Donor Lymphocyte Infusions in Pediatric Patients with Malignant and Non-Malignant Diseases After Allogeneic Bone Marrow Transplantation: A Single Center Experience

Donor lymphocyte infusions (DLI) are used after allogeneic bone marrow transplantation (allo BMT) to treat and prevent relapse in patients with leukemia, to prevent graft rejection for non-malignant diseases, and to treat post-transplant lymphoprolypherative disorder or viral infections. The data in children, particularly in non-malignant diseases, are limited and based on case reports and small series. We describe our experience in using DLI in pediatric patients with both malignant and non-malignant diseases after allo BMT over a 3-year period.

From November 2009 to October 2012, 11 pediatric patients, median age 9.5 years (range, 1.5-18.5 years), were treated with 22 doses of DLI. Median follow-up duration after DLI was 7 months (range, 2-32 months).

Six patients had hematological malignancies (3 –acute lymphoblastic leukemia, 2 – acute myeloid leukemia, 1 – chronic myeloid leukemia (CML)). DLI was given after salvage chemotherapy (5 children) to treat relapse and achieve remission status or to prevent relapse without previous chemotherapy (1 patient). Median time between BMT and DLI was 7 months (range, 4-18 months). Median CD3-T-cell dose of DLI in patients with acute leukemia was 5x10⁷/kg (range, 1-10); a child with CML received 5 DLIs in escalating cell doses. Four of six patients had DLI from matched unrelated donors, and developed severe multisystemic graft versus host disease (GVHD).

Five children with non-malignant diseases (2 - thalassemia major, 2 - metabolic diseases, 1 -Immunodeficiency) had progressively decreasing chimerism and received DLI to prevent graft rejection. DLI was given 8 months (median; range, 2-9 months) after BMT. Median dose was 1x10⁷/kg (range, 0.1-5). All patients had matched family donors (MFD). In 4/5 children, DLI prevented full rejection. In 2/5 children, stable mixed chimerism (25-35%) was enough to induce full remission of their basic disease. All were alive at the end of follow-up; none had GVHD.

Based on this experience, DLI achieved an excellent response for the patient with CML; but was not effective for treatment of full relapse in children with acute leukemia, and resulted in a high incidence of severe multisystemic GVHD. DLI could be an effective and safe method to prevent graft failure in children with non-malignant diseases after MFD. The absence of GVHD in this group is most likely due to family donors and reduced cell dose. Prospective studies of DLI in children are needed.