Serial determination of the bcl-2 gene in the bone marrow and peripheral blood after central lymphatic irradiation for stages I-III follicular lymphoma: a preliminary report

• Published in: Clinical cancer research Vol. 3; no. 2; pp. 215 - 219
• Main Authors: HA, C. S, CABANILLAS, F, LEE, M.-S, BESA, P. C, MCLAUGHLIN, P, COX, J. D
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01-02-1997
• Subjects: Adult; Aged; Biological and medical sciences; Bone Marrow - metabolism; Bone Marrow - radiation effects; Female; Follow-Up Studies; Humans; Leukocytes, Mononuclear - metabolism; Leukocytes, Mononuclear - radiation effects; Lymphatic Irradiation; Lymphoma, Follicular - blood; Lymphoma, Follicular - metabolism; Lymphoma, Follicular - radiotherapy; Male; Medical sciences; Middle Aged; Neoplasm Staging; Polymerase Chain Reaction; Prospective Studies; Proto-Oncogene Proteins c-bcl-2 - analysis; Proto-Oncogene Proteins c-bcl-2 - blood; Proto-Oncogene Proteins c-bcl-2 - genetics; Radiation therapy and radiosensitizing agent; Treatment with physical agents; Treatment. General aspects; Tumors; Human; Prognosis; Early stage; Malignant hemopathy; Tumoral marker; Non Hodgkin lymphoma; Radiotherapy; Blood; Polymerase chain reaction; Treatment; Lymphoproliferative syndrome; Irradiation; Follicular lymphoma; Bone marrow; Clinical trial; Advanced stage; Onc gene
• ISSN: 1078-0432; 1557-3265

Two-thirds of patients with follicular lymphoma have rearrangement of bcl-2 major breakpoint region (MBR) through t(14;18)
(q32;q21). This rearrangement can serve as a sensitive marker for follicular lymphoma cells. This study was undertaken to
assess the molecular complete response rate of stages I-III follicular lymphoma to central lymphatic irradiation (CLI) by
detection of PCR-amplifiable bcl-2 MBR rearrangement in the bone marrow and peripheral blood before and after CLI. Twenty
patients with stages I-III follicular lymphoma were treated with CLI. Twelve of them were part of a prospective randomization
trial comparing CLI with multi-agent chemotherapy. Bone marrow and peripheral blood samples were obtained from the patients
before the initiation of treatment. By using the PCR technique, the DNA sequences from the bone marrow and peripheral blood
samples that flank the bcl-2 MBR involved in t(14;18) (q32;q21) were amplified. In PCR-positive patients, bone marrow and
blood samples were followed at regular intervals during and after CLI. The results of the PCR amplification were correlated
with clinical findings. All 20 patients achieved clinical complete response after CLI. Median follow-up was 22 months (range,
12-37 months), and no patient has relapsed. Pretreatment PCR results were available in all patients (19 patients for peripheral
blood samples and 16 patients for bone marrow samples). Nine of 19 peripheral blood samples and 9 of 16 bone marrow samples
were PCR-positive for bcl-2 MBR rearrangement. Eight PCR-positive patients converted to negative (8 of 9 blood samples and
2 of 3 bone marrow samples) 2-20 months from the first day of CLI. Bone marrow and peripheral blood with PCR-amplifiable bcl-2
MBR rearrangement can be converted from positive to negative after chemotherapy in patients with follicular lymphoma. Early
results from our study show for the first time that peripheral blood and bone marrow can be converted from positive to negative
after CLI. The prognostic significance of the observed conversions requires longer follow-up.