ALBERT

Description: Background: Imatinib mesylate, that is tyrosine kinase inhibitor, is highly effective drug for chronic myeloogenous leukemia(CML). Imatinib induces cytogenetical and molecular remission for CML without bone marrow transplantation. Imatinib is effective for not only CML but Gastrointestinal Tumor (GIST). Imatinib targets mutation of c-kit or platelet derived growth factor receptor alpha (PDGF-alpha) in GIST. Before these days, the case of double cancer of CML with GIST has not been reported yet. Clinical Course: A 43-year-old man, who admitted our hospital, had leukocytosis, thrombocytosis, and melaena. His white blood cell (WBC) count was 65×10 4 /μL, hemoglobin level was 13.5 g/dl, and platelet count was 114.2×10 4/μL. The WBC fraction was as follows: blast 1%; promyelocyte 1.5%; myelocyte 13.5%; metamyelocyte 2.5%; band 5.5%; segment 46.5%; lymphocyte 16.5%; monocyte 4.5%; basophil 3.0% and eosinophil 5.5%. The bone marrow aspiration demonstrated the hypercellular bone marrow and blast cells did not increase and metaplasia of cells was not observed. Karyotypic FISH analysis revealed the chromosome of t(9;22)(q34:q11) and he was diagnosed as CML in chronic phase. He had no splenomegaly. At this time, gastric submucosal tumor was detected by endoscopy of the upper gastrointestinal tract. The tumor located lesser curvature of the mid-stomach and had no mobility. Under the fiberscopic ultrasonography, the submucosal tumor had low and heterogenous echogenic pattern. The computed tomography showed that the tumor, which size was six cm, was solid mass and associated with calcification. For the therapy, in the first, Imatinib (400mg) was started against CML. His WBC and platelet was slowly decreased and after four months he reached at morphological remission. FISH showed the presence of 30% bcr/abl+ transcript in his bone marrow. In this period, although the size of his submucosal tumor did not change on the CT, it seemed that the elevation of mucosa was decreased under the gastrointestinal fiberscopy. After nine months from start of Imatinib, he received surgical resection of gastric submucosal tumor. The size of removed tumor was about six cm and the tumor associated with broad necrotic lesion. Histological analysis indicated from limited alive lesion. Microscopically, fibrotic and hyalinized lesions cover approximately 99% of the area examined. The residual tumor consists of spindle cells with mild nuclear atypia. Immunohistochemically, the tumor is positive for KIT/CD117 and CD34, and negative for muscle specific actin (HHF35), smooth muscle actin (1A4), desmin and S100 protein. These features are characteristic of GIST. The c-kit mutation was studied by PCR. And we identified the tumor was gastrointestinal stromal tumor (GIST). Discussion: That is first report of simultaneous occurrence CML and GIST in one patient. We selected that after the remission of CML with Imatinib, resection of GIST was performed. That was very curative therapy for him.

Description: Abstract 4763 INTRODUCTION Peripheral blood involvement (leukemic presentation) is considered as a part of bone marrow involvement and detected about 18% of bone marrow (BM) involvement of follicular lymphoma (FL). It is not known whether leukemic presentation is an adverse prognostic factor in rituximab era. METHOD We retrospectively evaluate prognostic value of peripheral blood involvement in patients with follicular lymphoma received rituximab containing regimen as an initial therapy from October 2000 to January 2009. Leukemic presentation was defined by morphologic identification of an abnormal lymphoid population in the peripheral blood. RESULT Total 129 patients were treated with rituximab containing initial therapy. Bone marrow involvement was detected in 39 /108 (36.1%) patients and leukemic presentation was identified in 8 / 39 (20.5%) of patients with BM involvement. Leukemic presentation shows significant poorer progression free survival than BM involvement without peripheral blood involvement. (2yr PFS 23.4% vs 73.3% p=0.015) Multivariate analysis conducted by Cox proportional hazard analysis including five variables of FLIPI revealed Hb

