scholarly journals Clinical Application of Autologous Adipose Stem Cells in Patients with Multiple Sclerosis: Preliminary Results

2016 ◽  
Vol 2016 ◽  
pp. 1-5 ◽  
Author(s):  
Adam Stepien ◽  
Natalia L. Dabrowska ◽  
Marzena Maciagowska ◽  
Renata Piusinska Macoch ◽  
Aleksandra Zolocinska ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Disease Progression ◽  
Progression Free Survival ◽  
Entire Group ◽  
Adipose Stem Cell ◽  
Free Survival ◽  
Inflammatory Phase ◽  
Efficacy Measures ◽  
One Year

The clinical outcome of autologous adipose stem cell (ASC) treatment of patients with multiple sclerosis (MS) was investigated following one year of observation.Methods. The clinical and MRI outcomes of 16 ASC-treated patients with RRMS and SPMS are reported after a one-year follow-up period.Results.At 18 months of follow-up, some patients showed “enticing” improvements on some exploratory efficacy measures, although a significant benefit was not observed for any measure across the entire group. Neither the progression of disability nor relapses were observed in any cases. In four patients, we found new gadolinium+ (Gd+) lesions on MRI. Our results indicate that ASC therapy is safe and does not produce any substantial side effects. Disease progression-free survival (PFS) of 18 months was seen in all patients with RRMS and SPMS. In these patients, EDSS scores did not progress above baseline scores. Gd-enhancing lesions were observed in two cases with RRMS, but these patients did not exhibit changes in EDSS score.Conclusion. Intrathecal treatment with ASCs is an attractive form of therapy for patients with MS but should be reserved for cases with aggressive disease progression, for cases that are still in the inflammatory phase, and for the malignant form.

scholarly journals One-Year Progression-Free Survival of Therapy-Naive Patients With Malignant Pheochromocytoma and Paraganglioma

2013 ◽  
Vol 98 (10) ◽  
pp. 4006-4012 ◽  
Author(s):  
Ségolène Hescot ◽  
Sophie Leboulleux ◽  
Laurence Amar ◽  
Delphine Vezzosi ◽  
Isabelle Borget ◽  
...  
Keyword(s):  
Evaluation Criteria ◽  
Progression Free Survival ◽  
Malignant Pheochromocytoma ◽  
Inherited Disease ◽  
High Power Field ◽  
Free Survival ◽  
History Of ◽  
Wait And See ◽  
One Year

Abstract Context: The natural history of malignant pheochromocytoma or paragangliomas (MPP) remain unknown. Objective: The primary aim of this study was to define progression-free survival at 1 year in therapy-naive patients with MPP. Secondary objectives were to characterize MPP and to look for prognostic parameters for progression at 1 year. Design and Setting: The files of MPP followed up between January 2001 and January 2011 in two French Endocrine Networks were retrospectively reviewed. Therapy-naive patients were enrolled. Main Outcome Measures: The main outcome was progression-free survival at 1 year in therapy-naive MPP patients according to Response Evaluation Criteria In Solid Tumors 1.1 criteria. Results: Ninety files (46 men, 44 women, mean age of 47.5 ± 15 years) were reviewed on site by one investigator. MPP characteristics were as follows: presence of an adrenal primary, a mitotic count exceeding 5 per high power field, hypertension, inherited disease, and presence of bone metastases in 50%, 22%, 60%, 49%, and 56% patients, respectively. Fifty-seven of the 90 patients with MPP (63%) were classified as therapy-naive. The median follow-up of these 57 patients was 2.4 years (range, 0.4–5.7). At 1 year, progression-free survival was 46% (CI 95: 33–59). Twenty-six of 30 (87%) patients with progression at 1 year had exhibited progressive disease at the first imaging workup performed after a median of 5.7 months. No prognostic parameter was identified. Conclusions: Half of the therapy-naive patients with MPP achieved stable disease at 1 year. In symptom-free patients with MPP, a wait-and-see antitumor policy seems appropriate as first line. Modality for a prospective follow-up is proposed.

