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

Blood ◽  
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.

Multiple Myeloma Multicenter Registry in Colombia: The Impact of Autologous Stem Transplantation on Overall and Disease-Free Survival

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 47-48
Author(s):  
Virginia Abello ◽  
Claudia Lucia Sossa ◽  
Henry Idrobo ◽  
Guillermo Quintero ◽  
William Mantilla ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Research Funding ◽  
Clinical Characteristics ◽  
Univariate Analysis ◽  
Disease Free Survival ◽  
Entire Group ◽  
Hematologic Neoplasms ◽  
First Line ◽  
Free Survival ◽  
The Impact

Aim: RENEHOC (Registro Epidemiológico de Neoplasias Hematológicas en Colombia) is a multicenter clinical quality database established in January 2018. The primary aim of the database is to provide local information on diagnosis and treatment of Multiple Myeloma (MM) and other hematologic neoplasms; this is key to show authorities the improvements that must be made to achieve better outcomes for Colombian patients and pose research questions relevant to our population. The aim of this report is to analyze variables related to event free survival (EFS) and overall survival (OS) in MM Colombian patients. Study population: An ambispective registry of adult MM patients, treated in approved centers over the last 10 years in Colombia. As of July 2020, 890 patients have been registered. Descriptive statistics were used for patient's demographic and clinical characteristics. The Kaplan-Meier method was used to assess DFS and OS. Hazard Ratios (HR) using Cox proportional hazards regression modeling was estimated. &lt;65 yrs. patients were considered transplant eligible (TE) and older than 65 yrs. transplant ineligible (TI). Results: Data from 890 MM patients were reviewed. Median age at diagnosis was 66.8 (SD 11.17) years (TE 57 yrs., SD 6.71; TI 74.8 yrs., SD 6.87); 398 (57%) were TE; 52.9% were male. At diagnosis median hemoglobin was 10.1 (SD 2.5), 242 (27.2%) had renal failure, and 379 (42.6%) pathological fractures. IgG was the most common M component (n=328, 36.8%). Most patients were in an advanced stage by Durie Salmon at diagnosis (DS IIIA or IIIB: n=523, 77.4%), and had high risk ISS (ISS 1: n=128, 20.6%; ISS 2: n=180, 29.0%; ISS 3: n=312, 50.3%; NA n=270). Only 17,9% (n=160) had cytogenetic prognostic characterization. There were not significant differences in clinical characteristics at diagnosis between TE and TI patients. The most common induction regimen for TE were Cyclophosphamide-Bortezomib-Dexamethasone (CyBorD) (n=190, 49%) and Bortezomib-Thalidomide-Dexamethasone (VTD) (n=103, 27%). For TI patients, most common regimens in first line were CyBorD (n=111, 245), VTD (n=90, 19%) and Bortezomib-Dexamethasone (Vd) (n=84, 18%). 69% TE and 59% TI patients had partial response or better after first line. 41% of TE patients actually received an Autologous Stem Cell Transplantation (ASCT) after 1 line. 19% of TI patients received an ASCT. Of note, in 78% of patients considered to have indication not taken to transplant, administrative barriers of access are reported. Mean follow-up for the entire group was 28.35 months (SD 29.27, CI 26.41-30.29). The median DFS was 62 months being significantly longer in TE patients (74 vs 53 months for TI, p=0.0002), estimated 5 years DFS 52% (TE 56% vs 46% for TI). Median OS was 88 months (Not reached for TE vs 75 moths for TI, p=0.0001), estimated 5 years OS 62% (TE 70% vs 56% for TI). Univariate analysis showed ISS at diagnosis, age and ASCT were significantly related to OS. On multivariate analysis ISS 3 (HR 1.89; p=0.004; CI 1.22-2.93) at diagnosis and ASCT (HR 0.26, p=0.0001, CI (0.18-0.39) were the only factors significantly associated with OS. 5 yrs. OS for patients that received ASCT was 80% in comparison to 48% if not done. Conclusion: At this timepoint data from RENEHOC is still limited, however, the potential of this growing registry is evident; until now little information about hematologic neoplasms in Colombia was available, this effort allows us to know the reality of our patients and plan relevant trials in our settings. We report here characteristic of a large cohort of MM patients in Colombia. OS and DFS are comparable with what have been published for similar patients in other latitudes. Consolidation with ASCT was the most important factor affecting prognosis in this cohort; the low transplant rate has to be addressed to improve outcomes for myeloma patients in Colombia. Figure Disclosures Abello: Abbvie: Consultancy, Research Funding; Dr. Reddy's: Consultancy, Research Funding; Takeda: Honoraria, Research Funding; Amgen: Consultancy, Research Funding; Novartis: Consultancy, Honoraria. Sossa:Takeda: Honoraria; Novo: Honoraria; Astellas: Honoraria; Roche: Honoraria. Idrobo:Takeda: Honoraria, Speakers Bureau; Abbvie: Honoraria, Speakers Bureau; Janssen: Honoraria, Speakers Bureau; Tecnofarma: Honoraria, Speakers Bureau; Amgen: Honoraria, Speakers Bureau. Henao-Uribe:Alexion: Consultancy, Speakers Bureau; Pfizer: Speakers Bureau; Takeda: Consultancy, Speakers Bureau.

