scholarly journals Interim Serum Soluble Interleukin-2 Receptor Levels Are Strongly Associated with Prognosis in Newly Diagnosis DLBCL Patients

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4118-4118
Author(s):  
Haruya Okamoto ◽  
Akihiro Miyashita ◽  
Hiroaki Nagata ◽  
Yasuhiko Tsutsumi ◽  
Yuri Kamitsuji ◽  
...  
Keyword(s):  
Poor Prognosis ◽  
Interleukin 2 ◽  
B Cell Lymphoma ◽  
Clinical Variable ◽  
Rank Test ◽  
Prognostic Impact ◽  
Interleukin 2 Receptor ◽  
Log Rank Test ◽  
Soluble Interleukin 2 Receptor

<Background> Serum soluble interleukin-2 receptor (sIL2R) levels are often measured to evaluate the state of lymphoma. The serum sIL2R level at diagnosis has been reported to be correlated with the prognosis of diffuse large B cell lymphoma (DLBCL) patients treated with the R-CHOP regimen. However, it is unclear whether interim sIL2R levels are associated with prognosis in DLBCL. Here, we analyzed the prognostic impact of interim serum sIL2R levels in DLBCL. <Patients and Methods> We retrospectively examined data for DLBCL patients who started receiving chemotherapy at the Japanese Red Cross Society Kyoto Daini Hospital between January 2012 and December 2018. All of the patients received R-CHOP-like regimens (rituximab plus pirarubicin or adriamycin, cyclophosphamide, vincristine, and prednisolone). The interim sIL2R level (I-IL2R) was defined as the value measured after the third chemotherapy cycle. I-IL2R levels of >700 U/ml were regarded as positive. The primary endpoints of this study were progression-free survival (PFS) and overall survival (OS). The unadjusted probabilities of PFS and OS were estimated using the Kaplan-Meier method. The log-rank test and multivariate Cox regression analysis were used to assess the prognostic value of each clinical variable. <Results> In total, 102 patients were enrolled. The patients' median age was 73.5 years (range, 35-88), 58 patients (56.9%) were male, and 52 (51.0%) had poor revised International Prognostic Index scores. The median follow-up time was 25.2 months (range, 3.7-88.6). Twenty-three patients (22.5%) were I-IL2R-positive (>700 U/ml). Univariate analysis revealed that I-IL2R-positivity was associated with a poor prognosis. The 3-y PFS rates of the I-IL2R-negative (<700 U/ml) and I- IL2R-positive (>700 U/ml) patients were 60.4% (95% confidence interval [95%CI], 46.2-71.9) and 37.5% (95%CI, 15.7-59.4; p<0.001, log-rank test), respectively, and their 3-y OS rates were 82.2% (95%CI, 69.7-89.9) and 37.4% (95%CI, 13.8-61.4; p<0.001, log-rank test), respectively. Multivariate analysis confirmed that the I-IL2R level is independently associated with prognosis. <Conclusion> The I-IL2R level of >700 U/ml patients had poor prognosis. The I-IL2R level can be used to predict the outcomes of DLBCL patients. IL2R levels should be measured during chemotherapy, and I-IL2R-positive patients could be targeted with high-dose or novel therapies. As this study was based on a retrospective analysis and involved a small cohort and a limited follow-up period, further studies are needed to confirm the prognostic impact of I-IL2R. Figure Disclosures No relevant conflicts of interest to declare.

scholarly journals Serum Soluble Interleukin-2 Receptor as a Possible Biomarker for the Early Detection and Follow-up of Nivolumab-Induced Pneumonitis

2019 ◽  
Vol 14 (5) ◽  
pp. e90-e91 ◽  
Author(s):  
Kazufumi Yoshida ◽  
Yuko Morishima ◽  
Toshihiro Shiozawa ◽  
Kensuke Nakazawa ◽  
Masashi Matsuyama ◽  
...  
Keyword(s):  
Early Detection ◽  
Interleukin 2 ◽  
Interleukin 2 Receptor ◽  
Soluble Interleukin 2 Receptor

Multicenter Phase II Study of the CyclOBEAP Plus Rituximab in Diffuse Large B-Cell Lymphoma with Analysis of Biomakers.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2725-2725
Author(s):  
Nozomi Niitsu ◽  
Mika Kohri ◽  
Yuki Hagiwara ◽  
Ken Tanae ◽  
Handa Kohsuke ◽  
...  
Keyword(s):  
B Cell ◽  
Phase Ii ◽  
Interleukin 2 ◽  
B Cell Lymphoma ◽  
Risk Groups ◽  
Chop Regimen ◽  
Total Period ◽  
Interleukin 2 Receptor ◽  
Large B Cell Lymphoma ◽  
Soluble Interleukin 2 Receptor

