Search

Background: Rituximab (R) plus CHOP (R-CHOP) is the standard of care for patients with diffuse large B-cell lymphoma (DLBCL). The International Prognostic Index (IPI) and revised IPI were reported as prognostic indicators for DLBCL in 1993 and 2007, respectively. Although they are widely accepted, the performance status (PS) factor is sometimes ambiguous or subjective. Therefore, we developed a new prognostic index, the SIL, that includes only three objective prognostic factors: the clinical stage (S), a soluble interleukin-2 receptor level >2,500 U/mL (I), and an elevated lactate dehydrogenase level (L) (Cancer Sci. 2012). This study was conducted to confirm the value of the SIL index in a larger cohort and in each risk stratification of patients and to validate the SIL index in an independent patient cohort. Methods: Between 2003 and 2012, we registered and treated 781 consecutive patients with DLBCL, excluding those with mediastinal large B-cell lymphoma, intravascular large B-cell lymphoma, and primary effusion lymphoma. All the included patients were scheduled to undergo primary therapy with six cycles of full-dose R-CHOP. Patients in whom the initial therapy dose was reduced by >20% were excluded. Finally, 572 of 781 patients were retrospectively analyzed. Patients with partial remission (PR) after the initial four cycles underwent eight R-CHOP cycles in total, whereas those who did not achieve PR after the initial four R-CHOP cycles or those who exhibited disease progression at any given time received salvage therapy. If deemed necessary by the attending physician, additional local irradiation was performed in patients with PR or complete remission.Furthermore, we verified the value of the SIL index in an independent cohort of 89 DLBCL patients. Results: The median age at diagnosis was 63 years (range, 18-89 years). The median number of therapy cycles was 6 (range, 1-8), and 90% of patients received >6 cycles. Sixty-one patients (11%) received radiation therapy as primary treatment, which was often used to treat sites of residual masses at the end of chemotherapy. The median observation time for survivors was 55 months (range, 1-131 months). For 572 patients, the 5-year progression-free survival (PFS) and 5-year overall survival (OS) rates were 70% and 81%, respectively. The 5-year PFS rate was significantly different as 86%, 73%, 63%, and 41% for 0, 1, 2, and 3 of SIL index, respectively (Fig 1; P < 0.0001). The 5-year OS rate was also significantly different as 92%, 87%, 78%, and 52% for 0, 1, 2, and 3 of SIL index, respectively (P < 0.0001). According to the SIL index, 367 (64%) and 205 patients (36%) were classified as having standard (SIL index: 0 or 1) and high (SIL index: 2 or 3) risks, respectively. In patients with a low/low-intermediate risk on the IPI, 84% were categorized as having standard risk according to the SIL index, whereas in patients with a high-intermediate/high risk on the IPI, 82% were categorized as having high risk according to the SIL index. Five-year PFS rates in the standard and high risk groups according to the SIL index were 79% and 53%, respectively (Fig 2; P < 0.0001). Five-year OS rates in the standard risk and high risk groups were 90% and 66%, respectively (P < 0.0001). Cox regression analysis of the SIL index, age (>60 years), PS (2-4), sites of extranodal involvement (>1), and sex showed that the SIL index (P 60 years), the SIL index was a good prognostic indicator for PFS and OS in both groups. When they were divided by the number of extranodal involvement sites (0-1 and >1), and sex, the SIL index was still a good prognostic indicator for PFS and OS in both groups. Lastly, when they were divided by the PS (0-1 and 2-4), the SIL index was effective in the good PS group. However, in the poor PS group, the SIL index showed a statistically significant difference in the OS, but not in the PFS. In the validation cohort analysis, 5-year PFS rates in the standard and high risk groups were 81% and 49%, respectively (Fig 3; P = 0.001). Five-year OS rates in the standard risk and high risk groups were 87% and 59%, respectively (P = 0.003). Conclusion: The SIL index is a simple and objective prognostic indicator for DLBCL patients treated with R-CHOP. Disclosures Fujita: Chugai Pharmaceutical CO.,LTD.: Honoraria.