Description: Introduction: There are various poor prognosis factors in diffuse large B cell lymphoma (DLBCL). CD5 positive (CD5+) is estimated as one of the poor prognosis markers in DLBCL. CD5+ DLBCL is completely distinguished from CLL or Mantle cell lymphoma, and de Novo CD5+ DLBCL is related to a high incidence of cytogenetic abnormalities of 8p21 and 11q13. In many cases, CD5+ DLBCL is associated with an aggressive clinical status and advanced stages. Several chromosomal studies have demonstrated the gene expression was similar to non-GCB type of DLBCL. In the clinical phase, it is easy to express chemo-resistance and CNS invasion. However, the clear characterization and mechanisms of chemo-resistance have not been demonstrated yet. In this study, we examined our previous CD5+ DLBCL patients in our institute, then evaluated the prognosis and clinical characteristics regarding GCB or non GCB type. Methods: We studied 372 newly diagnosed DLBCL patients including 42 cases of CD5+ from 2005 to 2015 in our institution retrospectively. The pathological diagnoses were performed with immunohistochemical analysis by two or three hematological pathologists. CD5 expression was evaluated by immunohistostaining and flowcytometry, then cyclin D1 positive cases were excluded. GCB or non-GCB subtype was evaluated with CD10, bcl-6, and MUM-1 of immunohistostaining. The clinical stage of patients and evaluation of the effect of the therapy were performed using PET-CT scan. The statistical analyses were performed by Dr. SPSS II. Results: In all our treated patients, 350 DLBCL patients (female;161) and 41 CD5+ patients (female 22) could be evaluated. 192 patients were GCB type and 158 patients were non-GCB type. The median age was 64.5 yrs (25-86 yrs) and the median follow up time was 45 months (1-133 months). All patients were treated by rituximab-CHOP (R-CHOP) therapy. CR rate of CD5- DLBCL was 94.2% and CD5+ was 73.1% respectively (p =0.0093). 3.5-year event free survival (EFS) was 79.16% and 52.20% (p

Description: Abstract 4145 [Introduction] Recently, we reported that gene mutations of CD20 were involved in resistance to rituximab therapy, and we proposed that C-terminal deletion mutations of CD20 might be related to relapse/resistance after rituximab therapy. Many of these cases were diagnosed as CD20 negative by the immunohistochemical analysis using the L26 monoclonal antibody used routinely in most clinical laboratories. L26 recognizes the cytoplasmic region of CD20 molecules, but no more detailed information about its epitope had been reported. So, we could not distinguish whether protein expression of CD20 extremely decreased or whether the epitope of the antibody was lost by these mutations. To make this clear, we determined the binding site of L26 antibody on CD20 protein in the present study. In addition, we developed new antibodies that recognize amino acid sequence close to the amino terminal of CD20 molecule. Then we investigated clinical specimens with these antibodies together with L26 to elucidate characteristics of CD20 molecules having C-terminal mutations. [Methods] To determine the binding site of L26 antibody on CD20, we made a series of constructs of the CD20 molecules with deletion mutations in the C-terminal cytoplasmic domain and introduced them into retrovirus vectors. A CD20 negative multiple myeloma cell line, KMS12PE cells were then transformed, and we established six kinds of sub-lines with the various C-terminal deletion mutations of CD20 and used them for epitope-mapping. On the other hand, we screened the CD20 gene sequence of the clinical specimen of rituximab-resistant patients and identified several cases with the mutation in the C-terminal cytoplasm region. The immunochemistry using L26 and newly developed antibodies, as well as membrane expression of CD20 molecules using the rituximab were analyzed. [Results] The epitope analysis of L26 antibody using a series of CD20 deletion mutations revealed that L26 recognizes near the C-terminus of CD20 cytoplasmic region. These results showed that most of CD20 molecules with the C-terminal deletion mutation and frame-shift mutation could not be recognized by L26. The immunohistochemical analysis performed for clinical specimens revealed that the cells that were stained by antibodies recognizing N-terminal region of CD20 but not by L26 were indeed included in some rituximab-resistant cases. DNA sequencing analysis revealed that all these cases had mutated CD20 genes in its C-terminal cytoplasmic region. In addition, a cell-surface expression analysis using flowcytometry demonstrated that the cells having these mutations has reduced cell surface expression of CD20 compared with those of normal CD20. [Discussion] In this study, we determined the recognition site of L26 and demonstrated that L26 couldn't recognize CD20 with the resistant mutations. In contrast, newly developed antibodies against N-terminal region of CD20 could stain even these CD20 molecules. These results suggest that combination use of these antibodies and L26 enables to detect the onset of irreversible rituximab-resistant clones with the CD20 mutations. Disclosures: Hatake: Chugai Pharmaceutical Co., Ltd: Honoraria, Research Funding.