Abstract Abstract 2725 Poster Board II-701 Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin's lymphoma, accounting for approximately 30% of all new patients. The addition of rituximab to CHOP regimen has been found to improve the outcome of DLBCL. However, it dose not provide a satisfactory treatment outcome in the high-risk group according to the international prognostic index (IPI). More recent study, however, suggested that intensified regimens may indeed yield superior results to CHOP. We administered the CyclOBEAP (cyclophosphamide, vincristine, bleomycin, etoposide, doxorubicin, prednisolone) regimen to patients with DLBCL, and previously reported its safety and efficacy. The CyclOBEAP regimen was administered over a total period of 12 weeks, in which the dose intensities of cyclophosphamide, doxorubicin, and vincristine are equal to or higher than those in the CHOP regimen, and bleomycin were added to the CHOP regimen. The results showed that 106 (80%) of the 121 patients achieved complete response (CR), the 5-year overall survival (OS) rate was 72%, and the 5-year progression-free survival (PFS) rate was 62%. Here, we report the results of a multicenter phase II study of the R-CyclOBEAP regimen. This was a prospective, single-arm phase II trial in the Adult Lymphoma Treatment Study Group (ALTSG) in Japan. Patients were enrolled in the study between April 2004 and March 2008. Patients aged between 15 and 60 years who were in the low-intermediate, high-intermediate, or high risk groups, were eligible for this study. The CyclOBEAP regimen was administered over a total period of 12 weeks. Rituximab 375mg/m2 was given every 2 weeks. There were 101 eligible patients and the median age was 51 years. A CR was achieved in 96 patients (95%). The 5-year OS rate was 85% and PFS rate was 76%. When the patients were divided according to the IPI or revised IPI, the 5-year OS and PFS rates did not significantly differ among the risk groups. We next examined survival curve of the patients with DLBCL in whom soluble interleukin-2 receptor data were available. The 5-year survival rates for the high (≧2000 IU/ml) and low soluble interleukin-2 receptor groups (<2000 IU/ml) were 60 and 94%, respectively (p=0.0003), with PFS values of 64 and 81% (p=0.05). Lymphoma tissue was analyzed by immunohistochemistry for biomarkers of CD5, CD10, BCL2, BCL6, MUM1, and nm23-H1. CD5, CD10, BCL2, BCL6, and MUM-1 had no prognostic impact with R-CyclOBEAP. As for nm23-H1 expression in DLBCL in the present study, the 5-year OS of the nm23-H1-positive group was 65% and that of the nm23-H1-negative group was 97%, indicating that the nm23-H1-positive group showed significantly poorer prognosis (p = 0.001). The 5-year PFS of the germinal center B-cell (GCB) group was 80% and that of the non-GCB group was 74%, showing no significant difference. Univariate analysis showed that the stage, presence of B symptoms, number of extranodal lesions, and soluble interleukin-2 receptor were significant prognostic factors, and in multivariate analysis, the soluble interleukin-2 receptor was a significant independent prognostic factor. Grade 4 neutropenia was observed in 91 patients and thrombocytopenia in 9 patients. The addition of rituximab to CyclOBEAP therapy may enhance the effect of CyclOBEAP therapy for DLBCL. Disclosures: No relevant conflicts of interest to declare.

Association of improved survival (OS) and tumor control (TC) with interleukin-2 (IL2) with development of immune-related events (IREs): Data from the PROCLAIMSM registry.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 9528-9528
Author(s):  
Brendan D. Curti ◽  
Gregory A. Daniels ◽  
David F. McDermott ◽  
Joseph Clark ◽  
Howard Kaufman ◽  
...  
Keyword(s):  
Interleukin 2 ◽  
Rank Test ◽  
Tumor Control ◽  
Test Results ◽  
Exact Test ◽  
Log Rank Test ◽  
Kaplan Meier ◽  
Long Term Impact

