Clonal Hematopoiesis Chemotherapy and Radiation Effects Study

The objective of this protocol is to obtain clinical information and facilitate the collection and distribution of specimens obtained during the course of clinical care or research participation.

Blood, buccal swabs, or other body fluids may be specifically acquired for research in order to perform molecular and other types of analyses for research purposes. These materials will be collected from all eligible participants. It is expected that about 5,000 people will take part in this research study.

• Samples (Other): Tissue samples will be collected during a routine visit. Participants will be asked to donate any of the following tissue types: Blood, Buccal swab (saliva) or mouthwash, Urine, Stool, Biopsy or surgical tissue (i.e., bone marrow),Bodily fluids, Other tissues

Primary outcomes

• Prevalence of clonal hematopoiesis [Baseline]: Prevalence of clonal hematopoiesis detected by the study's targeted unique molecular identifier-based sequencing panel in population of adults with advanced non-metastatic solid cancers.
• Gene distribution of clonal hematopoiesis [baseline]: Distribution of genes mutated among subpopulation with clonal hematopoiesis in population of adults receiving chemotherapy and radiation therapy for solid malignancy.
• Change in clonal hematopoiesis variant allele fraction [Up to 5 years; assessed at time 0, 6 months, and annually]: Change in clonal hematopoiesis allelic fractions over follow-up in patients receiving chemotherapy and radiation for advanced non-metastatic solid malignancy, based on serial sequencing of stored blood specimens.
• Solid malignancy progression [Up to 5 years]: Solid malignancy progression in relation to the presence of clonal hematopoiesis, based on clinical progression data abstracted from the electronic health record and follow-up data collected under protocol 22-200.
• Overall survival [Up to 5 years]: Overall survival in relation to the presence of clonal hematopoiesis, based on abstracted date of death and cause of death.
• Development of hematologic toxicity [Up to 5 years]: Development of hematologic toxicity in relation to the presence of clonal hematopoiesis, using abstracted clinical and laboratory data, including CBC values and related treatment information.
• Development of therapy-related myeloid neoplasm (t-MN) [Up to 10 years]: Development of therapy-related myeloid neoplasm in relation to the presence of clonal hematopoiesis, using abstracted dates of diagnosis of hematologic malignancies and related follow-up data.

Secondary outcomes

• Development of a predictive algorithm for adverse clinical outcomes in patients with clonal hematopoiesis [Up to 5 years]: Aggregate study data will be utilized to identify features most predictive of adverse clonal hematopoiesis-related outcomes in patients receiving chemotherapy and/or radiation for solid malignancies. These features will be combined into the development of a predictive algorithm that is capable of identifying patient populations at-risk for t-MN.

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* Participants to be included in this study include the following:
* Adults age >18 years
* Diagnosed with solid malignancy (breast, ovarian, lung, gastric, colorectal, esophageal, uterine, head and neck, or sarcoma cancers)
* Have a pending plan to receive chemotherapy or radiation for their solid malignancy (cancer).
* Has not received cytotoxic chemotherapy or radiation for their solid cancer diagnosis in the past.

Exclusion Criteria:

* Individuals without plans for cytotoxic chemotherapy, radiation or PARP inhibitor exposure
* Individuals who have received prior chemotherapy and or radiation for their current solid malignancy (cancer)
* Individuals with any prior history of blood cancer (leukemia, myelodysplastic syndrome, lymphoma, multiple myeloma, including smoldering multiple myeloma). Persons with blood cancer precursors including clonal hematopoiesis of indeterminate potential (CHIP), clonal cytopenia of uncertain significance (CCUS), monoclonal B lymphocytosis (MBL), monoclonal gammopathy of uncertain significance (MGUS) are eligible for study participation.

• Weeks LD, Ebert BL. Clonal Hematopoiesis as a Driver of Solid Tumors. N Engl J Med. 2025 Apr 24;392(16):1654-1656. doi: 10.1056/NEJMe2504775. No abstract available. PMID 40267434
• Morganti S, Gibson CJ, Jin Q, Santos K, Patel A, Wilson A, Merrill M, Vincuilla J, Stokes S, Lipsyc-Sharf M, Parker T, King TA, Mittendorf EA, Curigliano G, Hughes ME, Stover DG, Tolaney SM, Weeks LD, Tayob N, Lin NU, Garber JE, Miller PG, Parsons HA. Prevalence, Dynamics, and Prognostic Role of Clonal Hematopoiesis of Indeterminate Potential in Patients With Breast Cancer. J Clin Oncol. 2024 Nov;42(31):3666-3679. doi: 10.1200/JCO.23.01071. Epub 2024 Jan 8. PMID 38190580
• Weeks LD, Ebert BL. Causes and consequences of clonal hematopoiesis. Blood. 2023 Dec 28;142(26):2235-2246. doi: 10.1182/blood.2023022222. PMID 37931207
• Weeks LD, Niroula A, Neuberg D, Wong W, Lindsley RC, Luskin M, Berliner N, Stone RM, DeAngelo DJ, Soiffer R, Uddin MM, Griffin G, Vlasschaert C, Gibson CJ, Jaiswal S, Bick AG, Malcovati L, Natarajan P, Ebert BL. Prediction of risk for myeloid malignancy in clonal hematopoiesis. NEJM Evid. 2023 May;2(5):10.1056/evidoa2200310. doi: 10.1056/evidoa2200310. Epub 2023 Apr 25. PMID 37483562

• Lachelle D Weeks, MD, PhD, Principal investigator, Dana-Farber Cancer Institute