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April 2000, Volume 25, Number 8, Pages 843-851
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Minimal Residual Disease
Mixed chimerism in the B cell lineage is a rapid and sensitive indicator of minimal residual disease in bone marrow transplant recipients with pre-B cell acute lymphoblastic leukemia
H Zetterquist1,2, J Mattsson2,3, M Uzunel2, I Näsman-Björk2, P Svenberg2, L Tammik2, G Bayat2, J Winiarski4 and O Ringdén2,3

1Department of Surgery, Karolinska Institute at Huddinge Hospital, Huddinge, Sweden

2Department of Clinical Immunology, Karolinska Institute at Huddinge Hospital, Huddinge, Sweden

3Centre for Allogeneic Stemcell Transplantation, Karolinska Institute at Huddinge Hospital, Huddinge, Sweden

4Department of Pediatrics, Karolinska Institute at Huddinge Hospital, Huddinge, Sweden

Correspondence to: Dr H Zetterquist, Dept of Surgery, Center for Gastroenterology, Huddinge Hospital, F53, SE-141 86 Huddinge, Sweden

Abstract

One of the major problems after allogeneic bone marrow transplantation (BMT) is a high frequency of leukemia relapse. We have prospectively studied the presence of donor- and recipient-derived chimeric cells in bone marrow recipients with pre-B cell acute lymphoblastic leukemia (pre-B-ALL). The chimeric status of BMT recipients was compared to minimal residual disease (MRD) detection by analysis of immunoglobulin heavy chain (IgH) and T cell receptor (TcR) genes. Post-transplant blood and bone marrow samples from 12 patients with pre-B-ALL were studied. Five patients showed mixed chimerism (MC) in the CD19-positive cell fraction. Four of them have relapsed to date. The remaining patient with MC in the B cell lineage was also MRD positive in the same samples. All seven patients with donor chimerism in the B cell fraction remain in clinical remission (P = 0.01). In samples from all five patients having MC in the B cell lineage, the patient-specific IgH or TcR rearrangement was also detected. In three of four patients who relapsed, MC in the B cell lineage was seen more than 2.5 months prior to morphologically verified relapse. The results of this comparison suggest that routinely performed MC analysis of the affected cell lineage may facilitate post-BMT monitoring and rapid therapeutic decisions in transplanted patients with pre-B-ALL. Bone Marrow Transplantation (2000) 25, 843-851.

Keywords

acute lymphoblastic leukemia; chimerism; minimal residual disease; relapse; allogeneic hematopoietic cell transplantation

Received 22 March 1999; accepted 10 January 2000
April 2000, Volume 25, Number 8, Pages 843-851
Table of contents    Previous  Abstract  Next   Full text  PDF
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