Single nucleotide polymorphisms (SNPs) in endoplasmic reticulum (ER) stress response genes to predict first-line treatment outcome in patients (pts) with metastatic colorectal cancer (mCRC): Data from the MAVERICC and FIRE-3 trials.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 103-103
Author(s):  
Francesca Battaglin ◽  
Hiroyuki Arai ◽  
Joshua Millstein ◽  
Sebastian Stintzing ◽  
Aparna Raj Parikh ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Treatment Outcome ◽  
Stress Response ◽  
Er Stress ◽  
P Value ◽  
Line Treatment ◽  
First Line ◽  
Er Stress Response ◽  
Stress Response Genes ◽  
First Line Treatment

103 Background: ER stress, triggered by the disruption of intracellular protein homeostasis, promotes the activation of a highly conserved adaptive program called unfolded protein response (UPR). UPR signaling has been reported to contribute to tumor initiation and progression, as well as microenvironment remodeling and chemoresistance in multiple cancer types, including CRC. Several studies point to a direct role of the UPR in tumor angiogenesis and an interaction with EGFR signaling. We therefore hypothesized that genetic variants in ER stress response genes may predict first-line treatment outcome in mCRC pts. Methods: The impact on outcome of 17 functional SNPs in 8 core genes of the ER stress response pathway ( IRE1, PERK, ATF6, XBP1, CHOP, GRP78, GADD34, ATF4) was analyzed on a total of 560 pts enrolled in two independent randomized first-line trials: MAVERICC (FOLFIRI/bevacizumab, [bev] n = 163; FOLFOX6/bev, n = 161), and FIRE-3 (FOLFIRI/bev, n = 107; FOLFIRI/cetuximab [cet], n = 129). Genomic DNA from blood samples of pts was genotyped through the OncoArray, a custom array manufactured by Illumina. The association between SNPs and clinical outcomes was evaluated using Cox regression and log-rank tests. The SNP*treatment interaction was assessed in both trials. Results: IRE1 rs16947383 any T allele variant was associated with shorter progression free survival (PFS) and overall survival (OS) compared to the C/C genotype in pts treated with FOLFIRI/bev in the MAVERICC trial both in uni- and multivariate analysis: 10.5 vs 14.1 months for PFS, adjusted hazard ratio (HR) 1.83, 95% confidence interval (CI) 1.12-2.99, adjusted P-value = 0.02; 23.8 vs 38.4 months for OS, adjusted HR 2.12, 95%CI 1.1-4.09, adjusted P-value = 0.02. The association with OS was validated in the FIRE-3 FOLFIRI/bev arm where any T allele carriers showed significantly shorter OS compared to the C/C genotype in both uni- and multivariate analysis: 21.1 vs 44.2 months, adjusted HR 2.06, 95%CI 1.01-4.18, adjusted P-value = 0.05. This effect was not observed in MAVERICC FOLFOX6 and FIRE-3 cet cohorts. A significant interaction was found between IRE1 rs16947383 and treatment on OS in both trials: P = 0.04 in MAVERICC (FOLFIRI vs FOLFOX6), and P = 0.03 in FIRE-3 (bev vs cet). In the MAVERICC FOLFOX6/bev arm, XBP1 rs2239815 and PERK rs6731022 SNPs were associated with shorter PFS and OS, while GADD34 rs610308 with longer OS, in multivariable analysis ( P < 0.05). Conclusions: Our results provide evidence that germline polymorphisms in ER stress response genes may have a predictive value in mCRC pts receiving first-line bev-based treatment and contribute to modulate anti-VEGF efficacy.

