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P-glycoprotein expression in human plasma cell myeloma: correlation with
prior chemotherapy
TM Grogan, CM Spier, SE Salmon, M Matzner, J Rybski, RS Weinstein, RJ Scheper and WS Dalton
Department of Pathology, University of Arizona, College of Medicine, Tucson
85724.
Multidrug-resistant (MDR) myeloma patients failing chemotherapy may express
P-glycoprotein (PGP), which serves as an efflux pump protecting the
neoplastic cells. Unknown is whether PGP expression might relate to prior
cytotoxic drug exposure. To address this question, we studied 106
consecutive bone marrow samples from 104 myeloma patients with samples
studied either before or after therapy and at the time of relapse. We
performed an established immunocytochemical assay of PGP using an MDR-1-
specific monoclonal antibody and correlated PGP status with prior
chemotherapy dosage. Myeloma patients with no prior therapy had a low
incidence of PGP expression (6%, 3/47), whereas those receiving
chemotherapy had a significantly higher incidence (43%, 21/49) (P <
.0001). A substantially higher incidence of PGP expression (50%, 83%,
respectively) occurred when the total vincristine dose exceeded 20 mg and
when doxorubicin exceeded 340 mg. In the 11 patients who received both high
vincristine and doxorubicin dosages (> 20 mg, > 340 mg total dose)
there was 100% incidence of PGP expression in the tumor cells. These data
provided the basis for a predictive mathematical model from which
dose-related PGP expression normograms were generated. Time with myeloma
for PGP-negative patients (mean 33 months) had overlapping confidence
limits with PGP-positive patients (mean 42 months), suggesting that disease
duration was not a significant variable. PGP expression did not correlate
with other clinical factors or immunophenotypic factors. Our findings
indicate a strong correlation between PGP expression in myeloma and past
chemotherapy in myeloma, in particular, related to prior exposure to the
natural product agents vincristine and doxorubicin. Additionally, the
proportion of PGP- positive plasma cells was significantly higher in the
doxorubicin- treated patients than the nondoxorubicin-treated patients
(87.7% v 65.17%; P = .013). Combined high vincristine and doxorubicin total
dosage appear highly predictive of PGP expression.
Volume 81,
Issue 2,
pp. 490-495,
01/15/1993
Copyright © 1993 by The American Society of Hematology
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