Unrelated donor leukocyte infusions to treat relapse after unrelated donor bone marrow transplantation

Jose Leis, David L. Porter

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Allogeneic stem cell transplantation (SCT) may cure many patients with hematologic malignancies due to both the intensive conditioning therapy, and in many patients, the potent graft-vs-leukemia (GVL) effect of the donor graft. The GVL effect is mediated in large part by mature T-cells contained in the donor graft and has been defined in detail in animal models of transplantation. The GVL activity has been observed in the clinical setting after SCT from both matched siblings and unrelated donors. The best demonstration and most direct evidence of GVL activity in humans come from the use of donor leukocyte infusions (DLI). For patients who relapse with chronic myelogenous leukemia after matched sibling SCT, infusions of leukocytes collected from the original transplant donor will re-establish complete and durable remission in 60-80% of patients. DLI is less effective for more advanced phases of CML and for patients who relapse with diseases other than CML. DLI after matched sibling SCT is complicated primarily by graft-vs-host disease (GVHD), marrow aplasia, and unfortunately, relapse in some cases. There has been little information regarding the use of unrelated DLI (UDLI). Available data now shows that despite initial concerns that UDLI would result in excessive toxicity, it is an effective approach to relapse after unrelated donor marrow grafting. Response rates are similar to those seen after the use of matched sibling DLI, and many remissions remain durable. Graft-vs-host disease is a frequent complication after UDLI though the incidence and severity of GVHD is also similar to the use of matched sibling DLI. It is not clear that the GVL and GVHD effects can be separated, since the majority of responding patients also develop GVHD. The most effective cell dose for UDLI has not been established, though there does not appear to be either a dose-response or dose-toxicity relationship from UDLI. Although second unrelated donor bone marrow transplantation (BMT) may cure a small minority of patients, GVL induction with UDLI offers a safer and potentially more effective therapy for relapsed leukemia, and offers insights in methods to manipulate the human immune system for therapeutic benefit.

Original languageEnglish (US)
Pages (from-to)9-17
Number of pages9
JournalLeukemia and Lymphoma
Volume43
Issue number1
DOIs
StatePublished - 2002
Externally publishedYes

Fingerprint

Unrelated Donors
Bone Marrow Transplantation
Leukocytes
Tissue Donors
Graft vs Host Disease
Recurrence
Siblings
Stem Cell Transplantation
Leukemia
Transplants
Graft vs Leukemia Effect
Bone Marrow
Behavior Therapy
Hematologic Neoplasms
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Human Activities
Immune System
Animal Models
Transplantation
T-Lymphocytes

Keywords

  • Bone marrow transplantation
  • Leukemia relapse
  • Unrelated DLI donor lymphocyte infusions
  • Unrelated donor transplant

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

Cite this

Unrelated donor leukocyte infusions to treat relapse after unrelated donor bone marrow transplantation. / Leis, Jose; Porter, David L.

In: Leukemia and Lymphoma, Vol. 43, No. 1, 2002, p. 9-17.

Research output: Contribution to journalArticle

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