scholarly journals First thalidomide clinical trial in multiple myeloma: a decade

Blood ◽  
2008 ◽  
Vol 112 (4) ◽  
pp. 1035-1038 ◽  
Author(s):  
Frits van Rhee ◽  
Madhav Dhodapkar ◽  
John D. Shaughnessy ◽  
Elias Anaissie ◽  
David Siegel ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Multiple Myeloma ◽  
Overall Survival ◽  
Disease Recurrence ◽  
Newly Diagnosed ◽  
Event Free Survival ◽  
Free Survival ◽  
The Poor ◽  
High Risk Disease

AbstractThe clinical outcomes of 169 patients enrolled in the first clinical trial of thalidomide for advanced or refractory myeloma are updated. Seventeen patients remain alive and 10 are event-free, with a median follow-up of 9.2 years. According to multivariate analysis of pretreatment variables, cytogenetic abnormalities, present in 47% of patients within 3 months of enrollment, and λ light chain isotype both affected overall survival and event-free survival adversely. Forty percent of the 58 patients lacking these 2 unfavorable features, one-half of whom had no disease recurrence, survived at least 6 years, in contrast to fewer than 5% among those with 1 or 2 risk features (P < .001). Patients who had received cumulative thalidomide doses in excess of 42 g in the first 3 months enjoyed superior overall and event-free survival. The poor outcome associated with λ-type myeloma may relate to its overrepresentation in molecularly defined high-risk disease gleaned from studies in newly diagnosed myeloma.

Immune Suppression By High-Density Neutrophils Predicts Short Progression-Free Survival in Multiple Myeloma

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4459-4459
Author(s):  
Alessandra Romano ◽  
Jose Manteiga ◽  
Vittorio Simeon ◽  
Nunziatina L Parrinello ◽  
Cesarina Giallongo ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Healthy Subjects ◽  
Expression Profiles ◽  
Progression Free Survival ◽  
High Density ◽  
Angiogenic Factor ◽  
Functional Evaluation ◽  
Newly Diagnosed ◽  
Free Survival ◽  
Potential Biomarker

