AS611 - Effect of clonal hematopoesis of indeterminate potential and calcium and Vitamin D supplementation on risk of hematological malignancies

Investigator Names and Contact Information

Pinkal Desai (pid9006@med.cornell.edu)

Introduction/Intent

Our hypothesis is that risk of HM due to antecedent CHIP is prospectively identifiable and potentially modifiable by CaD supplementation. We will utilize data from the WHI and blood samples collected at WHI baseline, all prior to development of HM. We will perform deep sequencing using a custom HM panel on peripheral blood samples of participants who developed HM with their age-matched controls, with the following aims and objectives:

Specific aim 1: To determine the relationship between baseline measurements of CHIP and development of specific HM among participants in the WHI. We will select 200 Diffuse Large B cell Lymphoma (DLBCL), 200 CLL and 200 cases of multiple myeloma along with age matched 200 controls (each) that did not develop HM during WHI follow up.

1.1. To determine the relationship between CHIP and the development of site specific HM including specifically DLBCL, multiple myeloma and CLL.

1.2. To determine the specific risk of HM conferred by individual CHIP mutations. We will investigate whether it is possible to identify a specific gene risk signature associated with DLBCL, CLL and multiple myeloma.

1.3. To determine the time to specific HM (CLL, DLBCL and multiple myeloma) in participants with and without CHIP

Specific aim 2: To determine the relationship between CaD supplementation and development of HM among participants in the WHI CaD study.

We will utilize data from 36,282 women aged 50-79 who were enrolled between 1995-2000 in the WHI CaD trial and randomized to active treatment (1000 mg elemental calcium carbonate and 400 IU vitamin D3 daily) or placebo (allocation ratio: 1:1). In this cohort there were 349 women diagnosed with HM (44 myeloid, 70 multiple myeloma and 235 lymphoid cancer) over an average follow-up time of 10.8 years (10))

2.1 To determine the impact of CaD supplementation on risk of development of HM in subjects with CHIP and without CHIP.

2.2 To evaluate the impact of CaD supplementation on time to development of HM in CHIP positive participants.

Specific aim 3: To evaluate the relationship between cardiometabolic abnormalities (BMI, waist circumference, history of DM,) and markers of chronic inflammation (WBC, CRP, IL-6,) on risk of HM.

3.1 To determine the relationship between cardiometabolic abnormalities and markers of chronic inflammation and CHIP.

3.2 To determine the impact of cardiometabolic abnormalities and markers of chronic inflammation on the relationship between CHIP and HM.