Soluble Interleukin-2 Receptors (sIL-2R) Is An Independent Prognostic Factor for Patients with Diffuse Large B Cell Lymphoma Treated with R-CHOP

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2678-2678
Author(s):  
Noriko Nishimura ◽  
Masahiro Yokoyama ◽  
Kengo Takeuchi ◽  
Naoko Tsuyama ◽  
Eriko Nara ◽  
...  
Keyword(s):  
Risk Factors ◽  
Prognostic Factors ◽  
Prognostic Factor ◽  
Serum Level ◽  
Prognostic Model ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Abstract 2678 Background: Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease characterized by a wide range of clinical outcomes. Rituximab added to CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy, R-CHOP has made a marked improvement in outcome in patients with DLBCL. The International Prognostic Index (IPI), which consists of age > 60 years, stage III/IV, elevated lactate dehydrogenase (LDH) level, Eastern Cooperative Oncology Group (ECOG) performance status (PS) † 2, and more than one extranodal (EN) site of disease, remains the most commonly used system for risk classification in DLBCL. However, recent studies suggested that new agent has altered the significance of previously recognized risk factors. Here we investigate the prognostic impact of reported risk factors in a large DLBCL patient cohort in a single institute to determine a better prognostic model in rituximab era. Patients and Methods: In total, 250 newly diagnosed DLBCL patients treated with R-CHOP regimen at the Cancer Institute Hospital of JFCR between October 2003 and December 2008 were included and analyzed. Progression free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method and compared among risk groups using the log rank test. The Cox proportional hazards model was used to test the significance of prognostic factors. ROC curve was used to determine optimal serum level of sIL-2R and LDH as a cut off value for 4-year mortality risk. Results: The median age of patients was 65 years (range 23–88 years), 56% were male. The median follow-up time was 49 months (range 1–90 months) and 39 deaths had been recorded by the time of the last follow-up. The IPI still remains predictive with an OS ranging from 52.4% to 91.6% at 4 years; however it cannot discriminate between low and low-intermediate group. Revised IPI was valid as well with an OS ranging from 63.3% to 97%. In univariate analysis, elevated sIL-2R level, B symptom, elevated LDH level, PS>2, age>65, stage III/IV, CD5 positive, and EN>1 were significant as poor prognostic factors whereas sex, bulky mass, MIB1 index >90%, Non-GCB were not. Furthermore, multivariate analysis showed that only sIL-2R>924U/ml, CD5 expression, and EN>1 were significant with relative hazard 1.4∼17.5, 1.4∼8.9, and 1.3∼4.7, respectively. As elevated sIL-2R was the most powerful prognostic factor, we performed further analysis on this parameter. Average serum sIL-2R level was 2,775U/ml (range from 220U/ml to 43,100U/ml) with a normal limit of upper is 230U/ml. ROC curve demonstrated that serum sIL-2R was more optimal value than serum LDH to identify high risk patients for 4-year mortality after initiation of R-CHOP therapy and cutoff value of sIL-2R was 924U/ml (1.73 upper limit of normal). sIL-2R level can be divided into three distinctprognostic groups. Patients with sIL-2R<925U/ml fall into a very good group with a 4-year OS:98% and 4-year PFS:90.7%, patients with 925U/ml<=sIL-2R<4,625U/mlfall into a good group with a 4-year OS:82% and 4-year PFS:77.7%, and patients with sIL-2R>=4,625U/ml fall into a poor group with a 4-year OS:59.6% and 4-year PFS:54.7% (P < 0.001). Conclusions: sIL-2R level is an independent and powerful prognostic factor in serum level dependent manner in DLBCL patients treated with R-CHOP. This prognostic model should be reassessed on a larger scale and prospective study. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Central nervous system relapse in diffuse large B-cell lymphoma: analysis of risk factors and a new prognostic model