Abstract Background and Objective : Our previous work showed that neutrophils sedimenting on top of red cells after density gradients, defined as high-density neutrophils (HDN) are emerging as pro-tumoral players with immunesuppressive properties, by depleting the surrounding microenvironment from arginine (arg) and tryptophan (trp) through increased expression of arginase (Arg-1) and 2-3 indoleamine deoxygenase (IDO), but little is known about their clinical relevance in Multiple Myeloma (MM). Experimental design : We integrated two distinct unbiased approaches. First, we assessed gene expression profiles (GEP) and functional evaluation of HDN sorted from 60 newly diagnosed MM patients, 30 patients with MGUS, and 30 healthy subjects.. Second, we adopted ultra-high performance liquid and gas chromatography followed by mass spectrometry (UHPLC/GC-MS) on an independent series of 167 samples of bone marrow (BM) and peripheral plasma collected ad hocfrom 125 individuals, comprising newly diagnosed MM, MGUS, smoldering MM, and age-matched healthy volunteers (n=29). Progression-free survival in newly diagnosed MM patients was correlated respectively to HDN functional and expression features or metabolic profiles in the two series. Results : GEP analyses disclosed that, compared to MGUS and HD, MM-HDN showed increased expression of Arg-1, IDO-1 and the angiogenic factor PROK-2/BV8 , confirmed by qRT-PCR and immunofluorescence. Indeed, MM-HDN (but not MGUS- and HD-HDN) revealed immunosuppressive activity in co-cultures with allogeneic T-cells, reverted by the selective Arg-1 inhibitor nor-NOHA. In addition, circulating Arg-1 in serum was higher in MM (169.5 ± 17.6) than MGUS (93.2 ± 10.4, p=0.0028) and healthy subjects (70.1 ± 16.5 ng/ml, p=0.0017). In MM patients there was a progressive increase from ISS stage I through III (p=0.014). High Arg-1 in MM patients' sera at diagnosis predicted clinical outcome after first line therapy, being associated to shorter progression-free survival (respectively 22.4 months versus unreached median, p=0.01). Metabolic profiling independently identified the same immunosuppressive Arg-1-urea-arginine (arg) and tryptophan (trp)-kinurenine-IDO pathways, with arg and trp significantly reduced along MM evolution. Lower levels of arg were associated to shorter PFS (37.2 versus 17.6 months, p=0.023). We then tested if aminoacid depletion (arg and trp) favors PCs growth. When exposed to trp-free or arg-free medium, human MM cell lines expressed more CHOP, p62, m-TOR and Blimp-1 (markers respectively of autophagy induction and immunoglobulin production); conversely, p62 silencing reduced Blimp-1, confirming the important role of p62-dependent mechanism in supporting PCs fitness. Conclusion : In MM, HDN are immunosuppressive due to increased Arg-1 and IDO expression. We propose the arginine/Arg-1 axis as a novel potential biomarker for MM prognosis. Disclosures Ciceri: MolMed SpA: Consultancy.

Extra-abdominal fibromatosis: Can aggressive management be avoided in a subgroup of patients?

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 10077-10077
Author(s):  
S. Bonvalot ◽  
H. Eldweny ◽  
V. Haddad ◽  
G. Missenard ◽  
D. Vanel ◽  
...  
Keyword(s):  
Systemic Treatment ◽  
Univariate Analysis ◽  
Tumor Evolution ◽  
Surgical Removal ◽  
Tumor Site ◽  
Event Free Survival ◽  
Free Survival ◽  
Quality Of Surgery ◽  
The Impact

10077 Background: The objective was to evaluate the impact of surgery as first-line treatment on event -free survival (EFS) of primary aggressive fibromatosis. Methods: Treatments were categorized into: surgery with or without radiotherapy and non surgical strategies with systemic treatment alone or wait and see policy. Event-free survival curves were estimated using the Kaplan-Meier method. Results: The sex ratio was 39 males/73 females. The median age at the time of the first diagnosis was 30 years. The median size of the primary was 60 mm. Eighty-nine patients (79.5%) had initial resection of their primary tumor followed by postoperative radiotherapy in 13 cases. Twenty-three patients (20.5%) did not undergo surgery but received systemic treatment or watch and wait policy. Median follow-up was 76 months. Three years EFS was 49%. In the univariate analysis, patients with microscopically complete surgery had a similar outcome to that of patients in the non-surgery group (65% vs 68% for 3-yr EFS respectively). Gender, age, tumor size, treatment period and strategy (surgery versus no surgery) were not statistically significant. Quality of resection according to margins and the tumor site were the only prognostic factors. There was a significant correlation between the tumor site and the quality of surgery (p= 0.0002). Tumor site was the only prognostic factor that remained in the multivariate analysis. Conclusions: Surgical removal as initial treatment was not found to influence the outcome. A subset of patients could be managed with a non aggressive policy. When surgery is finally necessary, it should be performed with the aim of achieving negative margins. Predictive biological factors influencing tumor evolution have to be defined No significant financial relationships to disclose.

