Donor lymphocyte infusion (DLI) is a form of cellular immunotherapy which is known to be effective in preventing relapse in leukemia by inducing graft versus leukemia (GVL) effect. In hematopoietic stem cell transplantation (HSCT) for benign hematological conditions including primary immune deficiency, mixed chimerism is seen with the use of reduced intensity conditioning. DLI can help prevent graft rejection by boosting the existing graft in these situations. There is scant data on the use of DLI in children who have undergone HSCT for benign hematological disorders. We present our case series with early withdrawal of immunosuppression and DLI as a means to mitigate relapse of leukemia and prevent graft rejection in mixed chimerism in children transplanted for benign hematological disorders. Donor lymphocyte infusion was given in a graded regimen with the cell dose of 1 × 105 CD3 cells/kg (1 × 104/kg in haploidentical transplant), 5 × 105 CD3 cells/kg, 1 × 106 CD3 cells/kg depending on the graft kinetics and the clinical status of the children. A total of fifty eight children including those with haploidentical donors underwent DLI with an overall survival of 81.1%. The use of fresh whole blood in very small aliquots from the donor has made this technique cost effective and an attractive form of immunotherapy.
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Marsh RA, Vaughn G, Kim MO, Dandan Li, Jodele S, Joshi S, et al. Reduced-intensity conditioning significantly improves survival of patients with hemophagocytic lymphohistiocytosis undergoing allogeneic hematopoietic cell transplantation. Blood. 2010;116:5824–31.
Peters C, Steward CG. Hematopoietic cell transplantation for inherited metabolic diseases: an overview of outcomes and practice guidelines. Bone Marrow Transplant. 2003;31:229–39.
Cooper N, Rao K, Gilmour K, Hadad L, Adams S, Cale C, et al. Stem cell transplantation with reduced-intensity conditioning for hemophagocytic lymphohistiocytosis. Blood. 2006;107:1233–6.
Kolb HJ, Mittermuller J, Clemm C, Holler E, Ledderose G, Brehm G, et al. Donor leukocyte transfusions for treatment of recurrent chronic myelogenous leukemia in marrow transplant patients. Blood. 1990;76:2462–5.
Kolb HJ, Schattenberg A, Goldman JM, Hertenstein B, Jacobsen N, Arcese W, et al. Graft-versus-leukemia effect of donor lymphocyte transfusions in marrow grafted patients. European group for blood and marrow transplantation working party chronic leukemia. Blood. 1995;86:2041–50.
Collins RH Jr, Shpilberg O, Drobyski WR, Porter DL, Giralt S, Champlin R, et al. Donor leukocyte infusions in 140 patients with relapsed malignancy after allogeneic bone marrow transplantation. J Clin Oncol. 1997;15:433–44.
Kolb HJ, Mittermuller J, Holler E, Thalmeier K, Bartram CR. Graft-versus-host reaction spares normal stem cells in chronic myelogenous leukemia. Bone Marrow Transplant. 1996;17:449–52.
Castagna L, Sarina B, Bramanti S, Perseghin P, Mariotti J, Morabito L. Donor lymphocyte infusion after allogeneic stem cell transplantation. Transfus Apher Sci. 2016;54:345–55.
Mark DI et al. The toxicity and efficacy of donor lymphocyte infusions given after reduced-intensity conditioning allogeneic stem cell transplantation. Blood. 2002;100:3108–114.
Rujkijyanont P, Morris C, Kang G, Gan K, Hartford C, Triplett B, et al. Risk-adapted donor lymphocyte infusion based on chimerism and donor source in pediatric leukemia. Blood Cancer J. 2013;3:e137.
Haines L, Bleesing J, Davies S, Hornung L, Jordan M, Marsh RA, et al. Outcomes of donor lymphocyte infusion for treatment of mixed donor chimerism after a reduced-intensity preparative regimen for pediatric patients with nonmalignant diseases. Biol Blood Marrow Transpl. 2015;21:288e292.
Abraham A, Hsieh M, Eapen M, Fitzhugh C, Carreras J, Keesler D, et al. Relationship between mixed donor-recipient chimerism and disease recurrence after hematopoietic cell transplantation for sickle cell disease. Biol Blood Marrow Transplant. 2017;23:2178–83.
Fitzhugh CD, Walters MC. The case for HLA-identical sibling hematopoietic stem cell transplantation in children with symptomatic sickle cell anemia. Blood Adv. 2017;1:2563–7.
George B, Viswabandya A, Abraham A, Sindhuvi E, Ganapule A, Fouzia NA, et al. Increased incidence of mixed chimerism with the use of fludarabine-treosulfan based conditioning in patients undergoing allogeneic stem cell transplantation for thalassaemia major. Biol Blood Marrow Transpl. 2015;21:284–5.
Luznik L et al. Donor lymphocyte infusions to treat hematologic malignancies in relapse after allogeneic blood or marrow transplantation. Cancer Control. 2002;9:123–37.
Dr. Anil Tarigopula MD, Department of Molecular diagnosis, Apollo Hospitals, Chennai. Unrelated stem cell donors for their gratitude in helping the children.
Conflict of interest
The authors declare that they have no conflict of interest.
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