2015 ◽  
Vol 26 ◽  
pp. vii85
Author(s):  
Yusuke Kanemasa ◽  
Tatsu Shimoyama ◽  
Yuki Sasaki ◽  
Sawada Takeshi ◽  
Eisaku Sasaki ◽  
...  
Keyword(s):  
Risk Factors ◽  
Central Nervous System ◽  
Nervous System ◽  
B Cell ◽  
Prognostic Model ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Central Nervous System Relapse ◽  
Large B Cell Lymphoma ◽  
Large B Cell

High Rate of Initial Treatment Failure in Patients with Primary Mediastinal B-Cell Lymphoma Treated with R-CHOP

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1601-1601 ◽  
Author(s):  
Jeremy S. Abramson ◽  
Matthew D Hellmann ◽  
Yang Feng ◽  
Jeffrey A. Barnes ◽  
Tak Takvorian ◽  
...  
Keyword(s):  
Risk Factors ◽  
B Cell ◽  
Cell Lymphoma ◽  
Univariate Analysis ◽  
B Cell Lymphoma ◽  
Refractory Disease ◽  
Large B Cell Lymphoma ◽  
Ann Arbor ◽  
Large B Cell

Abstract Abstract 1601 Introduction: Primary Mediastinal B-cell Lymphoma (PMBCL) is an uncommon variant of Diffuse Large B-cell Lymphoma (DLBCL). Given the rarity of this disease, data guiding management is extrapolated from DLBCL trials, or from small retrospective analyses limited to PMBCL. Prospective evaluation of R-CHOP in the MiNT trial showed excellent results in PMBCL, but this trial was limited to young low risk patients. We present the largest retrospective series to date of R-CHOP for PMBCL in all risk groups. Methods: We identified cases of PMBCL at our institution using a comprehensive clinicopathologic database derived from tumor registry data. Natural language processing software was used to search pathology reports for terms of “mediastinal lymphoma,” “mediastinal large cell lymphoma,” “mediastinal large B-cell lymphoma,” as well as “lymphoma” in mediastinal biopsy specimens. Cases were included if they met clinicopathologic criteria for PMBCL, defined as a large B-cell lymphoma with typical features for PMBCL presenting with a dominant anterior mediastinal mass. All patients had to have been treated with R-CHOP. Progression-free survival (PFS) and overall survival (OS) are calculated by the Kaplan-Meier method and univariate analysis is performed to assess predictors of outcome. Results: Fifty-eight cases from 2000–2011 met inclusion criteria and are included in the analysis. The median age was 38 years (range 20–82) and 60% were male. Forty-four patients (76%) presented at limited Ann Arbor stage and 12 patients (21%) at advanced stage; presenting stage could not be discerned in 2 patients. Fifty-five percent of patients presented with mediastinal bulk ≥10cm in size; median size was 11cm (range 5–17cm). LDH was elevated at diagnosis in 60% of patients, normal in 21%, and unknown in 19%. By revised IPI score, 19% were low-risk (0 risk factors), 60% were intermediate risk (1–2 risk factors) and 12% were high-risk (≥3 risk factors). R-CHOP was given for a median of 6 cycles (range 1–8); 51 of 58 patients received 6 or 8 cycles. Among patients who achieved initial remission, 78% underwent consolidative radiotherapy and the remainder were observed after chemotherapy alone. The overall response rate was 81% (90%CI [71%–89%]) with 72% complete responses and 9% partial responses. Ten patients (17%) had primary refractory disease defined as progression on treatment or within 3 months of completion of therapy. Among 46 patients who achieved a response, 5 (11%) subsequently relapsed. Two patients, both elderly, died during treatment. Among the 10 patients with primary refractory disease, 6 have died from progressive lymphoma, 2 patients are alive with active disease undergoing salvage therapy, 1 is alive and free of disease greater than 8 years from diagnosis, and 1 was lost to follow-up. Among 5 patients with relapsed disease, 2 are alive without disease at last follow-up, while 3 have died of progressive lymphoma. Median follow-up for the entire series is 58 months. Five-year PFS is 68% (95% CI, 55% to 80%) and 5-year OS is 76% (95% CI, 65% to 88%). On univariate analysis, advanced Ann Arbor stage and high R-IPI score were associated with inferior PFS and OS. (p=0.006 and p<0.001, respectively for PFS, p=0.005 and p<0.001 for OS, log-rank test). Conclusion: PMBCL treated with R-CHOP carries an overall favorable prognosis, though primary refractory disease occurs in a significant number of patients, and is rarely curable with second line therapy. Advanced stage disease and high R-IPI scores are associated with inferior outcome. Novel treatment approaches warrant evaluation in high-risk patients. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Lymphocyte-to-Monocyte Ratio at Diagnosis and Survival in De Novo Double/Triple Hit Diffuse Large B-Cell Lymphoma