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

2014 ◽  
Vol 2014 ◽  
pp. 1-5 ◽  
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.

CNS Involvement in Children With Newly Diagnosed Non-Hodgkin’s Lymphoma

2000 ◽  
Vol 18 (16) ◽  
pp. 3018-3024 ◽  
Author(s):  
John T. Sandlund ◽  
Sharon B. Murphy ◽  
Victor M. Santana ◽  
Frederick Behm ◽  
Dana Jones ◽  
...  
Keyword(s):  
Overall Survival ◽  
Univariate Analysis ◽  
Prognostic Significance ◽  
Large Cell ◽  
Tumor Burden ◽  
Newly Diagnosed ◽  
Event Free Survival ◽  
Cns Involvement ◽  
Free Survival ◽  
Cns Disease

PURPOSE: To determine the frequency of CNS involvement at diagnosis of non-Hodgkin’s lymphoma (NHL), to characterize its pattern of presentation, and to determine its prognostic significance. PATIENTS AND METHODS: We reviewed the records of 445 children (1975 through 1995) diagnosed with NHL (small noncleaved cell NHL/B-cell acute lymphoblastic leukemia [SNCC NHL/B-ALL], 201 patients; lymphoblastic, 113; large cell, 119; other, 12). Tumor burden was estimated by serum lactate dehydrogenase (LDH) measurement and reclassification of disease stage irrespective of CNS involvement (modified stage). RESULTS: Thirty-six of 445 children with newly diagnosed NHL had CNS involvement (lymphoma cells in the CSF [n = 23], cranial nerve palsy [n = 9], both features [n = 4]), representing 13%, 7%, and 1% of small noncleaved cell lymphoma, lymphoblastic lymphoma, and large-cell cases, respectively. By univariate analysis, CNS disease at diagnosis did not significantly impact event-free survival (P = .095), whereas stage and LDH did; however, children with CNS disease at diagnosis were at 2.0 times greater risk of death than those without CNS disease at diagnosis. In a multivariate analysis, CNS disease was not significantly associated with either overall or event-free survival, whereas both serum LDH and stage influenced both overall and event-free survival. Among cases of SNCC NHL/B-ALL, CNS disease was significantly associated with event-free and overall survival (univariate analysis); however, in multivariate analysis, only LDH had independent prognostic significance. Elevated serum LDH or higher modified stage were associated with a trend toward poorer overall survival among children with CNS disease. CONCLUSION: A greater tumor burden at diagnosis adversely influences the treatment outcome of children with NHL and CNS disease at diagnosis, suggesting a need for ongoing improvement in both systemic and CNS-directed therapy.

Time to Post-Remission Therapy (PRT) Is an Independent Prognostic Factor for Relapse and Overall Survival in Adults with Acute Lymphocytic Leukemia (ALL).

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1883-1883 ◽  
Author(s):  
Anjali Advani ◽  
Tao Jin ◽  
Ramon Tiu ◽  
Giridharan Ramsingh ◽  
Christopher Lowe ◽  
...  
Keyword(s):  
Overall Survival ◽  
Multivariate Analysis ◽  
Prognostic Factor ◽  
Univariate Analysis ◽  
Independent Prognostic Factor ◽  
High Dose ◽  
Newly Diagnosed ◽  
Free Survival ◽  
Poor Risk ◽  
The Impact