Prognostic impact of serum cytokeratin 19 fragments in patient with metastatic urothelial cancer (mUC) treated with first-line chemotherapy.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 473-473
Author(s):  
Yuki Endo ◽  
Go Kimura ◽  
Jun Akatsuka ◽  
Masato Yanagi ◽  
Hikaru Mikami ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Prognostic Factors ◽  
Urothelial Cancer ◽  
Cytokeratin 19 ◽  
Intermediate Risk ◽  
Line Treatment ◽  
First Line ◽  
Poor Risk ◽  
Metastatic Urothelial Cancer ◽  
First Line Treatment

473 Background: Even today, when several immune checkpoint Inhibitors have been approved for the treatment of metastatic urothelial cancer (mUC), cytotoxic chemotherapy (CTC) still remains the mainstay for first-line treatment. We believe that the prognostic factors for the first-line CTC have become more important again and need to be re-analyzed. Current guidelines do not yet provide recommendations for any serum tumor markers in patients with mUC. Previous studies have shown that serum cytokeratin 19 fragments levels (sCK) were correlated with depth of tumor invasion and metastatic burden in patients with bladder cancer. In this study we evaluated whether sCK, and other clinical parameters could predict overall survival (OS) in patients with mUC treated with CTC. Methods: Two hundreds fifty two patients with mUC received CTC from December 2006 to 2016 at our institution. sCK had been measured in 128 patients at diagnosis of mUC. OS rate were analyzed by Kaplan–Meier curves and log–rank test. Multivariate analysis was carried out using the Cox hazards model. Tumor burden (TB) was measured based on Response Evaluation Criteria In Solid Tumor (version 1.1). Results: Of 128 patients, with median age of 72 (44-93), 36 (28%) had lung metastasis, 11 (9%) had bone metastasis, 10 (8%) had liver metastasis (LM). Ninety five (74%) patients received platinum based chemotherapy as a first-line treatment. During the median follow-up period of 19 (1-89) months, 72 patients (70%) had died. A 1-year (1y) OS was 51% and a 2y-OS was 36%. On univariate analysis, performance status (PS) (HR2.0, p<0.005), sCK (HR3.9, p<0.001), CRP (HR4.0, p<0.001), neutrophil-lymphocyte ratio (HR1.9, p<0.049), LM (HR2.0, p=0.042) and TB (HR2.4, p<0.001) were the significant prognostic factors for OS. On multivariate analysis, PS (HR2.0, 95%CI (1.05-3.85) p=0.036 ), sCK (HR3.1, 95%CI (1.3-8.3), p=0.011), and LM (HR3.0, 95%CI (1.06-6.98), p=0.022) were the independent prognostic factors for OS. Based on these 3 factors we divided patients into three groups, good risk (G, 0 factor), intermediate risk (I, 1 factor) and poor risk (P, 2-3 factors). There was a significant difference between the three groups. (G vs I: p<0.001, I vs P: p=0.001). Conclusions: PS, sCK, and LM were the independent prognostic factors for OS in patients with mUC receiving CTC. For the patients in good or intermediate risk with this score, early exposure of ICIs should be performed after CTCs. Treatment strategy should be changed in patients with poor risk since CTC is primary refractory in such population.

Rituximab (Mabthera) Improves the Treatment Results of DHAP-VIM-DHAP and ASCT in Relapsed/Progressive Aggressive CD20+ NHL. A Prospective Randomized HOVON Trial.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 328-328 ◽  
Author(s):  
Edo Vellenga ◽  
Annelise Notenboom ◽  
Mars van ‘t Veer ◽  
Josée Zijlstra ◽  
Willem E. Fibbe ◽  
...  
Keyword(s):  
Disease Free Survival ◽  
Response Duration ◽  
Rank Test ◽  
P Value ◽  
Line Treatment ◽  
First Line ◽  
Post Transplantation ◽  
Free Survival ◽  
Significant Difference ◽  
First Line Treatment

