ALBERT

Description: Abstract 1574 Follicular lymphoma (FL) is an indolent non-Hodgkin lymphoma (NHL), with a highly variable natural history ranging from an indolent disease to a rapidly progressive one such as its transformation to aggressive NHL. We have used the Follicular Lymphoma International Prognostic Index (FLIPI) that uses patient- or tumor-specific characteristics for the risk-stratification of patients with FL at the time of diagnosis. The tumor microenvironment, including variable monocyte-derived cell infiltration, has recently shown to play an important role in the clinical course of FL patients. Wilcox et al. showed that an elevated absolute monocyte count (AMC) is associated with inferior overall survival of FL patients receiving varying treatment strategies (Wilcox RA, et al. Leuk Lymphoma 2012). We retrospectively evaluated the prognostic changes in AMC at diagnosis in FL patients treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) therapy alone. This study included 157 consecutive FL patients treated with the R-CHOP therapy at 1 of the 7 participating hospitals between 2001 and 2009. Since 2001, the Yokohama City University Hematology Group in Japan uniformly and curatively treated patients with FL, except for those with stage 1 FL; the patients were treated with 6 cycles of standard R-CHOP therapy for 21 days. Patients who showed partial response (PR) after the initial 4 cycles were administered a total of 8 R-CHOP cycles, and those who did not show PR after the initial 4 cycles or patients in whom the disease progressed at any given time received salvage therapy. Patients who had bulky masses at diagnosis received involved field radiation following 6—8 cycles of R-CHOP therapy. Patients for whom the doses had to be reduced by more than 20% were excluded from the study. The study included 80 men and 77 women, with a median age of 63 years at diagnosis (range, 18—80 years). The FL of the 157 patients were classified as grade 1 (n = 65), grade 2 (n = 60), grade 3a (n = 20), and grade 3b (n = 12) according to the World Health Organization (WHO) scheme. The median AMC at diagnosis was 349 cells/μL (range, 10—1110 cells/μL). The median observation period for surviving patients was 45 months. The 5-year progression-free survival (PFS) estimated for the entire cohort was at 71.3%. The differences in the PFS when patients were stratified according to their AMCs were not significant. The effect of the following variables on PFS were assessed: (1) AMC 〉 390 cells/μL; (2) age 〉 60 years; (3) hemoglobin level 〈 120 g/L; (4) elevation of serum lactate dehydrogenase levels; (5) nodal areas 〉 4; and (6) advancement of clinical stage. In the univariate analysis, the presence of more than 4 nodal areas (hazard ratio [HR] = 2.65, 95% CI, 1.58—4.47, P 〈 0.001) and advanced clinical stage (HR = 2.75, 95% CI, 1.26—6.03, P= 0.01) were associated with inferior PFS. However, in the multivariate analysis, the association between the presence of more than 4 nodal areas and survival was found to be significant (HR = 2.33, 95% CI, 1.28—4.24, P = 0.006). Therefore, both univariate and multivariate analyses indicate that AMC was not a prognostic factor for PFS. There was no statistically significant correlation between AMC and FL patients' clinical outcome. AMC is not a prognostic factor in FL patients treated by R-CHOP. Disclosures: No relevant conflicts of interest to declare.