Abstract Only 30% of adults with ALL are cured. The identification of modifiable prognostic factors is important in designing future treatment paradigms, and improving the outcome of patients. PRT is integral in the treatment of ALL, and eradicates minimal residual disease (MRD) after complete remission (CR) has been achieved with induction chemotherapy (IC). Decreasing the time from the start of IC to the initiation of PRT may improve prognosis by eradicating MRD at an earlier stage, and preventing the development of resistant leukemic clones. The goal of this study was to retrospectively evaluate the impact of time from the start of IC to PRT, and determine whether or not this affects progression-free survival (PFS) and overall survival (OS). Methods: We retrospectively evaluated adults with newly diagnosed ALL treated at CCF between the years 1996–2005. 116 patients with ALL were seen. 57 patients were newly diagnosed and received IC and PRT. Cox proportional hazards analysis was used to identify univariate and multivariate correlates of CR, OS, relapse after remission, and PFS. Only variables significant in the univariate setting were included in multivariate analysis. Results were summarized as the hazard ratio (HR) with 95% confidence intervals (CI). The following variables were used in the analysis: pre-treatment characteristics (age, WBC, cytogenetic (CG) risk group, LDH), time to WBC recovery (time from the initiation of IC to an ANC of 500 after IC), CD20 expression, and time from the initiation of IC to start of PRT. CG risk was defined by CALGB criteria. Results: Characteristics at diagnosis: median age of 38 years [range 16–72], median LDH 673 U/L [112–5753], and median WBC 17.8 × 103/L [1.2–364]. 33.6% of patients had poor risk CG, 22.4% normal CG, 15% miscellaneous, and 29% unknown. Most patients received a vincristine/prednisone based IC (88%). However, 12% received high dose cytarabine/mitoxantrone IC. The CR rate was 75.3% for patients age < 60, and 60% for age ≥ 60. Median disease-free survival was 20.2% at 5 years. The median time from IC to PRT was 7.0 weeks [4.1–17.0]. On univariate analysis, increased age and increased time to WBC recovery were associated with a lower CR rate. Age and time from IC to PRT (per week increase (PWI)) [HR 1.17(CI 1.04–1.32), p=0.009] were significant predictors for relapse after remission. Increased age, poor risk CG, and time from IC to PRT (PWI) [HR 1.13(1.02–1.25), p=0.024] predicted decreased PFS. All of these factors (including time to WBC recovery) predicted decreased OS, with time from IC to PRT (PWI) having a HR of 1.11[(1.01–1.23), p=0.039]. On multivariate analysis, there was a trend for longer time from IC to PRT (PWI) [HR 1.53(0.92–2.54, p=0.10] predicting decreased OS and increased chance of relapse (PWI) [HR 1.12(0.98–1.29), p=0.09]. When patients age > 60 and poor risk CG were excluded, time from IC to PRT (PWI) was the only factor associated with decreased OS [HR 1.34(1.08–1.67), p=0.009], PFS [HR 1.27(1.04–1.55, p=0.019)], and an increased chance of relapse [HR 1.26(0.99–1.61), p=0.06]. Conclusions: Strategies to improve the prognosis of ALL are needed. Time from IC to PRT is an independent prognostic factor for treatment outcome, and administering PRT on time may improve our outcomes in adult patients with ALL.

Translocation t(4;14) Is Not an Adverse Prognostic Factor in Patients with Multiple Myeloma Undergoing Allogeneic Stem Cell Transplantation.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4743-4743
Author(s):  
Timon Hansen ◽  
Georgia Schilling ◽  
Avichai Shimoni ◽  
Jose-Antonio Simon-Perez ◽  
Wolfgang Bethge ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Complete Remission ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Univariate Analysis ◽  
Prognostic Impact ◽  
Event Free Survival ◽  
Free Survival

