ALBERT

Description: 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 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.

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 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 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.

Description: Background: In the AZA-001 trial, azacitidine (AZA; 75 mg/m2per day for 7 consecutive days of every 28-day cycle) demonstrated improved survival compared with conventional care regimens in patients with high-risk myelodysplastic syndromes (MDS). Although a 7-day regimen of AZA is the standard treatment of high-risk MDS, it is difficult to administer AZA treatment in outpatient settings on weekends. In this study, we investigated outcomes of a 5-day regimen of AZA in patients with high-risk MDS. Methods: Clinical data were retrospectively collected from consecutive high-risk MDS patients treated with AZA at Fujisawa City Hospital. “High-risk MDS” was defined as MDS with transfusion dependency or MDS with an International Prognostic Scoring System (IPSS) risk of intermediate-2 or high. Every month, AZA was administered at 75 mg/m2per day: for 5–7 days in the hospitalization for the first cycle, and for 5 days in an outpatient center for all subsequent cycles. Patients with neutropenia received antimicrobial prophylaxis with levofloxacin. Responses to AZA were evaluated according to the International Working Group 2006 criteria. Results: Between April 2011 and December 2013, 50 patients with MDS (40 men and 10 women; age, 40–86 years; median age, 73 years) initiated the AZA treatment. All patients had an Eastern Cooperative Oncology Group performance status of 0–2. Thirty-nine patients had primary MDS and 11 patients had secondary MDS. According to the World Health Organization MDS classifications, 13 patients had RCMD, 12 had RAEB-1, 15 had RAEB-2, 1 had CMML and 9 had AML with 20–30% bone marrow blasts. The IPSS risk was intermediate-1 in 19 patients, intermediate-2 in 19 patients, and high in 11 patients. The IPSS of 1 RAEB-2 patient could not be estimated due to insufficient data of chromosome analysis. The cytogenetic risk, known for 49 patients, was good for 23 patients, intermediate for 14, and poor for 12. Thirty-six patients were red blood cell transfusion-dependent and 17 patients were platelet transfusion-dependent. With the exception of 1 AML patient who received AZA as consolidation therapy after induction of chemotherapy, all other 49 patients received AZA as first-line therapy. The median time to treatment from diagnosis was 1.5 months (range, 1–153). The median number of AZA cycles was 7 (range, 1–27). AZA was discontinued before the third cycle in 12 patients due to: 3 cases of hematopoietic stem cell transplantation, 2 cases of pneumonia, 2 cases of insufficient blood cell recovery, 1 case of cerebral hemorrhage, 1 case of gastrointestinal hemorrhage, 1 case of stomach cancer, 1 case of rash, and 1 case involving a geographical move. Among 37 patients who received more than 3 cycles of AZA as fist-line therapy, 23 (62%) achieved any hematological improvement. The median time to first response was 3 cycles (1–5). Hematological improvement was obtained irrespective of IPSS risk or of primary and secondary MDS classifications. Grade 3/4 neutropenia occurred in 39 patients, and grade 3/4 thrombocytopenia occurred in 38 patients. Most of these hematological adverse events occurred during cycles 1–2. The most common grade 3 or higher non-hematological adverse events were pneumonia (9 patients), febrile neutropenia (8 patients), and sepsis (5 patients). According to IPSS risk, median overall survival was 12 months (range, 1–24) in high risk MDS and 16 months (range, 1–28) in intermediate-2 risk MDS. Median overall survival in intermediate-1 risk MDS had not yet been reached (range, 6–29 months, p = 0.03). Median overall survival in primary and secondary MDS was 24 months (range, 1–29) in primary MDS and 12 months (range, 1–19) in secondary MDS (p = 0.05). Twenty-four patients died: 9 of overt leukemia, 9 of pneumonia, 2 of cerebral hemorrhage, 1 of sepsis, 1 of gastrointestinal hemorrhage, 1 of stomach cancer, and 1 of senility. Conclusion: In the AZA-001 trial, the median time to first response was 2 cycles. In our study, the median time to first response was 3 cycles. Although the first response was delayed, the 5-day regimen of AZA showed respectable continuation rates lasting longer than 3 cycles with equivalent efficacy to the 7-day regimen. Future studies comparing the 5-day regimen and the 7-day regimen would provide valuable follow-up information to the findings in this study. 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 368 consecutive DLBCL patients, uniformly treated with standard rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP-21) therapy in 7 institutions in Japan, between 2001 and 2009. 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 64 years (range, 18–80 years), and 209 (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 (56% vs. 44%, P = 0.02). A difference was also observed in the frequency of bone marrow (BM) involvement, which was primarily observed in male patients (8% in women vs. 18% in men, P = 0.006). No difference was observed between sexes in other baseline factors (additional IPI factors, bulky mass over 10 cm, B symptoms). Complete remission rate for R-CHOP-21 was 86% in female patients and 91% in male patients (P = 0.1). After a median follow-up of 36 months, the 3-year progression-free survival (PFS) and overall survival (OS) rates were 74.9% and 84.5%, respectively. The IPI on diagnosis was low for 158 (42.9%) patients, low-intermediate for 93 (25.3%) patients, high-intermediate for 57 (15.5%) patients, and high for 60 (16.3%) patients, with significant differences in survival among the 4 groups (3-year OS: 93.8%, 85.2, 82.6%, and 60.2%, 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. However, there was no significant difference in the survival rate between female and male patients (3-year PFS; 72.7% vs. 78.0%, P = 0.4; 3-year OS; 82.7% vs. 76.5%, P = 0.4). Moreover, gender did not have an impact on prognosis among younger (60 years), normal/elevated sLDH, and positive/negative BM involvement patients’ cohort. Multivariate analysis revealed that clinical stage (P = 0.001 for PFS, 0.02 for OS), sLDH (P = 0.03 for PFS), PS (P= 0.005 for OS), and bulky mass (0.02, 0.04) had a prognostic impact, whereas gender was not identified as a prognostic factor. Conclusion Although a difference in the rate of rituximab clearance has been previously reported, gender was not found to be a prognostic factor among DLBCL patients receiving uniform R-CHOP therapy in this study. Disclosures: No relevant conflicts of interest to declare.