Electrolyte and renal disorders in patients with newly diagnosed glioblastoma

Abstract BackgroundElectrolyte disturbances and altered renal function have been linked to the prognosis of critically ill patients and recently also of cancer patients. Little is known about the prevalence and prognostic impact of electrolyte and renal disorders in patients with glioblastoma (GBM), the most frequent malignant primary brain tumor. This study aimed to assess electrolyte and renal disorders in GBM patients and evaluate their effect on patients’ outcome.MethodsPatients treated for newly diagnosed GBM between 2005 and 2018 were included. Electrolytes and renal function parameters were assessed preoperatively. Medical records of patients were retrospectively reviewed for demographic and clinical parameters, as well as patients’ survival.ResultsElectrolyte and renal disorders at admission were present in 275 (30.6%) and 544 (60.4%) of 900 GBM patients respectively and were more common in patients with higher age, previous comorbidities and poor initial clinical performance status. In univariate analysis and Kaplan-Meier survival plots, presence of hyponatremia, hypochloremia, hypocalcemia, hyperuricemia and low glomerular filtration rate were associated with poorer survival. Multivariate analysis revealed hypochloremia as an independent prognostic factor for overall (p=0.004) and 1-year (p=0.021) survival. ConclusionsPreoperative electrolyte and renal disorders are common in GBM patients. Of them, only hypochloremia showed a strong association with GBM prognosis, independently of age, sex, extent of resection, clinical performance status, postoperative therapy, and molecular status. Further studies are needed to evaluate the impact of hypochloremia on GBM survival.

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Predicting survival in anaplastic astrocytoma patients in a single-center cohort of 108 patients

Radiation Oncology ◽

10.1186/s13014-020-01728-8 ◽

2020 ◽

Vol 15 (1) ◽

Author(s):

Helena C. W. Wahner ◽

Malte Träger ◽

Katja Bender ◽

Leonille Schweizer ◽

Julia Onken ◽

...

Keyword(s):

Life Expectancy ◽

Anaplastic Astrocytoma ◽

Karnofsky Performance Status ◽

Performance Status ◽

Univariate Analysis ◽

Survival Rates ◽

Multivariable Analysis ◽

Extent Of Resection ◽

Newly Diagnosed ◽

Survival Prognosis

Abstract Background Current guidelines for the treatment of anaplastic astrocytoma (AA) recommend maximal safe resection followed by radiotherapy and chemotherapy. Despite this multimodal treatment approach, patients have a limited life expectancy. In the present study, we identified variables associated with overall survival (OS) and constructed a model score to predict the OS of patients with AA at the time of their primary diagnosis. Methods We retrospectively evaluated 108 patients with newly diagnosed AA. The patient and tumor characteristics were analyzed for their impact on OS. Variables significantly associated with OS on multivariable analysis were included in our score. The final algorithm was based on the 36-month survival rates corresponding to each characteristic. Results On univariate analysis, age, Karnofsky performance status, isocitrate dehydrogenase status, and extent of resection were significantly associated with OS. On multivariable analysis all four variables remained significant and were consequently incorporated in the score. The total score ranges from 20 to 33 points. We designated three prognostic groups: A (20–25), B (26–29), and C (30–33 points) with 36-month OS rates of 23%, 71%, and 100%, respectively. The OS rate at 5 years was 8% in group A, 61% in group B and 88% in group C. Conclusions Our model score predicts the OS of patients newly diagnosed with AA and distinguishes patients with a poor survival prognosis from those with a greater life expectancy. Independent and prospective validation is needed. The upcoming changes of the WHO classification of brain tumors as well as the practice changing results from the CATNON trial will most likely require adaption of the score.

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The Impact of Hyperglycemia on Risk of Severe Infections during Early Period of Induction Therapy in Patients with Newly Diagnosed Multiple Myeloma

BioMed Research International ◽

10.1155/2014/413149 ◽

2014 ◽

Vol 2014 ◽

pp. 1-5 ◽

Cited By ~ 6

Author(s):

Sung-Hoon Jung ◽

Hee-Chang Jang ◽

Seung-Shin Lee ◽

Jae-Sook Ahn ◽

Deok-Hwan Yang ◽

...