Description: Background: Since the introduction of rituximab, an anti-CD20 monoclonal antibody, the prognosis of patients with CD20-positive non-Hodgkin lymphoma has significantly improved. Recent reports have shown a gender-associated difference in rituximab clearance and clinical response, suggesting that rituximab may be more effective in female patients. However, the prognostic impact of gender with regard to rituximab clearance in diffuse large B-cell lymphoma (DLBCL) patients has not been elucidated thus far. Methods: We retrospectively analyzed data from 576 consecutive DLBCL patients, uniformly treated with standard rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP-21) therapy in 9 institutions in Japan, between 2001 and 2012. Patients with a dose reduction greater than 20%, mainly elderly patients with low performance status, were excluded from this study. The median age of the cohort was 63 years (range, 18–89 years), and 331 (57%) of the patients were male. Results: With respect to the International Prognostic Index (IPI) factors, a significantly higher proportion of female patients had elevated serum lactate dehydrogenase (sLDH) levels than male patients (57% vs. 48%, P = 0.03). A difference was also observed in the frequency of bone marrow (BM) involvement, which was primarily observed in male patients (8% in female vs. 15% in male, P= 0.006).No difference was observed between sexes in other baseline factors (other IPI factors, bulky mass over 10 cm, B symptoms). Complete remission rate for R-CHOP-21 was 86% in female patients and 85% in male patients (P = NS). After a median follow-up of 48 months, the 3-year progression-free survival (PFS) and overall survival (OS) rates were 73.7% and 84.3%, respectively. The IPI on diagnosis was low for 238 (41.3%) patients, low-intermediate for 152 (26.4%) patients, high-intermediate for 94 (16.3%) patients, and high for 92 16.0%) patients, with significant differences in survival among the 4 groups (3-year OS: 93.2%, 85.1%, 81.1%, and 63.6%, respectively, P 〈 0.001). Univariate analysis revealed that advanced clinical stage, poor performance status (PS 2-4), elevated sLDH, more than 1 extranodal involvement, BM involvement, bulky mass over 10 cm, and B symptoms had prognostic impact for both PFS and OS (all P

Description: Background Positron emission tomography (PET) is being increasingly performed for evaluation of the therapeutic efficacy (post-therapy PET) after lymphoma treatment. Although post-therapy PET is effective in predicting the outcome in 18F-fluorodeoxyglucose (FDG)-avid lymphomas such as Hodgkin lymphoma and diffuse large B-cell lymphoma, its efficacy in predicting the outcome for peripheral T-cell lymphomas (PTCLs) is not fully elucidated. Hence, we evaluated the association between the results of post-therapy PET and prognosis in patients with PTCLs. Patients and Methods Of the 57 patients with PTCLs (peripheral T-cell lymphoma, not otherwise specified [PTCLnos] and angioimmunoblastic T-cell lymphoma [AITL]) who underwent first-line treatment in 5 hospitals of the Yokohama City University Hematology Group between 2005 and 2011, we enrolled 37 patients who were evaluated by post-therapy PET in this study. The histological diagnoses were PTCLnos in 16 cases and AITL in 21 cases. All 37 patients received adriamycin (ADR)- or THP-ADR (THP)-containing chemotherapy with curative intent. Of these, 2 patients received involved-field radiotherapy as a part of first-line therapy. For the evaluation of post-therapy PET, images were interpreted by local nuclear medicine physicians and detailed reports were prepared. The association between the results of the post-therapy PET and outcome of the patients was evaluated. Results The study population comprised 19 men and 18 women. Their median age was 63 years (range 16-83 years), and the median observation period among the surviving patients was 42 months. According to the International Prognostic Index (IPI), 7 (19%) patients were at low risk, 11 (30%) were at low-intermediate risk, 12 (32%) were at high-intermediate risk, and 7 (19%) were at high risk. The distribution of prognostic index for T-cell lymphoma was 5 (14%) in group 1, 12 (32%) in group 2, 15 (40%) in group 3, and 5 (14%) in group 4. At presentation, 15 (41%) patients had B symptoms and 6 (16%) showed bone marrow involvement. None had a bulky mass with a 〉10-cm diameter in the horizontal section. First-line treatment included CHOP, THP-COP, THP-COP followed by involved-field irradiation, and biweekly THP-COP in 6, 22, 2, and 7 patients, respectively. None of the patients received up-front stem cell transplantation. At presentation, 27 patients underwent PET, of which and 26 (96%) showed positive results. Of the 37 patients who underwent post-therapy PET, 12 (32%) showed positive results and 25 (68%) showed negative results. The 3-year progression-free survival rates in the positive and negative post-therapy PET result groups were 17% and 62%, respectively (P〈 0.001) (Figure). Ten of the 12 post-therapy PET patients showing positive results experienced PD (positive predictive value, 83%), while 16 of the 25 patients showing negative results did not experienced PD (negative predictive value, 64%). The 3-year overall survival rates in the positive and negative post-therapy PET result groups were 46% and 84%, respectively (P = 0.044). All of the 9 patients died during the observation period due to lymphoma. Conclusions Post-therapy PET predicts the outcome in patients with PTCLs (PTCLnos and AITL). Disclosures: No relevant conflicts of interest to declare.