Description: Introduction Several studies concerning extranodal diffuse large B-cell lymphoma (DLBCL) have been reported sporadically. However, no new, valuable prognostic factors have been reported since several risk factors, such as a high international prognostic index (IPI) score, elevated lactate dehydrogenase (LDH) level, poor Eastern Cooperative Oncology Group (ECOG) performance status (PS), advanced stage, and extranodal sites ≥2, were identified. Methods To identify new and valuable prognostic factors, we reviewed the medical records of patients with nodal and extranodal DLBCL who were newly diagnosed at the Cancer Institute Hospital of the Japanese Foundation for Cancer Research from February 2005 to September 2014, and retrospectively analyzed the data of a total of 463 consecutive DLBCL patients. The cases were nodal DLBCL in 237 patients and extranodal DLBCL in 226 patients. We investigated the relationships between overall survival (OS), progression-free survival (PFS), and age, gender, LDH level, beta-2 microglobulin level (b2MG), performance status (PS), stage, extranodal sites ≥2, Ki-67 index, and M protein in serum protein fraction electrophoresis at diagnosis. Univariate and multivariate analyses of estimated risk factors for OS and PFS in extranodal DLBCL patients were performed using the log-rank test and Cox proportional hazard regression analysis. Results In patients with extranodal DLBCL, the median age was 67 years (range, 20-89 years). The median follow-up was 41 months (range, 1-115 months). A serum electrophoresis study detected M protein in 7 patients (3.1%). To adjust the impact of age, gender, LDH level, b2MG, PS, stage, extranodal sites ≥2, Ki-67 index, and the presence of M protein in serum protein fraction electrophoresis at diagnosis for other significant factors for OS, we identified the following risk factors in extranodal DLBCL by univariate analysis: elevated LDH level, elevated b2MG level, stage ≥3, extranodal sites ≥2, and the presence of M protein. Then, we performed multivariate analyses by using all of these factors in the Cox proportional hazard model. M protein (HR 6.78, 95% CI 2.19-20.96, P

Description: Introduction Thymidine kinase (TK) activity has been investigated as a prognostic factor in hematological malignancies, and several studies have demonstrated that high TK activity correlates with the disease stage and provides prognostic information on overall survival (OS) and progression-free survival (PFS). We have reported that high thymidine kinase activity (TK) predicts poor prognosis for diffuse large B-cell lymphoma (DLBCL) patients treated with R-CHOP. In addition, CD5 positivity was reported as a poor predictor for DLBCL. The purpose of this retrospective study was to investigate the prognostic value of high TK activity and CD5 positivity compared with other laboratory findings in evaluating OS in patients undergoing R-CHOP for previously untreated DLBCL. Methods We retrospectively analyzed 176 patients newly diagnosed with DLBCL and treated with R-CHOP from September 2003 to October 2008 in our institute, and followed them until December 2012. The values of TK activity, CD5, non-germinal center type, C-reactive protein, lactate dehydrogenase, and beta2 microglobulin before R-CHOP were evaluated as prognostic factors for overall survival (OS). The cut-off of TK activity was defined as 14 IU/L because the median level of TK activity was 14.0 IU/L. CD5 positivity was defined if CD5 expression was detected by flow cytometry. Excluded were those positive for cyclin D1 or those with a history of chronic lymphocytic leukemia/small lymphocytic lymphoma. Germinal center type was defined by Hans classifier. The primary endpoint was OS. First, the OS and PFS were analyzed by the Kaplan-Meier method, and biological prognostic factors for OS were evaluated by Cox regression analysis. Second, we classified the patients into three risk groups due to significant poor predictors. All reported p-values were two-sided, and statistical significance was defined as p 〈 0.05. Results Median age of the evaluable patients was 65.2 years old. The number of CD5+ patients was 19 (10.8%). The median levels of TK activity, CRP, LDH, and Hb were 14.0 IU/L (range, 3.0–1,100), 0.3 IU/L (range, 0.1–21.2), 254.5 IU/L (range, 111.0–44,432), and 13.1 g/dL (range, 7.7–17.0), respectively. Median follow-up was 60.0 months. Five-year OS rate of all