1. DONOR LYMPHOCYTE INFUS I ON (DLI) Dr. Serdar ŞIVGIN February 2011 Kayseri

2. DLI  Marrow transplantation was initially developed as a procedure to rescue atomic bomb survivors from marrow aplasia induced by high-dose total body irradiation (TBI).

3. DLI  Donor leukocyte infusion (DLI) is a form of adoptive immunotherapy in which a patient with a hematologic malignancy who has previously received an allogeneic bone marrow transplant has relapsed.  The leukocytes are obtained from the original bone marrow donor through a leukapheresis procedure.

4. DLI  The principle use of donor leukocyte infusion (also know as donor lymphocyte or buffy coat transfusion) is to induce a graft-versus -tumor response by introducing white blood cells from the donor to the patient.

5. DLI  The objective is for the donor leukocyte cells to recognize the cancer cells and destroy them.  This differs from a repeat bone marrow transplant in that no chemotherapy is given prior to the infusion and the T-cells (which are part of the body’s immune system and fights infection) are not depleted.

6. DLI  DLI is considered a salvage therapy at the time of relapse.  DLI has been proposed for a variety of hematologic malignancies including;  CML, AML, ALL, multiple myeloma, CLL, MDS, Hodgkin’s disease, and NHL.

7. DLI  Graft-vs-host disease (GVHD) was a major cause of transplant-related mortality, but circumstantial evidence suggested that donor T cells, the mediators of GVHD, could also induce a therapeutic“graft-vs- leukemia” (GVL) effect.

8. DLI  Important characteristics of DLI that remain true today are:  First, there is a relationship between the infused cell dose and the likelihood of a clinically significant antitumor response.  Second, the antitumor response mediated by donor immunocompetent cells goes hand in hand with GVHD.

9.  DLI is an established therapy of hematologic malignanciesin relapse after allogeneic SCT.  DLI induces sustained complete remissions in more than 60% of patients with CML in early stage relapse but in fewer than 20% of patients with acute leukemia, multiple myeloma, and lymphoma.

10. Complications of Donor Lymphocyte Infusions  Graft-vs-Host Disease  Aplasia  Infection

11. DLI  The majority of patients experiencing myelosuppression after DLI recover a normal blood cell count spontaneously.  But, myelosuppression may be fatal approximately 10% of patients, with death being caused by infection or bleeding.

12. DLI  Grade II-IV acute GvHD develops in almost half of patients (50 %) given DLI.  The highest incidence being observed when the donor is an unrelated volunteer.

13. DLI  In fact, only 20- 30% of patients with AML achieve a hematologic remission after DLI and the value for patients with ALL is even lower.  DLI can provide a direct GVL effect and offer an effective therapy for relapsed hematologic malignancies after hematopoietic stem cell transplantation.

14. DLI  One of the most important, still unsolved problem of DLI is that concerning the much lower efficacy of GVL in patients with acute leukemia than in those with CML.  The more encouraging results obtained when DLI is used as consolidation therapy for patients who have obtained a complete remission after chemotherapy.