Abstract A total of 239 patients with relapsed/progressive aggressive CD20+ NHL after/during adriamycin containing regimens, were recruited to the randomized HOVON-44 trial comparing DHAP-VIM-DHAP followed by BEAM and autologous stem cell re-infusion (ASCT)(“DHAP-arm”) with DHAP-VIM-DHAP in conjunction with Rituximab (375 mg/m2) and ASCT (“R-DHAP arm”). Of the included patients, 202 were evaluable and randomized to the DHAP arm (n=101) or R-DHAP arm (n=101). Only patients with CR/PR after two courses of intensive chemotherapy were eligible for ASCT. Patients were well balanced for risk factors. In both arms the majority of patients had not been exposed to Rituximab during first line treatment. As of July 2006, median follow-up of all patients still alive is 24.5 months. After two courses of chemotherapy PR/CR was obtained in 49 % of the patients in the DHAP arm and 77% in the R-DHAP arm (p=<.01;intention to treat analysis). Post-transplantation PR/CR was obtained in 41% and 58% of the patients respectively (p=.40). A significant difference between both arms was observed for failure free survival (FFS), disease free survival (DFS) and overall survival (OS) in favor of the Rituximab arm (p<.05, table 1). The less pronounced difference in OS between both arms is most likely due to the fact that non-responding or relapsing patients in the DHAP arm received salvage treatment with a Rituximab containing regimen. Additionally, a subgroup analysis was performed according to type of response to first-line treatment:1) Response duration more than 3 months (n=138); 2) Progression or response duration less than 3 months (n=64). Within both subgroups, the hazard ratio’s for the endpoints were of equal magnitude (.40–.60), indicating that the beneficial effect of Rituximab existed in both subgroups. In conclusion these results demonstrate that the addition of Rituximab to second line of chemotherapy followed by ASCT results in a significant improved FFS, DFS, and OS in patients with relapsed/progressive aggressive CD20+ NHL. Table 1 FFS DFS OS *: 2 years estimate DHAP-arm* 21% 46% 48% R-DHAP arm* 52% 82% 62% Hazard ratio .40 .32 .61 p-value log rank test <0.001 0.003 0.03

Comparison of bevacizumab versus pemetrexed in combination with platinum-based doublets in first-line treatment of advanced non-small cell lung cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e18078-e18078 ◽  
Author(s):  
Augusto Akikubo Rodrigues Pereira ◽  
Sandro José Martins ◽  
Rafael Costa Lessa ◽  
Flavio Augusto Ismael Pinto ◽  
Debora De Melo Gagliato ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Multivariate Analysis ◽  
Prognostic Factors ◽  
Small Cell ◽  
Line Treatment ◽  
Small Cell Lung ◽  
Adrenal Metastases ◽  
First Line ◽  
Nonsquamous Nsclc ◽  
First Line Treatment

e18078 Background: First-line treatment of advanced nonsquamous non-small cell lung cancer (NSCLC) with platinum-based doublets, including pemetrexed (P) or bevacizumab (B), has achieved more than 12 months of survival. At the moment, there are no phase III head-to-head comparisons of these combinations. Methods: We retrospectively analyzed, from 05/2007 to 02/2011, in a single institution, all pts with stage IIIB or IV nonsquamous NSCLC treated with B or P combined with platinum compounds in first-line treatment to determine differences in OS, PFS, ORR and toxicity. We performed multivariate analysis to identify prognostic factors for survival. Results: Of the 82 pts included, 40 pts (48,8%) received carboplatin/paclitaxel or cisplatin/gemcitabine combined with B (BEV group), while 42 pts (51,2%) received cisplatin or carboplatin combined with P (PEM group). BEV had significantly fewer pts with age > 70 years (p=0,01) and CNS metastases (p<0,001) than PEM. Maintenance therapy was administered in 65,0% and 52,4% of pts in BEV and PEM groups, respectively (p=0,17). Significantly more pts in BEV received second-line treatment (72,5% vs. 52,4%; p=0,04) than in PEM, prevailing P as drug of choice (79,3%). ORR (60,0% vs. 35,7%; p=0,04) and median survival (26,4 vs. 16,4 months; p=0,009) were significantly superior for BEV. Median PFS were not different between BEV and PEM (10,5 vs. 7,7 months; p=0,06). In multivariate analysis, ECOG 2 (p=0,005), bone (p=0,01) and adrenal metastases (p=0,005) were independent prognostic factors for worst survival, while treatment with BEV did not reach statistical significance (p=0,07). Grade 3-4 neutropenia (27,5% vs. 9,5%; p=0,03) and neuropathy (17,5% vs. 0%;p=0,005) were more frequent in BEV. Conclusions: First-line treatment of advanced nonsquamous NSCLC patients with platinum-based doublets combined with B resulted in better ORR and higher rate of toxic effects as compared with P-based regimens. ECOG 2, bone and adrenal metastases were independent prognostic factors for poor survival. Although there was a survival benefit at univariate analysis, use of B combination was not an independent prognostic fator.