Keyword(s):

Multiple Myeloma ◽

Induction Therapy ◽

Performance Status ◽

Univariate Analysis ◽

Elevated Serum ◽

Poor Performance ◽

Poor Performance Status ◽

Newly Diagnosed ◽

Serious Infections ◽

The Impact

The association between hyperglycemia and infections during induction chemotherapy has been reported in a number of hematologic disorders. This retrospective study evaluated the incidence of hyperglycemia during induction therapy in 155 patients with newly diagnosed multiple myeloma (MM) and its effect on serious infections during the first 60 days of induction. A total of 20 (12.9%) patients developed overt hyperglycemia (≥200 mg/dL) during induction therapy. Serious infections occurred in 28 (18.1%) of 155 patients and infection-related mortality within 2 months after treatment was 0.6% (1 patient). In a univariate analysis, overt hyperglycemia, poor performance status (≥2), International Staging System III, lymphopenia (<500/μL), and elevated serum creatinine (≥2 mg/dL) were found to be associated with serious infections. In multivariate analysis, only overt hyperglycemia (HR 7.846, 95% CI 2.512–24.503,P<0.001) and poor performance status (HR 5.801, 95% CI 1.974–17.050,P=0.001) remained significant. In conclusion, this study demonstrated an association between hyperglycemia and serious infections during induction therapy in patients with MM.

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H3K27M-mutant Diffuse Midline Gliomas should be Further Molecularly Stratified: An Integrated Analysis of 669 Patients

10.21203/rs.3.rs-949930/v1 ◽

2021 ◽

Author(s):

Huy Gia Vuong ◽

Hieu Trong Le ◽

Tam N.M. Ngo ◽

Kar-Ming Fung ◽

James D. Battiste ◽

...

Keyword(s):

Cox Regression ◽

Fatal Outcome ◽

Extent Of Resection ◽

Tumor Location ◽

Genetic Alterations ◽

Integrated Analysis ◽

Prognostic Impact ◽

Kaplan Meier ◽

Hazard Ratios ◽

The Impact

Abstract Introduction: H3K27M-mutated diffuse midline gliomas (H3-DMGs) are aggressive tumors with a fatal outcome. This study integrating individual patient data (IPD) from published studies aimed to investigate the prognostic impact of different genetic alterations on survival of these patients.Methods: We accessed PubMed and Web of Science to search for relevant articles. Studies were included if they have available data of follow-up and additional molecular investigation of H3-DMGs. For survival analysis, Kaplan-Meier analysis and Cox regression models were utilized, and corresponding hazard ratios (HR) and 95% confidence intervals (CI) were computed to analyze the impact of genetic events on overall survival (OS).Result: We included 30 studies with 669 H3-DMGs. TP53 mutations were the most common second alteration among these neoplasms. In univariate Cox regression model, TP53 mutation was an indicator of shortened survival (HR = 1.446; 95% CI = 1.143-1.829) whereas ACVR1 (HR = 0.712; 95% CI = 0.518-0.976) and FGFR1 mutations (HR = 0.408; 95% CI = 0.208-0.799) conferred prolonged survival. In addition, ATRX loss was also associated with a better OS (HR = 0.620; 95% CI = 0.386-0.996). Adjusted for age, gender, tumor location, and the extent of resection, the presence of TP53 mutations, the absence of ACVR1 or FGFR1 mutations remained significantly poor prognostic factors.Conclusions: We outlined the prognostic importance of additional genetic alterations in H3-DMGs and recommended that these neoplasms should be further molecularly segregated. It could help neuro-oncologists better evaluate the risk stratification of patients and consider pertinent treatments.

