scholarly journals VTD in comparison with VCD does not affect stem cell yields with G-CSF only mobilization

2020 ◽  
Vol 51 (1) ◽  
pp. 42-46 ◽  
Author(s):  
Matevz Skerget ◽  
Barbara Skopec ◽  
Matjaz Sever
Keyword(s):  
Stem Cell ◽  
Outcome Measures ◽  
Standard Of Care ◽  
National Registry ◽  
Newly Diagnosed ◽  
Treatment Groups ◽  
Cell Counts ◽  
Significant Difference ◽  
The Impact ◽  
Cell Harvest

AbstractTriplet induction regimens are standard of care for newly diagnosed transplant eligible multiple myeloma patients. The combinations of bortezomib and dexamethasone with either cyclophosphamide (VCD) or thalidomide (VTD) are widely used. There are no data available on the impact of the two regimens on stem cell harvest by using G-CSF only mobilization. In this study, we retrospectively analyzed data from our national registry. The outcome measures were mobilization failure, CD34+ cell counts on collection day, number of apheresis procedures, and the number of collected cells. Overall, 72 patients were treated with either VCD or VTD. The mobilization failure rates were 7% and 9% (p = 0.771) and the total number of collected stem cells were 7.0 × 106 and 6.7 × 106 per kg body weight (p = 0.710) for VCD and VTD, respectively. We found no statistically significant difference between the treatment groups in the outcome measures. The addition of thalidomide to bortezomib and dexamethasone (VTD) does not adversely affect stem cell harvest in patients mobilized with G-CSF only.

VELCADE/Dexamethasone (Vel/D) Versus VAD as Induction Treatment Prior to Autologous Stem Cell Transplantion (ASCT) in Newly Diagnosed Multiple Myeloma (MM): Updated Results of the IFM 2005/01 Trial.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 450-450 ◽  
Author(s):  
Jean Luc Harousseau ◽  
Claire Mathiot ◽  
Michel Attal ◽  
Gerald Marit ◽  
Denis Caillot ◽  
...  
Keyword(s):  
Stem Cell ◽  
Phase Ii ◽  
Standard Of Care ◽  
Response Assessment ◽  
Primary Objective ◽  
Induction Treatment ◽  
Fish Analysis ◽  
Newly Diagnosed ◽  
Phase Ii Studies ◽  
The Impact

Abstract Introduction. ASCT is considered the standard of care for younger patients (pts) with MM. The benefit of ASCT is at least partly related to an increase in Complete Remission (CR) plus Very Good Partial Remission (VGPR) rate. One way to increase the CR rate is to improve the induction treatment prior to ASCT. Several phase II studies with Vel in combination as induction treatment yielded promising CR rates. We have previously tested the Vel/D combination with Vel 1.3mg/m2 d1,4,8,11 with 40mg/d d1–4, d 9–12 for 4 consecutive 21d cycles (D only on d1–4 during cycles 3–4) (Harousseau et al Haematologica 2006). Methods. In July 2005, the IFM initiated a randomized Phase II trial comparing Vel/D with VAD as induction treatment prior to ASCT in pts with newly diagnosed MM up to the age of 65.This IFM 2005/01 was closed for accrual in January 2007 after having recruited 482 patients. The primary objective was the CR (negative immunofixation) plus n-CR (negative electrophoresis) after 4 cycles. The second question was to evaluate the impact of a consolidation with 2 cycles of DCEP (D, Cyclophosphamide, Etoposide, Platinum). At diagnosis pts were randomized between 4 arms (A1:4 cycles of VAD, A2: 4 cycles of VAD + 2 cycles of DCEP, A3:4 cycles of Vel/D, A4:4 cycles of Vel/D + 2 cycles of DCEP). Randomization was stratified according to β2-microglobulin and del 13 by FISH analysis. Stem cell collection was performed between cycle 3 and 4 after G-CSF priming (10μg/kg x 6d). ASCT was prepared by melphalan 200mg/m2. Results. As of Aug 2007, data from the first consecutively enrolled 222 pts have been analyzed (A1:54,A2:56,B1:55,B2:57). In the VAD arms (A1+A2),88% of pts received the planned 4 courses versus 94% in the Vel/D arms (B1+B2). In arm A2,87.5% of pts received the 2 cycles of DCEP versus 82% in arm B2. ASCT was performed in 94% of evaluable pts in arms A1+A2 and in 92% in arms B1+B2. The number of SAE was the same in the VAD and the Vel/D arms. The incidence of grade 3–4 averse events was also comparable. However the proportion of pts with neurological symptoms (all grades) during induction treatment was higher with Vel/D (36% versus 11%). Response assessment is available for 208 pts (100 VAD, 108 Vel/D). The results are shown in the table (intent-to-treat analysis). Consolidation with DCEP did not increase the CR rate (16% pre-ASCT both in arms A1+B1 and in arms A2+B2). Conclusion. This analysis not only confirms that the post-induction CR rate is increased by Vel/D compared to VAD (Harousseau ASH 2006) but also shows that this benefit translates in higher CR+VGPR rates after ASCT. Longer follow-up is needed to demonstrate that this better tumor reduction induces longer PFS and OS. Currently 1-year PFS and OS rates are respectively 90% and 95% with VAD, 93% and 97% with Vel/D. Updated results will be presented at the meeting.