Outcomes Following Syngeneic Hematopoietic Stem Cell Transplantation for Multiple Myeloma: A Matched Comparison to Autologous Transplantation.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 50-50 ◽  
Author(s):  
Asad Bashey ◽  
Waleska S. Perez ◽  
Mei-Jie Zhang ◽  
David H. Vesole ◽  
Donna E. Reece ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Treatment Failure ◽  
Disease Progression ◽  
Propensity Scores ◽  
Progression Free Survival ◽  
Free Graft ◽  
Free Survival ◽  
Autologous Hct

Abstract Relapse is the main cause of treatment failure following autologous hematopoietic cell transplantation (HCT) for multiple myeloma (MM). Syngeneic HCT offers the advantage of a myeloma-free-graft. However, a potential disadvantage is the lack of a graft versus myeloma effect (GVM). We compared the probabilities of treatment-related mortality (TRM), disease progression, progression-free survival (PFS) and overall survival (OS) after syngeneic versus autologous HCT for MM done between 1988 and 2003. Median follow up was >70 months in both groups. 43 syngeneic HCT recipients were matched to 170 autologous HCT recipients using a propensity score. A numerical propensity score for each syngeneic HCT recipient was calculated using the variables of age, Durie-Salmon stage at diagnosis, sensitivity to pretransplant therapy, time from diagnosis to HCT and year of HCT. Propensity scores ranged from 0.004–0.286. Syngeneic HCT recipients (cases) were matched in random order to autologous transplant (control) recipients with similar propensity scores. Patients who underwent tandem transplants were excluded. Median age (range) was 53 and 52 years in cases and controls. Most patients in both groups (60% of cases, 64% of controls) were transplanted within 12 months of diagnosis. Except for a higher proportion of patients with IgG myeloma (59% vs. 39%, p<0.01) and PBSC grafts (92% vs. 51%, p<0.01) in the control group there were no statistically significant differences in baseline characteristics of the two groups. 5-year outcomes are summarized in the table. 5-year outcome, probability (95% CI) Syngeneic Autologous Treatment-related mortatlity 14 (5–26) 10 (6–15) Disease progression 42 (26–58) 71 (64–78) Progression-free survival 44 (28–60) 19 (13–26) Overall survival 59 (43–74) 40 (32–48) Medican follow up survivors, months 71 (23–161) 85 (3–145) In multivariate analysis, risks of progression and treatment failure were significantly lower after syngeneic than autologous HCT [disease progression RR= 0.43 (95%CI, 0.23–0.78, p=0.004); treatment failure RR= 0.59 (95%CI 0.35–0.98, p=0.04)]. TRM at 1 year was 14% (5–26) in the syngeneic group and 9% (5–13%) in controls (p=0.33). The 5-year risk of mortality was lower in the syngeneic group but the difference was not statistically significant (RR= 0.61, 95%CI 0.36–1.05, p=0.07). Disease recurrence accounted for 79% of deaths in the autologous and 47% in the syngeneic cohort. We conclude that syngeneic HCT for MM results in superior PFS and lower progression rates compared to autologous HCT, confirming previous smaller analyses and emphasizing the importance of a disease-free graft. Interestingly, these data suggest that relapse rates similar to those observed after nonmyeloablative allogeneic transplantation – another source of tumor free grafts – can occur in the absence of clinical graft versus host disease.

Bortezomib, Thalidomide, and Dexamethasone as Induction Therapy for Patients with Symptomatic Multiple Myeloma.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3605-3605 ◽  
Author(s):  
Jonathan L. Kaufman ◽  
Charise Gleason ◽  
Leonard Heffner ◽  
Sagar Lonial
Keyword(s):  
Induction Therapy ◽  
Progressive Disease ◽  
Response Rate ◽  
Progression Free Survival ◽  
High Response Rate ◽  
High Dose ◽  
High Dose Therapy ◽  
Free Survival ◽  
One Year

