Contact Us |
By Robert Soiffer, MD
BMT is not the only cellular therapy on the block anymore. With the recent FDA approval of engineered cell therapies to treat patients with refractory ALL and NHL, we are entering a brave new world. To achieve tumor eradication, we may be on the verge of morphing from the potent - but still hard to characterize - graft-versus-tumor effect, long the muscle of transplant therapeutics, to a (hopefully) more targeted cellular therapy approach that can utilize autologous T cells expressing chimeric antigen receptors (CARs) targeting cell surface antigens, in this instance CD19. Moreover, it is likely that CAR T cell therapy will soon be applicable to tumors expressing antigens other than CD19, such as BCMA for multiple myeloma. In addition, cellular intervention is not limited to CAR T cells but will like extend to engineered T cell receptor therapies, manipulated NK cells, and antigen specific polyclonal T cells targeting an array of viral pathogens.
While BMT can induce significant collateral damage in the form of GVHD, CAR T cell therapy avoids that and obviates the need for an allogeneic donor. However, significant and potentially life threatening off target effects can still occur, most notably cytokine release syndrome and devastating neurologic toxicity. Understanding the clinical and biologic risk factors precipitating these events, and determining best practices in treating them, is necessary to optimize the safety window.
The excitement generated by CAR T cells must be accompanied by a comprehensive assessment of its long-term efficacy and toxicity, particularly in light of the extremely high price tag attached to them. So where does the transplant community in general, and CIBMTR in particular, fit into this evolving landscape? It is likely for the foreseeable future that administration of commercial products will be limited to these settings at sites that are FACT accredited and well equipped to handle the spectrum of side effects that might be encountered with engineered cell therapies. As products from different commercial sources come on line, accurate compilation of these endpoints is critical so that patients, physicians, and payers alike can make accurate assessments to guide decision making. The CIBMTR is uniquely positioned to serve this role. With multiple decades of experience collecting and analyzing HCT, the CIBMTR has the tools to rapidly fill the void. Questions will naturally arise about the sequencing of engineered T cell therapies in a patient's care. The CIBMTR has access to comprehensive accurate outcomes data that will allow our community to place the short- and long-term results of CAR T cell therapy in context and perhaps to assess whether these treatments will serve as a bridge to, and adjunct with, or a replacement for autologous and allogeneic HCT for lymphoma, myeloma, and ALL.
Thus, the critical importance of constructing a vibrant database for cellular therapies cannot be understated. The transplant community has been remarkably cooperative in sharing clinical outcomes, demographic data, and biospecimens with the CIBMTR; this has resulted in unmistakable improvements in how we care for our patients. It is as important that we create an environment in the engineered cell community that mirrors this cooperative effort. The time to start is now.
Return to Top
2018 BMT Tandem Meetings
The BMT Tandem Meetings - the combined annual meetings of the CIBMTR and ASBMT - are North America’s largest international gathering of BMT clinicians and investigators, laboratory technicians, advanced practice professionals, transplant nurses, pharmacists, administrators, and clinical research associates since 1999.
Leading experts will convene at the Salt Palace Convention Center in Salt Lake City, Utah, February 21-25, to present the latest developments in blood and marrow transplantation and cellular therapy during the BMT Tandem Meetings. Scientific Program Chairs for the 2018 meetings are Fred Appelbaum, MD (CIBMTR), and Jerome Ritz, MD (ASBMT).
ASBMT will celebrate their 25th anniversary during the BMT Tandem Meetings, and there is some very exciting news to share about the 2019 meeting; you will not want to miss!
To register and view more details, visit the 2018 BMT Tandem Meetings webpage. As a reminder, January 23, 2018, is the last day for general registration rates. After registering, take advantage of special conference guest room rates at a wide variety of hotels within the BMT Tandem Meetings room block.
Remember to reserve your ticket to the BMT Tandem Meetings Reception on Saturday evening in the South Foyer of the Salt Palace for dancing, networking, and fun.
Questions regarding support opportunities at the 2018 BMT Tandem Meetings may be directed to Sherry Fisher, Director of Advancement for the CIBMTR. For general information, email email@example.com.
We look forward to seeing you in Salt Lake City!
Acute leukemia remains the most common indication for allogeneic HCT. With transplant practice undergoing dramatic changes, observational studies play key and complementary roles in determining trends and identifying risk factors and prognostic indicators in a fast-evolving field. Questions were added to the 2013 Pre-TED forms regarding cytogenetics and molecular markers to allow for better disease-risk categorization of patients. The development of reduced intensity conditioning regimens, wide availability of high-resolution HLA typing, new combinations of immunosuppressive agents, and use of post-transplant cyclophosphamide for the prevention of GVHD opened the door for broad applicability of alternative donor transplants, including haploidentical donors, and the expanded use of allogeneic transplantation to older patients.