Impact of Age on Survival after Intensive Therapy in Newly Diagnosed Multiple Myeloma. The Nordic Myeloma Study Group (NMSG).

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 924-924
Author(s):  
Stig Lenhoff ◽  
Martin Hjorth ◽  
Peter Gimsing ◽  
Jon Magnus Tangen ◽  
Jan Westin
Keyword(s):  
Stem Cell ◽  
Prognostic Factors ◽  
Median Survival ◽  
Intensive Therapy ◽  
Population Based ◽  
Control Group ◽  
Newly Diagnosed ◽  
Significant Difference ◽  
Historic Control ◽  
The Impact

Abstract Introduction: Intensive therapy (IT) including autologous stem cell transplantation (ASCT) is considered superior to conventional therapy in newly diagnosed myeloma pts <60 yrs. For older pts the benefit of IT is less clear. In 1998 the NMSG started a population-based, prospective trial (#7/98) aiming to study the impact of age on event-free survival (EFS) and survival after IT, and to compare survival to a conventionally treated historic control group. Patients: Newly diagnosed symptomatic pts <65 yrs were included into a protocol with four phases; I) VAD x 3–4; II) cyclophosphamide 2g/sqm, G-CSF (filgrastim) and stem cell harvest; III) melphalan 200 mg/sqm, stem cell infusion and G-CSF; IV) interferon maintenance. Double ASCT was optional. From Jan 1998 to June 2000, 452 pts were registered and 414 (92%) of these were included into the IT protocol (=Intensive Therapy Group (ITG)). 294 were <60 yrs (=ITG-60) and 120 were 60–64 yrs (=ITG-65). The historic control group was derived from a previous population-based, randomized NMSG study (#4/90) where melphalan and prednisone +/− interferon was given as initial therapy. Of the 281 pts <65 yrs registered in this trial, 243 (86%) fulfilled the eligibility criteria for IT stated in the #7/98 protocol and constituted the Control Group (CG). 146 were <60 yrs (=CG-60) and 97 were 60–64 years (=CG-65). Results: In the ITG-60, 261 pts (89%) were actually transplanted (80% single ASCT, 18% double ASCT and 2% allogeneic SCT). In the ITG-65, 98 pts (82%) were transplanted (84% single and 16% double ASCT). Median follow-up is 50 months. Major response rate (CR+PR) was 88% in the ITG-60 and 81% in the ITG-65. EFS at 4 yrs for the ITG-60 was 37% and median EFS 36 months, while the corresponding figures for the ITG-65 were 19% and 24 months (P=.005). Survival at 4 yrs for the ITG-60 was 67% and median survival 67 months, while the corresponding figures for the ITG-65 was 50% and 48 months (P=.004). In a multivariate analysis of the entire ITG, two variables were significantly associated with EFS and survival; beta-2-microglobulin at diagnosis and age < or ≥ 60 yrs. The survival in the ITG-60 was prolonged compared to the CG-60 with a risk ratio (RR) of 0.50 (95%CI 0.38–0.67; p<.0001). Survival at 4 yrs was 67% in the ITG-60 and 44% in the CG-60, with a median survival of 67 and 43 months, respectively. The survival advantage persisted (RR 0.57, 95%CI 0.42–0.78; p=.0004) after statistical analysis of prognostic factors and correction for differences between the groups. Also for patients 60–64 yrs old survival was prolonged in the ITG compared to the CG with a RR of 0.65 (95%CI 0.42–0.92; p=.02). Survival at 4 yrs was 50% in the ITG-65 and 40% in the CG-65 with a median survival of 48 and 28 months, respectively. However, after correction for the difference in prognostic factors between the groups there was no significant difference in survival (RR 0.80, 95%CI 0.55–1.16; p=.23). Conclusions: In this population-based study older age was found to have a negative influence on outcome after IT. Our results indicate that there is an upper age limit that remains to be defined for superiority of IT over conventional chemotherapy.