Association of progression free survival with the timing of genomic testing in non-small cell lung cancer: Evidence from the GuardantInform clinic-genomic database.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21143-e21143
Author(s):  
Mark D. Hiatt ◽  
Junhua Yu ◽  
Nicole Zhang ◽  
Amy McNeal ◽  
Julie Kaylor ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Progression Free Survival ◽  
P Value ◽  
Line Treatment ◽  
First Line ◽  
Free Survival ◽  
Egfr Tki ◽  
First Line Treatment ◽  
Group 1

e21143 Background: The clinical utility of ctDNA analysis for biomarker identification in advanced non-small cell lung cancer (NSCLC) has been established, supporting clinical adoption of this testing modality. All FDA-approved, immune-checkpoint inhibitor (ICI) immunotherapies require the prerequisite of negativity for ALK rearrangement and EGFR mutation, or prior toxicity or progression on oral therapies targeting mutations in these genes. Despite these recommendations and support from the American Society of Clinical Oncology and National Comprehensive Cancer Network, broad-panel marker testing for targeted therapy options in NSCLC continues to be underperformed. Data are even limited on when those tests are typically conducted and the effects of timing on the treatment outcomes. Methods: The GuardantINFORM™ clinic-genomic database was interrogated for patients over the age of 18 having a Guardant360 test positive for EGFR mutations of L858R or exon 19 after 2016 and known to have a confirmed diagnosis of lung cancer one year prior to testing. Patients had to have at least three claims prior to, and 90 days of follow-up after, their test. Patients were stratified into three groups by pre- and post-test treatment: 1) patients treated with an EGFR tyrosine kinase inhibitor (TKI) as a first-line treatment after the test, with no other chemotherapy, ICI immunotherapy (IO), or targeted therapy before the test; 2) patients with other first-line treatments prior to the test and then EGFR TKI immediately following the test; and 3) patients treated with ICI or chemotherapy after the test and before EGFR TKI or patients not treated after the test. Real-world time to next treatment (rwTTN) was defined as the index date to the treatment different than the index therapy. Progression free survival (PFS) time was defined as rwTTN or time to death, whichever came earlier. Patients who experienced adverse events (AEs) associated with chemotherapy or IO were reported as a percentage (p-value<0.001). Results: Among the 3 cohorts of patients (384 in each group who were matched on age with difference < 3, gender, and follow-up time with difference < 4 months) identified, a statistically significant difference in PFS was discovered between group 1 ( EGFR TKI as first-line treatment) and the other two groups based on the Cox proportional hazard model [hazard ratio=1.8, p-value<0.001, median survival time for group 1= 26 months (95% CI 23-29) vs. 17 months (95% CI 14-19)]. No difference existed in PFS between groups 2 and 3. The proportion of patients experiencing treatment-associated AEs was lowest in group 1 (13.5% vs 15.9% in group 2 vs 30.2% in group 3 for ICI-related AEs, 16.9% vs 23.2% vs 38.5% for chemo-related AEs, p-value<0.001). Conclusions: Performing genomic testing sooner, as early as first-line treatment, may improve the treatment response for patients with NSCLC.

