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September 2001, Volume 15, Number 9, Pages 1339-1346
Table of contents    Previous  Abstract  Next   Full text  PDF
Original Manuscript
Induction of graft-versus-leukemia to prevent relapse after partially lymphocyte-depleted allogeneic bone marrow transplantation by pre-emptive donor leukocyte infusions
N Schaap1, A Schattenberg1, B Bär1, F Preijers2, E van de Wiel van Kemenade2 and T de Witte1

1Department of Hematology, University Medical Center St Radboud Nijmegen, Nijmegen, The Netherlands

2Central Hematology Laboratory, University Medical Center St Radboud Nijmegen, Nijmegen, The Netherlands

Correspondence to: Dr N Schaap, Department of Hematology, University Medical Center St Radboud, PO Box 9101, 6500 HB Nijmegen, The Netherlands; Fax: 00 31 24 3542080

Abstract

In this prospective study we analyzed pre-emptive donor leukocyte infusions (DLI) in 82 consecutive patients transplanted with partially T cell-depleted grafts for acute myeloid leukemia, acute lymphoid leukemia, chronic myeloid leukemia, refractory anemia with excess of blasts, refractory anemia with excess of blasts in transformation and multiple myeloma. Donors were HLA-identical siblings. Patients without significant acute (>grade 1) and/or chronic GVHD were scheduled to be treated with DLI (35 patients) and 31 actually received DLI. Patients who developed acute GVHD >grade 1 and/or chronic GVHD were not scheduled to receive DLI and served as a comparison group (47 patients). The median interval between BMT and DLI was 22 weeks. The first six patients received 0.7 ´ 108 CD3+cells/kg body weight (b.w.). Five out of these six patients developed acute GVHD (grade 1: n = 2, grade 3: n = 2 and grade 4: n = 1) which was more frequent and more severe than we had anticipated. In the next 25 patients the number of T lymphocytes was diminished to 0.1 ´ 108 CD3+ cells/kg b.w. which resulted in less frequent and less severe GVHD. Eight patients in this group developed acute GVHD (grade 1: n = 4, grade 2: n = 4) and three patients had limited chronic GVHD. Patients in the DLI group needed more time to establish complete donor chimerism confirmed by a higher number of mixed chimeras at 6 months after BMT. The projected 3-year probability of disease-free survival was 77% for the 35 patients intended to treat with DLI and 45% for the patients of the comparison group (P = 0.024). Relapse rate at 36 months after transplantation was 18% in the patients who were intended to treat with DLI and 44% in the comparison group (P = 0.026). We conclude that pre-emptive DLI is feasible and generates favorable relapse rates in patients who are at high risk for relapse. Furthermore, the incidence and severity of GVHD disease after DLI is dependent on the number of CD3+ cells infused.

Leukemia (2001) 15, 1339-1346.

Keywords

allogeneic stem cell transplantation; T cell depletion; pre-emptive donor leukocyte infusions; graft-versus-leukemia; chimerism

Received 30 November 2000; accepted 9 May 2001
September 2001, Volume 15, Number 9, Pages 1339-1346
Table of contents    Previous  Abstract  Next   Full text  PDF
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