Dexamethasone and Cyclophosphamide: More Convenient and as Effective as VAD before High-Dose Melphalan and Autologous Transplantation in Newly Diagnosed Multiple Myeloma. Results of a Randomized NMSG Trial.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 793-793
Author(s):  
Ulf-Henrik Mellqvist ◽  
Stig Lenhoff ◽  
Martin Hjorth ◽  
Erik Holmberg ◽  
Gunnar Juliusson ◽  
...  
Keyword(s):  
Stem Cell ◽  
Initial Treatment ◽  
Autologous Transplantation ◽  
Group Versus ◽  
Initial Therapy ◽  
High Dose ◽  
Newly Diagnosed ◽  
Significant Difference ◽  
High Dose Melphalan ◽  
Cell Harvest

Abstract Background. High-dose melphalan with autologous stem cell transplantation (ASCT) is established in the first line treatment of myeloma patients. The initial tumour reducing therapy before high-dose treatment is usually VAD, i.e., vincristine and doxorubicin in continuous infusion plus high dose dexamethasone. The anti-myeloma effect of high dose corticosteroids is indisputable but the role of vincristine and doxorubicin is unclear, and never scrutinized in randomized studies. Both of these drugs do have well-known side effects and the administration of VAD is somewhat complicated. Melphalan is very effective in myeloma treatment but not suited for initial treatment because of the stem cell toxicity. However, another alkylating agent like cyclophosphamide is feasible to use before stem cell harvest and has well documented anti-myeloma effect. Trying to simplify initial treatment before ASCT, the Nordic Myeloma Study Group (NMSG) initiated a prospective, randomized multicentre study comparing conventional initial therapy of three 4-week courses of VAD with two 3-week courses of Cy-Dex. Patients and methods. From Nov 2001 to Oct 2003, 315 patients younger than 65 years with symptomatic newly diagnosed myeloma were randomized to receive 3–4 courses of VAD or 2–3 cycles of Cy-Dex (cyclophosphamide 1000mg/sqm and dexamethasone 40mg/d days 1–4 and 9–12). Thereafter, both groups received cyclophosphamide 2g/sqm plus rhG-CSF (filgrastim) sc as mobilization therapy followed by stem cell harvest and subsequent high dose melfalan 200 mg/sqm supported by stem cell infusion. CR was defined as the disappearance of M-protein from serum and urine in agarose gel electrophoresis and &lt; 5 % plasma cells in a bone marrow aspirate. Results. Patients in the Cy-Dex group came quicker to ASCT, 3.2 months versus 4.5 for the VAD group. The study showed no significant difference in the proportion of patients undergoing ASCT, 137/158 pts (87 %) in the Cy-Dex group versus 133/157 pts (85 %) in the VAD group. Neither were there any significant differences in response rate. After the initial therapy there were 54 % major responses (7 % CR and 47 % PR) in the Cy-Dex group versus 55 % (11 % CR and 44 % PR) in the VAD-group. After ASCT the response rates were 76 % (32 % CR and 44 % PR) versus 72 % (34 % CR and 38 % PR) in the Cy-Dex and the VAD group respectively. Also, survival data were identical with a median event free survival time of 29 months and 75 % overall survival at three years, calculated from start of therapy for both groups. Conclusion. This randomized trial indicates that Cy-Dex speeds up and simplifies initial treatment with an efficacy comparable to VAD. Cy-Dex can be recommended as a safe alternative for initial therapy in patients planned to undergo ASCT, and should be further studied in combination with novel agents, such as thalidomide, bortezomib and lenalidomide.