Abstract The optimal induction regimen for patients with symptomatic myeloma who are eligible for transplantation is currently unknown. While thalidomide and dexamethasone is an effective regimen, it only has a 60 to 65% response rate and few complete responses (CR). Bortezomib based inductions have demonstrated a high response rate and an improved CR as well. Recently the IFM reported the initial results of the randomized bortezomib plus dexamethasone versus VAD induction followed by transplant, which demonstrated that fewer patients treated with bortezomib required tandem transplants. Wang et al reported a high induction response rate with the combination of BTD for only 2 cycles given over a 28 day cycle. Here we report our experience with the combination of BTD as induction therapy. 38 patients with symptomatic myeloma were treated with BTD as induction therapy. Patients received standard dose and schedule bortezomib at 1.3 mg/m2 on days 1, 4, 8, and 11 with thalidomide at 100 mg/day, and 8 days of 40 mg dexamethasone every 21 days. The median age was 58 years (38–70) with 19 males. This was first line therapy for 29 patients, second line for 7 patients and 3rd line for 2. 12 patients had ISS stage 2 and 8 had ISS stage 3. The median β2M was 3.4 (1.66–41.89). Median creatinine was 1.1 (0.6–21.0). Nineteen patients had an IgG paraprotein, 6 an IgA, and 16 patients had light chain disease. The median number of cycles administered was 4 (2–8). Fifteen patients developed neuropathy of any grade. One patient developed grade 3 neuropathy. The overall response rate (CR, VGPR, plus PR) was 92%, with 58% of patients achieving a VGPR or better, and 21% of patients achieving an immunofixation negative CR. 1 patient had a minimal response and 2 patients had progressive disease (both patients presented with plasma cell leukemia). These two patients were treated with the combination of BTD with PACE chemotherapy. One of the two died from progressive disease and the other patient remains in complete remission after high dose therapy and autologous transplantation. 29 patients had consolidation therapy with high dose melphalan and autologous peripheral blood stem cell transplantation. Eight patients have collected stem cells without proceeding with immediate consolidation therapy. After a median follow up of 373 days, median progression free survival and overall survival have not been reached. One year overall survival is 97%. One year progression free survival is 87%. In conclusion, we report a very high response rate with a short course of bortezomib, thalidomide and dexamethasone with an acceptable toxicity profile. Follow up of patients in CR treated without high dose therapy and autologous transplant is in progress. Further studies of this active regimen are warranted.

Advanced Non Small Cell Lung Cancer Patients with Fewer Numbers of Blood Myeloid Dendritic Cells and CD4 Cells Prior to Treatment Have Inferior Progression-Free Survival: Implications for Cancer Immunotherapy

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4837-4837
Author(s):  
Nutan J. DeJoubner ◽  
Qunna Li ◽  
Wayne A.C. Harris ◽  
Zhibo Wang ◽  
Yuan Liu ◽  
...  
Keyword(s):  
Disease Progression ◽  
Progenitor Cells ◽  
Immune Cells ◽  
Advanced Nsclc ◽  
Progression Free Survival ◽  
Study Entry ◽  
Free Survival ◽  
Neutrophil Lymphocyte Ratio ◽  
Lymphocyte Ratio

