Hematopoietic Stem Cell Transplant Survivors Study (HTSS Study)

HSCT survivors are at an increased risk for premature aging. No one has evaluated the
biologic markers of premature aging and senescence in HSCT survivors and their correlation
with clinical outcomes, lifestyle, and nutrition. The investigators will evaluate age-related
changes in HSCT survivors, with specified measures of premature aging, and employ therapeutic
opportunities based on targeting senescent cells by conducting the first in-human pilot study
of senolytic drugs (in HSCT survivors utilizing a combination of senolytics).

Inclusion Criteria

- Allogeneic HSCT patients surviving ≥ 1 year post-HSCT

- Diagnosis of both malignant and non-malignant conditions as HSCT indications

- HSCT survivors receiving any type of conditioning chemo/radiotherapy for HSCT

- Ability to provide written and verbal informed consent

- Age ≥ 18 years

- Adequate blood counts i.e. platelets>50,000 per microliter; HB>9/dL, and ANC> 1000 per
microliter

Exclusion Criteria

- HSCT survivor with human immunodeficiency virus (HIV) infection

- HSCT survivor with active hepatitis B or C HSCT survivor on any TKI for either
Philadelphia chromosome positive cancers or for GVHD treatments or for any other
indication (e.g., imatinib for GIST, sorafenib for FLT3+ AML etc)

- HSCT survivor with any post-transplant maintenance chemotherapy

- Post-transplant relapse of cancer

- Active progressive CHRONIC chronic or overlap GVHD (per the NIH chronic GVHD criteria)

- Presence of uncontrolled psychiatric disorder

- Patient unable to give informed consent

- Extremely poor overall prognosis (<6 months as deemed by the primary transplant
physician)

- HSCT survivors with confirmed drug addiction

- HSCT survivors with active coronary artery disease (CAD) [including angina] or active
congestive heart failure (CHF)

- International HSCT survivors in whom loss to follow-up would be a concern as deemed by
primary transplant physician

- Known hypersensitivity or allergy to dasatinib, or quercetin

- Presence of uncontrolled lupus

- Presence of uncontrolled pleural/pericardial effusions or ascites

- Presence of active new cancer (solid or hematologic) except non-melanoma skin cancers

- Presence of progeroid syndromes in family

- Invasive fungal or viral infection not responding to appropriate antifungal or
antiviral therapies.

- Creatinine clearance < 60 mL/min/1.73 m2 based on the Cockcroft-Gault

- Inability to tolerate oral medications

- Total bilirubin>2x upper limit normal (unless deemed to be due to Gilbert's syndrome);
AST/ALT>2.5x ULN

- Active progressive ACUTE graft-versus-host disease

- Active progressive OVERLAP graft-versus-host disease

- Patients taking medications that are sensitive substrates or substrates with a narrow
therapeutic range for CYP3A4, CYP2C8, CYP2C9, or CYP2D6 or strong inhibitors or
inducers of CYP3A4(e.g. cyclosporine, tacrolimus or sirolimus). If antifungals are
absolutely necessary from infectious disease perspective, then they will be allowed
only if the levels are therapeutic. Levels will be checked at baseline and also at day
+4 post intervention.

- Patients taking H2-antagonists or proton pump inhibitors.

- Patients on therapeutic doses of anticoagulants (e.g. warfarin, heparin, low molecular
weight heparin, factor Xa inhibitors etc).

- On antiplatelet agents (e.g. full dose aspirin, clopidogrel etc.). Baby aspirin if
absolutely necessary from cardiac perspective will be allowed.

- On any quinolone antibiotic therapy for treatment or for prevention of infections.

- QTc>450 msec. Common drugs that are well known in prolonging QTc include azithromycin,
citalopram, escitalopram, fluconazole, and pentamidine. Baselines EKG will be obtained
in each patient and if QTc >450 msec, then they will be excluded from the trial.