In addition, the complexity of data collection continues to increase. For example, presence of minimal residual disease (MRD) pre- and post-HCT have been shown to influence post-HCT outcomes. MRD test details including flow cytometry, cytogenetics, and fluorescence in situ hybridization (FISH) have been added to the 2017 CRFs. Discussions are ongoing as to the best format for incorporating newer markers of pre- and post-HCT MRD, including next-generation sequencing and PCR. The emergence of post-HCT therapies to prevent relapse has also added another setting for data collection, and we will certainly see many debates and analyses proposed on these and other topics in this committee. HCT indications, approaches, and comparison with other therapies are all valid topics for study.
The success of the Acute Leukemia Working Committee (ALWC) derives predominantly from a dedicated team with collaborative input. Committee leadership works closely with committee members, data managers, and transplant groups in the US and abroad. ALWC leadership develops and promotes the scientific agenda established with input from Working Committee members; determines priorities in the selection of high-impact studies; and ensures timely progress in protocol development, statistical analyses, manuscript development, and publications. This committee strives to improve quality and efficiency and is guided by the three principles established by the CIBMTR Advisory Committee: Publish peer-reviewed papers of high scientific impact, complete studies within a reasonable time period, and ensure inclusiveness and fairness within the study process.
The ALWC’s recent academic activity includes two presentations at the 2016 ASH Annual Meeting and three submitted / accepted manuscripts. Thirty proposals were submitted for the 2017 BMT Tandem Meetings, and 10 proposals were selected for presentation to the committee. These numbers reflect a rapidly evolving field and a high-level of interest in the rich and vast data on acute leukemia within the CIBMTR Research Database. We are eager to review and discuss many new proposals from centers worldwide.
Number of Cases in the CIBMTR Research Database
View planned, in-progress, and completed studies and publications on the Acute Leukemia Working Committee webpage.
Zhenhuan Hu, MPH, CIBMTR Milwaukee
The main goal of the Chronic Leukemia Working Committee is to help establish the optimal timing of HCT for patients with MDS, CML, CLL, and myeloproliferative disorders as well as to improve outcomes for such patients. During the last several years, the efforts of the committee resulted in several published manuscripts as well as oral and poster presentations. The committee recently revised the CLL and CML data collection forms to better capture molecular and disease specific data of prognostic importance. In addition, these forms now also incorporate more recent novel therapies, which will help generate important future studies for the committee to perform. To help foster new study proposals, our committee not only provides our members with disease specific lists of accepted studies but also with prior proposals that were not accepted and the rationale for the decision. This information allows investigators to better focus their new study proposals on concepts that are feasible and not redundant. A few of the published studies and proposals underway are described below.
Dr. Brian Shaffer led an important study that developed a prognostic scoring system of outcomes in those undergoing allogeneic HCT for MDS. The 3-year overall survival after transplantation in patients with low, intermediate, high, and very high scores was 71% (95% CI, 58% to 85%), 49% (95% CI, 42% to 56%), 41% (95% CI, 31% to 51%), and 25% (95% CI, 4% to 46%), respectively (P < .001). Increasing score was predictive of increased relapse (P < .001) and treatment-related mortality (P < .001) in the HLA-matched set and relapse (P < .001) in the HLA-mismatched cohort.
Dr. Hien Liu reported a study on allogeneic HCT for adult chronic myelomonocytic leukemia (CMML), which concluded that higher CMML-specific prognostic scoring system score at time of transplantation, lower Karnofsky performance score (KPS), and a bone marrow graft were associated with inferior survival after HCT. Investigation of transplant studies with CML have continued to ask important questions. Dr. Bei Hu submitted an abstract investigating the optimal timing of allogeneic HCT for CML patients in the tyrosine kinase inhibitor (TKI) era while Dr. Sarah Ann Schmidt is leading a study that examines the benefit of donor lymphocyte infusion for such patients.
Despite the development of highly active non-transplant therapies for CLL, allogeneic HCT remains a potential curative treatment strategy for selected, higher risk patients. To help better guide physicians and patients about this transplant approach, Dr. Haesook Kim and colleagues developed and validated a novel prognostic scoring system of HCT outcomes after reduced-intensity conditioning. This is the first score in the literature to risk stratify CLL patients at the time of HCT. A novel cytogenetic based risk stratification system was also developed, and then the two systems were combined. This may serve as a platform for assessment of future investigational approaches and allow better comparison of results from different studies.
The committee welcomes new participants as well as new proposals. We also encourage collaboration with other committees and the use of outside data sets, which can better define the role and timing of transplantation as new non-transplant strategies emerge. We encourage young investigators to take part in the committee, which will provide them an excellent opportunity to become familiar with novel study designs for observational research and the statistical methodologies utilized. The next in-person meeting of the Chronic Leukemia Working Committee is at the BMT Tandem Meetings in Salt Lake City in February 2018. We look forward to seeing you there and welcoming new proposals.