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PATH-16. EVALUATION OF SEX-BASED DIFFERENCES IN CLINICAL OUTCOMES AND TUMOR GENOMICS IN PATIENTS WITH NEWLY DIAGNOSED IDH-WILDTYPE GLIOBLASTOMA RECEIVING CHEMORADIATION

Neuro-Oncology ◽

10.1093/neuonc/noab196.468 ◽

2021 ◽

Vol 23 (Supplement_6) ◽

pp. vi118-vi118

Author(s):

Diana Shi ◽

Mary Jane Lim-Fat ◽

Amin Nassar ◽

Jared Woods ◽

Gilbert Youssef ◽

...

Keyword(s):

Clinical Outcomes ◽

Karnofsky Performance Status ◽

Performance Status ◽

Methylation Status ◽

Multivariable Analysis ◽

Extent Of Resection ◽

Hazard Ratio ◽

Newly Diagnosed ◽

Loss Of Function ◽

Female Sex

Abstract BACKGROUND We evaluated sex-based differences in clinical outcomes and tumor genomics in patients with newly-diagnosed GBM. METHODS We reviewed 665 IDH-wild type GBM patients with Karnofsky Performance Status (KPS) ≥60 treated at our institution from 2010-2019 including; 585 patients with targeted exome sequencing of 447 cancer associated genes (OncoPanel). Deleterious mutations were defined as homozygous deletions or loss of function mutations of known tumor suppressors (as reported in TCGA, ≥ 3 times in the COSMIC database, or predicted as “damaging” in SIFT and/or “probably damaging” in Polyphen 2) or known oncogenic mutations in proto-oncogenes (reported in TCGA or ≥ 3 times in COSMIC). RESULTS There were 384 (57.7%) males and 281 (42.3%) females. Median OS was 22.5 months for females and 19.3 months for males (hazard ratio [HR] 0.81, 95% CI 1.03-1.48, p = 0.02). On multivariable analysis adjusted for age, KPS ≥90, extent of resection, and MGMT methylation status, female sex (adjusted hazard ratio 0.78, 95% CI [0.64-0.95], p = 0.015) was associated with improved OS. Superior OS in females was observed in MGMT-unmethylated patients (HR 0.69, 95% CI [0.54-0.90], p = 0.005) but not MGMT-methylated patients. Thirteen genes were deleteriously altered in ≥5% of our cohort: CDK4 (12.1% male vs. 7.8% female), CDKN2A (46.5% vs. 45.7%), CDKN2B (41.8% vs. 43.3%), EGFR (34.7% vs. 40.0%, MTAP (18.2% vs. 18.8%), NF1 (11.5% vs. 9.4%), PTEN (28.2% vs. 29.8%), TP53 (28.2% vs. 30.2%), RB1 (5.6% vs. 6.5%), MDM4 (6.2% vs. 5.7%), ATM (5.9% vs. 3.7%), MDM2 (7.4% vs. 4.1%), PIK3R1 (6.2% vs. 4.1%). There were no differences in frequency of mutations in these individual genes between males and females (χ 2 [1, N=585] = 0.05-2.86, p = 0.09-0.86). CONCLUSIONS Female sex is associated with improved survival. We did not identify sex-based differences in deleterious genomic alterations amongst commonly altered genes in GBM.

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Neutrophil-lymphocyte ratio in metastatic breast cancer is not an independent predictor of survival, but depends on other variables

Scientific Reports ◽

10.1038/s41598-019-53606-3 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 4

Author(s):

Alejandra Ivars Rubio ◽

Juan Carlos Yufera ◽

Pilar de la Morena ◽

Ana Fernández Sánchez ◽

Esther Navarro Manzano ◽

...