The impact of fibropapillomatosis on clinical characteristics, blood gas, plasma biochemistry, and hematological profiles in juvenile green turtles ( Chelonia mydas)

2020 ◽  
Vol 96 (4) ◽  
pp. 723-734
Author(s):  
Tsung-Hsien Li ◽  
Chao-Chin Chang
Keyword(s):  
White Blood Cells ◽  
Extracellular Fluid ◽  
Chelonia Mydas ◽  
Sea Turtle ◽  
Total Carbon ◽  
Blood Gas ◽  
Green Turtles ◽  
Cell Counts ◽  
Significant Difference ◽  
The Impact

Fibropapillomatosis (FP) is a tumor- forming disease that afflicts all marine turtles and is the most common in green turtles (Chelonia mydas). In this study, the morphometric characteristics, blood gas, biochemistry, and hematological profiles of 28 (6 FP-positive and 22 FP-negative) green turtles from the coast of Taiwan were investigated. The results indicated that body weight ( P < 0.001) and curved carapace length (CCL; P < 0.001) in green turtles with FP were significantly higher than in turtles without FP. Furthermore, green turtles with FP had a significantly lower value of hemoglobin (HB; P = 0.010) and packed cell volume (PCV; P = 0.005) than turtles without FP. Blood cell counts of white blood cells (WBC; P = 0.008) and lymphocytes ( P = 0.022) were observed with significant difference; green turtles with FP had lower counts than turtles without FP. In addition, turtles with FP had significantly higher pH ( P = 0.036), base excess in extracellular fluid (BEecf; P = 0.012), bicarbonate (HCO3– ; P = 0.008), and total carbon dioxide (TCO2 ; P = 0.025) values than turtles without FP. The findings of this study provide valuable clinical parameters for the medical care of the species in sea turtle rehabilitation centers and help us to understand the physiological response of green turtles to different tumor-forming conditions.

Influence of Cisplatin on Wound Healing—An Experimental Model

1986 ◽  
Vol 95 (2) ◽  
pp. 210-212 ◽  
Author(s):  
Charles M. Stiernberg ◽  
R. Mark Williams ◽  
James A. Hokanson
Keyword(s):  
Wound Healing ◽  
Chemotherapeutic Agents ◽  
Optimal Time ◽  
Subcutaneous Injections ◽  
Treatment Groups ◽  
Cell Counts ◽  
Proliferative Stage ◽  
Significant Difference ◽  
Surgical Staples ◽  
Outbred Mice

Recent clinical studies have shown that adjuvant chemotherapy may improve response rates to treatment for advanced head and neck carcinomas. Given preoperatively, some chemotherapeutic agents adversely affect wound heallng. The specific purpose of this study was to evaluate the Influence of cisplatin on wound healing when it is given preoperatively. Forty-four Swiss outbred mice were divided into control and treatment groups. One week before surgery, the treatment group received cisplatin (2 mg/ kg body weight) by subcutaneous injections on 2 consecutive days. Each control animal was given an equal volume of normal saline. A 1.5 cm transverse incision was made in each animal, and wounds were closed with surgical staples. The mean woundbreaking strength was determined for a minimum of 5 treatment and 5 control mice on postoperative days 6, 10, 13, and 16. Serum creatinine, blood cell counts, and changes in weight were also monitored. Results showed wound strength on postoperative day 10 to be significantly reduced in mice treated with cisplatin (P < 0.05). There was no significant difference for wound strength on any other days and all other variables were simllar between both groups. In conclusion, cisplatin has an adverse effect on wound healing, the peak of which probably occurs during the proliferative stage of wound healing. Further studies are needed to determine the optimal time for surgery after preoperative chemotherapy. All new chemotherapeutic agents, particularly those being considered in a preoperative regimen, should be tested in this manner.

