Basic Principles and Problems in Donor Lymphocyte Collection

Allogeneic hematopoietic stem cell transplantation (AHSCT) is the first curative adoptive immunotherapy. Hematological malignancies are the most common conditions in which diseased hematopoietic stem cells are replaced by healthy donor cells; however, relapse after AHSCT remains a frequent complication. Donor lymphocyte infusion (DLI) is used to treat patients with relapsed disease by overcoming immune tolerance between donor and recipient and enhancing the graft-versus-malignancy (GVM) effect. DLI mediates GVM primarily by reversing T-cell exhaustion in resident CD8+ T cells, which exhibit reduced effector function and proliferation. DLI is also associated with normalization of the T-cell receptor repertoire, clonal expansion of allogeneic T cells, and improved coordination of T- and B-cell immunity. Lymphocyte collection, a process targeting a fraction of mononuclear cells (MNC), is performed by apheresis under the supervision of specialized technicians and nurses. The efficacy of DLI varies with factors such as the type and burden of the underlying malignancy, the dose and type of infused lymphocytes, and aspects related to AHSCT. Escalated doses of CD3+ T-cell infusions enhance both the GVM and graft-versus-host disease (GVHD) effects. Major adverse events following DLI include GVHD and pancytopenia. Patients who respond to DLI typically show clinical improvement within 2–3 months, although a complete response may take 1 year or longer.