Abstract Abstract 4837 Background: The tumor microenvironment includes tumor cells, and host-derived endothelial cells, fibroblasts, innate and adaptive immune cells. Tumors may induce neo-vascularization that supports local tumor growth or immune suppression and tolerance that facilitates tumor metastasis. We hypothesized that the patients with higher numbers of circulating CD34+ endothelial progenitor cells (CD34+/CD146+/CD45-, CEC), a cellular bio-marker for vasculogenesis, would have worse post-treatment outcomes and patients with more hematopoietic progenitor cells (CD34+/CD45+/CD45dim/CD133+, HPC) and Immune cells including T-cells would have better outcomes. Methods: We analyzed blood samples from sixty-two patients with advanced NSCLC at 3 time points: before chemotherapy, after cycle one, and at completion of treatment or progression of disease, in an IRB-approved protocol. CEC, HPC, and immune subsets were measured by high throughput multi-parameter flow cytometry, 2.5,000,000 events were acquired using a lyse, no-wash method optimized for rare event detection. Primary outcomes were progression free survival(PFS) and Overall Survival(OS) from the time of study entry. The patient population was stratified into groups based on optimum cut-off point for each cell subset of interest. Statistical analysis was done with log-rank test and Cox regression. Results: Mean age at diagnosis was 64 (37–87 years), 30 events (death) occurred with median follow-up of 9.3 months. Forty-six patients (74%) had disease progression with a median follow-up of 4.7 months. At baseline lower numbers of WBC, Neutrophil lymphocyte ratio(NLR), CEC, HPC were associated with better PFS, while only WBC and Neutrophil lymphocyte ratio (NLR) were associated with a favorable OS. While lower numbers of Immune cells were associated with worse PFS and OS (increased HR death or relapse) in univariate analysis as noted in the Table. Only covariates that were significant and non collinear were entered in the Multivariable model adjusted for age, gender, smoking, race, TNM stage, pathology, and performance status at diagnosis. This showed that baseline numbers of CD4+ T-cell (HR 0.46; 95% CI 0.33–0.98; p= 0.045), Myeloid DC (HR 0.38; 95% CI 0.39–0.81; p=0.012), HPC (continuous variable) (HR 0.78; 95% CI 0.64–0.93; p= 0.008) were significant for disease progression, while NLR was significant for death after study entry (Figure; HR 3; 95% CI 1.45–6.25; p=0 0.003). Conclusions: In patients with advanced NSCLC, lower numbers of HPC and NLR were associated with improved PFS and OS respectively. Lower numbers of immune subsets at diagnosis were associated with inferior outcomes to treatment, supporting the role for immune-mediated disease control. Disclosures: No relevant conflicts of interest to declare.

Clinical outcome of patients with metastatic renal cell carcinoma who interrupted VEGFR-TKI after achieving stable disease or better response.

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 459-459
Author(s):  
Dong Hoe Koo ◽  
Inkeun Park ◽  
Jae-Lyun Lee ◽  
Jin-Hee Ahn ◽  
Dae Ho Lee ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Clinical Outcome ◽  
Cell Carcinoma ◽  
Disease Progression ◽  
Metastatic Renal Cell Carcinoma ◽  
Stable Disease ◽  
Renal Cell ◽  
Progression Free Survival ◽  
Free Survival

459 Background: The purpose of the this study is to evaluate the clinical outcome of VEGFR-TKIs interruption in patients with metastatic renal cell carcinoma (mRCC) after achieving stable disease (SD) or better response. Methods: A retrospective analysis of medical records and imaging studies was performed on all patients with mRCC treated with VEGFR-TKIs between January 2008 and July 2014 (n=505). Patients who achieved SD or better response under VEGFR-TKI and later discontinued VEGFR-TKIs for any reason with the exception of disease progression were included in the analysis. Outcomes analyzed were progression free survival (PFS) after VEGFR-TKIs discontinuation, patterns of disease progression, time to subsequent therapy (TST), response to VEGFR-TKI resumption, and time to treatment failure (TTF) after TKI resumption. Results: We identified 32 patients (sunitinib=20, sorafenib=7, and pazopanib=5). The responses to VEGFR-TKIs were CR (n=4), PR (n=11), SD (n=15), and controlled but non-measurable (n=2). Median time to interruption from the initiation of VEGFR-TKI therapy was 16.6 months (95% CI, 12.8-20.3). The main causes of VEGFR-TKI interruption was toxicity (n=19, 59.4%), will to have treatment holiday (n=7, 21.8%), patient’s refusal (n=3, 9.4%), and others (n=3, 9.4%). At the time of analysis, 16 patients had disease progression and 1 patient was dead. With a median follow-up duration of 56.6 months (range, 12.6-167.4), median PFS from VEGFR-TKI interruption was 23.8 months (95% CI, 12.5-35.0), and the median TST was 26.2 months (95% CI, 15.9-36.6). The progression was observed in pre-existing lesions in 7 patients (43.7%) or new lesions developed in 9 (56.3%). Among 11 patients who received VEGFR-TKI resumption, 2 patients (18.2%) achieved a PR and the stable disease was observed in 9 (81.8%) with a median TTF of VEGFR-TKI resumption of 6.2 months (95% CI, 4.0-8.4). Conclusions: In patients with mRCC controlled with VEGFR-TKIs, VEGFR-TKI could be interrupted at least temporarily when clinically warranted.