R-ESHAP as Salvage Therapy for Patients with Relapsed or Refractory Diffuse Large B-Cell Lymphoma: A Spanish GEL-TAMO Multicenter Study.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3438-3438
Author(s):  
Alejandro Martin ◽  
Eulogio Conde ◽  
Montserrat Arnan ◽  
Miguel A. Canales ◽  
Guillermo Deben ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Salvage Therapy ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Line Treatment ◽  
First Line ◽  
Large B Cell Lymphoma ◽  
Relapsed Disease ◽  
Large B Cell ◽  
First Line Treatment

Abstract The addition of Rituximab to CHOP-like chemotherapy (CT) regimens has improved survival in diffuse large B-cell lymphoma (DLBCL). For this reason, Rituximab is also extensively used in combination with salvage CT regimens, although the information published on this setting is scarce. In the present study, we have analysed a large series of patients (pt) treated with R-ESHAP. 151 pt with relapsed or refractory DLBCL received R-ESHAP (Rituximab, etoposide, cytarabine, cisplatinum and methylprednisolone) as salvage therapy between May 2000 and March 2007. Median age was 54 years (19–70). 22% of pt were refractory to front-line therapy, 19% were partial responders, and 56% had relapsed disease. 56% of pt had received Rituximab in addition to CT as first-line treatment. 15 pt had been treated with autologous stem-cell transplantation (ASCT) prior to R-ESHAP. Patients received a median of 3 cycles of R-ESHAP (1–6). Overall response (OR) rate was 72%, with 69 pt (46%) achieving complete response (CR) and 40 (26%) partial response (PR). Factors with significant influence on CR rates in multivariate analysis were: absence of bulky disease (RR: 3.1), PR to first-line treatment (RR: 3.9) or relapsed disease (RR: 5.8), low-risk IPI (RR: 6.6), and administration of ≥3 cycles (RR: 5). Patients who had received Rituximab prior to R-ESHAP had lower CR (39 vs 54%) and OR (66 vs 80%) rates than patients who had not received it, but the difference did not reach statistical significance. In total, 94 out of 151 pt underwent transplantation after the salvage therapy (91 autologous, and 3 allogeneic). With a median follow-up of 22 months (3–73), the 4-year freedom from treatmet failure (FFTF) and overall survival (OS) were 49% and 48%, respectively. Patients who received Rituximab prior to R-ESHAP had a significantly worse FFTF (26 vs 67% at 4 years) and OS (30 vs 63% at 4 years) as compared with patiens who did not receive it. On multivariate analysis, factors significantly associated with a poor OS were: prior exposure to Rituximab (RR: 2.8), high-risk IPI (RR: 5.2), thrombocytopenia <100x109/l at the time of R-ESHAP (RR: 9.5); and achievement of PR (RR: 6.4) or progressive disease (RR: 17) after R-ESHAP. Our results show the efficacy of R-ESHAP prior to ASCT for refractory or relapsed DLBCL. Although prior exposure to Rituximab was associated with a worse outcome, still a significant number of patients responded to the regimen. Future studies are needed in order to determine which patients will benefit from Rituximab re-treatment.

Outcome Of t(4;14) In Multiple Myeloma - Princess Margaret Cancer Centre Experience Over The Last 10 Years

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5315-5315
Author(s):  
Sophia Farooki ◽  
Manjula Maganti ◽  
Donna E Reece ◽  
Esther Masih-Khan ◽  
Victor H Jimenez-Zepeda ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Overall Survival ◽  
Research Funding ◽  
Conventional Treatment ◽  
Novel Agents ◽  
P Value ◽  
Line Treatment ◽  
First Line ◽  
Significant Difference ◽  
First Line Treatment