9528 Background: IREs are associated with immunotherapy (IT) for cancer and while reports suggest improvement in TC and OS with induced IREs, the long-term impact is unclear. IL2 has been the major IT for patients (pts) with renal cell carcinoma (RCC) and melanoma (MM) since 1992. We evaluated IREs reports in the PROCLAIMSM data base (2008-2016) of IL2-treated pts. Methods: Reports on 614 (MM) and 843 (RCC) pts were queried for IREs. IREs were categorized as occurring before, during, or after IL-2 and related to any checkpoint inhibitor (CPI). TC (CR+PR+SD) was compared between no IRE and IRE, using Fisher’s exact test. OS curves were estimated by Kaplan-Meier method, and comparison of no IRE/before IL2 with during/after IL2, was analyzed by log-rank test. Results: With a median (med) follow-up of 3.5+ years (range 1-8+ year), 140 IREs were reported in 118 pts (9.6% of all PROCLAIMSM pts): 93 (15%) in MM; 47 (5.6%) in RCC. 25 IREs were prior to IL2; 13 IREs were during IL2; 102 were after IL2. Of the latter 102, 31 were after IL2 and after subsequent CPI; 71 were attributed to IL2 only; and in 13, IREs were due to either IL2 or CPI. TC was 73% for IRE group vs 56% for no IRE group (p = 0.0054). OS was significantly greater for IRE group during/after IL2 compared to no IRE/before IL2 in MM, med 46 months (mo) vs 18 mo (p = 0.0001) and in RCC, med 61 mo vs 43 mo (p = 0.0196), independent of CPI IREs. Med # of IL2 doses was 19 in no IRE group, 39 in IRE during IL2 group, and 25 in IRE after IL2 group. IL2-related IREs were primarily vitiligo and thyroid dysfunction (70% of IL2 IREs), with limited further impact, while CPI-related IREs were often serious, requiring intervention (hypophysitis, colitis, hepatitis, uveitis) (52% of CPI IREs) and possibly chronic management. Conclusions: IREs following IL2 are associated with improved TC and OS. IREs resulting from IL2 and from CPIs are qualitatively different and likely reflect different mechanisms of action of immune activation and response.

scholarly journals Impact of Routine Surveillance Imaging on Outcomes in Patients with Diffuse Large B-Cell Lymphoma (DLBCL) Undergoing Autologous Hematopoietic Cell Transplantation (auto-HCT)

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4360-4360
Author(s):  
Narendranath Epperla ◽  
Namrata Shah ◽  
Kristin Richardson ◽  
Jonathan Kapke ◽  
George Carrum ◽  
...  
Keyword(s):  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Rank Test ◽  
Test Figure ◽  
Imaging Studies ◽  
Post Transplant ◽  
Log Rank Test ◽  
Large B Cell Lymphoma ◽  
Surveillance Imaging

Abstract Background It is common for diffuse large B-cell lymphoma (DLBCL) patients following autologous hematopoietic transplant (auto-HCT) to undergo surveillance imaging to monitor for lymphoma progression/relapse. Although a standard at most centers, this practice is not evidence-based, has not been shown to improve survival, and may pose a risk to patients due to radiation exposure. We studied DLBCL patients who underwent auto-HCT at three transplant centers to define how many surveillance imaging studies were obtained, how often relapses were detected by surveillance imaging versus clinically (based on signs, symptoms or laboratory findings), and whether survival was improved if relapse was detected by imaging versus clinically. Methods DLBCL patients who underwent auto-HCT during 2000-2013 were identified using clinical databases. Pre-transplant patient and disease characteristics were collected. Progression-free survival (PFS) and overall survival (OS) were determined. Patients were classified as having "radiographic" or "clinical" relapses. PFS and OS were compared for these two groups. Results A total of 209 patients with DLBCL who underwent auto-HCT between 2000 and 2013 were identified. There was insufficient follow-up information on 15 patients and hence only 194 patients were evaluable. Of these, 22 patients relapsed or progressed prior to or at their initial post-transplant disease assessment (day 100 evaluation). The remaining 172 patients were then analyzed to determine which patients relapsed and how relapses were detected. 48 patients relapsed at a median time of 287 days post-transplant. Of these patients, 14 (29%) had relapse detected clinically and 34 (71%) had relapse detected by surveillance imaging. Comparing the radiographic and clinically detected groups, median PFS post auto-HCT was 218 vs 402 days respectively (p= 0.49, log rank test, Figure 1) and median survival post auto-HCT was 643 vs 615 days respectively (p= 0.44, log rank test, Figure 1). For patients who never relapsed after auto-HCT, a median of 4 surveillance imaging studies were performed (with median follow up of 3.0 years post-transplant). Conclusions In DLBCL patients post auto-HCT, the majority of relapses were detected by surveillance imaging. However, the survival of patients with relapse detected by surveillance imaging was not superior to those whose relapse was detected clinically. Given this, combined with the radiation exposure and cost associated with surveillance imaging, the practice of surveillance imaging post auto-HCT appears to have limited utility in DLBCL. Disclosures Hari: Janssen: Consultancy; Novartis: Consultancy; Spectrum: Consultancy; Sanofi: Consultancy; Takeda: Consultancy; Celgene: Consultancy; BMS: Consultancy. Hamadani:Takeda: Research Funding; Cellerant: Consultancy; Celgene: Consultancy; MedImmune: Consultancy. Fenske:Celgene: Honoraria; Pharmacyclics: Honoraria; Seattle Genetics: Honoraria; Millennium/Takeda: Research Funding.