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3885-3885
Author(s):  
Luis Porrata ◽  
Kay Ristow ◽  
Ellen D. McPhail ◽  
William Macon ◽  
Matthew J Maurer ◽  
...  
Keyword(s):  
Prognostic Factor ◽  
B Cell ◽  
Research Funding ◽  
De Novo ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Lymphocyte To Monocyte Ratio ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract The lymphocyte-to-monocyte ratio at diagnosis (LMR-D) has been reported to be a prognostic factor for clinical outcomes in both T-cell and B-cell lymphomas. However, there are no reports testing the prognostic ability of LMR-D in patients diagnosed with de novo double/triple hit diffuse large B cell lymphoma (DLBCL). Thus, we set out to investigate if the LMR-D is a prognostic factor for survival in de novo double/triple hit lymphomas. From 10/5/1998 until 1/16/2015, thirty-four patients with de novo double/triple hit DLBCL were identified for this study. Double and triple hit were defined by interphase FISH evaluating three fusion signals to identify the BCL2 translocation and IGK/MYC D-FISH probe to identify whether the partner is IG or non-IG. Interphase fluorescence in situ hybridization (FISH) was performed on paraffin sections using probes that included 8q24 (5'MYC, 3'MYC); t (2;8), IGK/MYC; t(8,14), MYC/IGH; t(8;22), MYC/IGL; 3q27 (3'BCL6, 5'BCL'6); and 18q21 (3'BCL2, 5'BCL2). The cohort included 14 females and 20 males. The median follow-up for the cohort was 9.0 months (range: 0.4-72.6 months). Using the median for the LMR-D as the cut-off value, patients with a LMR-D ≥ 1.2 experienced superior overall survival (OS) [Hazard ratio (HR) of 0.127, 95% confidence interval (CI) of 0.019-0.530, p < 0.004] and progression-free survival (PFS) [HR of 0.107, 95 CI of 0.024-0.335, p < 0.0001]. The median follow up for OS for patients with a LMR-D ≥ 1.2 was not reached with a 5-year OS rate of 82% (95% CI of 49%-95%) compared with a median follow-up of 10 months for patients with a LMR-D < 1.2 with a 0% 5 year OS rate, p < 0.003 (Figure 1A). The median PFS for patients with a LMR-D ≥ 2 was not reached with a 5 years PFS of 74% (95%CI, of 43%-91%) compared with a median follow-up of 4.7 months for patients with a LMR-D < 1.2 and 0% 5 year PFS rate, p < 0.0001 (Figure 1B). After adjusting for the International Prognostic Index, multivariate analysis showed that the LMR-D remained an independent prognostic factor for OS [HR = 0.180, 95% CI of 0.254-0.784, p < 0.02] and for PFS [HR of 0.127, 95%CI of 0.029-0.409, p < 0.0003]. In spite of the small cohort of de novo double/triple hit DLBCL, the LMR-D was identified as a prognostic factor for clinical outcomes for this specific set of aggressive lymphomas. Further studies are warranted to confirm our findings. Table.LMR-D ≥ 1.2, N = 18Events = 2LMR-D < 1.2, N = 16Events = 8P < 0.003LMR-D ≥ 1.2, N = 18Events = 3LMR-D < 1.2, N = 16Events = 14P < 0.0001Figure 1AB Figure 1. Figure 1. Disclosures Maurer: Kite Pharma: Research Funding. Ansell:Bristol-Myers Squibb: Research Funding; Celldex: Research Funding. Off Label Use: New agent in a combination regimen..

