The primary objective of this proposal is to conduct the first-in-human randomized clinical trial evaluating prophylactic DLI-X (pro-DLI-X) for relapse prevention following matched sibling donor (MSD) or haploidentical (haplo) hematopoietic cell transplantation (HCT) in patients with hematologic malignancies. Additionally, the study aims to assess the safety and efficacy of therapeutic DLI-X (t-DLI-X) compared to t-DLI alone in patients with minimal residual disease (MRD+) or overt relapse post-alloHCT. For patients with CD19-positive lymphoid malignancies, the study will incorporate blinatumomab, while those with myeloid or CD19-negative lymphoid malignancies will receive t-DLI-X or t-DLI alone.
We hypothesize that both pro-DLI-X and t-DLI-X, with or without blinatumomab, will demonstrate safety and superior efficacy by enhancing graft-versus-leukemia (GvL) effects mediated by natural killer (NK) cells, γδ T cells, and CD8+ T cells, while maintaining manageable and treatment-responsive graft-versus-host disease (GvHD).
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)
Acute grade III-IV aGvHD or moderate/severe chronic GvHD.
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.