracks
Confirmed tracks include administrative director, advanced practice providers, BMT CTN coordinators, clinical research professionals / data management, new data manager onboarding, IT and informatics, nursing, pediatrics, and pharmacy.
Registration and Housing
Registration is now open with the option to register as either an in-person attendee or a virtual attendee. Once your registration is complete, you will receive information about how to book housing.
REGISTER NOW
Support Opportunities and Additional Information
Please direct questions regarding support opportunities for the 2023 Tandem Meetings to the Tandem Meetings Conference Office: TandemMeetings@mcw.edu.
We look forward to seeing you in 2023!
Follow ASTCT and CIBMTR on social media, as well as the official hashtag, #Tandem23, for updates.
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Bioinformatics Research Tools Benefit Users Around the World
By Michael Wright, PhD (Scientific Coordinator), and Pradeep Bashyal (Sr. Bioinformatics Software Architect)
The Bioinformatics Research group has created several web applications that allow the wider HLA matching and transplant community to carry out a range of tasks to improve their ability to find matches, improve the quality of donors found, and ultimately impact patient lives. Some of these tools were created years ago; for example, early versions of Haplostats have been available for more than ten years and have been added to and refined since then. Other tools have only recently been created, as the science supporting their use is based on recent discovery. For example, B-Leader is based on a paper published in 2020 (HLA-B leader and survivorship after HLA-mismatched unrelated donor transplantation by Effie Petersdorf, MD, and her group) and was made public in 2021. Because of the different time spans these tools have been available, they have different levels of public awareness and use. Some of the tools are newly created and still being tested before being made publicly available, whilst other tools are no longer used widely because science has progressed and better tools have replaced them.
Here we present the top five tools, as measured by the numbers of users throughout the last year.
Tool |
Users |
URL |
Description |
Haplostats |
156,547 |
haplostats.org |
Search frequency information for haplotypes and haplotype pairs relative to specific HLA types found in the US population. |
Frequencies |
2,427 |
frequency.nmdp.org |
Download high-resolution 6-locus haplotype frequencies derived from the entire DNA-typed NMDP registry for 21 detailed racial / ethnic categories and 5 broad categories. |
Haplo Donor Selector |
1,000 |
haplodonorselector.b12x.org |
Predict the probability of disease-free survival from attributes of a HCT donor-recipient pair (Fuchs E et al., 2021). |
B-leader |
841 |
bleader.nmdp.org |
Sort single HLA-B mismatches based on the HLA-B leader peptide for unrelated and/or haploidentical donors for HCT. (Sajulga et al., 2021). |
Search Prognosis |
234 |
search-prognosis.b12x.org |
Conduct a quick search prognosis at the onset of an adult unrelated donor search. This tool provides a simple scoring system based on a patient's race / ethnicity and genotype frequency. It could be a useful tool for transplant physicians to understand the difficulty of identifying a fully matched or suitably mismatched unrelated donor. |
When we look more closely at how the most frequently used tool, Haplostats, was used over the last year, the numbers fluctuate as different groups use it intensely for various projects. The most uses in a single day was just under 8,000 (equating to one use every 11 seconds), which indicates that researchers are so keen to get the information that they have written scripts to automatically process many HLA typings in as short a time as possible.
When evaluating user location, we can see that for Haplostats most users are from Canada. For other tools, it is interesting to look at the city with the most uses and relate that to medical centers. For example, we can tell that someone was investigating T-cell-epitope groups using one of our newer tools.
It is also important to remember that matching is an international process, so users are scattered across the globe. A perfect example is displayed below, showcasing the users for the B-leader tool:
In both cases, it is clear that there are a number of countries where the tools are used infrequently, but each use represents someone wanting to find the best match to help save someone's life.