Evaluating the benefit of adaptive randomization in the CC-115 arm of the Individualized Screening Trial of Innovative Glioblastoma Therapy (INSIGhT): A phase II randomized Bayesian adaptive platform trial in newly diagnosed MGMT unmethylated glioblastoma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 2006-2006
Author(s):  
Rifaquat Rahman ◽  
Lorenzo Trippa ◽  
Geoffrey Fell ◽  
Eudocia Quant Lee ◽  
Isabel Arrillaga-Romany ◽  
...  
Keyword(s):  
Mammalian Target Of Rapamycin ◽  
Progression Free Survival ◽  
Newly Diagnosed ◽  
Adaptive Randomization ◽  
Number Of Patients ◽  
Significant Difference ◽  
Enrollment Rates ◽  
Dependent Protein ◽  
The Impact ◽  
Screening Trial

2006 Background: Adaptive randomization adjusts enrollment rates based upon early trial results, which can allow for decreased enrollment for therapies less likely to meet the primary endpoint of a trial. CC-115, a CNS-penetrant, oral inhibitor of mammalian target of rapamycin kinase (mTOR) and deoxyribonucleic acid-dependent protein kinase (DNA-PK), was evaluated in the Individualized Screening Trial of Innovative Glioblastoma Therapy (INSIGhT) trial. As CC-115 was discontinued due to concerns about toxicity and unfavorable risk-to-benefit ratio, we sought to investigate the impact of adaptive randomization in its testing. Methods: In INSIGhT, adults with newly diagnosed MGMT-unmethylated glioblastoma and available genomic data are adaptively randomized to an experimental arm or the control arm of standard radiotherapy with concurrent and adjuvant temozolomide. Patients randomized to CC-115 received it (10mg po BID) with radiotherapy and as adjuvant monotherapy, and a safety lead-in 3+3 design was used for this arm. By simulating the INSIGhT trial with standard uniform randomization, we estimated the reduction of enrollment rate and sample size of the CC-115 arm that was attributable to adaptive randomization. Results: Twelve patients were randomized to CC-115; 58% (n = 7) patients had possible treatment-related CTCAE grade > 3 toxicity. Compared to the control arm, there was no significant difference in progression-free survival (PFS, HR 0.66, 95% CI 0.32-1.36, p = 0.3) or overall survival (OS, HR 0.93, 95% CI 0.43-2.03, p = 0.8). Based on early PFS results, randomization probability to CC-115 decreased from 25% to 16%. At the time of the CC-115 arm closure, 14% of enrolled INSIGhT patients had been randomized to this arm. Compared to average expected enrollment by standard randomization, the use of adaptive randomization decreased the number of patients randomized to CC-115 by 50% (12 patients vs. 18 patients [95% CI 11-25 patients]). Conclusions: The INSIGhT trial, designed with adaptive randomization, facilitated more efficient testing of CC-115 and decreased the number of patients allocated to the CC-115 arm relative to a standard randomization design. Clinical trial information: NCT02977780.

NIMG-13. RESPONSE ASSESSMENT IN GLIOBLASTOMA PATIENTS TREATED WITH DENDRITIC CELL-BASED IMMUNOTHERAPY: A COMPARATIVE ANALYSIS OF MACDONALD, RANO, MRANO, IRANO AND VOLUMETRIC MEASUREMENTS

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi130-vi130
Author(s):  
Johanna Heugenhauser ◽  
Malik Galijasevic ◽  
Stephanie Mangesius ◽  
Johanna Buchroithner ◽  
Friedrich Erhart ◽  
...  
Keyword(s):  
Dendritic Cell ◽  
Progression Free Survival ◽  
Response Assessment ◽  
Assessment Tools ◽  
Assessment Criteria ◽  
Newly Diagnosed ◽  
Significant Difference ◽  
Different Response ◽  
The Impact ◽  
Spearman Test