Keyword(s):

Breast Cancer ◽

Overall Survival ◽

Prognostic Factors ◽

Metastatic Breast Cancer ◽

Performance Status ◽

Univariate Analysis ◽

Metastatic Breast ◽

Prognostic Impact ◽

Neutrophil Lymphocyte Ratio ◽

Lymphocyte Ratio

AbstractThe prognostic impact of neutrophil-lymphocyte ratio (NLR) in metastatic breast cancer (MBC) has been previously evaluated in early and metastatic mixed breast cancer cohorts or without considering other relevant prognostic factors. Our aim was to determine whether NLR prognostic and predictive value in MBC was dependent on other clinical variables. We studied a consecutive retrospective cohort of patients with MBC from a single centre, with any type of first line systemic treatment. The association of NLR at diagnosis of metastasis with progression free survival (PFS) and overall survival (OS) was evaluated using Cox univariate and multivariate proportional hazard models. In the full cohort, that included 263 MBC patients, a higher than the median (>2.32) NLR was significantly associated with OS in the univariate analysis (HR 1.36, 95% CI 1.00–1.83), but the association was non-significant (HR 1.12, 95% CI 0.80–1.56) when other clinical covariates (performance status, stage at diagnosis, CNS involvement, visceral disease and visceral crisis) were included in the multivariate analysis. No significant association was observed for PFS. In conclusion, MBC patients with higher baseline NLR had worse overall survival, but the prognostic impact of NLR is likely derived from its association with other relevant clinical prognostic factors.

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High-dose cytarabine dose modification reduces the incidence of neurotoxicity in patients with renal insufficiency.

Journal of Clinical Oncology ◽

10.1200/jco.1997.15.2.833 ◽

1997 ◽

Vol 15 (2) ◽

pp. 833-839 ◽

Cited By ~ 63

Author(s):

G A Smith ◽

L E Damon ◽

H S Rugo ◽

C A Ries ◽

C A Linker

Keyword(s):

Renal Function ◽

Renal Insufficiency ◽

Univariate Analysis ◽

Myelogenous Leukemia ◽

High Dose ◽

Once Daily ◽

Dose Modification ◽

Daily Schedule ◽

High Dose Cytarabine ◽

The Impact

PURPOSE To determine the impact of high-dose cytarabine (ARA-C) (HDAC) dose modification, based on renal function, on the incidence of neurotoxicity (NT). PATIENTS AND METHODS We retrospectively analyzed the records of 256 patients treated with HDAC (> or = 2.0 g/m2 per dose) for acute myelogenous leukemia (AML) at the University of California, San Francisco (UCSF). From 1985 to 1994, a total of 358 cycles of HDAC were administered, using either a twice-daily schedule (n = 208) or a once-daily regimen (n = 48). In 1989, a dose-modification algorithm was initiated at our institution, which reduced ARA-C doses in the setting of renal insufficiency (RI). For patients with a serum creatinine (Cr) level of 1.5 to 1.9 mg/dL during treatment, or an increase in Cr during treatment (deltaCr) of 0.5 to 1.2 mg/dL, ARA-C was decreased to 1 g/m2 per dose. For patients with a Cr > or = 2.0 mg/dL or a deltaCr greater 1.2 mg/dL, the dose was reduced to 0.1 g/m2/d. RESULTS Overall, the incidence of NT was 16% (34 of 208) for patients treated with twice-daily HDAC and 0% (none of 48) for patients treated with daily HDAC (P = .003). NT occurred more often in patients treated on a twice-daily schedule with 3 g/m2 per dose compared with 2 g/m2 per dose (25% v 8%; P = .009). NT occurred in 55% of the twice-daily-treated patients with RI, compared with 7% of those with normal renal function (P = .00001). In patients with RI, NT occurred in none of 11 dose-modified cycles versus five of 11 (45%) total unmodified cycles (P = .01). None of 14 patients treated with once-daily HDAC given during RI developed NT, compared to 55% of patients (23 of 42) receiving twice-daily HDAC during RI (P = .009). By univariate analysis, NT was not associated with patient age or serum alkaline phosphatase, but NT was significantly increased in patients treated with twice-daily HDAC when the serum bilirubin was > or = 2.0 mg/dL compared with twice-daily HDAC given when the total bilirubin was less than 2.0 mg/dL (33% v 14%; P = .017). Multivariate analysis confirmed that RI was the most significant risk factor associated with the development of NT. CONCLUSION HDAC NT is strongly associated with RI. The risk of HDAC NT can be reduced by the following: (1) routinely reducing the ARA-C dose from 3 to 2 g/m2 per dose; (2) modifying the ARA-C dose based on daily Cr values; and (3) administering HDAC on a once-daily rather than twice-daily schedule.