scholarly journals Left Ventricular Ejection Fraction Measurement and Doxorubicin-Based Chemotherapy in Patients with Diffuse Large B-Cell Lymphoma

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1300-1300
Author(s):  
Deborah L Enns ◽  
David M Aboulafia
Keyword(s):  
Risk Factors ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction ◽  
Large B Cell Lymphoma ◽  
The Mean ◽  
Large B Cell

Abstract Purpose: Doxorubicin-based chemotherapy (DOX) is commonly administered to patients with diffuse large B-cell lymphoma (DLBCL). Prior to chemotherapy, left ventricular ejection fraction (LVEF) is routinely measured to assess left ventricular dysfunction. While LVEF screening is recommended by many national regulatory bodies, evidence supporting the usefulness of LVEF measurement prior to administering DOX is lacking. Our goal was to perform a retrospective analysis of patients with DLBCL to establish (1) how often LVEF was measured prior to administering DOX, and (2) whether the chemotherapy regimen was modified based on LVEF values. As cumulative doses of doxorubicin greater than 400 mg/m2 have been associated with an increased risk of congestive heart failure (CHF), we also determined the incidence of CHF in patients with DLBCL who did receive DOX. Patients and Methods: We identified 268 patients diagnosed with DLBCL at Virginia Mason Medical Center between 2001 and 2012 and collected the following data: age at diagnosis; stage of lymphoma; type of chemotherapy given; cumulative doxorubicin dose (mg/m2); LVEF status; and incidence of CHF or cardiac disease. We also compared the number of CHF risk factors between patients who did and did not have LVEF measured. Statistical analyses included a Fischer’s exact or Chi-squared test to compare study groups as well as the number of CHF risk factors. The level of significance was set at a P value of < 0.05. Results: LVEF was measured in 238 patients (89%) prior to initiation of chemotherapy. LVEF values were normal in 225 patients (95%) and low (< 50%) in 13 patients (5%). Of the patients with normal LVEF, 193 received DOX (86%), and of these patients, 14 developed CHF post-treatment (7%). For the 13 patients with low LVEF, 8 received DOX (62%) and 1 developed post-treatment CHF (13%). The remaining thirty patients did not have LVEF measured and none received DOX. Of the 268 patients studied, 176 are alive (66%) and 3 were lost to follow-up. The mean follow-up time was 43 months (range 3 d to 12.1 y). The mean number of CHF risk factors did not differ between patients who did and did not have LVEF measured (1.70 vs. 1.65, P = 0.87). Conclusion: Our results suggest that the decision to administer DOX was not directly affected by LVEF values. These findings challenge the existing policy of routinely screening patients with DLBCL with echocardiograms or MUGA scans prior to treatment. Disclosures No relevant conflicts of interest to declare.

Metabolic Tumor Volume Has Potential Clinical Impact Compared with SUVmax in Primary Gastrointestinal Diffuse Large B Cell lymphoma

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4983-4983
Author(s):  
Moo-Kon Song ◽  
Joo-seop Chung ◽  
Ho-Jin Shin ◽  
Joon Ho Moon ◽  
Jeong Ok Lee ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Prognostic Factor ◽  
Tumor Volume ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Metabolic Tumor Volume ◽  
Tumor Burden ◽  
Large B Cell Lymphoma ◽  
18F Fdg ◽  
Large B Cell

