Ruxolitinib With Tacrolimus and Methotrexate for the Prevention of Graft Versus Host Disease in Pediatric and Young Adult Patients Undergoing Allogeneic Hematopoietic Cell Transplant for Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, or Myelodysplastic Syndrome

Inclusion Criteria:

Documented informed consent of the participant and/or legally authorized representative

Assent, when appropriate, will be obtained per institutional guidelines

Agreement to allow the use of archival tissue from diagnostic tumor biopsies

If unavailable, exceptions may be granted with study primary investigator (PI) approval
Age: 2-22
Eastern Cooperative Oncology Group (ECOG) ≤ 2
Performance status: Karnofsky ≥ 60% for patients ≥ 16 years old OR Lansky status ≥ 60% for patients < 16 years old

Candidate for allogeneic bone marrow transplant with and available matched related donor (MRD) or an 8/8 matched unrelated donor (MUD) who is willing to donate bone marrow (BM) or mobilized peripheral blood stem cells

Note: Donor selection process will be in accordance with City of Hope (COH)-standard operating procedures (SOPs) (B.001.09 Allogeneic Cellular Therapy Product Donor Evaluation, Selection & Consent), which follows Food and Drug Administration (FDA) guidelines for donation of hematopoietic stem/progenitor cells (HPCs) obtained from peripheral blood or bone marrow
Diagnosis of acute leukemia (acute myeloid leukemia [AML] or acute lymphoblastic leukemia [ALL]) in complete remission, or myelodysplastic syndrome (MDS)
Fully recovered from the acute toxic effects (except alopecia) to ≤ grade 1 from prior anti-cancer therapy
Women of childbearing potential (WOCBP): negative urine or serum pregnancy test. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required (to be performed within 30 days prior to day 1 of protocol therapy)

Agreement by females and males of childbearing potential to use an effective method of birth control or abstain from heterosexual activity for the course of the study through at least 6 months after the last dose of protocol therapy

Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for > 1 year (women only)

Exclusion Criteria:

Autologous stem cell transplant within 1 year prior to day 1 of protocol therapy
Prior allogeneic transplantation

Chemotherapy, radiation therapy, biological therapy, immunotherapy within 14 days prior to day 1 of protocol therapy

Note: Conditioning regimen within 21 days prior to day 1 of protocol therapy is not considered as an exclusion criterion.
Note: Patients on maintenance chemotherapy with agents listed are not excluded
Herbal medications
History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agent
History of active tuberculosis
Patients with history of thrombosis including but not limited to myocardial infarction (MI)/stroke and pulmonary embolism (PE)/deep vein thrombosis (DVT) within 6 months of enrollment
Active diarrhea due to inflammatory bowel disease or malabsorption syndrome
Clinically significant uncontrolled illness
Active, uncontrolled systemic infection (viral, bacterial, or fungal) requiring antibiotics
Known history of immunodeficiency virus (HIV) or hepatitis B or hepatitis C infection
Other active malignancy
Females only: Pregnant or breastfeeding
Any other condition that would, in the investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures
Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)