title: Flow cytometric disease monitoring in multiple myeloma: the relationship between normal and neoplastic plasma cells predicts outcome after transplantation.
abstract: Conventional monitoring strategies for myeloma are not sufficiently sensitive to identify patients likely to benefit from further therapy immediately after transplantation. We have used a sensitive flow cytometry assay that quantitates normal and neoplastic plasma cells to monitor the bone marrow of 45 patients undergoing high-dose chemotherapy. Neoplastic plasma cells were detectable at 3 months after transplantation in 42% of patients. Once detected, neoplastic cell levels increased steadily until clinical progression: these patients had a significantly shorter progression-free survival (PFS) (median, 20 months) than those with no detectable disease (median, longer than 35 months; P =.003). Neoplastic plasma cells were detectable in 27% (9 of 33) of immunofixation-negative complete-remission patients. These patients had a significantly shorter PFS than immunofixation-negative patients with no detectable neoplastic plasma cells (P =.04). Normal plasma cells were present in 89% of patients immediately after transplantation, but were not sustained in most cases. Patients with only normal phenotype plasma cells present at 3 months after transplantation and also at second assessment had a low risk of disease progression. Patients with neoplastic plasma cells present at 3 months after transplantation, or with only normal plasma cells present at first assessment and only neoplastic plasma cells at second assessment, had a significantly higher risk of early disease progression (P <.0001) with a 5-year survival of 54% for the high-risk group, compared with 100% in the low-risk group (P =.036). Analysis of normal and neoplastic plasma cell levels is more sensitive than immunofixation and can identify which patients may benefit from additional treatment strategies at an early stage after transplantation.
authors.affiliation: Academic Unit of Haematology and Oncology, Algernon Firth Building, University of Leeds, Leeds LS1 3EX, UK. andy.rawstron@hmds.org.uk
authors.forename: Andy C
authors.initials: AC
authors.lastname: Rawstron
authors.forename: Faith E
authors.initials: FE
authors.lastname: Davies
authors.forename: Ranjit
authors.initials: R
authors.lastname: DasGupta
authors.forename: A John
authors.initials: AJ
authors.lastname: Ashcroft
authors.forename: Russell
authors.initials: R
authors.lastname: Patmore
authors.forename: Mark T
authors.initials: MT
authors.lastname: Drayson
authors.forename: Roger G
authors.initials: RG
authors.lastname: Owen
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Jack
authors.forename: J Anthony
authors.initials: JA
authors.lastname: Child
authors.forename: Gareth J
authors.initials: GJ
authors.lastname: Morgan
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use; D001853:Bone Marrow / Q000473:pathology*; D002452:Cell Count; D003131:Combined Modality Therapy; D016384:Consensus Sequence; D003520:Cyclophosphamide / Q000008:administration & dosage; D018450:Disease Progression; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D005434:Flow Cytometry; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain / Q000235:genetics; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D015993:Life Tables; D008297:Male; D008558:Melphalan / Q000008:administration & dosage; D008775:Methylprednisolone / Q000008:administration & dosage; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy / Q000473:pathology* / Q000628:therapy; D015999:Multivariate Analysis; D009194:Myeloma Proteins / Q000235:genetics; D018365:Neoplasm, Residual; D014411:Neoplastic Stem Cells / Q000473:pathology*; D010950:Plasma Cells / Q000473:pathology*; D016133:Polymerase Chain Reaction; D012074:Remission Induction; D012307:Risk Factors; D012680:Sensitivity and Specificity; D016019:Survival Analysis; D014182:Transplantation, Autologous; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D007143:Immunoglobulin Heavy Chains; D009194:Myeloma Proteins; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D008558:Melphalan; D008775:Methylprednisolone