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Prepublished online as a Blood First Edition Paper on June 7, 2002; DOI 10.1182/blood-2001-12-0297.
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Blood, 1 November 2002, Vol. 100, No. 9, pp. 3095-3100
CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS
Flow cytometric disease monitoring in multiple myeloma: the
relationship between normal and neoplastic plasma cells predicts
outcome after transplantation
Andy C. Rawstron,
Faith E. Davies,
Ranjit DasGupta,
A. John Ashcroft,
Russell Patmore,
Mark T. Drayson,
Roger G. Owen,
Andrew S. Jack,
J. Anthony Child, and
Gareth J. Morgan
From the Academic Unit of Haematology and Oncology,
University of Leeds, United Kingdom; Department of Haematology, Hull
Royal Infirmary, United Kingdom; and Department of Immunology,
University of Birmingham, United Kingdom.
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.
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