<i>MDR1</i> polymorphism influences the outcome of multiple myeloma patients

Buda, Gabriele; Maggini, Valentina; Galimberti, Sara; Martino, Alessandro Di; Giuliani, Nicola; Morabito, Fortunato; Genestreti, Giovenzio; Iacopino, Pasquale; Rizzoli, Vittorio; Barale, Roberto; Rossi, Anna Maria; Petrini, Mario

doi:10.1111/j.1365-2141.2007.06605.x

Cited by 43 publications

(27 citation statements)

References 9 publications

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“…29,30 We speculate that continuous exposure of MM and hematopoietic stem cells to doxorubicin suppressed the effect of the MDR-1 gene and thus exerted the observed anti-myeloma effect. 31 Of the non-hematologic side effects, metabolic abnormalities and toxicities involving the kidney, liver, and gastrointestinal systems dominated but were transient and easily manageable. These outcomes are in accordance with the general toxicity profile of metronomic therapy in various types of solid tumors 9,11,12 or lymphomas.…”

Section: Discussionmentioning

confidence: 99%

Metronomic therapy is an effective salvage treatment for heavily pre-treated relapsed/refractory multiple myeloma

Papanikolaou¹,

Szymonifka

Rosenthal

et al. 2013

Haematologica

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Articleshaematologica | 2013; 98 (7) 1147 IntroductionSince the introduction of novel agents, especially in the context of autologous transplantation, overall survival (OS) and progression-free survival (PFS) in multiple myeloma (MM) have been extended to more than seven and four years, respectively.1 It is now recognized that the dominant adverse features for outcome relate to MM genetics, captured by metaphase cytogenetic abnormalities, 2 fluorescence in situ hybridization (FISH)-derived amp1q21 3 and del17p 4 and, more recently, gene expression profiling (GEP)-derived high risk. 5 While present in a minority of newly diagnosed MM patients, these severe prognostic markers increase with disease progression. Additional challenges arise towards the end stage of MM when many patients further present with cytopenia due either to extensive bone marrow involvement, exhausted hematopoiesis or myelodysplastic syndrome (MDS).Applied with anti-angiogenic therapeutic intent, thalidomide proved to be a major breakthrough in the treatment of relapsed/refractory MM 6 and MM in general. 7,8 Based on the concept that low-dose continuous application of certain cytotoxic drugs (e.g. doxorubicin, cis-platinum, cyclophosphamide) can inhibit tumor progression by interrupting neoangiogenesis without increasing toxicity in experimental models and clinical practice, 9-12 we developed a treatment schema of metronomically scheduled drug therapy, especially in the setting of pancytopenia, for relapsed/refractory MM. 13We are now up-dating our experience in 186 patients treated with metronomic therapy between March 2004 and January 2012, with a median follow-up period of 26 months. Design and Methods PatientsOne hundred and eighty-six patients with relapsed/refractory MM between 31 and 82 years of age received at least one cycle of metronomic therapy at the Myeloma Institute of Research and Therapy of the University of Arkansas for Medical Sciences (Little Rock, AR, USA) between March 2004 and January 2012. All data were collected prior to November 29, 2012. Metronomic therapy was applied offprotocol to provide maximum flexibility in dosing. Patients signed a written informed consent in keeping with institutional and federal guidelines. The institutional review board approved the review of the patients' data and outcomes toward the generation of this report. Metronomic therapyWhile variations in dosing occurred, the main elements of metronomic therapy consisted of bortezomib: 1.0 or 1.3 mg/m 2 on Days 1, 4, 7, 10, 13, 16; thalidomide: 200 mg daily for 16 days; dexamethasone: 12, 20 or 40 mg on Days 1,4,7,10,13,16 1.0-3 mg/m 2 (adjusted according to renal function) as continuous 24-h intravenous infusion for 16 days, with or without the addition of the m-TOR inhibitor rapamycin: 3 mg on Day 1, then 1 mg for Days 2-16 (depending on renal function). For patients with a creatinine level of 2.0 mg/dL or over at the initiation of therapy, cisplatin and rapamycin were omitted. When side effects attributed to specific drugs of the regimen develo...