Description: Background The prognosis of diffuse large B-cell lymphoma (DLBCL) has considerably improved during the last decade, mainly due to the addition of rituximab to chemotherapy. However, a significant proportion of patients still experience relapses after achieving first complete remission (CR), leading to poor survival. Although a specific predictor of relapse of non-Hodgkin’s lymphoma has not been identified thus far, recently, the peripheral blood lymphocyte/monocyte ratio (LMR) at diagnosis, which reflects the host’s immune status, was reported to predict clinical outcomes in DLBCL patients treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). However, the significance of LMR as a predictor of relapse in DLBCL patients in remission is not clear. The aim of this study was to assess whether LMR at 6 months after remission is a predictor of relapse after R-CHOP therapy in DLBCL patients. Methods From 2003 to 2009, 357 consecutive DLBCL patients were diagnosed, treated with R-CHOP, and followed up at 1 of the 7 participating hospitals in Japan. Of these, 315 DLBCL patients achieved CR after 6–8 cycles of R-CHOP therapy. Among the 315, those who were in remission for more than 6 months (n = 280) were enrolled in this study. The cumulative incidence of relapse was calculated from 6 months after CR to the first subsequent relapse or last follow-up. The effects of risk factors of relapse were assessed in univariate and multivariate Cox regression analyses. In multivariate analysis, risk factors tested at the time of diagnosis, confirmed remission and 6 months after remission included gender, International Prognostic Index at diagnosis (age 〉 60 years, elevated lactate dehydrogenase level, poor Eastern Cooperative Oncology Group performance status [ECOG PS], the presence of 2 or more extranodal involvement sites, and advanced clinical stage), and LMR ≤ 3.3. Results The study included 161 men and 119 women, with a median age of 64 years at diagnosis (range, 18–80 years). The median LMR at 6 months after remission was 3.7 (range, 0.5–18.0). The median observation period for surviving patients was 63 months. In all, 35 (12.5%) patients had confirmed relapse after achieving first CR, with a median time to relapse of 23 months (range, 6–61 months). The estimated 5-year cumulative incidence rate of relapse for the entire cohort was 14.7%. According to the LMR at 6 months after remission, the 5-year cumulative incidence rate for LMR ≤ 3.3 was 17.0% compared to 12.7% for LMR 〉 3.3 (P = 0.188). In the univariate analysis, advanced clinical stage at diagnosis (hazard ratio [HR] = 2.61, 95% confidence interval [CI], 1.33–5.13, P = 0.005) and poor ECOG PS at diagnosis (HR = 2.62, 95% CI, 1.19–5.77, P = 0.017) were associated with the occurrence of relapse. Multivariate analysis identified advanced clinical stage at diagnosis (HR = 2.42, 95% CI, 1.11–5.27, P = 0.026) and LMR ≤ 3.3 at 6 months after remission (HR = 2.10, 95% CI, 1.01–4.35, P = 0.047) as the risk factors for relapse. Conclusions The LMR at 6 months after remission is an independent predictor of relapse in first CR in DLBCL patients treated with R-CHOP. Disclosures: No relevant conflicts of interest to declare.

Description: Background: In lymphoma patients, it is believed that serum lactate dehydrogenase (LDH) reflects the tumor mass and that soluble interleukin-2 receptor (sIL-2R) is indicative of activated T-cell reaction. Although it is important to characterize the pattern of LDH and sIL-2R in each subtype of lymphoma, limited information is available on this topic. We investigated LDH and sIL-2R in patients with representative subtypes of lymphoma. Patients and Methods: In the Yokohama City University Hematology Group Lymphoma Database, 3,484 untreated patients were registered between 1996 and 2014. We extracted the data of 3,005 patients with the 8 following subtypes: follicular lymphoma (FL), mucosa-associated lymphoid tissue lymphoma (MALT), mantle cell lymphoma (MCL), diffuse large B-cell lymphoma (DLBCL), Burkitt lymphoma (BL), Hodgkin lymphoma (HL), peripheral T-cell lymphoma (PTCL), and extranodal NK/T cell lymphoma (ENKL). In this retrospective study, we included 2,889 patients in whom both LDH and sIL-2R were recorded. We used the Kruskal-Wallis test to compare LDH and to compare sIL-2R in all 8 subtypes. Each subtype was compared using the Dwass, Steel, Critchlow-Fligner test (multiple comparison test). Results: The 2,889 patients consisted of 1,630 men and 1,259 women, with a median age of 65 years (range, 15-95 years). The median LDH was 1.0 x upper normal limit (N) (range, 0.1 N–53.9 N). The median sIL-2R was 1,150 U/ml (range, 53-142,000 U/ml). The distribution of lymphoma subtypes was as follows: 584 FL (20%), 219 MALT (8%), 82 MCL (3%), 1,579 DLBCL (54%), 39 BL (1%), 162 HL (6%), 162 PTCL (6%), and 62 ENKL (2%). Overall, LDH as well as sIL-2R showed significant difference in the 8 subtypes (P 〈 .0001 for both). The median values of LDH and sIL-2R in each subtype were as follows: 0.9 N and 1,114 U/ml in FL, 0.8 N and 467 U/ml in MALT, 1.15 N and 4,460 U/ml in MCL, 1.1 N and 1,230 U/ml in DLBCL, 2.4 