Long-Term Results of the HD2000 Trial Comparing ABVD Versus BEACOPP Versus COPP-EBV-CAD in Untreated Patients With Advanced Hodgkin Lymphoma: A Study by Fondazione Italiana Linfomi

2016 ◽  
Vol 34 (11) ◽  
pp. 1175-1181 ◽  
Author(s):  
Francesco Merli ◽  
Stefano Luminari ◽  
Paolo G. Gobbi ◽  
Nicola Cascavilla ◽  
Caterina Mammi ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Cumulative Risk ◽  
Progression Free Survival ◽  
Long Term Results ◽  
Entire Group ◽  
Second Malignancies ◽  
Free Survival ◽  
Post Hoc

Purpose The randomized HD2000 trial compared six cycles of ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine), four escalated plus two standard cycles of BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone), and six cycles of COPP-EBV-CAD (cyclophosphamide, lomustine, vindesine, melphalan, prednisone, epidoxorubicin, vincristine, procarbazine, vinblastine, and bleomycin; CEC) in patients with advanced-stage Hodgkin lymphoma. After a median follow-up of 42 months, patients who received BEACOPP were reported to have experienced better progression-free survival (PFS) but not better overall survival (OS) results than those receiving ABVD. We here report a post hoc analysis of this trial after a median follow-up of 10 years. Patients and Methods Three hundred seven patients were enrolled, 295 of whom were evaluable. At the time of our analysis, the median follow-up for the entire group was 120 months (range, 4 to 169 months). Results The 10-year PFS results for the ABVD, BEACOPP, and CEC arms were 69%, 75%, and 76%, respectively; corresponding OS results were 85%, 84%, and 86%. Overall, 13 second malignancies were reported: one in the ABVD arm and six each in the BEACOPP and CEC arms. The cumulative risk of developing second malignancies at 10 years was 0.9%, 6.6%, and 6% with ABVD, BEACOPP, and CEC, respectively; the risk with either BEACOPP or CEC was significantly higher than that reported with ABVD (P = .027 and .02, respectively). Conclusion With these mature results, we confirm that patients with advanced Hodgkin lymphoma have similar OS results when treated with ABVD, BEACOPP, or CEC. However, with longer follow-up, we were not able to confirm the superiority of BEACOPP over ABVD in terms of PFS, mainly because of higher mortality rates resulting from second malignancies observed after treatment with BEACOPP and CEC.

scholarly journals Combined Treatment of Bortezomib, Continuous Low-Dose Cyclophosphamide and Dexamethasone Followed By One Year of Maintenance Treatment for Refractory or Relapsed Multiple Myeloma Patients: A Prospective Phase II Study

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4733-4733
Author(s):  
Esther GM Waal de ◽  
Linda Munck de ◽  
Gerhard Woolthuis ◽  
Annet velden Van Der ◽  
Yvonne Tromp ◽  
...  
Keyword(s):  
Overall Survival ◽  
Maintenance Therapy ◽  
Research Funding ◽  
Low Dose ◽  
Progression Free Survival ◽  
Free Survival ◽  
First Relapse ◽  
Grade 3 ◽  
One Year