View planned, in-progress, and completed studies and publications on the Chronic Leukemia Working Committee webpage.
Left to right: Alyssa Carlson, Colleen Brady, Heather Severance, Stephanie Waldvogel, Ashley Spahn, Cynthia Vierra-Green, Alexandra (Allie) Erickson, Alan Howard, Maria Brown, and Steve Spellman.
The Immunobiology Research Program within CIBMTR is led by Assistant Scientific Director, Stephen Spellman, with scientific oversight provided by Senior Scientific Director, Dr. Stephanie Lee. The team is comprised of ten members and is based on the Minneapolis Campus.
The Immunobiology Research Program was established in 2010 and supports the Graft-versus-Host Disease, Graft Sources and Manipulation, and Immunobiology Working Committees. The program manages CIBMTR research sample collection and sample utilization. This includes the unrelated and related donor / cord blood pre-transplant sample collections and prospective clinical trial sample collection supporting the RCI BMT and BMT CTN. The CIBMTR Related and Unrelated Donor Transplant Repository contains samples from nearly 150,000 individuals, and the program distributed >16,000 samples to investigators during the 2016-2017 academic year. The Immunobiology Research team works closely with the Repository Steering Committee comprised of the NMDP Histocompatibility Advisory Group to monitor sample submission compliance, sample processing protocols, and approval of CIBMTR studies that use the stored samples. Details on the research sample inventory are available on the CIBMTR and BMT CTN websites.
The Immunobiology Research team manages the immunogenetic testing program that performs retrospective high-resolution HLA and killer immunoglobulin-like receptor (KIR) typing on stored donor and cord-recipient pairs. This testing program not only provides key immunogenetic data for histocompatibility research but also confirms sample identity in the repository for future analyses. In the past year, >1,300 related and >3,200 unrelated donor/recipient pairs were tested through the program. The immunogenetic database includes >25,000 pairs with retrospectively validated HLA data and >18,000 pairs with KIR presence/absence data. The HLA and KIR data are incorporated into the CIBMTR immunogenetics database and made available for future studies. In addition, the team provides HLA expertise for validation of all typing submitted on CIBMTR data collection forms prior to inclusion in research studies. The team also provides scientific expertise and logistical support to establish laboratory contracting and sample testing services for CIBMTR, BMT CTN, and RCI BMT studies.
The Autonomous University of San Luis Potosí awarded Guillermo J. Ruiz-Argüelles, MD, FRCP (Glasg), MACP, with its greatest honorary Doctorate for being a prominent figure nationally and internationally. His long history in research and teaching in the field of hematology as well as his contributions to medical science in bone marrow transplantation distinguish him as an outstanding graduate of the Faculty of Medicine of this house of study and professionally committed to his vocation of service to humanity.
Dr. Ruiz-Argüelles received the Doctorate Honoris Causa from the Maximum House of Studies Potosina in September. Dr. Ruiz-Argüelles is a hematologist doctor from the Faculty of Medicine of this University and full member of the National Academy of Medicine of Mexico, the National System of Researchers (Level III), the Mexican Academy of Sciences, and the Commission of Health Research of Mexico.
Congratulations Dr. Ruiz-Argüelles on this accomplishment!
BMT CTN Publications
There are 78 BMT CTN published articles, including 21 primary analyses. The following secondary analysis manuscripts were recently published:
0704/CALGB 100104: Holstein et al. Updated analysis of CALGB (Alliance) 100104 assessing lenalidomide versus placebo maintenance after single autologous stem-cell transplantation for multiple myeloma: A randomised, double-blind, Phase III trial. Lancet Haematology. 2017 Sep;4(9):e431-e442. Epub 2017 Aug 17. ncbi.nlm.nih.gov/pubmed/28826616
About the BMT CTN
The CIBMTR shares administration of the BMT CTN Data and Coordinating Center with National Marrow Donor Program/Be The Match® and The Emmes Corporation®. Together, these three organizations support all BMT CTN activities. The BMT CTN Steering Committee is currently under the leadership of Chair Steve Devine, MD, Ohio State University. Rick Jones, MD, Johns Hopkins, is Chair-Elect and Helen Heslop, MD, Baylor College of Medicine, is Vice-Chair.
To get up-to-date information about BMT CTN studies, meetings, and news:facebook.com/bmtctntwitter.com/bmtctn (@BMTCTN)
Our SupportersThe CIBMTR is supported by Public Health Service Grant/Cooperative Agreement 5U24CA076518 from the National Cancer Institute (NCI), the National Heart, Lung and Blood Institute (NHLBI) and the National Institute of Allergy and Infectious Diseases (NIAID); a Grant/Cooperative Agreement 4U10HL069294 from NHLBI and NCI; a contract HHSH25020170006C with Health Resources and Services Administration (HRSA/DHHS); two Grants N00014-17-1-2388 and N0014-17-1-2850 from the Office of Naval Research; and grants from our corporate and private contributors.