P-glycoprotein expression in human plasma cell myeloma

Correlation with prior chemotherapy

Thomas M. Grogan, Catherine S Perry, Sydney E. Salmon, Monica Matzner, James Rybski, Ronald S Weinstein, Rik J. Scheper, William S. Dalton

Research output: Contribution to journalArticle

174 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)490-495
Number of pages6
JournalBlood
Volume81
Issue number2
StatePublished - Jan 15 1993

Fingerprint

Plasma (human)
Chemotherapy
P-Glycoprotein
Multiple Myeloma
Drug Therapy
Doxorubicin
Vincristine
Incidence
Plasma Cells
Biological Products

ASJC Scopus subject areas

  • Hematology

Cite this

Grogan, T. M., Perry, C. S., Salmon, S. E., Matzner, M., Rybski, J., Weinstein, R. S., ... Dalton, W. S. (1993). P-glycoprotein expression in human plasma cell myeloma: Correlation with prior chemotherapy. Blood, 81(2), 490-495.

P-glycoprotein expression in human plasma cell myeloma : Correlation with prior chemotherapy. / Grogan, Thomas M.; Perry, Catherine S; Salmon, Sydney E.; Matzner, Monica; Rybski, James; Weinstein, Ronald S; Scheper, Rik J.; Dalton, William S.

In: Blood, Vol. 81, No. 2, 15.01.1993, p. 490-495.

Research output: Contribution to journalArticle

Grogan, TM, Perry, CS, Salmon, SE, Matzner, M, Rybski, J, Weinstein, RS, Scheper, RJ & Dalton, WS 1993, 'P-glycoprotein expression in human plasma cell myeloma: Correlation with prior chemotherapy', Blood, vol. 81, no. 2, pp. 490-495.
Grogan, Thomas M. ; Perry, Catherine S ; Salmon, Sydney E. ; Matzner, Monica ; Rybski, James ; Weinstein, Ronald S ; Scheper, Rik J. ; Dalton, William S. / P-glycoprotein expression in human plasma cell myeloma : Correlation with prior chemotherapy. In: Blood. 1993 ; Vol. 81, No. 2. pp. 490-495.
@article{5c97823747d5449c99686c5ae1904903,
title = "P-glycoprotein expression in human plasma cell myeloma: Correlation with prior chemotherapy",
abstract = "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.",
author = "Grogan, {Thomas M.} and Perry, {Catherine S} and Salmon, {Sydney E.} and Monica Matzner and James Rybski and Weinstein, {Ronald S} and Scheper, {Rik J.} and Dalton, {William S.}",
year = "1993",
month = "1",
day = "15",
language = "English (US)",
volume = "81",
pages = "490--495",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "2",

}

TY - JOUR

T1 - P-glycoprotein expression in human plasma cell myeloma

T2 - Correlation with prior chemotherapy

AU - Grogan, Thomas M.

AU - Perry, Catherine S

AU - Salmon, Sydney E.

AU - Matzner, Monica

AU - Rybski, James

AU - Weinstein, Ronald S

AU - Scheper, Rik J.

AU - Dalton, William S.

PY - 1993/1/15

Y1 - 1993/1/15

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0027507266&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0027507266&partnerID=8YFLogxK

M3 - Article

VL - 81

SP - 490

EP - 495

JO - Blood

JF - Blood

SN - 0006-4971

IS - 2

ER -