Stem Cell Transplantation for Participants With Germline RUNX1 Associated Blood Cancers

Background: Some blood cancers can be caused by germline variants (changes) in a person s RUNX1 gene. Germline variants are genetic inherited changes a person is born with. Stem cell transplants are used to treat many diseases including blood cancers. Stem cell transplantation for patients with germline RUNX1 mutation driven blood cancers is standard of care and available in most major medical centers. The difference with this transplantation protocol is that it is prospective, only available to participants with germline RUNX1 variants and designed to determine the extent to which tailoring chemotherapy and supportive care medication doses for each individual patient may improve outcomes compared to data derived from retrospective transplantation protocols for patients with RUNX1 varinats which is less accurate. Objective: The primary objective of this protocol is to determine how tailored doses of chemotherapy and supportive care medications may improve disease free survival as compared to historical/expected disease free survival. Eligibility: People aged 4 to 70 years with blood cancer caused by a RUNX1 gene mutation. Other participants are also needed: (1) stem cell donors; (2) relatives who do not have a mutation in the RUNX1 gene; and (3) healthy volunteers. Design: Participants with blood cancer will be screened during approximately 1-3 months before transplatation. They will have blood tests and tests of their heart and lung function. A sample of bone marrow may be taken. A flexible tube (central line) will be inserted into a vein in participants chest or lower neck. This line will remain in place during the hospitalization and be used to draw blood and administer drugs. These lines are almost always transitioned to a peripherally inserted central catheter (PICC) line at the time of hospital discharge. Participants will be inpatient for 4 to 5 weeks. They will receive drugs to prepare their body for the stem cell transplant. Some may also receive radiation treatment. Other tests will include imaging scans. The stem cell transplant will be given through the central line. After discharge from the clinic, participants will have follow-up visits at least once per week for approximately 100 days. Then they will have follow-up clinic visits for 3 years. Donors, relatives, and healthy volunteers may provide samples of blood, stool, and saliva. Adults may also opt to provide samples of skin and bone marrow.

* INCLUSION CRITERIA: * Affected participants (Recipients) * History of deleterious or suspected deleterious (defined as P/LP or VUS with RUNX1 phenotype) germline RUNX1 mutation as defined by ClinVar (nih.gov) * Histological confirmation of a myeloid malignancy - acute or chronic leukemia (\=50% by echocardiogram (ECHO) or Multigated Acquisition (MUGA) scan (101) * Recipients must have adequate organ function as defined below: * Total bilirubin \=92% oxygen saturation on room air and no dyspnea at rest * LVEF \>=40% by ECHO or MUGA obtained within 2 months of HSCT (Children s Oncology Group \[COG\] criteria). * Recipients must have adequate organ function as defined below: * Total bilirubin \=4 years * Participants or parent/guardian must be able to understand and willing to sign a written informed consent document. * Unaffected family members * Age \>=18 years * If the participant is a blood relative of the recipient, participant must be negative for RUNX1 mutations by molecular testing * Participants must be able to understand and willing to sign a written informed consent document. EXCLUSION CRITERIA: -All participants * Recipients who are receiving any investigational agent except virus specific T cells (VST) * Active non-hematologic malignancies * History of allergic reactions attributed to compounds of similar chemical or biologic composition to the drugs used in study. * Participants with the following cardiac conditions: symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia (except atrial fibrillation if cleared by cardiology consultation) * Participants without access to medical care at home. * Positive serum or urine beta-human chorionic gonadotropin (beta-hCG) test at screening * Uncontrolled intercurrent illness evaluated by history, physical exam, and laboratory studies or situations that would limit compliance with study requirements, interpretation of results or that could increase risk to the participant