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 ( Results The median patient age was 65 years (19–80 years); 192 were men and 146 were women. The median BMI was 22.9 kg/m2 (14.1–40.4 kg/m2); 66 patients (19.5%) were in the high BMI group (median, 27.4 kg/m2) and 272 (80.5%) were in the low BMI group (median, 21.6 kg/m2). The median follow-up of patients who were alive (n = 271) was 67.5 months (12.6–121.8 months). The 5-year progression-free survival (PFS) and overall survival (OS) of the high versus low BMI groups were 63.9% versus 74.0% (P = 0.196) and 77.2% versus 84.2% (P = 0.230), respectively (Figure1,2). Multivariate analysis considering the sex, International Prognostic Index, B symptoms, bulky mass, and BMI showed that high BMI (≥25 kg/m2) was a significant adverse prognostic factor for both OS (hazard ratio [HR], 1.906; 95% confidence interval [CI], 1.08-3.376; P = 0.027) and PFS (HR, 1.710; 95% CI, 1.054-2.774; P = 0.030). Conclusion The results of our study indicated that high BMI was an adverse prognostic factor of DLBCL. It is necessary to investigate BMI and its influence on patient background or treatment in much more cases. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures No relevant conflicts of interest to declare.

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.

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.

Background: Some studies evaluating differences in clinical features and outcome between supra-diaphragmatic (SpD) and infra-diaphragmatic (InD) primary lesions in Hodgkin lymphoma (HL) have been reported (Cancer 1991;68:1476-1481: Haematologica 2006;91:32-39). In regard to non-Hodgkin's lymphoma, there exist some previous studies that report on outcomes of patients with gastrointestinal (GI) involvement (J Clin Oncol 2005;23:2797-2804; Cancer 2003;97:2462-73). However, no studies comparing outcome between SpD and InD primary lesions have been conducted for patients with diffuse large B cell lymphoma (DLBCL). Thus, we retrospectively evaluated outcome differences between SpD and InD lesions, and the prognostic impact of GI involvement in limited-stage DLBCL. Patients and Methods: We analyzed data from 178 patients with limited-stage DLBCL who were treated with rituximab plus cyclophosphamide (CPA), doxorubicin (DXR), vincristine (VCR), and prednisone (PSL; R-CHOP) therapy at 7 institutions of the Yokohama City University Hematology Group between 2003 and 2009. Patients who needed a dose reduction of more than 20% per cycle of R-CHOP therapy were excluded from the study. We classified the patients into SpD lesions group or InD lesions group according to the location of lesions. The patients in the InD lesions group were subsequently classified into InD with GI involvement group or InD without GI involvement group according to the presence of GI lesions. The impact of primary site location on patient outcome was evaluated using univariate and multivariate analyses. Results: The study cohort included 104 men and 74 women with a median age of 63 years (range, 18-80 years). All patients were categorized as Ann Arbor stage I (n = 66) or II (n = 112). The primary sites were SpD in 109 patients and InD in 69 patients. There were no significant differences in distribution between the SpD lesions group and the InD lesions group with respect to age, sex, Ann Arbor stage, the IPI score, ECOG performance status, and the presence of a bulky mass. Significantly more patients in the InD group presented with B symptoms (P = 0.003). Comparing patients in the InD lesions group presenting with (n = 35) or without (n = 34) GI involvement, resulted in similar findings with respect to clinical characteristics. The group with GI involvement consisted of 20 patients with stomach lesions (57%), 7 with small intestine lesions (20%), 7 with colon lesions (20%), and 1 with both colon and rectum lesions (3%). The median observation period for all surviving patients was 52 months (range, 3 – 94 months). The 4-year progression-free survival (PFS) and overall survival (OS) rates of all 178 patients were 84% and 91%, respectively. Twenty-six patients presented with disease progression after R-CHOP therapy. In total, 16 patients died: 14 of recurrent lymphoma, 1 of secondary malignancy (acute lymphoblastic leukemia), and 1 as a result of an accident. No statistical differences in PFS or OS were observed between patients with SpD lesions and those with InD lesions (4-year PFS rate: 87% and 81%, respectively; P = 0.31; Fig 1; 4-year OS rates: 92% and 86%, respectively; P = 0.31). When patients were classified and assessed according to primary site location, and their GI involvement status, which were SpD group, InD with GI involvement group, or InD without GI involvement group, the PFS rate was higher in SpD group (4-year PFS rates 86%), and InD with GI involvement group (4-year PFS rates 97%) than InD without GI involvement group (4-year PFS rates 67%; P = 0.036, and P = 0.003, respectively; Fig 2). However, no significant differences in regard to OS were observed among 3 groups (4-year OS rates: 93%, 97%, and 78%, respectively; P = 0.09). The multivariate analysis revealed that SpD or InD localization had no independent effect on PFS or OS. In addition, primary sites according to the presence of GI lesions were incorporated into the multivariate analysis, whereas SpD, and InD were excluded as overlapping variable. The multivariate analysis revealed that the presence of GI involvement in patients with InD lesions was an independent prognostic factor in predicting favorable PFS (P = 0.024, HR 0.09). Conclusion: No outcome differences were observed between SpD and InD lesions in limited-stage DLBCL. However, the presence of GI lesions was associated with a favorable prognosis. Disclosures No relevant conflicts of interest to declare.

