Occult lymphoma cells prevalent in autologous marrow from non-Hodgkin's diffuse lymphoma.
The most effective treatment for recurrent non-Hodgkin's lymphoma (NHL) appears to be a high-dose cytotoxic chemotherapy (HDC) followed by autologous bone marrow transplantation (ABMT). However, it has been suggested that the presence of occult lymphoma cells in harvested marrow may be responsible for a significant fraction of treatment failures after HDC/ABMT. The present study examined randomly accrued NHL patients, independent of their cytogenic grades, for the presence of cells bearing bcl-2/immunoglobulin heavy chain (IgH) gene rearrangements in lymph node (LN) biopsies and the bone marrow by polymerase chain reaction (PCR) and Southern blot hybridization combined with a classical culturing technique. Among 41 NHL patients examined, bcl-2/IgH translocations were evident in LN biopsies and marrow from each of 10 follicular lymphoma patients, but not in any samples from 31 newly diagnosed diffuse lymphoma patients. Marrow aspirates from several patients that were cultured using a one-week "triggering culture" followed by an extended period of conventional culture resulted in emergence of a monoclonal, IgH-rearranged, bcl-2-normal lymphoid cell population. Such outgrowth was specifically seen in cultures of diffuse lymphoma marrow (7 of 28 evaluable patients). Southern analysis for IgH rearrangement within LN biopsies and of cells cultured from marrow of individual diffuse lymphoma patients produced identical patterns, suggesting that the occult lymphoma cells present in harvested marrow were derived from the predominant lymphoma cell population represented within involved lymph nodes. The culture of histologically occult lymphoma from diagnostic marrow and analysis of the derived cells by Southern blot hybridization can be used to detect potentially aggressive lymphoma cells within harvested marrow, despite their lack of bcl-2 gene rearrangement.
Yokoyama
Junkichi
J
Division of Head and Neck Cancer, Miyagi Cancer Center, Natori, Japan.
Fujimiya
Yoshiaki
Y
Yamaguchi
Toshikazu
T
Shiga
Kiyoto
K
Saijo
Yoshio
Y
Groveman
Debra S
DS
McBain
John A
JA
Suzuki
Youichi
Y
Ebina
Takusaburo
T
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001345:Autoradiography; D001706:Biopsy; D015139:Blotting, Southern; D001853:Bone Marrow / Q000473:pathology; D002883:Chromosomes, Human, Pair 14; D002887:Chromosomes, Human, Pair 18; D004273:DNA, Neoplasm / Q000032:analysis; D015245:Deoxyribonuclease BamHI; D015246:Deoxyribonuclease EcoRI; D015247:Deoxyribonuclease HindIII; D005260:Female; D015321:Gene Rearrangement; D019254:Genes, bcl-2 / Q000235:genetics; D005819:Genetic Markers; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D008198:Lymph Nodes / Q000473:pathology; D008224:Lymphoma, Follicular / Q000235:genetics; D008228:Lymphoma, Non-Hodgkin / Q000235:genetics / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D014178:Translocation, Genetic; D014407:Tumor Cells, Cultured
D004273:DNA, Neoplasm; D005819:Genetic Markers; D007143:Immunoglobulin Heavy Chains; D015245:Deoxyribonuclease BamHI; D015246:Deoxyribonuclease EcoRI; D015247:Deoxyribonuclease HindIII