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Lymphoma patients \>=60 receiving cytotoxic chemotherapy who have consented to DNA extraction and analysis for CHIP.

Patients will have one additional blood draw to be sent for DNA extraction and sequencing for CHIP.

Blood test for determination of CHIP

Prasha Sasitharakumar, MHSc

Anne Parmentier

Rena Buckstein, MD

Rena Buckstein, MD, FRCPC

Hubert Tsui, MD

Michael Rauh, MD

'CHIP' stands for Clonal Hematopoiesis of Indeterminate Significance, which are mutations in bone marrow stem cells that give that population of cells a survival or 'clonal' advantage for growth. This study investigates whether CHIP in lymphoma patients aged 60 years and older is a risk factor for chemotherapy-related complications like low blood counts, infections, cardiac events, hospitalizations, dose delays and dose reductions, and failure to recover normal blood counts after chemotherapy finishes.

'CHIP' stands for Clonal Hematopoiesis of Indeterminate Significance (1-4). Up to 20% of individuals in the general population acquire mutations in their bone marrow stem cells as they age that give that population of cells a survival or 'clonal' advantage for growth. The frequency of CHIP may be higher in patients with other cancers. CHIP increases with age, and has been shown to be a risk factor associated with cardiovascular disease and a tendency to the development of bone marrow cancers at a rate of 1% per year (1,2,5). CHIP is also associated with the development of bone marrow cancers that occur after chemotherapy. The investigators want to investigate whether CHIP is also a risk factor for chemotherapy-related complications like low blood counts, infections, cardiac events, hospitalizations, dose delays and dose reductions. They are also interested in determining if CHIP may explain why some patients do not recover normal blood counts after chemotherapy finishes.

The results from this study may help physicians better understand why some people have difficulty with chemotherapy (in the short and long-term) while others do not. Screening for CHIP in older patients may become a recommended standard that allows physicians to tailor anti-cancer treatment to the patient.

A peripheral blood ethylenediaminetetraacetic acid (EDTA) tube will be used to obtain blood for DNA extraction.

Clonal Hematopoiesis is a Risk Factor for Chemotherapy-Related Complications

A Single Centre Cohort Study to Determine if Clonal Hematopoieses of Indeterminate Potential (CHIP) is a Risk Factor for Chemotherapy-Related Complications in Lymphoma Patients >= 60 Receiving Cytotoxic Chemotherapy

Complications during chemotherapy defined as any or all of the following: febrile neutropenia, new grades 3-4 anemia, thrombocytopenia and neutropenia immediately (day -1 or 0) preceding next cycle of chemotherapy, secondary dose reductions or dose delays due to myelosuppression or toxicity, cardiovascular toxicity (arrhythmias, congestive heart failure, symptomatic coronary disease), secondary granulocyte colony-stimulating factor (GCSF) use due to neutropenia, inability to complete all scheduled cycles due to chemotherapy related complications, dose delays that exceed 7 days.

The number of patients with and without CHIP who, following at 6 and 12 months post chemotherapy have:

1. Hemoglobin, white blood cell (WBC) or platelet (PLT) count that does not recover to normal pre-chemotherapy levels
2. Persistant macrocytosis defined as mean cell volume (MCV) \> 96 fl
3. Persistant anisocytosis defined as red cell distribution width (RDW) \> 14.5%

Expansion of clonal hematopoietic stem cells over time measured using next generation sequencing of 40 myeloid genes in patients with CHIP at baseline defined by variant allele frequency (VAF) that increases by 10% of more or the emergence of new clones

Therapy-related myeloid neoplasm defined as any of myelodysplastic syndrome (MDS), acute myeloid leukemia (AML), myeloproliferative neoplasm (MPN), MDS/MPN diagnosed by bone marrow exam

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Clonal Hematopoiesis is a Risk Factor for Chemotherapy-Related Complications	NCT04053439	Lymphoma Chemotherapeuti...	Blood test for ...	60 Years -	Sunnybrook Health Sciences Centre
Clonal Hematopoiesis is a Risk Factor for Chemotherapy-Related Complications	NCT04053439	Lymphoma Chemotherapeuti...	Blood test for ...	60 Years -	Sunnybrook Health Sciences Centre
Clonal Hematopoiesis is a Risk Factor for Chemotherapy-Related Complications	NCT04053439	Lymphoma Chemotherapeuti...	Blood test for ...	60 Years -	Sunnybrook Health Sciences Centre

Spots Global Cancer Trial Database for clonal hematopoiesis of indeterminate significance