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.

Background Serum beta-2 microglobulin (β2MG) is an HLA class I protein. Its concentration is determined mainly from lymphoid tissue. Previous reports demonstrated that serum β2MG levels tend to increase with the stage of Hodgkin lymphoma (HL; Eur. J. Cancer. 1979; 15: 791-796: Cancer. 1980; 45: 318-326). Thus, this retrospective study aimed to examine the prognostic value of serum β2MG levels in HL. Patients and Methods We analyzed the data of 67 patients with previously untreated HL whose serum β2MG levels had been evaluated at diagnosis and who were treated at 7 institutions of the Yokohama City University Hematology Group between 1998 and 2011. We assessed the associations between survival and serum β2MG levels, all factors comprising the international prognostic index (sex, age, Ann Arbor stage, albumin levels, hemoglobin levels, white blood cell counts and lymphocyte counts at diagnosis), performance status, lactate dehydrogenase levels, and number of extra-nodular lesions, using univariate and multivariate analyses. Results The patients included 40 men and 27 women with a median age of 41 years (range, 16- 81 years). The HL subtype was nodular sclerosis classical HL in 37 patients, mixed cellular classical HL in 23 patients, lymphocyte-rich classical HL in 6 patients, and nodular lymphocyte-predominant HL in 1 patient. The Ann Arbor stage of HL was stage I in 9 patients, stage II in 30 patients, stage III in 19 patients, and stage IV in 9 patients. All the patients were treated with doxorubicin, bleomycin, vinbrastine, and dacarbazine (ABVD) therapy alone (n = 37) or ABVD therapy plus involved-field radiation therapy (IFRT; n = 30). The clinical stage of HL in the patients treated with ABVD therapy alone was stage II in 11 patients, stage III in 17, and stage IV in 9. The clinical stage of HL in the patients who received ABVD plus IFRT was stage I in 9 patients, stage II in 19, and stage III in 2. The median observation period in the surviving patients was 53 months (range, 5- 123 months). The 4-year progression-free survival (PFS) and overall survival (OS) rates of all 67 patients were 76% and 89%, respectively. Thirteen patients had disease progression after treatment of HL. In total, 9 patients died: 3 of recurrent lymphoma, 2 of infection, 1 of acute circulatory failure during chemotherapy for HL, 1 of secondary malignancy, 1 of brain hemorrhage, and 1 of pulmonary chronic graft versus host disease. The patients with serum β2MG levels ³2.5 µg/mL showed inferior PFS (n = 18; 4-year PFS rate, 42%) compared to those with serum β2MG levels below Conclusion Therefore serum β2MG level at diagnosis is a useful prognostic marker for patients with HL. Disclosures: No relevant conflicts of interest to declare.

Abstract 2645 Background Programmed cell death-1 (PD-1) is involved in one of the inhibitory pathways of the B7-cluster of differentiation (CD) 28 family; this pathway is known to be involved in the attenuation of T cell responses and promotion of T cell tolerance. PD-1 is known to negatively regulate T cell receptor-mediated proliferation and cytokine production, lead to alternation in the tumor microenvironment. Carreas et al. (J Clin Oncol. 2009; 27: 1470–1476) examined 100 follicular lymphoma (FL) patients and reported better prognosis in the group that had high levels of PD-1-positive cells. In contrast, in the study performed by Richendollar et al. (Human Pathol. 2011; 42: 552–557), which involved 91 FL patients, high levels of PD-1-positive cells were found to have a poor prognostic impact. Although these studies have shown that high levels of PD-1-positive cells in FL patients influence their prognosis, both studies included patients treated without rituximab, and the prognostic impact of PD-1 positivity in the rituximab-era (R-era) has not yet been elucidated. Materials and methods We retrospectively analyzed data for 91 FL patients uniformly treated by standard rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) therapy in 5 institutions between 2001 and 2009. The median age of the entire cohort was 58 years (range, 34–85 years), and 46 (51%) of the patients were men. We also collected and examined biopsy specimens for diagnosis with respect to PD-1 positivity. The PD-1-positive cells were counted using computer analysis at the Cancer Institute, Japanese Foundation for Cancer Research. Results The FL grade on diagnosis was grade 1 for 34 (37%) patients, grade 2 for 41 (45%) patients, and grade 3 for 16 (18%) patients. The median positivity for PD-1 staining was 16.0% (range, 0.01–51.9%) and was significantly higher in the high beta-2 microglobulin (B2M; at least 3) group (P = 0.009); the men had a high tendency for PD-1 positivity (P = 0.08). After a median follow-up of 29.1 months, the 3-year progression-free survival (PFS) and overall survival (OS) were 61.1% and 88.6%, respectively. Stage 4 FL at diagnosis (P = 0.02) and bone marrow involvement (P = 0.05) resulted in worse PFS, and an Eastern Cooperative Oncology Group (ECOG) performance status of 2–4 (P = 0.04), high Follicular Lymphoma International Prognostic Index (FLIPI; P = 0.02), B symptoms (P = 0.04), and high B2M levels (P = 0.005) worsened OS. Multivariate analysis showed that age over 60 years (P = 0.04) and high B2M levels (P = 0.07) were prognostic factors for PFS. PD-1 positivity was not found to be a prognostic factor with respect to both PFS and OS. Because the addition of rituximab to therapy regimens has altered the clinical course and prognosis of FL, some new prognostic factors have been proposed, and the impact of known prognostic factors has been changing. Rituximab might also have changed the prognosis of FL patients with high levels of PD-1-positive cells. Conclusion High levels of PD-1-positive cells were not found to be a prognostic factor in this study, indicating that the prognostic impact of PD-1 positivity might be eliminated in the R-era. Disclosures: No relevant conflicts of interest to declare.