patients was 51.1%. The OS was significantly worse in patients with high TK activity, CD5 positivity (CD5+), and high beta2 microglobulin level by univariate analysis. Five-year OS rates of the high-TK-activity arm and the low-TK-activity arm were 39.1% and 62.9%, respectively (p = 0.001). Five-year OS rates of the CD5+ arm and the CD5-negative arm were 21.1% and 53.8%, respectively (p = 0.002). The OS was significantly worse in patients with high TK activity and CD5+ by Cox regression analysis (hazard ratios 2.595 and 2.585; p = 0.044 and 0.026, respectively). We classified the patients into three groups based on the numbers with high TK activity and CD5+. There was a significant difference of OS in the three risk groups: five-year OS rates were 8.3% in the high-risk arm (two factors), 43.9% in the intermediate-risk arm (one factor), and 64.6% in the low-risk arm (zero factors) (p 〈 0.001). This prognostic model was suitable for PFS. Five-year PFS rates were 8.3% in the high-risk arm (two factors), 31.7% in the intermediate-risk arm (one factor), and 59.6% in the low-risk arm (zero factors) (p 〈 0.001). According to the chi square test and Fisher's exact test, there was no significant relationship between high TK and CD5+ (p = 0.153). Conclusions High TK activity and CD5+ were strong predictors of short OS in patients with newly diagnosed DLBCL treated with R-CHOP. Disclosures: No relevant conflicts of interest to declare.

Description: Background Breast lymphomas is a rare type of malignant lymphoma. The major histopathological type of breast lymphoma is diffuse large B-cell lymphomas (DLBCL). Although conventional treatment regimen is cyclophosphamide, doxorubicin, vincristine, and predonisolone with rituximab (R-CHOP), the optimal cycles of chemotherapy, role of additional radiotherapy, and efficacy of intrathecal (IT) prophylaxis are still unclear. Method We retrospectively analyzed the clinical features and treatment outcomes of 22 patients with newly diagnosed primary breast lymphoma (PBL) of stage IE and IIE and secondary breast lymphoma of stage IIIE and IVE, and evaluated details of 20 DLBCL patients. All patients were treated at our institution between May 2002 and July 2013. Patients of stage IE were treated by 8 cycles of rituximab plus three cycles of CHOP-21 with radiotherapy, and patients of stage IIE-IVE were treated by 8 cycles of rituximab plus 6-8 cycles of CHOP-21 with or without radiotherapy. All patients were considered to receive intrathecal prophylaxis unless clinical study setting or patients’ denial. Patients were divided into three groups; primary breast lymphoma (PBL) of stage IE, PBL of stage IIE, and secondary breast lymphoma of stage IIIE and IVE. Result There were 22 malignant lymphoma patients of breast such as one follicular lymphoma patient, one Burkitt lymphoma patient, and 20 DLBCL patients with no bilateral breast involvement. In patients with DLBCL of the breast, the median age was 60 years (range 32–69 years), with all female. The median largest tumor diameter was 5 cm, and eight patients had bulky disease (〉5 cm). Nine of 20 patients (45%) received at least once of IT prophylaxis during one to two cycles of R-CHOP therapy. Six patients were stage IE, nine patients were stage IIE, and five patients were stage III and IVE, who had another invasion including liver, bone, and bone marrow. CR rate after initial therapy was 90% (18/20). Five of 20 patients (25%) developed central nervous system (CNS) relapse with the median time to CNS relapse of 28 months. Although four of 11 (36.4%) patients without IT prophylaxis versus one of nine (11.1%) patients with IT prophylaxis developed CNS relapse with no significant difference between two groups (p=0.363), and IT prophylaxis tends to prevent CNS relapse. The median follow-up time was 48.5 months, and the 3-year progression free survival (PFS) and overall survival (OS) in each group were 75%, 87.5%, and 40.0% (p=0.154), and 100%, 85.7%, and 53.3% (p=0.244), respectively. Conclusions Primary and secondary breast lymphoma is still considered high-risk for CNS relapse in Rituximab era. IT prophylaxis might prevent CNS relapse in breast lymphoma patients, and, further study is needed to evaluate the efficacy of IT prophylaxis or another appropriate approach for CNS relapse. Disclosures: Nishimura: Chugai Pharmaceutical CO., LTD.: Consultancy. Yokoyama:Chugai Pharmaceutical CO., LTD.: Consultancy.