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Navigated Intraoperative 2-Dimensional Ultrasound in High-Grade Glioma Surgery: Impact on Extent of Resection and Patient Outcome

Operative Neurosurgery ◽

10.1093/ons/opz203 ◽

2019 ◽

Cited By ~ 1

Author(s):

Alessandro Moiraghi ◽

Francesco Prada ◽

Alberto Delaidelli ◽

Ramona Guatta ◽

Adrien May ◽

...

Keyword(s):

Real Time ◽

Karnofsky Performance Status ◽

Performance Status ◽

Intraoperative Ultrasound ◽

High Grade Glioma ◽

Extent Of Resection ◽

High Grade ◽

Glioma Surgery ◽

Supratentorial Gliomas ◽

The Impact

Abstract BACKGROUND Maximizing extent of resection (EOR) and reducing residual tumor volume (RTV) while preserving neurological functions is the main goal in the surgical treatment of gliomas. Navigated intraoperative ultrasound (N-ioUS) combining the advantages of ultrasound and conventional neuronavigation (NN) allows for overcoming the limitations of the latter. OBJECTIVE To evaluate the impact of real-time NN combining ioUS and preoperative magnetic resonance imaging (MRI) on maximizing EOR in glioma surgery compared to standard NN. METHODS We retrospectively reviewed a series of 60 cases operated on for supratentorial gliomas: 31 operated under the guidance of N-ioUS and 29 resected with standard NN. Age, location of the tumor, pre- and postoperative Karnofsky Performance Status (KPS), EOR, RTV, and, if any, postoperative complications were evaluated. RESULTS The rate of gross total resection (GTR) in NN group was 44.8% vs 61.2% in N-ioUS group. The rate of RTV > 1 cm3 for glioblastomas was significantly lower for the N-ioUS group (P < .01). In 13/31 (42%), RTV was detected at the end of surgery with N-ioUS. In 8 of 13 cases, (25.8% of the cohort) surgeons continued with the operation until complete resection. Specificity was greater in N-ioUS (42% vs 31%) and negative predictive value (73% vs 54%). At discharge, the difference between pre- and postoperative KPS was significantly higher for the N-ioUS (P < .01). CONCLUSION The use of an N-ioUS-based real-time has been beneficial for resection in noneloquent high-grade glioma in terms of both EOR and neurological outcome, compared to standard NN. N-ioUS has proven usefulness in detecting RTV > 1 cm3.

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Prognostic Impact of Stromal Immune Infiltration before and after Neoadjuvant Chemotherapy (NAC) in Triple Negative Inflammatory Breast Cancers (TNIBC) Treated with Dose-Dense Dose-Intense NAC

Cancers ◽

10.3390/cancers12092657 ◽

2020 ◽

Vol 12 (9) ◽

pp. 2657

Author(s):

Luca Campedel ◽

Paul Blanc-Durand ◽

Asker Bin Asker ◽

Jacqueline Lehmann-Che ◽

Caroline Cuvier ◽

...