Abstract Abstract 4983 Background: Primary gastrointestinal (GI) lymphoma is the most commonly involved extranodal site and represents 10–15% of all Non-Hodgkin's Lymphoma cases. Recent studies showed that the prognostic value of early 18F-FDG PET using maximum standardized uptake volume (SUVmax) on pretreatment was important prognostic factor in primary GI diffuse large B cell lymphoma (DLBCL). However, initial tumor burden is still an important subject associated with prognosis even extranodal DLBCL. The purpose of this study was to assess the prognostic impact of metabolic tumor volume (MTV) as tumor burden using by PET scan technique compared with initial SUVmax in primary GI DLBCL. Patients and methods: From April, 2006 to July, 2009, 125 stage IE (58 patients) or IIE (67 patients) primary GI DLBCL patients with localized lymph node involvement were enrolled and assigned to 6 or 8 cycles of R-CHOP therapy. Median follow-up was 36 months. Median age was 62 years (range, 20–79 years). Seventy-four patients were male and remainders were female. Numbers of patients above 60 years were 71. Twenty-five patients had an Eastern Cooperative Oncology Group performance status of more than two. Calculatory system by computer automatically delineated a extranodal target lesions above SUV, 2.5 and MTV of GI lesion was 3-dimensional reconstructed by fusion software. The SUVmax was collected from predominant GI lesion and calculated based on the attenuation-corrected images, the amount of injected 18F-FDG and body weight. Results: The extranodal sites of GI tract were included stomach and duodenum (64 patients, 51.2%), jejunum (10 patients, 8%), terminal ileum (30 patients, 24%), cecum (7 patients, 5.6%), ascending colon (8 patients, 6.4%), transverse colon (3 patients, 2.4%) and decending colon (3 patients, 2.4%). We used ROC curve analysis. 158.3cm3 was decided as best ideal cut-off value of MTV and 15.5 was decided as the cut-off value of SUVmax. Several factors (age, sex, disease status and IPI score) between high MTV (≥158.3cm3) and low MTV group (<158.3cm3) were not significantly different. However, SUVmax higher in high MTV group than low MTV group (p<0.001). In response by revised International Workshop Criteria, low MTV group had excellent response rates than high MTV group (CR, p<0.001; PR, p=0.014; SD & PD, p<0.001). Moreover, 3-year PFS was higher in low MTV group than high MTV group (low MTV group, 96.7%; high MTV group, 37.1%; p<0.001) and 3-year OS was also higher in low MTV group than high MTV group (low MTV group, 97.8%; high MTV group, 42.9%; p<0.001). The PFS and OS were higher in low SUVmax group (<15.5) than high SUVmax group (≥15.5) (p<0.001, p<0.001, respectively). In univariate analysis, high IPI score is still important prognostic factor for PFS and OS (PFS: HR, 4.181 [1.844-9.478] p=0.001 & OS: HR, 4.300 [1.801-10.263] p=0.001). High MTV and high SUVmax were also poor prognostic factors for PFS and OS (high MTV; PFS: HR, 26.543 [7.923-88.231] p<0.001 & OS: HR, 32.458 [7.579-139.018] p<0.001) (high SUVmax; PFS: HR, 6.998 [2.399-20.418] p<0.001 & OS: HR, 13.976 [3.257-59.979] p<0.001). In multivariate analysis, high MTV group (PFS: HR, 19.850 [5.193-75.870] p<0.001 & OS: HR, 17.918 [3.694-86.904] p<0.001) and high IPI score (PFS: HR, 2.659 [1.136-6.223] p=0.024 & OS: HR, 2.866 [1.175-6.989] p=0.021) were independent prognostic factors for PFS and OS. However, SUVmax had not significant value for survival. Conclusion: In primary GI DLBCL, high MTV is very important and potential prognostic factor compared with SUVmax for predicting the survival. Therefore, more aggressive treatment strategy would be performed in primary GI DLBCL patients having initial high tumor burden. Disclosures: No relevant conflicts of interest to declare.