Abstract INTRODUCTION Response assessment in the treatment of glioblastoma (GB) based on MR-imaging is still challenging, in particular for immunotherapeutic strategies. Several assessment tools have been proposed. In this post-hoc analysis we compared response assessment criteria (MacDonald, RANO, mRANO, Vol.-mRANO, iRANO) in newly diagnosed GB patients treated with tumor lysate-charged autologous dendritic cells (Audencel) and determined the differences in prediction of progression free survival (PFS) and overall survival (OS). METHODS 76 patients with newly diagnosed GB enrolled in a multicenter randomized phase II trial receiving standard of care (SOC, n= 40) or SOC + Audencel vaccine (n= 36) were included. Tumor volumes were calculated by semiautomatic segmentation. To detect differences in PFS among the assessment criteria Kruskal-Wallis-test, for correlation analysis Spearman test was used. RESULTS There was a significant difference in median PFS based on the different assessments (mRANO 8.55 months [9.10-14.03], Vol.-mRANO 8.61 months [9.72-14.92] compared to MacDonald 4.04 months [5.21-8.75] and RANO 4.16 months [5.28-8.61]. For the vaccination arm only, median PFS by iRANO was 5.95 months [5.70-11.54]). There was no difference in PFS between SOC and SOC + Audencel using the different response criteria. The best correlation between PFS and OS was detected for mRANO (r= 0.65, p&lt; 0.001) and Vol.-mRANO (r= 0.69, p&lt; 0.001). At an 8-month landmark, the impact of progressive disease on median OS was best shown for mRANO (13.70 months [13.13-18.98], and Vol.-mRANO 12.03 months [12.51-17.94]) compared to MacDonald 17.97 months [15.45-20.92], RANO 17.97 months [15.92-20.95] and iRANO 17.34 months [14.99-22.73]. CONCLUSION When comparing different response assessments in GB patients treated with dendritic cell-based immunotherapy the best correlation between PFS and OS was observed for mRANO and Vol.-mRANO. Overall, no difference in PFS and OS was seen between the two treatment arms. iRANO was not superior for predicting OS in patients treated with Audencel.

scholarly journals The impact of passive immunisation against BMPRIB and BMP4 on follicle development and ovulation in mice

Reproduction ◽  
2015 ◽  
Vol 149 (5) ◽  
pp. 403-411 ◽  
Author(s):  
S Al-Samerria ◽  
I Al-Ali ◽  
J R McFarlane ◽  
G Almahbobi
Keyword(s):  
Bone Morphogenetic Proteins ◽  
Primordial Follicle ◽  
Female Fertility ◽  
Passive Immunisation ◽  
Primordial Follicles ◽  
Treatment Groups ◽  
Significant Difference ◽  
Bmp Signalling ◽  
The Impact

The primordial follicle reserve is the corner stone of female fertility and determines the longevity and quality of reproduction. Complete depletion of this reserve will lead to primary infertility, and the key-limiting step of follicle depletion is the transition from primordial to primary follicles. It has been reported that this process is gonadotrophin-independent, but other conflicting reports are indicated otherwise and this discrepancy needs to be unequivocally clarified. The aim of this study was to investigate the role of bone morphogenetic proteins (BMPs) in the regulation of folliculogenesis in mice passively immunised against BMP receptor 1B (BMPRIB) and BMP4. While a stereological study revealed that the numbers of primordial follicles in immunised mice were significantly higher when compared with control animals, treatment with equine chorionic gonadotrophin showed no effect. In parallel, immunofluorescence microscopy revealed the presence of BMPRIB but not FSH receptor in primordial follicles. The number of primary follicles in immunised mice were also significantly increased when compared with control animals. After puberty, the rates of depletion of primordial and primary follicles were increased with age, particularly in treated animals; however, there was no significant difference between the treatment groups of the same age. Based on these results together with our previous reports in sheep and mice, we confirm that the attenuation of BMP signalling system can be an effective approach to sustain the primordial follicle reserve while promoting the development of growing follicles, ovulation and consequently overall female fertility.

scholarly journals Changes in Bone Marrow Fat upon Dietary-Induced Weight Loss

Nutrients ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1509
Author(s):  
Manuela Spurny ◽  
Yixin Jiang ◽  
Solomon A. Sowah ◽  
Ruth Schübel ◽  
Tobias Nonnenmacher ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Weight Loss ◽  
Study Cohort ◽  
Marrow Fat ◽  
Bone Marrow Fat ◽  
Randomized Controlled ◽  
Cell Counts ◽  
Significant Difference ◽  
Metabolic Biomarkers ◽  
The Impact

