This clinical trial evaluates the effects of hemoglobin threshold-specific packed red blood cell (PRBC) transfusions on quality of life and functional outcomes in patients who have undergone chemotherapy or an allogeneic hematopoietic stem cell transplant for a high-grade myeloid neoplasm, acute myeloid leukemia, or B acute lymphoblastic lymphoma/leukemia. Some types of chemotherapy and stem cell transplants can induce low platelet counts and/or anemia that requires PRBC transfusions. Given critical shortages in blood supply, and risks associated with transfusion of PRBC, there has been much investigation into the "minimum" hemoglobin level that effectively balances safety and toxicity in patients. This clinical trial evaluates the effects of giving PRBC transfusions based on a more restrictive hemoglobin threshold (> 7 gm/dL) compared to a more liberal hemoglobin threshold (> 9 gm/dL) on quality of life and functional outcomes. A more restrictive threshold may be just as effective at maintaining patient quality of life and function while decreasing side effects from blood transfusions and helping to conserve blood supply resources.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients undergo PRBC transfusion if at any point their hemoglobin level is 7 gm/dL or less, starting the day after standard of care (SOC) chemotherapy/stem cell infusion is complete and continuing for up to 42 days. Patients also undergo collection of blood samples on study.

ARM II: Patients undergo PRBC transfusion if at any point their hemoglobin level is 9 gm/dL or less, starting the day after SOC chemotherapy/stem cell infusion is complete and continuing for up to 42 days. Patients also undergo collection of blood samples on study.

After completion of study intervention, patients are followed up for 7 days and then periodically for up to 5 years.

Inclusion Criteria:

• Age ≥ 18 years
• Diagnosis of "high-grade" myeloid neoplasm (≥ 10% blasts in blood or bone marrow) or acute myeloid leukemia (AML) (other than acute promyelocytic leukemia [APL]) or B-cell acute lymphoblastic lymphoma/leukemia (ALL) according to the 2022 WHO classification. Outside diagnostic material is acceptable to establish diagnosis
• Plan to undergo intensive chemotherapy induction or post-remission therapy for their diagnosis (defined as "7+3," hyper-cyclophosphamide, vincristine, doxorubicin, and dexamethasone [CVAD], or regimen with cytarabine backbone ≥ 1,000mg/m^2), or allogeneic HSCT, expected to induce anemia requiring PRBC transfusion AND platelet counts of ≤ 30,000/uL for ≥ 5 days following the therapy (as determined by principal investigator)
• Plan to get all post-chemotherapy/post-HSCT care at the University of Washington (UW)/Fred Hutchinson Cancer Center (FHCC)
• Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

• Patients requiring a prophylactic platelet transfusion at thresholds > 10,000/uL
• Patients requiring systemic anticoagulation, anti-platelet agent, or antifibrinolytic therapy that will not be held once platelets reach a level of < 50,000/uL
• Patients with grade ≥ 2 bleeding (as determined by the WHO Bleeding Criteria) at the time of randomization
• Arterial or venous thrombotic event, including myocardial infarction within 6 months prior to initiation of the chemotherapy/HSCT
• Patients requiring renal replacement therapy at the time of randomization
• Patients who decline transfusion for personal or religious beliefs
• Pregnancy or lactation