The official website for the Bioinformatics group can be found at: https://bioinformatics.bethematchclinical.org/ (the bioinformatics section on bethematchclinical.org). This site currently does not host individual tools but provides HLA resources as well as links to the tools and data standards (for example HML). Last year there were 46,277 users, the majority of which were from the US, with the next largest group of users from Germany.
The team is in the process of updating the website. Soon you will be able to find information and links to all the tools and resources built and supported by the team, including upcoming applications.
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CIDR: Beyond the Finish Line
As we enter the fifth and final year of the CIDR award, we would like to take the time to reflect upon the immense work and dedication we've witnessed over the past months. As you may have heard, we recently submitted the U24 HCT infrastructure grant that will support the continuity of CIDR initiatives beyond the original grant's lifecycle. In response to the CIBMTR's achievements, the NIH has recognized our efforts through continued support to collect data for HCT and adoptive cell therapy, which includes cellular therapies like CAR-T.
This collaborative effort has been built by past and present leaders of the CIBMTR. Our institution is uniquely positioned to serve the community of patients, centers, researchers, clinicians, and many other stakeholders. We believe the CIBMTR has influenced the improvement of access to and outcomes of patients receiving HCT over the years, and we will continue to lead efforts on the forefront, such as expanding our efforts to include capturing data on adoptive cellular therapies. This belief drives our investment toward ensuring that CIBMTR is successful in pursuing its mission.
The organization, attention to detail, and drive to succeed we've witnessed in the preparation of the U24 submission confirms that we are surrounded by friends that share this belief. We are excited and curious to see how the CIBMTR will continue to achieve its mission.
CIDR Year 5 Goals
During the last year of the CIDR grant, the focus is to ensure the continuation and advancement of many initiatives. This grant year, we plan to:
- Launch data collection tools focused on solid tumors
- Operationalize the data embargo tool to allow centers to temporarily embargo pre-specified clinical trial data in the registry to incentivize centers to report pre-commercial data to the CIBMTR and use its infrastructure for long-term follow-up protocols
- Pilot data collection at the time of leukapheresis to assess dropout from collection to infusion of cells
- Continue enrollment of cellular therapy recipients to the PRO protocol
- Formalize the cellular therapy audit metrics to align with CIBMTR standards
- Establish mechanisms to support consortia development
We plan to continue previous initiatives that aim to improve data collection, quality, and accessibility to the resource for the benefit of our communities.
2022 AcCELLerate Forum
The second annual virtual AcCELLerate Forum: Creating a Sustainable Ecosystem of Cell and Gene Therapy, is scheduled for November 17-18, 2022. ASTCT, CIBMTR, and NMDP/Be The Match have collaborated to host this two-day virtual workshop offering educational and advocacy opportunities for providers, payers, government agencies, and industry members in the cell and gene therapy field. Please visit the AcCELLerate Forum website for additional information and to register for this exciting event.
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MEASURE Now Enrolling
NMDP/Be The Match and the CIBMTR are excited to announce the opening of accrual and the first enrollments to the Molecular Evaluation of AML Patients After Stem Cell Transplant to Understand Relapse Events (MEASURE) protocol NCT05224661! This new study is managed by the RCI BMT, in partnership with the NHLBI
While transplant is a curative therapy for many patients with AML, the risk of relapse remains high after transplant. The MEASURE study's goal is to determine the optimal post-transplant monitoring strategy for AML patients to predict and better treat relapse. This will be accomplished by creating a coordinated national framework to prospectively collect samples, building on a previous study, which demonstrated that the presence of MRD prior to transplant was associated with increased rates of relapse.
Over the next 4 years, the study will enroll 1,000 participants receiving allogeneic HCT to treat AML and follow them for 3 years post-transplant, with the goal of study results translating into the following lifesaving practices:
- Harmonize MRD testing across US transplant centers
- Develop personalized strategies for post-transplant monitoring of AML patients to detect relapse sooner
- Assist physicians in making clinical decisions, like the best conditioning regimens or post-transplant therapy for patients based on AML type
Results from the Pre-MEASURE study were presented at ASCO, made the ASH Clinical News top-5 most-read list for July 2022, and are currently under review for publication in The New England Journal of Medicine.