Clinical Significance of MYC, BCL2 and BCL6 Rearrangement and Protein Expression in GCB and Non-GCB Type Diffuse Large B-Cell Lymphoma

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1445-1445
Author(s):  
Keisuke Kawamoto ◽  
Jun Takizawa ◽  
Hiroaki Miyoshi ◽  
Noriaki Yoshida ◽  
Yasuhiko Shibasaki ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Prognostic Factor ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Prognostic Indicators ◽  
Newly Diagnosed ◽  
Poor Prognostic Factor ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Background: Diffuse large B-cell lymphoma, not other specified (DLBCL, NOS) is the most common type of malignant lymphoma and accounts for approximately one-third of all non-Hodgkin lymphomas. Translocation of MYC, BCL2, and BCL6 genes detected by fluorescence in-situ hybridization (FISH) were found in approximately 10%, 14%, and 20% DLBCL, respectively. MYC translocation is already reported to be an independent poor prognostic factor in DLBCL. Immunohistochemical(IHC) analysis has revealed that concurrent protein expression of MYC and BCL2 could be a predictive factor for overall survival (OS). However, the relationship between translocation and expression of MYC, BCL2 and BCL6 is still unknown, and it is not clear what proportion of MYC and BCL2 IHC is predictive for OS. Objectives: The purpose of this study was to clarify the clinical prognostic value of immunostaining and chromosomal translocation of MYC, BCL2 and BCL6 among the populations in whom these results were investigated. Patients and Methods: Sixty-one adult patients, newly diagnosed as DLBCL, NOS between October 2003 and October 2012 at Niigata University Hospital, were analyzed retrospectively. MYC, BCL2 and BCL6 rearrangements were detected by FISH, and the expression of MYC, BCL2, and BCL6 proteins were investigated by IHC. To assess the proportion of these proteins, we created a tissue microarray (TMA). The median age was 62 years (range: 17-85 years), and the median follow up period was 42 months (range: 2-127 months). All patients were treated with R-CHOP or R-CHOP-like regimens. OS was estimated by the Kaplan-Meier method. Multivariate Cox regression for OS was used to identify the independent prognostic factors. Results: According to univariate analysis, MYC rearrangement (10%) was a prognostic factor (P = 0.026); however, BCL2 and BCL6 translocation were not prognostic indicators (11%, P = 0.899; 13%, P = 0.819, respectively). On the other hand, the expression of MYC detected by IHC showed no statistical significance for OS, even if the cut-off level by MYC and BCL6 immunostaining was modified. However, if we divided the patients into two groups, i.e., those with 0-9% and those with ≥10% expression of BCL2 immunostaining, ≥10% expression of BCL2 may be a prognostic factor (P = 0.0087). We subsequently analyzed whether the concurrent expression of MYC and BCL2 or that of MYC and BCL6 would be prognostic factors for OS. In this study, patients with ≥30% expression of MYC and ≥30% expression of BCL2 showed poor prognosis compared to other patients (P = 0.00234, 5-year OS 42%, 84% respectively). Furthermore, we divided the patients in two groups i.e., the germinal center B-cell-like (GCB) type and non-GCB type as described by Hans et al., and the non-GCB type was observed to be a poor prognostic factor in both groups (P = 0.013). Further, we investigated whether these factors could be independent factors for OS. Multivariate analysis revealed IPI3-5 (HR, 3.1510 [range: 1.181-3.151), P = 0.022), MYC translocation (HR, 3.686 [range: 1.113-12.210], P = 0.033), and MYC (≥30%)/BCL2 (≥30%) double-expression (HR, 4.051 [range: 1.447-11.340], P = 0.0078) were independent poor prognostic indicators in newly diagnosed DLBCL patients treated with R-CHOP or R-CHOP like regimens. Conclusions MYC translocation by FISH and MYC (≥30%)/BCL2 (≥30%) double-expression detected by IHC could be independent prognostic factors for OS. However, MYC expression is not a surrogate marker for MYC translocation by FISH. In conclusion, FISH analysis of MYC translocation and MYC and BCL2 co-expression are important for predicting the prognosis of DLBCL. These results indicate that further validation is required using another population. Disclosures No relevant conflicts of interest to declare.

