Proliferation to Apoptosis Tumor Cell Ratio as a Biomarker to Improve Clinical Management of Pre-Malignant and Symptomatic Plasma Cell Neoplasms
Proliferation and apoptosis of neoplastic cells are prognostic biomarkers in plasma cell neoplasms (PCNs). The prognostic capacity of proliferation to apoptosis ratio (Ratio-PA) in the era of immunomodulatory treatments is re-evaluated in 316 gammopathy of undetermined significance (MGUS), 57 smolde...
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doaj-ad6fa32678b344a1b73144d02adb52ce2021-04-09T23:04:24ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-04-01223895389510.3390/ijms22083895Proliferation to Apoptosis Tumor Cell Ratio as a Biomarker to Improve Clinical Management of Pre-Malignant and Symptomatic Plasma Cell NeoplasmsMaría A. Vasco-Mogorrón0José A. Campillo1Adela Periago2Valentin Cabañas3Mercedes Berenguer4María C. García-Garay5Lourdes Gimeno6María F. Soto-Ramírez7María D. Martínez-Hernández8Manuel Muro9Alfredo Minguela10Immunology Service, Clinic University Hospital Virgen de la Arrrixaca (HCUVA), Biomedical Research Institute of Murcia (IMIB), 30120 Murcia, SpainImmunology Service, Clinic University Hospital Virgen de la Arrrixaca (HCUVA), Biomedical Research Institute of Murcia (IMIB), 30120 Murcia, SpainHematology Service, General University Hospital Rafael Méndez, Biomedical Research Institute of Murcia (IMIB), 30813 Murcia, SpainHematology Service, Clinic University Hospital Virgen de la Arrrixaca (HCUVA), Biomedical Research Institute of Murcia (IMIB), 30120 Murcia, SpainHematology Service, General University Hospital Santa Lucía, Biomedical Research Institute of Murcia (IMIB), 30202 Murcia, SpainHematology Service, Clinic University Hospital Virgen de la Arrrixaca (HCUVA), Biomedical Research Institute of Murcia (IMIB), 30120 Murcia, SpainImmunology Service, Clinic University Hospital Virgen de la Arrrixaca (HCUVA), Biomedical Research Institute of Murcia (IMIB), 30120 Murcia, SpainImmunology Service, Clinic University Hospital Virgen de la Arrrixaca (HCUVA), Biomedical Research Institute of Murcia (IMIB), 30120 Murcia, SpainImmunology Service, Clinic University Hospital Virgen de la Arrrixaca (HCUVA), Biomedical Research Institute of Murcia (IMIB), 30120 Murcia, SpainImmunology Service, Clinic University Hospital Virgen de la Arrrixaca (HCUVA), Biomedical Research Institute of Murcia (IMIB), 30120 Murcia, SpainImmunology Service, Clinic University Hospital Virgen de la Arrrixaca (HCUVA), Biomedical Research Institute of Murcia (IMIB), 30120 Murcia, SpainProliferation and apoptosis of neoplastic cells are prognostic biomarkers in plasma cell neoplasms (PCNs). The prognostic capacity of proliferation to apoptosis ratio (Ratio-PA) in the era of immunomodulatory treatments is re-evaluated in 316 gammopathy of undetermined significance (MGUS), 57 smoldering multiple myeloma (SMM), and 266 multiple myeloma (MM) patients. Ratio-PA of 0.77 ± 0.12, 1.94 ± 0.52, and 11.2 ± 0.7 (<i>p</i> < 0.0001) were observed in MGUS, SMM, and MM patients. Ten-year overall survival (10y-OS) rates for patients with low/high Ratio-PA were 93.5%/77.3% <i>p</i> < 0.0001) for MGUS, 82.5%/64.7% (<i>p</i> < 0.05) for SMM, and 62.3%/47.0% (<i>p</i> < 0.05) for MM. For patients with low, intermediate, and high risk, 10y-OS for low/high Ratio-PA were 95.5%/72.9% (<i>p</i> < 0.0001), 74.2%/50.4% (<i>p</i> < 0.0001), and 35.3%/20.0% (<i>p</i> = 0.836), respectively. Ratio-PA was an independent prognostic factor for OS (HR = 2.119, <i>p</i> < 0.0001, Harrell-C-statistic = 0.7440 ± 0.0194) when co-analyzed with sex, age, and standard risk. In patients with Ratio-PA<sup>high</sup>, only first-line therapy with VRd/VTd, but not PAD/VCD, coupled with ASCT was associated with high 10y-OS (82.7%). Tumor cell Ratio-PA estimated at diagnosis offers a prognostic biomarker that complements standard risk stratification and helps to guide the clinical management of pre-malignant and symptomatic PCNs. Every effort should be made to provide first-line therapies including VTd or VRd associated with ASCT to patients with Ratio-PA<sup>high</sup> at higher risk of progression and death.https://www.mdpi.com/1422-0067/22/8/3895plasma cell neoplasmMGUSSMMMMtreatmentproliferation |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
