Tumour kinetics in multiple myeloma before, during, and after treatment.
Tumour progression was monitored in seven multiple myeloma (MM) patients undergoing a novel oral chemotherapy regimen (cyclophosphamide, idarubicin and dexamethasone; CID) followed by early autologous stem cell transplantation (ASCT). Allele-specific oligonucleotide PCR (ASO-PCR) was used to semi-quantitate the number of tumour cells within the peripheral blood (PB) and PB progenitor cell (PBPC) harvests and compared with paraprotein levels and morphological bone marrow (BM) assessments. Tumour cells were detected in the PB of all patients at diagnosis, but decreased in response to CID therapy. All but two of the 22 PBPC collections contained MM cells, the levels of which were statistically correlated with overall clinical response to therapy, but not with individual BM or PB tumour loads prior to mobilisation. We also found no correlation between the day of leucapheresis collection and the number of contaminating MM cells, CD34+ cells or MM cells per CD34+ cell. Regardless of tumour contamination levels in the PBPC collections, the majority of patients demonstrated post-ASCT clearing of circulating MM cells. This study suggests that levels of circulating MM cells may be the best indication of patient response to treatment and argues against the theory of differential mobilisation of tumour cells and CD34+ cells in response to cytokine treatment.
Lincz
L F
LF
Hunter Haematology Research Group, Mater Misericordiae Hospital, NSW, Waratah, Australia. leukres@hunter-link.net.au
Crooks
R L
RL
Way
S L
SL
Granter
N
N
Spencer
A
A
D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000494:pharmacology; D001483:Base Sequence; D002452:Cell Count; D002455:Cell Division / Q000187:drug effects; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000494:pharmacology; D003907:Dexamethasone / Q000008:administration & dosage / Q000494:pharmacology; D005260:Female; D015321:Gene Rearrangement; D019650:Hematopoietic Stem Cell Mobilization / Q000009:adverse effects; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D015255:Idarubicin / Q000008:administration & dosage / Q000494:pharmacology; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007700:Kinetics; D007937:Leukapheresis / Q000592:standards; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009101:Multiple Myeloma / Q000235:genetics / Q000473:pathology* / Q000628:therapy*; D018365:Neoplasm, Residual / Q000097:blood / Q000175:diagnosis; D009360:Neoplastic Cells, Circulating / Q000187:drug effects* / Q000473:pathology; D014182:Transplantation, Autologous
D007143:Immunoglobulin Heavy Chains; D003907:Dexamethasone; D003520:Cyclophosphamide; D015255:Idarubicin