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Section: Discussionmentioning

confidence: 99%

Metronomic therapy is an effective salvage treatment for heavily pre-treated relapsed/refractory multiple myeloma

Papanikolaou¹,

Szymonifka

Rosenthal

et al. 2013

Haematologica

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“…however, the statistical comparison within the MM patient group of Northern Irish ethnicity showed that although rs1045642 had an influence on overall survival, it was insignificant in statistical comparisons between healthy controls and MM patients (173). Another study involving 115 post-transplant MM patients investigating C 3435 T polymorphism reported that C/T and T/T genotypes showed a longer overall survival than C/C genotype under dexamethasone, adriamycin (doxorubicin) and vincristine (VAD) treatment regimen (174).…”

Section: P-gpmentioning

confidence: 97%

Multiple myeloma and persistence of drug resistance in the age of novel drugs (Review)

Krishnan

Jaiswal

Brown

et al. 2016

International Journal of Oncology

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“…As with the Pgp expression results, mean uncorrected MAF values were low in comparison to the DLKP-A cell line used for validation (Table 3). DISCUSSION ABC-transporter-mediated MDR remains a complex issue in the treatment of haematological malignancies, with the MDR phenotype being associated with several different proteins (1,9,18,20,21), and particularly since SNPs within these genes are now under scrutiny as further potential modifiers of the MDR proteins and hence phenotype (11,12,14). Genotype at rs1045642 within the ABCB1 gene has been shown previously to affect overall survival (OS) within PCM (14) but it was as yet undetermined if it affected P-gp expression and/or activity in PCM.…”

Section: P-gp Activity In Pcmmentioning

confidence: 99%

“…Previous research has highlighted a single nucleotide polymorphism within ABCB1, rs1045642, which may mediate P-gp activity and could be a useful predictor for overall survival in PCM (12)(13)(14)(15)(16). rs1045642 has also demonstrated a degree of linkage disequilibrium (LD) with two further SNPs (rs2032582 and rs1128503) raising the possibility that rs1045642 is simply ''tagging'' for the effects of another SNP (17).…”

mentioning

confidence: 99%

Neither P‐gp SNP variants, P‐gp expression nor functional P‐gp activity predicts MDR in a preliminary study of plasma cell myeloma

Drain

Catherwood

Bjourson³

et al. 2012

Cytometry Part B Clinical

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Background: The objective of this work was to obtain a controlled subjective and objective in vivo clinical comparison of the Passy‐Muir, Shiley, and Ball speaking valves. Methods: Ten patients free of laryngeal pathology but dependent on tracheotomy for respiration were tested with each of the speaking valves. Olfaction was assessed for each patient using the University of Pennsylvania Smell Identification Test (UPSIT). Acoustic and perceptual analyses included subjective assessments, noninstrumental objective assessments (including maximum phonation time, and S:Z ratio), and instrumental objective assessments (including fundamental frequency:maximum phonation range, vocal intensity, perturbation, naturalness, and turbulence). Oxygen saturation was assessed by pulse oximetry. Results: There was a highly significant statistical difference in olfaction and speech naturalness, in favor of the Ball valve (The Airway Company, Forest Hill, MD). The Ball valve's speech parameters were generally better than with the Passy‐Muir and Shiley valves, including maximum phonation, S:Z ratio, jitter, noise, and turbulence, although the differences were not statistically significant. There were no differences among the valves in oxygen saturation levels. Conclusion: This study illustrates that olfaction and certain speech parameters, most noticeably speech naturalness, are significantly improved with the Ball valve as compared to the Passy‐Muir and Shiley valves. © 2012 ARS–AAOA, LLC.

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MDR1 polymorphism influences the outcome of multiple myeloma patients

Cited by 43 publications

References 9 publications

Metronomic therapy is an effective salvage treatment for heavily pre-treated relapsed/refractory multiple myeloma

Metronomic therapy is an effective salvage treatment for heavily pre-treated relapsed/refractory multiple myeloma

Multiple myeloma and persistence of drug resistance in the age of novel drugs (Review)

Neither P‐gp SNP variants, P‐gp expression nor functional P‐gp activity predicts MDR in a preliminary study of plasma cell myeloma

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