Abstract Translocation (4;14) is identified by FISH cytogenetics in approximately 15% of myeloma patients (pts). Pts with this translocation have a poor outcome characterized by initial response to induction chemotherapy but followed by rapid relapse and resistance to alkylating agents. Recent studies have suggested that novel agents such as bortezomib may improve both event-free survival and overall survival (OS). We reviewed the outcome of 74 consecutive myeloma pts with t(4;14) managed at Princess Margaret Cancer Centre between October 2002 and July 2012. Our goal was to evaluate the impact of specific pts' characteristics on OS and to assess outcome according to treatments received. Clinical characteristics at time of diagnosis for the 74 myeloma pts with t(4;14) are presented in table 1. The average age was 57 years (range 31-82 years) and 58% were male. Pts received a median of 2 lines of therapy (range 1-6). Of the 69 pts requiring treatment, 46% of pts received one year of bortezomib as part of the Canadian t(4;14) clinical trial, 32% of pts were treated with novel agents including bortezomib (given for an average of 4 months) and lenalidomide, 22% of pts received conventional treatment such as dexamethasone alone, thalidomide and/or melphalan. 20 pts underwent autologous stem cell transplantation (ASCT) as part of their first line treatment; 16 were single ASCT, 4 were tandem ASCT. The overall response rate to induction chemotherapy was 70%, with 60% complete response/very good partial response and 10% partial response. The median OS was 5 years and 3 year OS was 66%. Presence of p53 significantly decreased the 3 year OS (71% vs 29% for absence and presence of p53, respectively, log-rank p value=0.0017). Median follow-up was 2.43 years (range: 0.24-11.81 years). There was no significant difference in OS based on the type of first line treatment received. The 3 year OS was 69% for pts enrolled in the t(4;14) clinical trial, 65% for pts who received novel agents and 53% for pts who received conventional treatment (log-rank p value=0.33). In a multivariable analysis looking at pts' initial characteristics, p53 deletion, LDH, bone lesions and age at diagnosis were found to be significant predictors of overall survival while ISS staging and immunoglobulin isotype were not found to be significant for overall survival. In conclusion, in our retrospective single institution study, the median OS for pts with t(4;14) was 5 years. Older age, addition of p53 deletion, high LDH and presence of bone disease predicted a worse OS. Although the lack of significant difference in OS based on the type of first line treatment received may be due to the limited number of pts in our study, there was a trend towards improvement in OS for pts that received a bortezomib containing regimen versus those who received conventional agents. While the median OS for pts with t(4;14) in our study has increased compared to historical controls, new therapeutic options are still needed to further improve the outcome in this subset of pts3. 3 Keats JJ et al. In multiple myeloma, t(4;14)(p16;q32) is an adverse prognostic factor irrespective of FGFR3 expression. Blood. 2003 Feb 15;101(4):1520-9.Table 1Clinical characteristics for the 74 myeloma pts with t(4;14)Clinical characteristicsAverageRange%Hemoglobin (g/L)10051-157Creatinine (μmol/L)13933-796Calcium (mmol/L)2.41.89-3.84B2-microglobulin (mg/L)4.51.58-20.25Albumin (g/L)3518-46ISS stage 145%ISS stage 236%ISS stage 319%Presence of bone lesions68%Mean % of nuclei positive for t(4;14)3%-71.5%25%Presence of del 13q/monosomy 13 by FISH77%Presence of del 17p by FISH10% Disclosures: Reece: Celgene: Honoraria, Research Funding; Jansen: Honoraria, Research Funding; Onyx: Honoraria; Novartis: Honoraria; BMS: Research Funding; Merk: Honoraria, Research Funding; Millennium: Research Funding.

Autologous Stem Cell Transplantation in Patients with Mantle Cell Lymphoma: A Retrospective Study of the Geltamo Group (1994-2011)

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3980-3980
Author(s):  
Ana García-Noblejas ◽  
Eulogio Conde ◽  
Alejandro Martín ◽  
María Jesús Vidal ◽  
Rafael Rojas ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Prognostic Factors ◽  
Cell Lymphoma ◽  
Disease Status ◽  
Line Treatment ◽  
First Line ◽  
Kaplan Meier ◽  
Mantle Cell ◽  
First Line Treatment