Additionally, the MEASURE study is piloting the use of a custom-built LabVantage Laboratory Inventory Management System (LIMS) module to manage the shipment of samples between study sites, the NMDP/Be The Match Repository, and study partner labs. LabVantage LIMS has been used by the NMDP/Be The Match Repository to manage the CIBMTR and BMT CTN research sample inventory since 2015.
The study protocol includes as many as 12 sample collection time points for each participant. With a projected enrollment of 1,000 subjects, sample management will be critical to the success of this study. RCI BMT immunobiology, data management, CIBMTR Information Technology, and NMDP/Be The Match IT have put in tremendous effort collaborating over the last year to make this platform a reality for our RCI BMT prospective clinical trials, for both this study and future protocols.
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Our Supporters
The CIBMTR is supported primarily by Public Health Service U24CA076518 from the National Cancer Institute (NCI), the National Heart, Lung and Blood Institute (NHLBI) and the National Institute of Allergy and Infectious Diseases (NIAID); U24HL138660 and U24HL157560 from NHLBI and NCI; U24CA233032 from the NCI; OT3HL147741 from the NHLBI; HHSH250201700005C, HHSH250201700006C, and HHSH250201700007C from the Health Resources and Services Administration (HRSA); and N00014-20-1-2832 and N00014-21-1-2954 from the Office of Naval Research.
Additional federal support is provided by P01CA111412, R01CA100019, R01CA152108, R01CA218285, R01CA231141, R01CA231838, R01CA262899, R01AI128775, R01AI150999, R01AI158861, R01HL155741, R01HL131731, UM1CA121947, U01AI069197, U01AI126612, UG1HL06924.
Support is also provided by Be The Match Foundation; Boston Children's Hospital; Dana Farber; St. Baldrick's Foundation; PBMTF; Stanford University; Medical College of Wisconsin; National Marrow Donor Program; and from the following commercial entities: AbbVie; Actinium Pharmaceuticals, Inc.; Adaptimmune; Adaptive Biotechnologies Corporation; ADC Therapeutics; Adienne SA; Allogene; Allovir, Inc.; Amgen, Inc.; Angiocrine; Anthem; Astellas Pharma US; AstraZeneca; Atara Biotherapeutics; BeiGene; bluebird bio, inc.; Bristol Myers Squibb Co.; CareDx Inc.; CRISPR; CSL Behring; CytoSen Therapeutics, Inc.; Eurofins Viracor, DBA Eurofins Transplant Diagnostics; Gamida-Cell, Ltd.; Gilead; GlaxoSmithKline; HistoGenetics; Incyte Corporation; Iovance; Janssen Research & Development, LLC; Janssen/Johnson & Johnson; Jasper Therapeutics; Jazz Pharmaceuticals, Inc.; Kadmon, a Sanofi Company; Karius; Kiadis Pharma; Kite, a Gilead Company; Kyowa Kirin; Legend Biotech; Magenta Therapeutics; Mallinckrodt Pharmaceuticals; Medac GmbH; Medexus Pharma; Merck & Co.; Mesoblast; Millennium, the Takeda Oncology Co.; Miltenyi Biotec, Inc.; MorphoSys; Novartis Pharmaceuticals Corporation; Omeros Corporation; OptumHealth; Orca Biosystems, Inc.; Ossium Health, Inc.; Pfizer, Inc.; Pharmacyclics, LLC, An AbbVie Company; Pluristem; PPD Development, LP; Sanofi; Sobi, Inc.; Stemcyte; Takeda Pharmaceuticals; Talaris Therapeutics; Terumo Blood and Cell Technologies; TG Therapeutics; Vertex Pharmaceuticals; Vor Biopharma Inc.; Xenikos BV.
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