Abstract 3100 The Follicular Lymphoma International Prognostic Index (FLIPI) is the most useful prognostic index for follicular lymphoma (FL). FLIPI was developed from retrospective data, which was based on treatment without rituximab (R) therapy and did not contain β2-microglobulin data of some cases. Recently the working group that had suggested FLIPI proposed FLIPI2, based on prospectively collected data. However, FLIPI2 contains data on several different treatment methods, such as treatment with or without R therapy. The present study aimed to retrospectively analyze the prognosis of FL uniformly treated with the combination of R, cyclophosphamide, doxorubicin, vincristin, and prednisone (R-CHOP). This study involved 114 patients consecutively diagnosed with FL who were treated with R-CHOP and were registered in the data-base of the Yokohama City University Hematology Group between January 2001 and October 2009. All the parameters required for FLIPI and FLIPI2 calculation were present in 108 patients (men, 53; women, 55, median age; 57 years [34- 78 years]). The median follow-up period was 31.7 months (0.8- 97.5 months). According to the FLIPI score, 50 patients (46.3%) were in the high-risk group (HR); 31 patients (28.7%), the intermediate-risk group (IR); and 27 patients (25.0%), the low-risk group (LR). On the basis of the FLIPI2 score, 45 patients (41.7%) were in HR; 52 patients (48.1%), IR; and 11 patients (10.2%), LR. According to FLIPI, the 5-year overall survival (5yOS) was 74.1% (95% CI, 58.1– 94.4%) for HR, 89.5% (95%, CI, 76.6– 100%) for IR, and 100% for LR (p = 0.0049); the 5-year time to failure (5yTTF) was 42.3% (95% CI, 26.0– 68.9%) for HR, 39.1% (95% CI, 22.7– 67.3%) for IR, 66.4% (95% CI, 47.2– 93.4%) for LR (p = 0.244). According to the FLIPI2 score, 5yOS was 71.3% (95% CI, 53.2– 95.6%) for HR, 85.6 % (95% CI, 72.0– 100%) for IR, and 100% for LR (p = 0.197), the 5yTTF was 35.8% (95% CI, 20.0– 64.2%) for HR, 46.7% (95% CI, 31.1– 70.3%) for IR, and 76.2% (95% CI, 52.1– 100%) for LR (p = 0.075). In conclusion, in FL patients treated with R-CHOP, FLIPI provided a more accurate OS than that provided by FLIPI2; however, FLIPI2 provided a more accurate TTF than that provided by FLIPI. Disclosures: No relevant conflicts of interest to declare.