María A. Vasco-Mogorrón José A. Campillo Adela Periago Valentin Cabañas Mercedes Berenguer María C. García-Garay Lourdes Gimeno María F. Soto-Ramírez María D. Martínez-Hernández Manuel Muro Alfredo Minguela |
spellingShingle |
María A. Vasco-Mogorrón José A. Campillo Adela Periago Valentin Cabañas Mercedes Berenguer María C. García-Garay Lourdes Gimeno María F. Soto-Ramírez María D. Martínez-Hernández Manuel Muro Alfredo Minguela Proliferation to Apoptosis Tumor Cell Ratio as a Biomarker to Improve Clinical Management of Pre-Malignant and Symptomatic Plasma Cell Neoplasms International Journal of Molecular Sciences plasma cell neoplasm MGUS SMM MM treatment proliferation |
author_facet |
María A. Vasco-Mogorrón José A. Campillo Adela Periago Valentin Cabañas Mercedes Berenguer María C. García-Garay Lourdes Gimeno María F. Soto-Ramírez María D. Martínez-Hernández Manuel Muro Alfredo Minguela |
author_sort |
María A. Vasco-Mogorrón |
title |
Proliferation to Apoptosis Tumor Cell Ratio as a Biomarker to Improve Clinical Management of Pre-Malignant and Symptomatic Plasma Cell Neoplasms |
title_short |
Proliferation to Apoptosis Tumor Cell Ratio as a Biomarker to Improve Clinical Management of Pre-Malignant and Symptomatic Plasma Cell Neoplasms |
title_full |
Proliferation to Apoptosis Tumor Cell Ratio as a Biomarker to Improve Clinical Management of Pre-Malignant and Symptomatic Plasma Cell Neoplasms |
title_fullStr |
Proliferation to Apoptosis Tumor Cell Ratio as a Biomarker to Improve Clinical Management of Pre-Malignant and Symptomatic Plasma Cell Neoplasms |
title_full_unstemmed |
Proliferation to Apoptosis Tumor Cell Ratio as a Biomarker to Improve Clinical Management of Pre-Malignant and Symptomatic Plasma Cell Neoplasms |
title_sort |
proliferation to apoptosis tumor cell ratio as a biomarker to improve clinical management of pre-malignant and symptomatic plasma cell neoplasms |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1661-6596 1422-0067 |
publishDate |
2021-04-01 |
description |
Proliferation and apoptosis of neoplastic cells are prognostic biomarkers in plasma cell neoplasms (PCNs). The prognostic capacity of proliferation to apoptosis ratio (Ratio-PA) in the era of immunomodulatory treatments is re-evaluated in 316 gammopathy of undetermined significance (MGUS), 57 smoldering multiple myeloma (SMM), and 266 multiple myeloma (MM) patients. Ratio-PA of 0.77 ± 0.12, 1.94 ± 0.52, and 11.2 ± 0.7 (<i>p</i> < 0.0001) were observed in MGUS, SMM, and MM patients. Ten-year overall survival (10y-OS) rates for patients with low/high Ratio-PA were 93.5%/77.3% <i>p</i> < 0.0001) for MGUS, 82.5%/64.7% (<i>p</i> < 0.05) for SMM, and 62.3%/47.0% (<i>p</i> < 0.05) for MM. For patients with low, intermediate, and high risk, 10y-OS for low/high Ratio-PA were 95.5%/72.9% (<i>p</i> < 0.0001), 74.2%/50.4% (<i>p</i> < 0.0001), and 35.3%/20.0% (<i>p</i> = 0.836), respectively. Ratio-PA was an independent prognostic factor for OS (HR = 2.119, <i>p</i> < 0.0001, Harrell-C-statistic = 0.7440 ± 0.0194) when co-analyzed with sex, age, and standard risk. In patients with Ratio-PA<sup>high</sup>, only first-line therapy with VRd/VTd, but not PAD/VCD, coupled with ASCT was associated with high 10y-OS (82.7%). Tumor cell Ratio-PA estimated at diagnosis offers a prognostic biomarker that complements standard risk stratification and helps to guide the clinical management of pre-malignant and symptomatic PCNs. Every effort should be made to provide first-line therapies including VTd or VRd associated with ASCT to patients with Ratio-PA<sup>high</sup> at higher risk of progression and death. |
topic |
plasma cell neoplasm MGUS SMM MM treatment proliferation |
url |
https://www.mdpi.com/1422-0067/22/8/3895 |
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