Abstract Introduction: Combination therapy for longer periods but at low dose, also called metronomic scheduling, might be an effective manner to treat patients with relapsing myeloma. In particular if the used agents attack the malignant clone in an alternative manner. Therefore we used the combination of bortezomib, dexametasone and daily low dose of oral cyclophosphamide as an induction regimen followed by one year of maintenance therapy consisting of bortezomib and cyclophosphamide. Methods: Relapsing myeloma patients, bortezomib naïve, were treated with three cycles of 1.3 mg/m2 bortezomib at day 1, 4, 8 and 11, cyclophosphamide 50 mg daily, and 20 mg dexamethasone at day 1, 2, 4, 5, 8, 9, 11 and 12 followed by three cycles of bortezomib 1.6 mg/m2 (day 1, 8, 15 and 2), cyclophosphamide (50 mg) daily and dexamethasone (20 mg) at day 1, 2, 8, 9, 15, 16, 22 and 23. Maintenance therapy consisting of bortezomib 1.3 mg/m2 every two weeks and daily dose of 50 mg cyclophosphamide for one year was applied to patients in partial or complete remission. Primary endpoints were toxicity during re-induction and maintenance therapy. Secondary endpoints were response to treatment and progression free and overall survival. Results: 59 patients with relapsing multiple myeloma were included of whom 69% were in first relapse (Table 1). The upfront treatment consisted mainly of thalidomide-based and vincristine-based chemotherapy and 40% of the patients have been treated with an autologous stem cell transplantation. All 6 cycles of induction chemotherapy could be given in 49% of the patients. Premature discontinuation before starting maintenance therapy was due to toxicity (31%), progressive disease (7%), death (7%) or other reasons (6%). Myelosuppression was the most common side effect with WHO grade 3-4 in 31% of the patients. Neuropathy grade 3-4 was observed in 16% of patients, partially due to the fact that bortezomib was given intravenously during the first 2 yrs of the protocol which included 76% of the patients. Maintenance therapy was started in 47% of the patients with a median duration of 7.3 months (range 0.36.-13.4). Grade 3-4 toxicity was observed in 25% of the patients including infections (n=3) and myelosuppression (n=3) which did not resulted in discontinuation of therapy. Median follow up time was 29 months with an overall response of 62%, and a very good partial response (VGPR), complete remission (CR) in 21% and 7% of the patients respectively. During the maintenance phase an improvement in responsiveness was observed in 25% of the patients. The CR rate increased with 9% to a total of 16%. VGPR rate was 20% and 16% of the patient had a PR. At end of the maintenance therapy 50% of patients started with maintenance had stable disease. The median progression free survival (PFS) was 17.2 months (range 0.13 – 43.5) as depicted in figure 1. and the median overall survival was 21.6 months (range 0.46-54.4, figure 2). During follow up 33 % of the patients died due to progression of MM. Conclusion: The present study demonstrates that combination therapy with bortezomib, continuous low dose cyclophosphamide and dexamethasone is an effective and manageable regimen. Adding a year of maintenance was feasible with limited side effects and an increase in CR rate. Table 1: patient characteristics Patients (%) Age, mean (min,max) 69 (46-86) Sex Male 56 Female 44 Relapse number First relapse 75 Second relapse 20 Third relapse 5 Performance status 0 65 1 29 2 5 M-protein heavy chain IgA 18 IgG 65 Light chain disease 18 Polyneuropathy No 61 Yes 39 Figure 1: Progression free survival Figure 1:. Progression free survival Figure 2: Overall survival Figure 2:. Overall survival Disclosures Waal de: Jansen Cilag: Research Funding. Munck de:Jansen Cilag: Research Funding. Woolthuis:Jansen Cilag: Research Funding. velden Van Der:Jansen Cilag: Research Funding. Tromp:Jansen Cilag: Research Funding. Hoogendoorn:Jansen Cilag: Research Funding. Vellenga:Jansen Cilag: Research Funding. Hovenga:Jansen Cilag: Research Funding.

Velcade®, Thalidomide, Dexamethasone (VTD) Induction Therapy Followed by Melphalan, Prednisone, Thalidomide (MPT) Maintenance as a First Line Treatment for the Patients (pts) with Multiple Myeloma (MM) Who Are Non-Transplant Candidates: Early Analysis from the Korean Multiple Myeloma Working Party.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4831-4831
Author(s):  
HyeonSeok Eom ◽  
Yeo-Kyeoung Kim ◽  
Jooseop Chung ◽  
Kihyun Kim ◽  
HyoJeong Kim ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Disease Progression ◽  
Working Party ◽  
Progression Free Survival ◽  
Response Rates ◽  
Severe Adverse Reaction ◽  
Free Survival ◽  
Transplant Candidates ◽  
Grade 3