By the new treatment approaches, such as rituximab, anti-CD20 radioimmunotherapy, high-dose therapy, transplantation, the outcome of treatment for follicular lymphoma has been improved. However, there are wide alternatives in a treatment of follicular lymphoma to stemcell transplantation from watchful waiting, and analysis of prognosis is important in choice of a therapy. The international non-Hodgkin’s lymphoma prognostic index (IPI) has been used for follicular lymphoma. Recently, a new method of the follicular lymphoma international prognostic index (FLIPI) is reported and attracts attention. We apply these two prognostic models for newly diagnosed follicular lymphoma, and reviewed its availability. 5 factors were used, The IPI (age>60, EN≥2, LDH>N, PS≥2, CS≥3), and the FLIPI (age>60, HbN, CS≥3, nodal sites>4), respectively. Between 1988 and 2001, 107 patients of newly diagnosed follicular lymphoma (grade I-III) were analyzed. Response rate, overall survival (OS), and progression free survival (PFS) were calculated for each prognostic model. Patients characteristics were male/female 49/58, median age 54yr. (range 21–87yr.), and histological grade I, II/III 103/4. The median follow-up of our series was 84 months (range 40–206 months). CR, PR was 60.7%, 31.8%, and response rate was 92.5%. Median OS at 10 years was 64.4%, and median PFS at 10 years was 28.5%. Patient distribution by the IPI and the FLIPI were the followings; the IPI (L/LI/HI/H 49/41/15/2), the FLIPI (L/I/H 41/29/37). There were few patients equivalent to high risk group in IPI, and it was the patient distribution which was more equal in FLIPI in comparison with IPI. OS by the IPI and the FLIPI risk group at 10 year were L: 85%, LI: 54%, HI: 44%, H: 50% (p=0.0088), and L: 87%, I: 66%, H: 47% (p

Background: By the new treatment approaches, such as anti-CD20 monoclonal antibody, purine analogues, high-dose therapy with SCT, the outcome of treatment for follicular lymphoma (FL) has been improved, but there is no consensus on any of these approaches except cases with early stage. Therefore, a reliable prognostic index would be needed in order to select the most appropriate treatment. Follicular Lymphoma International Prognostic Index (FLIPI) has recently been reported. We assessed characteristics at diagnosis and applied two prognostic models, the FLIPI and the IPI, to newly diagnosed Japanese patients (pts) with FL in this study. Methods: Response rate, overall survival (OS), and progression free survival (PFS) were calculated by the FLIPI and the IPI. For two prognostic models, 5 factors were used, The IPI (age>60, EN≥2, LDH>N, PS≥2, CS≥3), and the FLIPI (age>60, HbN, CS≥3, nodal sites>4), respectively. Results: Between 1988 and 2001, 107 pts of newly diagnosed FL (grade I-III) were analyzed. Patients characteristics were male/female 49/58, median age 54yr. (range 21–87yr.), and histological grade I, II/III 103/4. Initial therapy was CHOP-like regimen for 56 patients, ACOMP-B (the third generation regimen) for 44 patients, and another for 7 patients. The median follow-up of our series was 84 months (range 40–206 mo.). CR, PR was 60.7%, 31.8%, and response rate was 92.5%. Median OS at 15 years was 64.4%, and median PFS at 15 years was 28.5%. Patient distribution by the IPI and the FLIPI were the followings; the IPI (L/LI/HI/H 49/41/15/2), the FLIPI (L/I/H 41/29/37). There were few patients equivalent to high risk group in IPI, and it was the patient distribution which was more equal in FLIPI in comparison with IPI. OS by the IPI and the FLIPI risk group at 10 year were L: 85%, LI: 54%, HI: 44%, H: 50% (p=0.0088), and L: 87%, I: 66%, H: 47% (p Conclusions: The FLIPI is a promising consequence prediction model in follicular lymphoma in Japan. Standard treatment of FL is one of the most controversial issues. Outcome of CHOP were poor in high-risk group of the FLIPI, so to improve survival new treatment strategy is needed. The therapeutic strategy on the basis of different risks by reliable prognostic index, such as the FLIPI is necessary in future, in order to select the most appropriate treatment. As for grade 3, there was a little number of patients in our series, but further examination is necessary for adaptation of the FLIPI about this group.

A new method for hemopoietic colony formation that allows the preparation of permanent slides and medium changes during the incubation period was developed in vitro. Bone marrow cells from mice were spread over glass-fiber filters, which were placed on agar medium and cultivated for 7 days. Hemopoietic colonies appeared on the glass- fibers filters. The glass-fiber filters with colonies were stained by a peroxidase and nonspecific esterase double-staining method and mounted as permanent slides. Each colony could be clearly identified and easily counted after the staining. The dose-response relationship between the number of seeded cells and the colony counts was a linear one, with the line very nearly passing through the origin on extrapolation. The colonies were classified into three types by the staining results: granuloid type, monocyte-macrophage type, and mixed type, the last containing both granuloid and monocyte-macrophage cells. Medium change during the incubation period was attempted in the experiment for phagocytic activity of the cultured cells and proved to be useful. This system appears to be useful and convenient in the study of hemopoietic colony formation.