Keyword(s):

Breast Cancer ◽

Neoadjuvant Chemotherapy ◽

Triple Negative ◽

Univariate Analysis ◽

Tumor Infiltrating Lymphocytes ◽

Complete Response ◽

Prognostic Impact ◽

Breast Cancers ◽

Dose Dense ◽

The Impact

Inflammatory breast cancers are very aggressive, and among them, triple negative breast cancer (TNBC) has the worst prognosis. While many studies have investigated the association between tumor-infiltrating lymphocytes (TIL) before neoadjuvant chemotherapy (NAC) and outcome in TNBC, the impact of post-NAC TIL and TIL variation in triple negative inflammatory breast cancer (TNIBC) outcome is unknown. Between January 2010 to December 2018, all patients with TNIBC seen at the breast disease unit (Saint-Louis Hospital) were treated with dose-dense dose-intense NAC. The main objective of the study was to determine factors associated with event-free survival (EFS), particularly pathological complete response (pCR), pre- and post-NAC TIL, delta TIL and post-NAC lymphovascular invasion (LVI). After univariate analysis, post-NAC LVI (HR 2.06; CI 1.13–3.74; p = 0.02), high post-NAC TIL (HR 1.81; CI 1.07–3.06; p = 0.03) and positive delta TIL (HR 2.20; CI 1.36–3.52; p = 0.001) were significantly associated with impaired EFS. After multivariate analysis, only a positive TIL variation remained negatively associated with EFS (HR 1.88; CI 1.05–3.35; p = 0.01). TNIBC patients treated with intensive NAC who present TIL enrichment after NAC have a high risk of relapse, which could be used as a prognostic marker in TNIBC and could help to choose adjuvant post-NAC treatment.

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Mature Results of a Prospective Trial of Rituximab in Patients (Pt) with Post Transplant Lymphoproliferative Disorder (PTLD) Unresponsive or Ineligible for Reduced Immunosuppression (RIS).

Blood ◽

10.1182/blood.v108.11.2755.2755 ◽

2006 ◽

Vol 108 (11) ◽

pp. 2755-2755

Author(s):

Jeff P. Sharman ◽

Donald E. Tsai ◽

Clare J. Twist ◽

Steven M. Horwitz ◽

Carol D. Jones ◽

...

Keyword(s):

Site Response ◽

Karnofsky Performance Status ◽

Performance Status ◽

Univariate Analysis ◽

Prospective Trial ◽

Large Cell ◽

Cytotoxic Therapy ◽

Free Survival ◽

Co Morbidity ◽

The Impact

Abstract Background: PTLDs are typically B-cell neoplasms occurring as uncommon but serious complications of reduced T-cell immune surveillance associated with organ transplantation. RIS benefits only a subset of PTLD patients and cytotoxic therapy may be poorly tolerated. Therefore, in October 1998 we initiated a prospective study of rituximab in patients who failed or were unable to receive RIS and now report mature results. Methods: Patients with CD20+ PTLD were eligible if they had failed to completely respond to RIS or RIS was contraindicated and had Karnofsky performance status >60, age 3–70 years (y), measurable disease, and no change in immunosuppression for at least 2 weeks and no cytotoxic therapy within 4 weeks. Rituximab was given as 375 mg/m2 weekly x 4 with disease evaluation at 1, 3, 6, 9, 12 and 18 months. Response data, survival curves, and the impact of clinical and pathological factors were evaluated. Results: 24 of 26 enrolled pt were eligible and evaluable. Median age was 42y with 5 <17 y, 18 were male, and 14 progressed on RIS. Median time to PTLD from transplant was 47 months (m) (8 <24 m). 17/22 were EBV+, 17 were large cell or Burkitt histology, and 10 PTLD occurred in the allograft site. Response rate was 63% (46 %CR, 17% PR) and CRs were durable (1/11 progressed). With median follow-up of 65 m (range 44–82), outcomes at 5 y are: overall survival 48%, freedom from progression 41% and failure-free survival 21%. 7 pt died without progression, yielding 5 y cause-specific survival of 69%. Nine of 13 pt with disease progression were successfully salvaged with second-line therapy. In univariate analysis PTLD characteristics did not significantly correlate with outcome but 2/2 Burkitt pt quickly progressed. Conclusions: Rituximab provided effective, durable treatment for ~40% of pt failing RIS in this series of mainly late PTLD and a majority of pt progressing after rituximab could be treated successfully. However, overall and failure-free survival reflect significant co-morbidity in this population.