Description: [Background] Bortezomib (VELCADE® for Injection 3 mg) was approved in Japan on October 10, 2006 for the treatment of relapsed or refractory MM. As required for most oncology drug approvals in Japan, a special post-marketing surveillance program was implemented on December 1, 2006, enrolling all patients treated with bortezomib to assess its safety and efficacy from actual medical practice experience in Japan. [Patients and Methods] This surveillance is a prospective program designed to enroll patients before starting treatment with bortezomib. It included 1048 consecutive patients treated with bortezomib in the first year after the drug approval in Japan. This report summarizes the results of an interim analysis of safety and preliminary efficacy of the first two cycles of bortezomib in 525 patients. Patients are to be observed for 3 years at maximum. Observational items include: gender, age, medical history, prior therapies, administration of bortezomib, concomitant drug/therapy, laboratory testing, physical examination, clinical symptoms, anti-tumor effects, and adverse event (AE) collection. In addition, for AEs of special interest, such as lung disorder/interstitial lung disorder (LD/ILD), cardiac dysfunction, tumor lysis syndrome (TLS), peripheral neuropathy, hematotoxicity, pyrexia, skin disorder, hypotension and gastrointestinal disorder, heightened surveillance was conducted to capture onset, clinical course and outcomes. [Results] Males outnumbered females (55.8% [293/525] vs. 44.2% [232/525]). Patients elder than 50 years old accounted for 92.6% (486/525). Most of the patients were in stage III by both the International Staging System and Durie & Salmon system. More than half of the patients (59.1% [310/525]) had a duration of illness ranged from 1 to 5 years. Coexisting medical conditions were present in 62.3% (327/525) of patients; the most common was hypertension (17.5%). 7.6% and 10.5% of patients had coexisting medical conditions related to lung disease or heart disease, respectively. Most of the patients had received prior treatment for MM, which included MP (melphalan, prednisolone), thalidomide, dexamethasone, VAD (vincristine, doxorubicin, dexamethasone), and stem cell transplantation. The most commonly observed adverse drug reactions (ADRs) were abnormal changes in hematological laboratory tests (74.3%). Incidence of serious ADRs was 21.1% (111/525). The most frequent serious ADRs were low platelet count (5.3% [28/525]) and peripheral neuropathy (2.1% (11/525). LD/ILD was seen in 4.2% (22/525). TLS was observed in 5.0% (26/525). With regard to the preliminary analysis of anti-tumor effect, the overall response rate as determined by the investigator-based clinical evaluations was 50.2% (257/512). The overall response rate based on M-protein concentration was 41.8% (214/512). 12 (2.3%) patients died within 30 days after the final administration of bortezomib. Progression of disease was the most common cause of death, and worse performance status prior to initiating bortezomib was associated with early mortality. [Conclusion] Based on the interim analysis, this post-marketing surveillance reveals no new safety signals in Japanese patients with relapsed/refractory MM treated with bortezomib. The incidence rates of AEs of special interest were comparable to those observed outside Japan except for LD/ILD which was less than those initially reported for the Japanese population.