N and 1,700 in BL, 1.0 N and 1,460 U/ml in HL, 1.2 N and 3,193 U/ml in PTCL, and 1.0 N and 679 U/ml in ENKL, respectively. In LDH analysis, BL showed higher value than any other subtypes and MALT showed lower value than any other subtypes. In sIL-2R analysis, MCL showed a higher value than any other B-cell lymphomas, except for BL, and MALT showed lower value than any other subtypes. In the comparison of the most frequent subtypes of FL and DLBCL, LDH was significantly higher in DLBCL (P 〈 .0001); however, sIL-2R was not significantly different (P = 0.31). The correlation between LDH and sIL-2R in each subtype was depicted in the Figure. The diameter of the circle indicated the number of patients. Conclusion: Our findings suggested that the tumor mass was greatest in BL and that T-cell reaction was greater in MCL. Furthermore, both tumor mass and T-cell reaction were lowest in MALT. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Description: Background Obesity has been pointed out as one of the risk factors for the development in several neoplastic diseases including malignant lymphoma. However the impact of obesity on the outcome of malignant diseases is unclear. L.Weiss et al have shown that high body mass index (BMI) is a significantly better prognostic factor in diffuse large B-cell lymphoma (DLBCL) (Increased body mass index is associated with improved overall survival in diffuse large B-cell lymphoma. Annals of Oncology 2014; 25: 171-176.). We evaluated this hypothesis in Japanese patients with DLBCL. Patients and Methods We analyzed 338 patients with newly diagnosed DLBCL who received full-dose (80% or more of the prescribed dose) R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) between April 2003 and December 2009 across 7 institutes. Patients of all stages were treated 6 or 8 cycles of full-dose R-CHOP therapy. All the patients were classified into 2 groups: high BMI (≥25 kg/m2 ) or low BMI (

Description: Background Peripheral T-cell lymphoma (PTCL) is known to have an aggressive clinical course and be associated with poor survival. The International Prognostic Index (IPI) score and the Prognostic Index for T-cell lymphoma (PIT) have been suggested as methods to predict the prognosis of PTCL. Ferritin, the iron storage protein, is associated with chronic inflammation. Although higher levels of serum ferritin are detected in many cancer patients, the significance of elevated serum ferritin as a prognostic factor for lymphoma has yet to be established. Thus, our retrospective study aimed to examine the prognostic value of serum ferritin levels in PTCL. Patients and Methods Serum ferritin levels were evaluated in 78 patients with PTCL, who were treated with anthracycline-containing regimens in 8 institutions affiliated to the Yokohama City University Hematology Group between 1998 and 2011. Fourteen patients received cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP); 44 receivedpirarubicin, cyclophosphamide, vincristine, and prednisone (THP-COP); 3 received THP-COP followed by radiotherapy; 3 received up-front autologous peripheral blood stem cell transplantation; and 14 received THP-COP at 2-week intervals in a clinical trial. Results The study population comprised 50 male and 28 female patients with a median age of 64 years at the time of diagnosis (range, 16–83 years). With regard to the PTCL subtype, 39 patients had PTCL, not otherwise specified, and 39 had angioimmunoblastic T-cell lymphoma. Twelve patients had localized disease and 66 patients had advanced Ann Arbor stage lymphoma. Twenty-three patients had a poor Eastern Cooperative Oncology Group performance status (PS) of 2–4. B symptoms were present in 34 patients. Risk stratification according to the IPI was as follows: low risk, 9 patients; low–intermediate risk, 20 patients; high–intermediate (HI) risk, 30 patients; and high (H) risk, 19 patients. According to the PIT, 4 patients were categorized into group 1, 25 into, group 2 , 28 into, group 3, 21 into, as group 4. The median observation period for the surviving patients was 50 months. The median serum ferritin level was 183 ng/ml (range, 5–14,622 ng/ml). Factors associated with a poor overall survival (OS) in univariate analysis were HI and H risk status with regard to IPI (P = 0.024), assignment to group 3 or 4 with regard to PIT (P = 0.017), poor performance status (P〈 0.001), and ferritin levels ≥ 300 ng/ml (P〈 0.001). The 4-year OS rate of all 78 patients was 54%. The 4-year OS rate was poorer in patients with serum ferritin levels ≥300 ng/ml (n = 21) than in those with serum ferritin levels〈 300ng/ml (n = 57; 22% vs. 65%; P〈 0.001) (Figure). Multivariate analysis including each factor comprising the IPI (age, lactate dehydrogenase level, PS, Ann Arbor stage, and number of extranodal lesions), gender, bone marrow involvement, and serum ferritin level showed that poor PS (P = 0.002, relative risk [RR] 3.6) and a serum ferritin level ≥300 ng/ml (P = 0.014, RR 2.7) were independent risk factors for poor OS. Conclusion The serum ferritin level is a useful prognostic marker for PTCL. Disclosures: No relevant conflicts of interest to declare.

