Evaluation of the kinetics of the bone marrow tumor load in the course of sequential high-dose therapy assessed by quantitative PCR as a predictive parameter in patients with multiple myeloma

Citation
Fw. Cremer et al., Evaluation of the kinetics of the bone marrow tumor load in the course of sequential high-dose therapy assessed by quantitative PCR as a predictive parameter in patients with multiple myeloma, BONE MAR TR, 26(8), 2000, pp. 851-858
Citations number
23
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Hematology,"Medical Research Diagnosis & Treatment
Journal title
BONE MARROW TRANSPLANTATION
ISSN journal
0268-3369 → ACNP
Volume
26
Issue
8
Year of publication
2000
Pages
851 - 858
Database
ISI
SICI code
0268-3369(200010)26:8<851:EOTKOT>2.0.ZU;2-R
Abstract
The aim of this investigation was to examine the possible clinical signific ance of the kinetics of bone marrow (BM) tumor load during the course of se quential high-dose therapy (HDT) as assessed by quantitative PCR in patient s with multiple myeloma. In 20 patients with multiple myeloma (MM) treated with two consecutive cycles of HDT followed by autologous peripheral blood stem cell transplantation (PBSCT), clonotypic cells in the peripheral blood (PB) and BM were quantitated by PCR using allele-specific oligonucleotides (ASO) prior to the first, immediately prior to the second, and after the s econd HDT. The median proportion of clonotypic cells in the BM was 1.27% be fore the first HDT (range, 0.03-70%), 0.17% after the first (range, 0.001-2 2%), and 0.05% after the second HDT (range, 0.000091.44%). The median numbe r of circulating clonotypic cells was 65/ml (range, 0.9-10842) prior to HDT , 2.7/ml (range, 0-315) after the first, and 3.5/ml PB (range, 0.7-97) afte r the second HDT. While the median BM tumor load decreased during the first (P = 0.03) and second (P = 0.044) HDT cycles, only the first cycle resulte d in a reduction of clonotypic cells in the PB (P = 0.00078 and P = 1.0, re spectively). In seven patients, the BM tumor load did not decrease below th e initial level after one or two cycles of HDT. All of these patients devel oped progressive disease (median, 19 months post first cycle; range, 10-21) . Of the remaining 13 patients, only four relapsed (18, 19, 21 and 22 month s after the first cycle of HDT), while nine remain in response (median foll owup, 29 months; range, 18-41) (log-rank test P = 0.0009). Our results indi cate that the kinetics of the BM tumor load is a predictive parameter in pa tients with MM and identifies those patients who could benefit from further therapy including new treatment modalities.