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Growth Differentation Factor 15 Is a Survival Factor for multiple myeloma cells and its plasma Concentration In Patients Is Related to Reduced Survival

Blood ◽

10.1182/blood.v116.21.614.614 ◽

2010 ◽

Vol 116 (21) ◽

pp. 614-614

Author(s):

Jill Corre ◽

Elodie Labat ◽

Nicolas Espagnolle ◽

Hervé Avet-Loiseau ◽

Murielle Roussel ◽

...

Keyword(s):

Multiple Myeloma ◽

Plasma Concentration ◽

Cell Line ◽

Healthy Subjects ◽

Univariate Analysis ◽

Culture Conditions ◽

Newly Diagnosed ◽

Event Free Survival ◽

Free Survival ◽

The Impact

Abstract Abstract 614 We previously reported that bone marrow mesenchymal stem cells (BMMSCs) from newly diagnosed multiple myeloma (MM) patients were abnormal. In particular, we showed that Growth Differentiation 15 (GDF15) expression was higher in MM BMMSCs than in normal BMMSCs. GDF15 is a divergent member of the human TGFβ superfamily. GDF15 overexpression has been described in numerous malignancies and its concentration is increased in the serum of patients with glioma, prostate, colorectal or pancreatic cancers. Contradictory data prevent to understand clearly GDF15 implication in pathophysiology of tumors. Furthermore, GDF15 has never been studied in haematological malignancies. Our first objective was thus to determine the effect of human recombinant GDF15 (rGDF15) on MOLP-6 stroma-dependent cell line and MM1.S stroma-independent cell line under serum free culture conditions. rGDF15 could significantly increase cell survival in MOLP-6 but not in MM1.S. Interestingly, rGDF15 was able to induce Akt phosphorylation on Threonine 308 in MOLP-6 and primary MM cells but not in MM1.S cells. Furthermore, pre-treatment of MOLP-6 with Akt pharmacologic inhibitor abrogated the prosurvival effect of GDF15, suggesting an Akt-dependent mechanism. In the same culture conditions, we observed that rGDF15 could abrogate toxicity of drugs classically used in MM treatment (melphalan, bortezomid and lenalidomide) for both cell lines MOLP-6 and MM1.S, suggesting that this cytoprotective effect may be Akt-independent. Because of the in vitro effects of GDF15, our second objective was to determine whether the plasma concentration of GDF15 (pGDF15) in patients with MM may be indicative of the seriousness of the disease or correlate with the response to the treatment. Thus, we investigated the pGDF15 in 131 patients with newly diagnosed MM and 13 healthy subjects. We first found that it was significantly higher for patients with MM (0.90±1.10 ng/mL) than for healthy subjects (0.25±0.08 ng/mL) (P< .001). In patients with MM, pGDF15 correlated with the main prognostic factor of the disease (i.e. International Staging System, b2 microglobulin level, presence or absence of deletion of chromosome 13, and bone status). For the 81 patients with high pGDF15 level (≥ 0.50 ng/mL), the probabilities of event-free and overall survival 30 months after diagnosis were 50% and 75%. For the 50 patients with low pGDF15 level (< 0.5 ng/mL), the probabilities were 80% and 97% (P< .0045 and P< .013, respectively). However, we did not find a clear relationship between pGDF15 and response to treatment. We analysed the impact of prognostic factors on event-free survival for the 131 patients with MM. On univariate analysis, event-free survival was significantly related to age (P= .003), b2-microglobulin level (P= .02) and pGDF-15 level (P= .003). On multivariate analysis, event-free survival was significantly related to age (P= .001) and pGDF15 level (P= .04). Our study demonstrates that GDF15 is a survival and cytoprotective factor for MM cells and that pGDF15 is related to initial parameters of the disease and survival, which specifically implicates the MM microenvironment in the pathophysiology and the prognosis of the disease. Disclosures: No relevant conflicts of interest to declare.

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