Abstract VTD and MPT chemotherapies have been known to be active regimens in pts with MM. The objective of this study is to examine response and toxicities and to estimate survival of pts with VTD followed by MPT, who are non-transplant candidates with previously untreated MM. Total of 29 pts were enrolled from March, 2006 through August, 2007 and this study is still ongoing. 13 pts were men and 16 pts were women. The median age was 67 years (range, 61–75 years) and median follow up was 5 months (range, 1–16 months). Here 23 pts who completed at least first two cycles of VTD were analyzed. Pts received bortezomib (Velcade®) 1.3 mg/m2 on days 1, 4, 8, 11, thalidomide 100 mg daily, dexamethasone 40 mg on days 1–4 every 3 weeks for a maximum of 6 cycles of treatment, and thereafter melphalan 4 mg/m2 on days 1–7, prednisone 40 mg/m2 days 1–7, thalidomide 100 mg daily every 4 weeks for a maximum of 12 cycles. In these 23 pts, 92% of them showed responses (18% CR, 4% nCR, and 70% PR). 17 pts completed 4 cycles of VTD and all of them showed 100% response rates (CR 35%, nCR 18%, PR 47%). 13 out of 14 who completed 6 cycles of VTD showed responses (CR 50%, nCR 14%, PR 29%, PD 7%). It is too early to see whether improved response rate translates into improved overall survival (OS) and progression free survival (PFS). The median OS and PFS have not been reached yet. 11 pts (37%) stopped protocol therapy because of consent withdrawal (2 pts), death (4 pts), disease progression (2 pts) and severe adverse reaction (3 pts). The causes of death were infection-related in 2 pts who had been in remission. Other 2 pts were related to disease progression. Although peripheral neuropathy affected all of pts, only 20% of the pts were grade 3. The most common side effects of the chemotherapies greater than grade 3 were pneumonia (24%), asthenia (12%), diarrhea (16%), nausea (4%), thrombocytopenia (16%), neutropenia (12%) and anemia (12%). Although VTD followed by MPT chemotherapy in pts with previously untreated MM, who are non-transplant candidates showed high response rates with manageable toxicities, they showed high withdrawal rates from the study which attributed partly to the characteristics of the pts at baseline who were non-transplant candidates because of old age and morbidities, and a few major neuropathies. Follow up data will be presented.

Comparison Of Treatment Outcomes with EPOCH-Rituximab Versus CHOP-Rituximab in Patients with De-novo Intermediate and High Risk International Prognostic Index(IPI)Diffuse Large B Cell Lymphoma(DLBCL): A Single Center Retrospective Analysis

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5115-5115
Author(s):  
Hasmukh Jain ◽  
Manju Sengar ◽  
Hari Menon ◽  
Uma Dangi ◽  
Bhausaheb Bagal ◽  
...  
Keyword(s):  
High Risk ◽  
Treatment Outcomes ◽  
Disease Progression ◽  
Retrospective Analysis ◽  
Poor Prognosis ◽  
De Novo ◽  
Performance Status ◽  
Progression Free Survival ◽  
Free Survival