Absolute Lymphocyte Count at the Time of Relapse Predicts Survival in Patients with Diffuse Large B-Cell Lymphoma.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1763-1763
Author(s):  
Luis F. Porrata ◽  
Kay Ristow ◽  
Thomas M Haberman ◽  
Thomas E Witzig ◽  
David James Inwards ◽  
...  
Keyword(s):  
Prognostic Factor ◽  
Clinical Outcome ◽  
B Cell ◽  
Lymphocyte Count ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Absolute Lymphocyte Count ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract The International Prognostic Index at the time of relapse (IPI-R) has been reported to predict clinical outcome in patients with relapsed diffuse large B-cell lymphoma (DLBCL) undergoing autologous stem cell transplantation (ASCT) [Jabbour et al, Leukemia & Lymphoma2005;46(6):861–867; Lerner et al, Biology of Blood and Marrow Transplant2006;13:486–492; and Costa et al, Bone Marrow Transplant2008;41:715–720]. The absolute lymphocyte count (ALC) has been reported as a prognostic factor for survival at diagnosis, during standard chemotherapy and at day 15 post-ASCT for multiple hematological malignancies; however, no reports have addressed whether ALC at the time of relapse (ALC-R) predicts survival. Thus, we assessed the prognostic significance of ALC-R in patients with relapsed DLBCL. To be included in the study, patients were required to have been diagnosed with relapsed DLBCL, have ALC values available from the time of relapse, and to be followed at Mayo Clinic, Rochester. From Feb 2,1987 until March 6, 2006, 121 DLBCL patients qualified for the study. The overall survival (OS) was measured from the time of relapse to the date of death or last follow-up and progression-free survival (PFS) was defined as the time from relapse to the time of progression, relapse, death, or last follow-up. The median age at relapse was 68 years (range:25–88 years) and the median ALC-R was 1.21 x 109/L (range: 0.33–5.99 x 109/L). The value of ALC-R ≥ 1.0 x 109/L was used for the analysis based on previous publications. The groups (ALC-R ≥ 1 or &lt; 1 x 109/L) were balanced for the IPI-R (p=0.1), as well as for undergoing ASCT (p=0.4). Superior OS was observed in patients with an ALC-R ≥ 1.0 x 109/L (N = 76) [median OS: 27.5 months, 3 years OS rates of 42%] compared with patient with an ALC-R &lt; 1.0 x 109/L (N =45) [median OS: 9.4 months, 3 years OS rates of 13%] (p &lt;0.0001). Superior PFS was also observed in patients with an ALC-R ≥ 1.0 x 109/L (N = 76) [median PFS: 14.8 months, 3 years PFS rates of 30%] compared with patient with an ALC-R &lt; 1.0 x 109/L (N =45) [median PFS: 6.2 months, 3 years PFS rates of 11%] (p &lt;0.001). ALC-R was an independent prognostic factor for OS [RR = 0.551, p &lt; 0.009] and PFS [RR = 0.674, p &lt; 0.02] in the multivariate analysis when compared with the IPI-R and whether patients underwent ASCT or not. Our study supports the hypothesis that ALC at relapse predicts clinical outcome in DLBCL and suggests that patient host immunity is an important variable predicting survival in relapsed DLBCL.

