Removing naive T cells from donor stem cell grafts in older adults with leukemia

Who can take part

• PARTICIPANT: Age > 60 years
• PARTICIPANT: Diagnosis of acute leukemia or myelodysplastic syndrome (MDS):; Acute lymphocytic leukemia (ALL) in first or subsequent morphological remission (< 5% marrow blasts by morphology); Acute myeloid leukemia (AML) in first or subsequent morphological remission (< 5% marrow blasts by morphology); Other acute leukemia or related neoplasm (including but not limited to 'mixed phenotype' 'biphenotypic', 'acute undifferentiated' or 'ambiguous lineage' acute leukemia, blastic plasmacytoid dendritic cell neoplasm, lymphoblastic lymphoma, Burkitt leukemia/lymphoma, mast cell leukemia, chronic myeloid leukemia [CML] with blast crisis or other chronic myeloproliferative neoplasm) in first or subsequent morphological remission (< 5% marrow blasts by morphology); Myelodysplastic syndrome (MDS) with a history of excess blasts (≥ approximately 5% in marrow blasts by morphology) and a history of receiving cytoreductive therapy (including but not limited to BCL-2 inhibitors or cytotoxic chemotherapy) within the past 3 months
• PARTICIPANT: Karnofsky performance status (KPS) ≥ 60% at pre-HCT evaluation
• PARTICIPANT: Ability to provide informed consent
• PARTICIPANT: Prior autologous or allogeneic HCT is permitted
• DONOR: Human leukocyte antigen (HLA) matching: HLA-identical related donors or unrelated donors matched for HLA-A, -B, -C, - DRB1, and -DQB1 by high-resolution deoxyribonucleic acid (DNA) typing. A single allele-level mismatch at HLA class I is permitted
• DONOR: Stem cell source: Donors must be able to undergo peripheral blood stem cell (PBSC) collection. Only G-CSF-mobilized PBSC are permitted as the hematopoietic stem cell (HSC) source on this protocol

Who cannot take part

• PARTICIPANT: Patients with active extramedullary disease are excluded. History of extramedullary disease is allowed if only minimal residual disease is present prior to HCT
• PARTICIPANT: Patients with active central nervous system (CNS) leukemia at the time of treatment are excluded. A history of CNS leukemia is allowed if CNS disease has resolved prior to treatment initiation
• DONOR: Preexisting immunoreactivity:; Determined per institutional standard practices; For patients with a 10/10 HLA allele-level match, panel reactive antibody (PRA) screens to class I and class II antigens are recommended before HCT. If PRA >10%, then flow cytometric or B- and T-cell cytotoxic crossmatches must be obtained. The donor is excluded if any crossmatch is positive; For patients with a Class I allele mismatch, flow cytometric or B- and T-cell cytotoxic crossmatches must be performed regardless of PRA results. A positive anti-donor cytotoxic crossmatch is an absolute exclusion; Vector homozygosity: Donors are excluded if the patient is homozygous in the graft rejection vector against the donor's mismatched HLA class I allele
• PARTICIPANT: Cardiac insufficiency requiring treatment or symptomatic coronary artery disease
• PARTICIPANT: Active infectious disease requiring deferral of conditioning (per Infectious disease consult). Upper respiratory tract infection is not considered to represent an uncontrolled infection in this context
• PARTICIPANT: Fungal infection with radiologic progression despite appropriate antifungal therapy
• PARTICIPANT: Viral infection risk: HIV-1, HIV-2, human T-lymphotropic virus (HTLV) 1 or HTLV2 positivity or active infectious hepatitis
• PARTICIPANT: Other malignancies:; Active non-hematologic malignancies (except non-melanoma skin cancers); Non-hematologic malignancy in remission but with > 20% risk of recurrence within 5 years; Exclusion does not apply to indolent non-hematologic malignancies not requiring therapy
• PARTICIPANT: Patients with a life expectancy < 12 months from co-existing disease other than the leukemia or MDS
• PARTICIPANT: Hypersensitivity to cyclophosphamide, fludarabine, tacrolimus or mycophenolate mofetil (MMF)
• DONOR: Medical contraindications: HIV-1, HIV-2, HTLV-1, HTLV-2 seropositive or with active hepatitis B or hepatitis C virus infection
• PARTICIPANT: Ejection fraction < 35% (or shortening fraction < 26% if ejection fraction [EF] unavailable)
• PARTICIPANT: Serum creatinine must be within institutional normal limits
• PARTICIPANT: If serum creatinine > upper limit of normal, a 24-hour creatinine clearance will be performed; patients are excluded if < 50 mL/min/1.73 m\^2
• PARTICIPANT: Exclude patients with any of the following:; Fulminant liver failure; Cirrhosis with evidence of portal hypertension; Alcoholic hepatitis; Esophageal varices or history of variceal bleeding; Hepatic encephalopathy; Uncorrectable synthetic dysfunction (prolonged prothrombin time); Ascites due to portal hypertension; Bridging fibrosis; Bacterial or fungal liver abscess; Biliary obstruction; Chronic viral hepatitis with total bilirubin >3 mg/dL; Symptomatic biliary disease
• PARTICIPANT: Circulating blasts:; Acute leukemia: circulating abnormal blasts detectable by standard pathology; MDS: > 5% circulating abnormal blasts by standard pathology
• PARTICIPANT: Patients with promyelocytic leukemia (APL)
• PARTICIPANT: Patients with shortening fraction < 26% may enroll if approved by a cardiologist
• PARTICIPANT: Carbon monoxide diffusing capability (DLCO) < 40%, total lung capacity (TLC) < 40%, forced expiratory volume in 1 second (FEV1) < 40%, and/or requiring continuous supplemental oxygen
• PARTICIPANT: If pulmonary function tests (PFTs) cannot be obtained: any patient with room air oxygen saturation < 89% during a 6-minute walk test (6MWT) will be excluded
• PARTICIPANT: Weight > 110kg
• PARTICIPANT: Inability to provide informed consent
• PARTICIPANT: Alternative treatment: Patients who are suitable for and willing to receive a standard high intensity (myeloablative) preparative regimen
• DONOR: Stem cell source restriction: Donors (or centers) that can exclusively provide bone marrow harvests
• DONOR: Donors donating outside of the United States of America (USA)