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| Name | Class |
|---|---|
| The Leukemia and Lymphoma Society | OTHER |
| Queen's University | OTHER |
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'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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Lymphoma patients >=60 receiving cytotoxic chemotherapy | Lymphoma patients >=60 receiving cytotoxic chemotherapy who have consented to DNA extraction and analysis for CHIP. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Blood test for determination of CHIP | Other | Patients will have one additional blood draw to be sent for DNA extraction and sequencing for CHIP. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Determine if CHIP is an independent risk factor for chemotherapy-induced complications. | 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. | Up to 24 weeks |
| Emerging dysmyelopoiesis after chemotherapy | The number of patients with and without CHIP who, following at 6 and 12 months post chemotherapy have:
| Up to 12 months after completion of chemotherapy |
| Measure | Description | Time Frame |
|---|---|---|
| Expansion of clonal hematopoietic stem cells | 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 | Up to 5 years after completion of chemotherapy |
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Inclusion Criteria:
Exclusion Criteria:
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Elderly patients (>= 60 years old) being treated at a tertiary cancer centre in Toronto, ON.
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Prasha Sasitharakumar, MHSc | Contact | (416) 480-5000 | 7937 | prasha.sasitharakumar@sunnybrook.ca |
| Anne Parmentier | Contact | 416 480 5000 | 3803 | anne.parmentier@sunnybrook.ca |
| Name | Affiliation | Role |
|---|---|---|
| Rena Buckstein, MD, FRCPC | Sunnybrook Health Sciences Centre | Principal Investigator |
| Hubert Tsui, MD | Sunnybrook Health Sciences Centre | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Sunnybrook Health Sciences Centre | Recruiting | Toronto | Ontario | M4N 3M5 | Canada |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 25426837 | Background | Jaiswal S, Fontanillas P, Flannick J, Manning A, Grauman PV, Mar BG, Lindsley RC, Mermel CH, Burtt N, Chavez A, Higgins JM, Moltchanov V, Kuo FC, Kluk MJ, Henderson B, Kinnunen L, Koistinen HA, Ladenvall C, Getz G, Correa A, Banahan BF, Gabriel S, Kathiresan S, Stringham HM, McCarthy MI, Boehnke M, Tuomilehto J, Haiman C, Groop L, Atzmon G, Wilson JG, Neuberg D, Altshuler D, Ebert BL. Age-related clonal hematopoiesis associated with adverse outcomes. N Engl J Med. 2014 Dec 25;371(26):2488-98. doi: 10.1056/NEJMoa1408617. Epub 2014 Nov 26. | |
| 25426838 |
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| ID | Term |
|---|---|
| D008223 | Lymphoma |
| ID | Term |
|---|---|
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
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| ID | Term |
|---|---|
| D006403 | Hematologic Tests |
| ID | Term |
|---|---|
| D019411 | Clinical Laboratory Techniques |
| D019937 | Diagnostic Techniques and Procedures |
| D003933 | Diagnosis |
| D008919 | Investigative Techniques |
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A peripheral blood ethylenediaminetetraacetic acid (EDTA) tube will be used to obtain blood for DNA extraction.
| Development of therapy-related myeloid neoplasm | 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 | Up to 5 years after completion of chemotherapy |
| Overall survival | Overall survival | Up to 5 years after completion of chemotherapy |
| Michael Rauh, MD |
| Queen's University |
| Principal Investigator |
| Background |
| Genovese G, Kahler AK, Handsaker RE, Lindberg J, Rose SA, Bakhoum SF, Chambert K, Mick E, Neale BM, Fromer M, Purcell SM, Svantesson O, Landen M, Hoglund M, Lehmann S, Gabriel SB, Moran JL, Lander ES, Sullivan PF, Sklar P, Gronberg H, Hultman CM, McCarroll SA. Clonal hematopoiesis and blood-cancer risk inferred from blood DNA sequence. N Engl J Med. 2014 Dec 25;371(26):2477-87. doi: 10.1056/NEJMoa1409405. Epub 2014 Nov 26. |
| 25732814 | Background | McKerrell T, Park N, Moreno T, Grove CS, Ponstingl H, Stephens J; Understanding Society Scientific Group; Crawley C, Craig J, Scott MA, Hodkinson C, Baxter J, Rad R, Forsyth DR, Quail MA, Zeggini E, Ouwehand W, Varela I, Vassiliou GS. Leukemia-associated somatic mutations drive distinct patterns of age-related clonal hemopoiesis. Cell Rep. 2015 Mar 3;10(8):1239-45. doi: 10.1016/j.celrep.2015.02.005. Epub 2015 Feb 26. |
| 25326804 | Background | Xie M, Lu C, Wang J, McLellan MD, Johnson KJ, Wendl MC, McMichael JF, Schmidt HK, Yellapantula V, Miller CA, Ozenberger BA, Welch JS, Link DC, Walter MJ, Mardis ER, Dipersio JF, Chen F, Wilson RK, Ley TJ, Ding L. Age-related mutations associated with clonal hematopoietic expansion and malignancies. Nat Med. 2014 Dec;20(12):1472-8. doi: 10.1038/nm.3733. Epub 2014 Oct 19. |
| 25931582 | Background | Steensma DP, Bejar R, Jaiswal S, Lindsley RC, Sekeres MA, Hasserjian RP, Ebert BL. Clonal hematopoiesis of indeterminate potential and its distinction from myelodysplastic syndromes. Blood. 2015 Jul 2;126(1):9-16. doi: 10.1182/blood-2015-03-631747. Epub 2015 Apr 30. |
| D006425 | Hemic and Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |