Genomic Diagnosis of Burkitt's Lymphoma
http://www.100md.com
《新英格兰医药杂志》
To the Editor: In the article by Dave et al. (June 8 issue)1 concerning the molecular diagnosis of Burkitt's lymphoma, almost half the patients with Burkitt's lymphoma were children. The data in the companion article by Hummel et al.2 were not stratified according to age. If the patients are separated into adults and children, are the results similar? Can the same method be applied to patients with immunodeficiency?
Bryan T. Lin, M.D., Ph.D.
Encino–Tarzana Regional Medical Center
Tarzana, CA 91356
btltarzana@hotmail.com
References
Dave SS, Fu K, Wright GW, et al. Molecular diagnosis of Burkitt's lymphoma. N Engl J Med 2006;354:2431-2442.
Hummel M, Bentink S, Berger H, et al. A biologic definition of Burkitt's lymphoma from transcriptional and genomic profiling. N Engl J Med 2006;354:2419-2430.
Drs. Dave and Staudt reply: The tumors from children and adults with Burkitt's lymphoma were indistinguishable on the basis of the expression of the predictor genes. There was also no difference in outcome between children and adults who received intensive therapies. However, all nine Burkitt's lymphoma–discrepant cases (i.e., cases of Burkitt's lymphoma identified on the basis of gene expression but not standard diagnostic methods) were in adults. Thus, cases in adults may be more variable with regard to morphologic characteristics and other diagnostic criteria than in cases in children, perhaps reflecting the influence of additional genomic abnormalities in adults.
Although our study did not examine tumors from Burkitt's lymphoma associated with immunodeficiency, it seems to be likely that this type of Burkitt's lymphoma would share the gene-expression hallmarks of sporadic Burkitt's lymphoma, but this possibility requires a separate study. The turnaround time for a diagnosis based on DNA microarray could be about 48 hours, which is similar to that for conventional methods used in the diagnosis of Burkitt's lymphoma. We agree with Dr. Lin that correctly distinguishing Burkitt's lymphoma from diffuse large B-cell lymphoma is critical, since it dictates the optimal treatment for each patient.
Sandeep S. Dave, M.D.
Louis M. Staudt, M.D., Ph.D.
National Cancer Institute
Bethesda, MD 20892
lstaudt@mail.nih.gov
Dr. Hummel and colleagues reply: In our study, 24 of 44 cases of molecular Burkitt's lymphoma (mBL), 1 of 128 non-mBL cases, and 6 of 48 intermediate cases arose in children (<18 years of age). When age and clinical stage were included in the multivariate model, molecular diagnosis was not a significant independent prognostic factor for survival. The results of a univariate comparison of survival among children and adults with mBL who were treated with acute lymphoblastic leukemia (ALL)–like chemotherapy (14 children and 7 adults) or with chemotherapy regimens based on cyclophosphamide, doxorubicin, vincristine, and prednisone (2 children and 1 adult) were not meaningful, owing to the small number of cases. Whether it is possible to apply the mBL signature to patients with immunodeficiency will require further investigation.
Michael Hummel, Ph.D.
Harald Stein, M.D.
Charité Campus Benjamin Franklin
D-12200 Berlin, Germany
Harald.Stein@charite.de
Reiner Siebert, M.D.
Christian-Albrechts-Universit?t zu Kiel
25105 Kiel, Germany
Bryan T. Lin, M.D., Ph.D.
Encino–Tarzana Regional Medical Center
Tarzana, CA 91356
btltarzana@hotmail.com
References
Dave SS, Fu K, Wright GW, et al. Molecular diagnosis of Burkitt's lymphoma. N Engl J Med 2006;354:2431-2442.
Hummel M, Bentink S, Berger H, et al. A biologic definition of Burkitt's lymphoma from transcriptional and genomic profiling. N Engl J Med 2006;354:2419-2430.
Drs. Dave and Staudt reply: The tumors from children and adults with Burkitt's lymphoma were indistinguishable on the basis of the expression of the predictor genes. There was also no difference in outcome between children and adults who received intensive therapies. However, all nine Burkitt's lymphoma–discrepant cases (i.e., cases of Burkitt's lymphoma identified on the basis of gene expression but not standard diagnostic methods) were in adults. Thus, cases in adults may be more variable with regard to morphologic characteristics and other diagnostic criteria than in cases in children, perhaps reflecting the influence of additional genomic abnormalities in adults.
Although our study did not examine tumors from Burkitt's lymphoma associated with immunodeficiency, it seems to be likely that this type of Burkitt's lymphoma would share the gene-expression hallmarks of sporadic Burkitt's lymphoma, but this possibility requires a separate study. The turnaround time for a diagnosis based on DNA microarray could be about 48 hours, which is similar to that for conventional methods used in the diagnosis of Burkitt's lymphoma. We agree with Dr. Lin that correctly distinguishing Burkitt's lymphoma from diffuse large B-cell lymphoma is critical, since it dictates the optimal treatment for each patient.
Sandeep S. Dave, M.D.
Louis M. Staudt, M.D., Ph.D.
National Cancer Institute
Bethesda, MD 20892
lstaudt@mail.nih.gov
Dr. Hummel and colleagues reply: In our study, 24 of 44 cases of molecular Burkitt's lymphoma (mBL), 1 of 128 non-mBL cases, and 6 of 48 intermediate cases arose in children (<18 years of age). When age and clinical stage were included in the multivariate model, molecular diagnosis was not a significant independent prognostic factor for survival. The results of a univariate comparison of survival among children and adults with mBL who were treated with acute lymphoblastic leukemia (ALL)–like chemotherapy (14 children and 7 adults) or with chemotherapy regimens based on cyclophosphamide, doxorubicin, vincristine, and prednisone (2 children and 1 adult) were not meaningful, owing to the small number of cases. Whether it is possible to apply the mBL signature to patients with immunodeficiency will require further investigation.
Michael Hummel, Ph.D.
Harald Stein, M.D.
Charité Campus Benjamin Franklin
D-12200 Berlin, Germany
Harald.Stein@charite.de
Reiner Siebert, M.D.
Christian-Albrechts-Universit?t zu Kiel
25105 Kiel, Germany