ALBERT

Description: Abstract 1561 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 disease such as transformation to aggressive NHL. The MIB-1 labeling index, based on the Ki67 immunostaining, is widely used for evaluating the proliferation of tumor cells. We retrospectively evaluated the prognostic impact of the MIB-1 labeling index at diagnosis in patients with FL treated with rituximab plus cyclophosphamide, doxorubicine, vincristine, and prednisolone (R-CHOP) alone. Ninety-eight consecutive FL patients (48 men and 50 women; median age, 57 years [range, 34–85 years]) were enrolled in one of the 7 participating hospitals between 2001 and 2009. Since 2001, the Yokohama City University Hematology Group in Japan has uniformly treated FL patients with curative intent, except for those in stage 1 disease, with 6 cycles of standard R-CHOP therapy for 21 days. Patients who had partial response (PR) after the 4 initial cycles were administered a total of 8 R-CHOP cycles, whereas patients who did not achieve PR after the 4 initial R-CHOP cycles or those who exhibited disease progression at any given time received salvage therapy. Patients who had a bulky mass defined as any mass exceeding 10 cm in diameter in a horizontal plane or a mediastinal mass with a maximum diameter exceeding one-third of the maximum chest diameter, received additional irradiation following CR with 6–8 cycles of R-CHOP. Patients who required a dose reduction of more than 20% were excluded from this study. The pathological diagnosis and MIB-1 labeling index were reviewed by 3 hematological pathologists (S. S., N. Ts., and K.T.). The WHO pathological grading in patients was as follows: grade1 in 63 patients, grade 2 in 21 patients, grade 3a in 12 patients, and grade 3b in 2 patients. The median MIB-1 index was 12.9% (range, 0.8%-79.9%). The median observation period for living patients was 59 months. The estimated 5-years progression-free survival (PFS) and 5-years overall survival (OS) rates were 48% and 84%, respectively. Patients with a MIB-1 index above 10% (n = 60) showed inferior survival curves compared with patients with a MIB-1 index below 10% (n = 38) in PFS (5-year PFS of 35% versus 67%, P = 0.02; Figure 1) and OS (5-year OS of 77% versus 94%, P = 0.009), respectively. Pathological grading was not correlated with PFS and OS. The following variables were assessed for their impact on PFS: (1) gender, (2) age 〉 60 years, (3) elevated serum lactate dehydrogenase level, (4) advanced clinical stage, (5) pathological grade, and (6) a MIB-1 labeling index above 10%. A MIB-1 labeling index above 10% was independently associated with poor PFS (P = 0.01, RR = 2.6), as well as advanced clinical stage (P = 0.004, RR = 2.7). A MIB-1 labeling index of above 10% is a useful prognostic factor in FL 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 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

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: 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.

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.