Abstract INTRODUCTION Autologous stem cell transplantation (ASCT) is one of the current treatment options for first-line treatment of mantle cell lymphoma (MCL) in young and fit patients in first complete response (CR). Nevertheless its role in less than CR, after intensive chemotherapy schemas or as consolidation after salvage regimens has not been established. AIM To analyze the impact of patient and treatment characteristics on outcome of MCL patients treated with ASCT. METHODS Retrospective analysis of MCL patients treated with ASCT and registered in the GELTAMO database from 1994 to 2011. An outcome up-date was performed on December 2013. The study was approved by local ethical committees. Statistical analysis was performed using SPSS 15.0. RESULTS Two hundred and forty eight patients were registered from the GELTAMO database. Patients’characteristics : median age was 55 years old (range 21-70 y), 70% male. One hundred and fifty eight patients (68%) were transplanted in CR, 125 were in first CR (79% of all CR) and 33 in second or third CR (21%). Fifty two patients (22%) were transplanted in first partial response and 15 (6%) with chemosensitivity disease after relapse. Only 8 patients (3%) were transplanted with refractory disease. Response : forty-eight out of 75 patients (64%) without CR at ASCT converted to CR after transplant. Survival: Sixteen percent of patients were lost to follow-up one year after transplantation. Median follow-up for alive patients was 47 months (range 0-245 months). Progression free survival for patients transplanted in first CR was 45 months (CI95%: 33-56 months), for patients transplanted in first partial response (PR) was 28 months (CI95%: 15-21months) and for patients transplanted in other response was 19 months (CI95%: 12-26 months). In the whole series, median overall survival (OS) from transplantation was 69 months (CI95% 51-87 months) and for those patients transplanted in first CR was 98 months (CI95% 67-130 months). When patients without CR before transplant are analyzed separately, those who achieved CR after transplantation have better PFS (38 vs 10 months, p<0.001) and OS (74 vs 16 months, p<0.001) than others. Treatment related mortality was 4%. We analyzed the variables that could be associated with PFS and OS. We considered age (≤60 vs >60), ECOG (<2, ≥2), IPI (<2, ≥2), status at transplant (1st CR vs others), conditioning with TBI and HDAC in first line treatment. In univariate analysis, ECOG (p=0.04) and status at transplant (p=0.01) were the variables associated with PFS. For OS, the same variables resulted significant (p<0.001 and p=0.07, respectively) and also, HDAC emerged as significant variable associated with outcome. (p=0.05). In multivariate analysis, ECOG and status at transplant remained as independent prognostic factors for PFS while ECOG and HDAC in first line had impact for OS, see Table 1. Table 1. Variables identified as independent prognostic factors for PFS and OS in multivariate analysis. PFS OS p RR (95% CI) p RR ECOG 0.01 3.6 (1.3-9.9) 0.04 4.5 (1.6-12.5) Status at trasplant 0.03 1.4 (1-2) 0.09 (ns) ---- HDAC at 1st line 0.7 (ns) ---- 0.014 0.5 (0.3-0.8) Afterwards, a survival analysis for PFS and OS was performed according to have received high dose AraC (HDAC) in first line treatment or not and disease status (DS) before ASCT (Table 2). Table 2. Survival analysis according to have received HDAC in 1st line treatment and disease status (DS) before ASCT DS before ASCT N Firts line treatment N PFS (CI95%)(Kaplan Meier) p OS (CI95%)(Kaplan Meier) p 1st CR 125 No HDAC 52 37 (22-51) 0.13 64 (37-91) 0.01 HDAC 72 56 (33-78) No reached 1st PR 52 No HDAC 35 33 (3-63) 0.59 61 (0-126) 0.9 HDAC 17 27 (18-37) 69 (46-92) ≠1st CR/PR 51 No HDAC 46 20 (13-27) 0.16 35 (5-66) 0.9 HDAC 5 11 (7-16) No reached CONCLUSION This retrospective study reproduces previous results published about the role of ASCT in MCL: ASCT consolidation in first CR induces high survival rates with a median PFS of 45 months and median OS of 98 months. Patients without CR after ASCT had a significant inferior outcome. ECOG < 2 and status at transplantation are crucial for PFS and first line treatment with AraC improves significantly OS, particularly in patients with first CR. Disclosures No relevant conflicts of interest to declare.

scholarly journals A Role for SIR-2.1 Regulation of ER Stress Response Genes in Determining C. elegans Life Span

2005 ◽  
Vol 9 (5) ◽  
pp. 605-615 ◽  
Author(s):  
Mohan Viswanathan ◽  
Stuart K. Kim ◽  
Ala Berdichevsky ◽  
Leonard Guarente
Keyword(s):  
Stress Response ◽  
Er Stress ◽  
Life Span ◽  
C Elegans ◽  
Er Stress Response ◽  
Stress Response Genes
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