Description: Background : The International Prognostic Index (IPI) is useful for prognostic prediction in patients with diffuse large B-cell lymphoma (DLBCL). Besides the IPI, previous reports demonstrated that some biomarkers (e.g., thymidine kinase [TK] activity and soluble interleukin-2 receptor [sIL-2R] levels) were useful for prognostic prediction in patients with DLBCL. However, few studies have analyzed many biomarkers together. This retrospective study aimed to determine a biomarker that would predict the prognosis of patients with DLBCL most strongly. Patients and Methods : A total of 781 patients were newly diagnosed with DLBCL at 9 institutions of the Yokohama City University Hematology Group between 2003 and 2012. We analyzed 319 of these 781 patients who were treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) therapy (median 6 cycles) with curative intent, and evaluated 6 biomarkers before R-CHOP treatment. We excluded patients from this study for whom reduction of the initial therapy dose by more than 20% was required owing to any major comorbidities, or who were not evaluated any one of 6 biomarkers, or who were stopped observation during R-CHOP therapy. Using univariate and multivariate analyses, we assessed the association between progression free survival (PFS) and the serum levels of the following 6 biomarkers: lactate dehydrogenase (LDH), sIL-2R, TK activity, beta-2 microglobulin (b2MG), C-reactive protein (CRP), and ferritin. The cut-off values for the 6 biomarkers analyzed were decided by using the receiver operating characteristic curves to determine the association between the values of the biomarkers and PFS. In addition, we assessed the association of the PFS with clinical characteristics including age, sex, presence of B symptoms, presence of bulky masses, Ann Arbor stage, performance status, and presence of extra-nodular lesions. Multivariate analysis includes both 6 biomarkers and clinical characteristics. Results : The analyzed patients included 181 men and 138 women, with a median age of 63 years (range, 22–89 years). The median PFS was 40.1 months (range, 0.1–130.8 months). The 3-year PFS rate of the 319 patients analyzed in this study was 77.7% (95% confidence interval [CI], 72.6–82.1%). The cut-off for LDH , sIL-2R, TK activity, b2MG, CRP, and ferritin levels were defined as 1.4 times the upper normal limit, 1660 U/mL, 19 U/L, 1.75 µg/mL, 2.3 µg/mL, and 179 ng/mL, respectively. On univariate analysis, the patients with serum b2MG levels 〉 1.75 µg/mL showed inferior PFS (n = 210; 3-year PFS rate, 71.2% [95% CI, 64.3–77.0]) compared to those with serum b2MG levels ≤ 1.75 µg/mL (n = 109; 3-year PFS rate, 90.0% [95% CI, 82.1–94.6]). In addition, patients with high levels of LDH, sIL-2R, and CRP as well as high TK activity showed inferior PFS rates compared to patients with low levels of these markers. On multivariate analysis, serum b2MG levels were most strongly correlated with poor PFS (hazard ratio [HR], 2.11; 95% CI, 1.04–4.31; P = 0.04). TK activity as well as CRP, sIL-2R, and ferritin levels did not predict the prognosis of patients with DLBCL. Conclusion : The serum b2MG level at diagnosis is a useful prognostic marker for patients with DLBCL. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.