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.
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.
Zetterquist
H
H
Department of Surgery, Karolinska Institute at Huddinge Hospital, Huddinge, Sweden.
Mattsson
J
J
Uzunel
M
M
Näsman-Björk
I
I
Svenberg
P
P
Tammik
L
L
Bayat
G
G
Winiarski
J
J
Ringdén
O
O
D000293:Adolescent; D000328:Adult; D018941:Antigens, CD19 / Q000097:blood; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology; D015415:Biomarkers; D016026:Bone Marrow Transplantation; D019070:Cell Lineage; D002648:Child; D002675:Child, Preschool; D004247:DNA / Q000097:blood; D017931:DNA Primers; D005260:Female; D019676:Genes, T-Cell Receptor delta; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D018189:Immunomagnetic Separation; D008297:Male; D018598:Minisatellite Repeats; D018365:Neoplasm, Residual / Q000097:blood* / Q000235:genetics; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000097:blood*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000097:blood*; D011446:Prospective Studies; D012008:Recurrence; D012680:Sensitivity and Specificity; D017422:Sequence Analysis, DNA; D018183:Transplantation Chimera / Q000235:genetics*
D018941:Antigens, CD19; D015415:Biomarkers; D017931:DNA Primers; D007143:Immunoglobulin Heavy Chains; D004247:DNA