Follow-up of soluble interleukin-2 receptor levels after thymectomy in patients with myasthenia gravis

1992 ◽  
Vol 62 (2) ◽  
pp. 190-198 ◽  
Author(s):  
S. Cohen-Kaminsky ◽  
Y. Jacques ◽  
C. Aime ◽  
D. Safar ◽  
E. Morel ◽  
...  
Keyword(s):  
Myasthenia Gravis ◽  
Interleukin 2 ◽  
Interleukin 2 Receptor ◽  
Soluble Interleukin 2 Receptor

Influence of the fusion gene ETV6-RUNX1 in the prognosis of the Pediatric B- Precursor Acute Lymphoblastic Leukemia

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2515-2515
Author(s):  
Alejandro Contento-Gonzalo ◽  
Antonio Jimenez-Velazco ◽  
Alcala-Peña Magdalena ◽  
Manuel Barrios ◽  
Katie Hurst ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Conflicts Of Interest ◽  
Lymphoblastic Leukemia ◽  
Disease Free Survival ◽  
Rank Test ◽  
Prognostic Impact ◽  
Excellent Outcome ◽  
Log Rank Test ◽  
Significant Difference

Abstract Abstract 2515 INTRODUCTION AND OBJECTIVES: The ETV6-RUNX1 (TEL-AML1) rearrangement comes from the translocation of two chromosomes t(12;21)(p12;q22), and represents one of the most frequently detected anomalies (15–30%) in the B-precursor Acute Lymphoblastic Leukemia (B-ALL). It must be identified by polymerase chain reaction (PCR) or fluorescent in situ hybridization (FISH) methods, since this translocation is not detected by conventional cytogenetic techniques. The prognostic value of ETV6-RUNX1 is still a matter of controversy. Recently, the group of the St Jude Children's Hospital reported an excellent outcome in patients carrying the translocation, whereas the BMF group did not find any significant difference in the survival of ETV6-RUNX1 positive patients when compared to ETV6-RUNX1 negative. The aim of our study has been to determine the prognostic impact of the ETV6-RUNX1 rearrangement in patients diagnosed of B-ALL in our Hospital, after a long period of follow-up and with the same Spanish treatment protocols (from PETHEMA and SHOP groups). PATIENTS AND METHODS: All patients with B-ALL diagnosis from January 1997 to May 2011 were included in the study: in total, 114 patients with a mean of age of 6 ys (0.3–14). The type of leukemia was ALL common (83 patients), pro-B (17 patients), pre-B (13 patients) and mature (1 patient). All the children over 1 yr received treatment according to PETHEMA group protocols, adjusted to the risk. Children under 1 yr were treated following SHOP group protocols. Seventeen patients received an allogeneic transplantation. The main clinical features of the positive and negative patients for ETV6-RUNX1 are detailed in table 1. ETV6-RUNX1 assay was performed in our laboratory by RT-PCR, according to the European BIOMED project methodology. RESULTS: ETV6-RUNX1 was found in 31 of the 114 patients (27.2%). These patients showed a significantly higher frequency of myeloid antigens (p<0.001), and were always positive for CD10 (p=0.006). All cases of positive ETV6-RUNX1 were over 2 years old. No significant differences between positive and negative ETV6-RUNX1 were obtained when complete remissions (100 vs 80%), relapse (16 vs 20%) or deaths (10 vs 13%) were analyzed. Furthermore, estimation of disease free survival (DSF) at 14 ys for both groups were similar: 80 ± 8% for positive vs 66 ± 7% for negative (p=0.21, log-rank test). And the same happened for overall survival (OS): 87 ± 7% for positive vs 83 ± 5% for negative (p=0.4, log-rank test). DISCUSSION: In our series, including patients with B-ALL treated with similar protocols with long periods of follow-up, we could not find differences between positive and negative ETV6-RUNX1 patients. It is well known that the intensity of the chemotherapy regimen and the age of inclusion in different protocols may influence the prognosis. Therefore, at present, it is still a matter of discussion if previous reported differences in the B-ALL ETV6-RUNX1 positive group could be explained by a different stratification in risk groups or by different chemotherapy regimens. This work has been funded by a grant from AECC, Carmen Lavigne Prize 2010 Disclosures: No relevant conflicts of interest to declare.

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