Background: Bone marrow fat is implicated in metabolism, bone health and haematological diseases. Thus, this study aims to analyse the impact of moderate weight loss on bone marrow fat content (BMFC) in obese, healthy individuals. Methods: Data of the HELENA-Trial (Healthy nutrition and energy restriction as cancer prevention strategies: a randomized controlled intervention trial), a randomized controlled trial (RCT) among 137 non-smoking, overweight or obese participants, were analysed to quantify the Magnetic Resonance Imaging (MRI)-derived BMFC at baseline, after a 12-week dietary intervention phase, and after a 50-week follow-up. The study cohort was classified into quartiles based on changes in body weight between baseline and week 12. Changes in BMFC in respect of weight loss were analysed by linear mixed models. Spearman’s coefficients were used to assess correlations between anthropometric parameters, blood biochemical markers, blood cells and BMFC. Results: Relative changes in BMFC from baseline to week 12 were 0.0 ± 0.2%, −3.2 ± 0.1%, −6.1 ± 0.2% and −11.5 ± 0.6% for Q1 to Q4. Across all four quartiles and for the two-group comparison, Q1 versus Q4, there was a significant difference (p < 0.05) for changes in BMFC. BMFC was not associated with blood cell counts and showed only weaker correlations (<0.3) with metabolic biomarkers. Conclusion: Weight loss is associated with a decrease of BMFC. However, BMFC showed no stronger associations with inflammatory and metabolic biomarkers.

Phase II Trial of Combination Therapy With Bortezomib, Pegylated Liposomal Doxorubicin, and Dexamethasone in Patients With Newly Diagnosed Myeloma

2009 ◽  
Vol 27 (30) ◽  
pp. 5015-5022 ◽  
Author(s):  
Andrzej J. Jakubowiak ◽  
Tara Kendall ◽  
Ammar Al-Zoubi ◽  
Yasser Khaled ◽  
Shin Mineishi ◽  
...  
Keyword(s):  
Stem Cell ◽  
Phase Ii ◽  
Initial Treatment ◽  
Liposomal Doxorubicin ◽  
Phase Ii Trial ◽  
Pegylated Liposomal Doxorubicin ◽  
Combination Regimen ◽  
Newly Diagnosed ◽  
Painful Neuropathy ◽  
The Impact

PurposeThis single-center, open-label, phase II trial evaluated the bortezomib, pegylated liposomal doxorubicin (PLD), and dexamethasone combination regimen (VDD) as initial treatment for patients with newly diagnosed multiple myeloma (MM).Patients and MethodsEnrolled patients (N = 40) received up to six 3-week cycles of treatment with bortezomib 1.3 mg/m2intravenously (IV) on days 1, 4, 8, and 11; PLD 30 mg/m2IV on day 4; and dexamethasone 20 to 40 mg daily as specified in the study design. The primary end point was the complete/near-complete response (CR/nCR) rate after six cycles. Secondary end points included overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). The impact of VDD on stem-cell mobilization and collection also was evaluated.ResultsAfter six cycles, the ORR was 85.0% (CR/nCR, 37.5%; very good partial response [VGPR] or better, 57.5%). Patients who underwent stem-cell transplantation (SCT) after VDD (n = 30) experienced increased rates of VGPR or better (53.3% to 76.6% after SCT). Overall, 1-year PFS and OS rates were 92.5% and 97.5%, respectively. Those who achieved VGPR or better after treatment with VDD showed a significantly greater 1-year PFS versus those who achieved less than VGPR (100% v 82%, respectively; P = .03). Similar results were observed in patients who underwent SCT. Grades 3 or 4 hematologic toxicities occurred in ≤ 10% of patients; grade 2 painful neuropathy occurred in 7.5%; and grade 3 palmar-plantar erythrodysesthesia occurred in 2.5%.ConclusionVDD is highly effective for initial treatment of MM followed by SCT in appropriate patients, and it has a reasonable safety profile. Achievement of VGPR or better with this initial therapy predicted longer PFS, regardless of the consolidation therapy given.

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