Prophylactic DLI-X for Leukemia Relapse After HCT

• Exercise Mobilized Prophylactic DLI (Biological), also known as pro-DLI-X: Pro-DLI-X will be given through the patient's central line at an initial dose of 100,000 CD3+ cells/kilogram (kg) of recipient weight for haploidentical hematopoietic cell transplantation (haploHCT) and 300,000 CD3+ cells/kg for matched sibling donor hematopoietic cell transplantation (MSD HCT). Participants will receive up to 3 doses of pro-DLI-X, and each dose will be increased as follows: dose 2 will be 300,000 CD3+ cells/kg for haploHCT and 1,000,000 CD3+ cells/kg for MSD HCT; dose 3 will be 1,000,000 CD3+ cells/kg for haploHCT and 3,000,000 CD3+ cells/kg for MSD HCT.
• Standard Prophylactic DLI (Biological), also known as pro-DLI: Pro-DLI will be given through the patient's central line at an initial dose of 100,000 CD3+ cells/kilogram (kg) of recipient weight for haploidentical hematopoietic cell transplantation (haploHCT) and 300,000 CD3+ cells/kg for matched sibling donor hematopoietic cell transplantation (MSD HCT). Participants will receive up to 3 doses of pro-DLI-X, and each dose will be increased as follows: dose 2 will be 300,000 CD3+ cells/kg for haploHCT and 1,000,000 CD3+ cells/kg for MSD HCT; dose 3 will be 1,000,000 CD3+ cells/kg for haploHCT and 3,000,000 CD3+ cells/kg for MSD HCT.

Primary outcomes

• Prophylactic endpoint: Graft-versus-Host Disease-Free, Relapse-Free Survival (GRFS) [Assess between 1 to 3 years post HCT]: Graft-versus-Host Disease-Free, Relapse-Free Survival (GRFS) is defined as survival without evidence of disease relapse or grade III-IV acute graft-versus-host-disease (aGvHD) or chronic graft-versus-host-disease (cGvHD) requiring systemic therapy. In essence, GRFS serves as a meaningful measure encompassing not only survival but quality of life. GRFS will be compared in patients randomized to pro-DLI-X versus standard pro-DLI control group.

Sex: All, ages: any to 65 Years

DLI Recipient Inclusion Criteria:

* Provision of signed and dated informed consent form
* Stated willingness to comply with all study procedures and availability for the duration of the study
* Male or female, aged 0-65 years
* Diagnosis of acute leukemia (lymphoid, myeloid or undifferentiated) myelodysplastic syndrome (MDS), chronic myeloid leukemia (CML) or non-Hodgkin's lymphoma (NHL)
* Undergoing myeloablative or reduced intensity matched sibling donor (MSD) HCT or haploidentical HCT
* Have a locally available healthy matched or haploidentical (≥5/10 HLA antigen matched) related donor between 12 and 50 years of age, consented and able to perform the exercise sessions. (see donor inclusion criteria)

DLI Donor Inclusion Criteria:

* Provision of signed and dated informed consent form
* Must have already met transplant donor eligibility as a matched sibling donor, or HLA-haploidentical relative of the patient, including biological parents, siblings, or children, half-siblings, cousins or aunts and uncles
* Weight is greater than 30 kg
* Age 12 and 50 years
* Ability to undergo phlebotomy
* Be able complete the fitness evaluation to determine VO2max and peak cycling power. Following successful completion of the donor fitness evaluation, the patients willing to participate in the randomized trial will be enrolled
* Donor's recipient has met eligibility requirements and agreed to participate

DLI Recipient Exclusion Criteria:

* Acute grade II-IV aGvHD or moderate/severe chronic GvHD at time of scheduled DLI.
* Requiring immunosuppression therapy for treatment of GvHD.
* Co-morbidities: AST/ALT greater than 5 x ULN; Bilirubin greater than 2 x ULN; Creatinine greater than 2 x ULN for age or creatinine clearance/GFR <40 ml/min/1.73m2; Pulmonary function: DLCO less than 40% of normal or O2 Sat less than 92%; Cardiac: left ventricular ejection fraction less than 35%; active infection; HIV positive; Karnofsky score (adults) less than 60% or Lansky score less than 50% (pediatrics)
* Uncontrolled or severe bacterial, fungal or viral infection.
* Positive serum or urine pregnancy test for girls post menarche or women of childbearing age.
* Severe psychiatric illness or mental deficiency making compliance to treatment unlikely and/or and/or would preclude informed consent according to IRB requirements for the study.
* Any reason, at the investigator's discretion, that the participation of the patient in this protocol would not be in patient's best interest, or where the patient would be unable to adhere to the study requirements.

DLI Donor Exclusion Criteria:

* Unable to perform graded exercise test
* Cardiac or pulmonary disease/condition that would restrict exercise
* Positive anti-donor HLA antibody
* Pregnant or lactating
* Active infection
* Severe psychiatric illness or mental deficiency making compliance with donation unlikely and/or would preclude informed consent according to IRB requirements for the study.

• Emmanuel Katsanis, MD, Principal investigator, University of Arizona