Abstract We analyzed the prognostic impact of the most frequent genetic abnormalities detected by fluorescence-in situ-hybridization combined with immunofluorescent cytoplasm immunoglobulin staining (cIg-FISH) in 101 patients with multiple myeloma, who underwent allogeneic stem cell transplantation after reduced melphalan/fludarabine-based conditioning from related (n=34) and unrelated (n=67) donors. The abnormalities were del(13q14) [62%], t(11;14)(q13;q32) [11%], t(4;14)(p16.3;q32) [16%], CMYC-gains (8q24) [17%], del(17p13.1) [16%], t(14;16)(q32;q23) [4%], whereas none of the patients had t(6;14)(p25;q32). Translocation t(4;14), CMYC-gains and del 17p were frequently associated with del(13q14): 64%, 80% and 92%, respectively. The complete remission (CR) rate was 45% for all patients. Patients with del(17p13) achieved fewer complete remission than others (7% vs. 56%; p=0.001), while no difference was seen for t(4;14) and other abnormalities. Univariate analysis revealed higher relapse rates for age > 50 years (p=0.002), del(13q14) (p=0.006) and del(17p13) (p=0.003). Patients with translocation t (4;14) had a similar four year event-free survival than others (50 vs 45%). In a multivariate analysis, only del(13q14) [HR: 2.34, p=0.03] and del(17p13) [HR: 2.24; p=0.04] influenced the risk of relapse, while for event-free survival, only age [HR 2.8; p=0.01] and del(17p13) [HR: 2.05; p=0.03] retained the prognostic value. These data seem to indicate that some adverse cytogenetic risk factors such as t(4;14) can be overcome by allogeneic stem cell transplantation, probably due to the graft versus myeloma effect. Del(17p13.1) is a significant factor for a lower chance of complete remissions and shorter event free survival following allogeneic stem cell transplantation. The presented data will have implications for risk-adapted strategies in the future.

Growth Differentiation Factor 15 Plasma Level in patients with Multiple Myeloma: A Study of Intergroupe Francophone Du Myelome

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2700-2700
Author(s):  
Jill Corre ◽  
Murielle Roussel ◽  
Anne Huynh ◽  
Melanie Gadelorge ◽  
Elodie Labat ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Prognostic Factors ◽  
Significant Relationship ◽  
Human Subjects ◽  
Univariate Analysis ◽  
Response To Treatment ◽  
Event Free Survival ◽  
Disease Evolution ◽  
Free Survival

Abstract We previously reported that bone marrow mesenchymal stem cells (BMMSCs) from 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 and that GDF15 was a growth factor for the MOLP-6 stromal cell-dependant myeloma cell line. GDF15 is a divergent member of the human TGFβ superfamily. In normal human subjects, it is highly expressed in the placenta and its serum concentration increases during pregnancy. GDF15 concentration is increased in the serum of patients with prostate, colorectal or pancreatic cancers. However, GDF15 has never been studied in haematological malignancies. The first objective of this study was to evaluate the relashionship between GDF15 plasma concentration (pGDF15) of 131 MM patients and main prognostic factors of the disease. We found a significant relationship with ISS (p&lt;0.003) and DS stage (p&lt;0.02), b2 microglobulin, haemoglobin, creatinin, calcemia (p&lt;0.001), deletion of chromosome 13 (p&lt;0.004), serum monoclonal protein, bone status (p&lt;0.02), and albumin (p&lt;0.05). The second objective of this study was to appreciate the potential relationship between pGDF15 and survival. We demonstrate such a relationship. Indeed, in the group of 81 patients with high pGDF15, the probabilities of event-free and overall survival 30 months after diagnosis is 50 percent and 75 percent, respectively. In the group of 50 patients with low pGDF15, the probabilities of event-free and overall survival 30 months after diagnosis is 80 percent and 97 percent, respectively (p&lt;0.0045 and p&lt;0.013, respectively). On the opposite, pGDF15 is not related to response to treatment. We analysed impact of known prognostic factors and pGDF15 on event-free survival for all the 131 patients. In univariate analysis, event-free survival was significantly related to age (p=0.003), ISS (p=0.09), b2-microglobulin (p=0.02) and pGDF-15 (p=0.003). In multivariate analysis, event-free survival was significantly related to age (p=0.001) and pGDF15 (p=0.04). In conclusion, our study demonstrates a significant relationship between GDF15 and MM survival. This result strongly suggests the implication of microenvironment in the disease evolution. The exact role of GDF15 in MM physiopathology (directly responsible or simple reflect of an abnormal microenvironment) is still unclear and should be investigated.

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