Abstract Poor prognosis DLBCL, including intermediate and high risk disease according to IPI accounts for approximately 20% of new cases of DLBCL. The addition of rituximab to conventional chemotherapy (CHOP) has improved the outcomes in this subset, with a 2-year overall survival (OS) of about 50%. However, 40-50% of these patients still have either primary refractory disease or relapse after an initial response. Rituximab-EPOCH (R-EPOCH), an infusional regimen has a dynamic dose adjustment strategy based on the hematopoietic nadir in previous cycle to achieve an optimal drug concentration. Phase II studies with R-EPOCH in untreated DLBCL with intermediate and high risk IPI have reported improved outcomes, with an estimated 2-year OS of 75% which appears superior to that of R-CHOP. Hence we analysed the outcomes of patients with de-novo, poor prognosis (intermediate and high risk IPI) DLBCL who received R-EPOCH and compared it to the  historical cohort of patients who were treated with R CHOP at our centre. Methods Treatment-naïve patients of DLBCL with intermediate or high risk IPI, registered at our centre between November 2011 to June 2013, who received R-EPOCH regimen, were included for the analysis. Case records were reviewed for – demography, histology, stage, bulk of disease, extranodal sites,  performance status, IPI, LDH, albumin, details of chemotherapy, grade ¾ toxicities (CTCAE version 4) and need for hospitalization.  Responses were evaluated at mid and end of chemotherapy. Overall and progression free survival were calculated. Similar analysis was done for poor prognosis DLBCL patients treated with R-CHOP between Jan 2007 to December 2010. Results Baseline characteristics and treatment outcomes of  32 patients (males-24, females-8) treated with R-EPOCH were compared to 42 patients (males-28, females-14) who received R- CHOP. Median age in R- EPOCH group was 47 years (range-20-75 years) versus 55 years (23-72 years )in R- CHOP. Performance status≥ 2 was seen in 47% in R- EPOCH as compared to 28% in R-CHOP group. Significant proportion of patients in R-EPOCH had bulky disease(81% versus  16%) and stage III/IV disease (90% versus 81%) as compared to R-CHOP. Patients with IPI of two represented 8(25%), IPI of three, 11(34%), and IPI of four and five, 10(32%) on R- EPOCH compared to 21(50%), 19(45%) and 2(5%) on R-CHOP, respectively. Serum albumin<3.5 gm/dL was seen in 10(32%) on R-EPOCH and 14(33%) on R-CHOP. LDH was elevated in all but two patients on R-EPOCH compared to 37(88%) patients on R-CHOP. Complete response was seen in 60%, and disease progression in 18% patients on R-EPOCH, compared to 59%, and 20% on R-CHOP respectively. There were 5 deaths on R-EPOCH, 3 due to toxicity and 2 due to disease progression, and in comparison there were 4 deaths on R-CHOP, all of them due to disease progression.  With a median follow up of 6 months, the estimated OS at 1 year is 74% and progression free survival (PFS) is 62% for patients on R- EPOCH. For patients on R- CHOP, with a median follow up of 31 months, 1 year OS is 68% and PFS is 64%. Conclusion Our retrospective analysis indicates that treatment with R-EPOCH regimen resulted in similar results as with R-CHOP regimen. However patients treated with R-EPOCH had more adverse features in terms of disease bulk, poor performance status and high IPI score. A prospective randomized comparison is warranted between these two regimens. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Treatment of relapsing–remitting multiple sclerosis with high-dose cyclophosphamide induction followed by glatiramer acetate maintenance

2011 ◽  
Vol 18 (2) ◽  
pp. 202-209 ◽  
Author(s):  
Daniel M Harrison ◽  
Douglas E Gladstone ◽  
Edward Hammond ◽  
Jeffrey Cheng ◽  
Richard J Jones ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Glatiramer Acetate ◽  
Induction Therapy ◽  
Progression Free Survival ◽  
Infectious Complications ◽  
High Dose ◽  
Free Survival ◽  
Relapsing Remitting

Background: Previous studies have described stabilization of aggressive multiple sclerosis (MS) with one-time induction therapy with high-dose cyclophosphamide (HiCy). The long-term benefit of this stabilization followed by conventional therapy has not been explored. Objective: The objective of this study was to evaluate the safety and clinical outcomes following treatment of relapsing–remitting MS with HiCy induction therapy followed by glatiramer acetate maintenance. Methods: A retrospective review of a closely followed population of thirty two MS patients treated with HiCy (200mg/kg intravenous infusion over 4 days) followed by maintenance with glatiramer acetate was performed. Results: Annualized relapse rate was reduced from 1.37 in the 2 years prior to treatment to 0.27 over a mean post-treatment follow-up period of 14 months (range 0.5–33.8). The projected probability of relapse-free survival at 2 years was 0.64 (95% CI 0.37–0.82). The projected probability of Expanded Disability Status Scale (EDSS) progression-free survival at 2 years was 0.77 (95% CI 0.43–0.92). The mean number of gadolinium-enhanced lesions was reduced from 0.86 (SD 1.6) at baseline to 0 at 12 months and 0.08 (SD 0.28) at 15–24 months. A total of 55% of patients had no evidence of disease activity in follow-up. Infectious complications occurred in 47% with no long-term morbidity and no deaths. Conclusions: Induction therapy with HiCy followed by long-term maintenance with glatiramer acetate is well tolerated in patients with MS, and appears to be efficacious in reducing the risk of relapse, disability progression, and new MRI lesions.

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