Real-time polymerase chain reaction estimation of bone marrow tumor burden using clonal immunoglobulin heavy chain gene and bcl-1/JH rearrangements in mantle cell lymphoma.
OBJECTIVE
In mantle cell lymphoma (MCL), detection of minimal residual disease in bone marrow (BM) samples by qualitative polymerase chain reaction (PCR) is insufficient to predict relapse. The aim of this study was to evaluate whether a quantitative estimation of tumor burden in consecutive BM samples from MCL patients was feasible and of clinical value.


METHODS
In combination with standard qualitative PCR, we developed a sensitive and accurate real-time PCR for detection of bcl-1/JH (joining region) rearrangement and used a recently described real-time PCR analysis of clonal immunoglobulin rearrangement. To assess clinical utility, we quantified tumor cells in 27 BM samples from three MCL patients undergoing combined CHOP (cyclophosphamide, doxorubicin [hydroxydaunomycin], vincristine [Oncovin], prednisone) and anti-CD20 antibody treatment and three MCL patients undergoing up-front autologous stem cell transplantation.


RESULTS
The approach is capable of detecting tumor cells over a wide range of BM contamination compared to qualitative PCR analysis alone. Tumor burden in consecutive BM samples decreases during therapy and either increases or stabilizes at low levels in patients who relapse or remain in continuous clinical remission, respectively.


CONCLUSIONS
Dynamic range estimation of BM tumor burden is feasible in MCL patients undergoing therapy using clonal immunoglobulin heavy chain gene and bcl-1/JH rearrangement-based real-time PCR.
Andersen
Niels S
NS
Department of Hematology, Rigshospitalet, Copenhagen, Denmark. nanders68@hotmail.com
Donovan
John W
JW
Zuckerman
Amy
A
Pedersen
Lone
L
Geisler
Christian
C
Gribben
John G
JG
D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20 / Q000276:immunology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use; D001853:Bone Marrow / Q000473:pathology*; D001856:Bone Marrow Examination / Q000379:methods*; D003131:Combined Modality Therapy; D003199:Computer Systems; D003520:Cyclophosphamide / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D005803:Genes, Immunoglobulin; D019940:Genes, bcl-1; D006801:Humans; D007144:Immunoglobulin J-Chains / Q000235:genetics*; D007167:Immunotherapy; D020522:Lymphoma, Mantle-Cell / Q000188:drug therapy / Q000235:genetics / Q000473:pathology* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D014411:Neoplastic Stem Cells / Q000737:chemistry / Q000648:ultrastructure; D016133:Polymerase Chain Reaction / Q000379:methods*; D011241:Prednisone / Q000008:administration & dosage; D012008:Recurrence; D012074:Remission Induction; D000069283:Rituximab; D012680:Sensitivity and Specificity; D014750:Vincristine / Q000008:administration & dosage
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20; D007144:Immunoglobulin J-Chains; D000069283:Rituximab; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone