Session 1: Hematology and Cancer

Overview

Session 1 opened with one of the most powerful moments of the entire Summit: Damian Carbajal, a former U.S. Air Force flight engineer, sharing his personal journey through two stem cell transplants and medical retirement. His story set an emotional foundation for a day of talks that painted a picture of a field working to answer some of the hardest questions faced by families living with Telomere Biology Disorders (TBDs). What is my risk of cancer, and when should I be screened for it? When a stem cell transplant becomes necessary, and how do we choose the safest path and donor? And looking further ahead, could future therapies reduce or even eliminate the need for transplant altogether by directly addressing shortened telomeres?

Dr. Marena Niewisch and Dr. Daria Babushok each tackled a piece of the cancer risk puzzle, from solid tumors to blood cancers, showing how a patient’s genotype (their specific genetic change) and age shape that risk, and how surveillance guidelines are being refined using real patient data. Dr. Christen Ebens and Dr. Nico Gagelmann examined transplant itself and showed how the field is questioning long-held assumptions, such as the discovery that a donor’s telomere length may better predict transplant safety than their age alone. Finally, Dr. Kasiani Myers and Dr. Chi-Kang Tseng introduced two early-stage experimental approaches, cell therapy and RNA therapy, aimed at lengthening telomeres directly. Together, this session reflects the field moving from lab to clinic and using better data to inform more personalized, less toxic care.

Highlights from Each Talk

Solid Tumor Risk: Dr. Marena Niewisch, University Hospital Ulm, Germany 

Dr. Niewisch shared findings from a study of 230 genetically confirmed TBD patients, and showed that they face roughly three times the general population’s risk of solid tumors, often head and neck cancers, and are diagnosed at younger ages with higher risk further after transplant. That risk varies by the patient’s genetics, and certain patients face higher and earlier risk than others. The key takeaway for families: cancer screening may eventually be tailored to a patient’s specific genetic subtype rather than following one standard schedule, and new patient registries in Germany aim to individualize those recommendations over time.

BM Surveillance in TBD: Dr. Daria Babushok, University of Pennsylvania

Dr. Babushok reviewed how doctors monitor for blood cancers linked to TBDs through bone marrow biopsies. Current guidelines call for annual biopsies starting at age 10 for higher-risk children, though TBD’s variability makes these recommendations imperfect. Early results from SAFE-TBD, a study of more than 700 patients, found the cancer risk is low in children (3.4%), but higher in adults (16%). Notably, over 80% of these cancers were discovered because they led to a patient’s original TBD diagnosis, not through routine surveillance, which raises real questions about how effectively frequent biopsies actually catch early-stage cancer.

Modern Transplant Strategies: Dr. Christen Ebens, University of Minnesota

Dr. Ebens explained why TBD patients need specialized approaches to stem cell transplant, since they are especially sensitive to traditional chemotherapy and radiation, and even a matched sibling donor may not be safe because of short telomere inheritance. Reduced-intensity conditioning regimens have improved two-year survival to roughly 75 to 80%, though complications can persist afterward. Researchers are exploring ways to make donor grafts safer, such as removing certain donor immune cells, although more evidence is needed. A multi-institution effort called CCCTAA is now pooling data across centers to build stronger evidence and, eventually, gentler, more targeted transplant approaches for individual patients.

Donor Telomere Length Redefines the Donor Age Paradigm in Allogeneic Hematopoietic Cell Transplantation: Dr. Nico Gagelmann, Dana-Farber Cancer Institute 

Dr. Gagelmann presented findings from a large analysis of nearly 20,000 transplant patients, examining why younger donors have traditionally been preferred. His team found that longer donor telomeres, measured directly in donors 35 and older, were linked to a nearly 30% reduction in early non-relapse death. This was largely because donor cells took hold more successfully. Telomere length explained only part of the effect of donor age on transplant success, suggesting it captures something meaningfully different about which donor cells will be successful in implantation. The practical implication: an older donor with longer telomeres may be just as good a match as a younger one, though more research is needed to confirm this.

Persistence of Hematopoiesis with Telomere Extension after Infusion of Autologous CD34+ Cells Exposed to ZSCAN4 in Patients with TBD: Dr. Kasiani Myers, Cincinnati Children’s Hospital Medical Center

Dr. Myers shared updates from a first-in-human trial testing a cell therapy for TBDs, where a patient’s own blood-forming stem cells are briefly treated with a protein called ZSCAN4, which known to help lengthen telomeres, then infused back without chemotherapy beforehand. Six patients, including three children, have been treated and followed for 9 to 52 months, with an excellent safety profile. The treated cells showed measurable telomere lengthening that has persisted up to three years, as well as with or improved blood counts. The trial is currently paused between phases and is expected to reopen enrollment this fall.

Circular Human Telomerase RNA as a Therapeutic Strategy for TBD: Dr. Chi-Kang Tseng, National Taiwan University

Dr. Tseng introduced an experimental RNA-based approach that restores telomerase function, the machinery that maintains telomere length. His lab engineered a circular form of telomerase RNA that is designed to resist the breakdown caused by many TBD mutations, which leads to more RNA available to make telomerase and restore telomeres. The engineered RNA is delivered with lipid nanoparticles. In laboratory studies on patient-derived stem cells, the treatment restored telomerase activity, lengthened telomeres, and reversed signs of cellular aging, and the effects lasted up to three years in cell culture. This is early, preclinical research, not yet tested in patients, but it represents a genetics-independent strategy that could someday benefit patients regardless of which TBD gene is affected.

What This Means for the Field

Taken together, the talks in this session reveal a field that is maturing from broad associations and generalized management toward precise, actionable data and individualized treatments. Cancer risk in TBDs is real and elevated, but it is not uniform. It varies by genotype and age, and researchers like Dr. Niewisch and Dr. Babushok are working to translate that nuance into smarter, less burdensome surveillance and screening recommendations, rather than one-size-fits-all protocols. On the transplant side, Dr. Ebens and Dr. Gagelmann’s talks both point toward a shift away from rigid, tradition-based rules, like always choosing the youngest available donor, and toward decisions grounded in biology and outcomes data, whether that means new graft engineering techniques or measuring a donor’s actual telomere length. Several speakers acknowledged how much data is still missing, and pointed to collaborative, multi-center efforts, which are working to close those gaps by pooling experience across institutions. Finally, the ZSCAN4 cell therapy and circular telomerase RNA research offer a genuinely hopeful long-term horizon: early, promising steps toward therapies that address telomere shortening directly, rather than only managing its downstream consequences. None of these approaches are ready for widespread clinical use today, but the research community all together is working, with urgency and rigor, toward a future with more options, more personalized care, and better outcomes for people living with TBDs.