Prospective Cohort Study with Risk-Adapted Central Nervous System (CNS) Evaluation in Diffuse Large B-Cell Lymphoma Patients Treated with Rituximab-CHOP: Analysis of Incidence and Risk Factors for Secondary CNS Involvement.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2683-2683
Author(s):  
Seok Jin Kim ◽  
Yong Park ◽  
Soon Il Lee ◽  
Hyeon Seok Eom ◽  
Jin Seok Kim ◽  
...  
Keyword(s):  
Risk Factors ◽  
Central Nervous System ◽  
Bone Marrow ◽  
Nervous System ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Cns Involvement ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Abstract 2683 Background Secondary central nervous system (CNS) involvement in diffuse large B-cell lymphoma (DLBCL) includes CNS relapse or CNS involvement with systemic disease progression. Although many publications have provided information regarding the incidence and risk factors for CNS involvement in DLBCL, its incidence reported across those studies varies widely. It might be related with that the majority of data were from retrospective analyses. Furthermore, the role of CNS prophylaxis for DLBCL has been challenged, especially in the era of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone). As a result, this rare but fatal clinical problem still remains a therapeutic dilemma in the management of DLBCL. In this study, we prospectively explored the risk factors of CNS involvement and the clinical impact of screening evaluation for CNS involvement. Methods We analyzed the incidence of secondary CNS involvement in pathologically confirmed DLBCL patients enrolled in the Prospective Cohort Study with Risk-adapted Central Nervous System Evaluation in Diffuse Large B-cell Lymphoma (PROCESS study, NCT01202448). Patients should be treated with at least one cycle of R-CHOP, and provide written informed consents. We assessed the risk of CNS involvement based on previously reported risk factors: serum LDH elevation, the number of extranodal involvements, serum albumin, bone marrow invasion, HIV positivity, the involvement of testis, breast, paranasal sinus, bone, retroperitoneal lymph nodes, orbit, and epidural space. If patients had any of these risk factors, they underwent CSF study to screen the CNS involvement at diagnosis. If the results were abnormal, additional studies including brain MRI could be done depending on physicians' decision. CNS prophylaxis was done with intrathecal chemotherapy with methotrexate for patients who had positive findings of screening evaluation or were determined to have a risk of CNS involvement based on physicians' decision. Results 564 patients were enrolled between 2010 and 2012 from 26 institutions belonged to the Consortium for Improving Survival of Lymphoma (CISL). They were prospectively monitored with the median follow-up duration of 10.5 months. The median age was 59.5 years old (range 20–89 years), and approximately a half of patients had Ann Arbor stage III/IV (n = 276, 48.9%) and 193 patients involved two or more than two extranodal sites (34.2%). Based on the International Prognostic Index (IPI) risk, 192 patients belonged to high or high-intermediate risk (34%). Among patients (n = 368) who had at least one of risk factors for CNS involvement, 243 patients underwent CNS evaluation, and the evidence of CNS involvement was found in16 patients including positive cytology (n = 11), and brain parenchyma lesion (n = 5). The other 78 patients showed equivocal results of CSF analysis including the presence of atypical cells (n = 17). Intrathecal prophylaxis was done for 51 patients whereas high dose methotrexate chemotherapy was combined with R-CHOP for patients with brain lesion. During follow-up, 14 cases of additional CNS involvement including brain parenchyma (n = 8), leptomeningeal (n = 5), and ocular invasion (n = 1) were observed. The median time to CNS event in these 14 patients was 7.5 months (range 1.2 – 15.9 months). Thus, 30 cases of secondary CNS involvement were documented in our study population at the time of analysis (5.3%) including 16 cases at diagnosis and 14 cases during follow-up. The univariate analysis for evaluation of risk factors demonstrated serum LDH, the number of extranodal involvements, bone marrow invasion, and the involvement of retroperitoneal lymph nodes, breast, paranasal sinus and orbit were significantly associated with CNS involvement. The high/high-intermediate risk of IPI was also predictive of CNS involvement (P < 0.05). However, in the multivariate analysis, bone marrow invasion and the involvement of breast, paranasal sinus and orbit were independently predictive for CNS involvement. Conclusions The incidence of secondary CNS involvement in DLBCL patients treated with R-CHOP was around 5%, and a half of cases had the evidence of CNS involvement at diagnosis. Considering a particular risk of CNS involvement of disease-related factors, risk-adapted active screening against CNS involvement may help to improve treatment outcome of patients with DLBCL. Disclosures: No relevant conflicts of interest to declare.

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