Description: Introduction: Inotuzumab ozogamicin (CMC-544) is an antibody-targeted chemotherapeutic agent composed of a monoclonal antibody which targets the CD22 antigen, conjugated to calicheamicin, a potent cytotoxic antitumor antibiotic. Since CD22 is expressed on more than 90% of B-lymphoid malignancies, CMC-544 may be useful for treating patients (pts) with B-cell non-Hodgkin lymphoma (B-NHL). In a phase I study in the US and EU, CMC-544 showed definite clinical activity in pts with relapsed/refractory B-NHL (both follicular and diffuse large) with clinically manageable thrombocytopenia as the main toxicity. In this phase 1 study, the safety, tolerability, efficacy and pharmacokinetics (PK) of CMC-544 was evaluated in Japanese pts with relapsed or refractory B-cell NHL. Methods: CMC-544 was administered IV once every 28 days ± 2 days (1 cycle). A dose escalation was planned using 1.3 mg/m2 and 1.8 mg/m2, the maximum tolerated dose (MTD) which was previously determined in non-Japanese pts. Pts were allowed to enroll in the study if they had relapsed or refractory CD22+ B-NHL. Tumor responses were evaluated by investigator’s assessment according to the International Workshop Criteria for NHL. Results: Enrollment for this study is complete and included 13 pts (6 women, 7 men, median age [range] of 49 yrs [43–72]). All of the 13 pts who were enrolled had follicular lymphoma and had received at least one regimen of rituximab alone or rituximab-containing chemotherapy in their prior treatments. The median number of prior treatment regimens was 1 (range: 1–13). In dose escalation, no pts had dose limiting toxicities and the tolerability in the MTD previously determined in non-Japanese pts (1.8mg/m2) was confirmed for Japanese pts. 3 pts and 10 pts were treated with 1.3 mg/m2 and 1.8 mg/m2 of CMC-544, respectively. The median number of CMC-544 treatment cycles was 3 (range: 2–8). The most common drug-related adverse events (AEs, all grades ≥ 35% pts) included thrombocytopenia (100%), leukopenia (92%), neutropenia (85%), elevated AST (85%), anorexia (85%), lymphopenia (85%), nausea (77%), elevated ALT (54%), malaise (46%), and headache (46%). Grade 3/4 AEs ≥ 15% pts were: thrombocytopenia (54%), lymphopenia (31%), neutropenia (31%), and leukopenia (15%). 7 pts discontinued treatment due to AEs; 1 pt because of grade 2 rash, 1 pt because of grade 2 urticaria and 5 pts because of AEs which required treatment delays of 〉3 wks (2 pts with prolonged thrombocytopenia, 1 pt with prolonged thrombocytopenia and neutropenia, 1 pt with neutropenia and elevated alkaline phosphatase, and 1 pt with prolonged neutropenia and elevated total bilirubin). PK analyses demonstrated that maximum serum concentration (Cmax) and area under the curve (AUC) of CMC-544 increased in a dose dependent manner. Both parameters increased with the second dose in the second cycle. At all dose levels, terminal half-life (t1/2) was prolonged, and total clearance (CL) was decreased in the second cycle. Overall, the PK profile was similar to that of the previous study with non-Japanese pts. 7 pts had CRs (CR + CRu), 4 pts had PRs, and 2 pts had stable disease. The objective response rate (ORR) was 85% (11/13). Conclusions: The tolerability of CMC-544 for Japanese pts with relapsed or refractory follicular B-NHL who had been pretreated with rituximab was confirmed at 1.8 mg/m2 administered once every 28 days. This is the same dose level as the MTD for non-Japanese pts. The PK profile of CMC-544 in Japanese pts was similar to that in non-Japanese pts. Based on the acceptable safety profiles and a high preliminary ORR, CMC-544 should be considered for further investigations in Japanese pts with relapsed or refractory B-NHL who have been pretreated with rituximab.

Description: Background: In recent years, diffuse large B-cell lymphoma (DLBCL) has been classified into the germinal center B-cell (GC) type, the activated B-cell (ABC) type, and the type 3 using global gene expression profiling or immunohistochemical staining. It has been reported that the GC type DLBCL showed significantly longer survival than the non-GC (ABC and the type 3) type DLBCL treated with CHOP or CHOP like regimen not using rituximab. Methods: We analyzed retrospectively the prognosis between the GC and non-GC types of DLBCL treated with R-CHOP regimen. All 50 patients with DLBCL, diagnosed between July 2003 and July 2005 were included in this study. The pathology was reviewed by hematopathologist and confirmed to be de novo DLBCL according to the WHO classification. Patients with primary CNS- and post-transplant lymphomas were excluded. GC type or non-GC type DLBCL was determined by immunohistochemistry such as the expression patterns of CD10, BCL-6, and IRF-4 (MUM1). All patients were initially treated with six cycles of R-CHOP regimen consisting of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone. If we evaluated partial response after six cycles of R-CHOP, the patients have added radiation therapy. Results: The patients consisted of 30 GC type and 20 non-GC type DLBCL with a median age of 61.0 yr (range 31–83 yr). The median follow up of surviving patients was 24 months. CR rate between GC and non-GC types were 57.0% vs. 75.0%, p=0.186, and overall response rate were 87.0% vs. 90.0%, p=0.929, respectively. The median of progression free survival was 17.3 months vs. 19.6 months, p=0.80. There is no statistical significance difference between two groups. Conclusion: These results suggest that addition of rituximab to CHOP regimen improves clinical outcome of non-GC type DLBCL as well as GC type DLBCL.