CHOP-like Regimens Research Articles

Diagnosis and treatment in patients with B-cell lymphoma unclassified that is intermediate between diffuse large B-cell lymphoma and Burkitt's lymphoma

To characterize a group of patients with B-cell lymphoma (BCLU) unclassified that is intermediate between diffuse large B-cell lymphoma and Burkitt's lymphoma, to identify poor prognostic factors, and to evaluate therapeutic efficiency in patients with BCLU. Twenty-five patients with BCLU were examined. Double-hit lymphoma (DHL) was diagnosed in 8 (32%) patients. According to the Ann-Arbor classification of lymphoma, its stages II, III, and IV were diagnosed in 3 (12%), 2 (8%), and 20 (80%) patients, respectively. MYC rearrangement was observed in 11 (48%) out of 23 patients: single-hit lymphoma in 3 patients and DHL in 8 (BCL2+/MYC+ in 6 cases and BCL6+/MYC+ in 2). The expression of с-MYC (cut off ≥40%) was revealed in 17 (74%) out of 23 patients; that of BCL2 (cut off ≥50%) was detected in 14 (58%) out of 24 patients; coexpression of both proteins was seen in 12 (52%) out of 23 patients. The DHL group showed a correlation between the rearrangement of the BCL2+/MYC+ genes and the expression of MYC and BCL2 proteins in 5 out of 6 patients. Taking into account the heterogeneity of the entire patient group, DHL and non-DHL subgroups were considered separately. Both subgroups were comparable by clinical characteristics. BCLU patients younger than 60 years of age received treatment according to the LB-M-04 ± rituximab; those aged 60 or older had CHOP-like regimens ± rituximab. Autologous stem cell transplantation (auto-SCT) was performed in 5 patients belonging to a high-risk group. The 3-year overall survival (OS) was 62% and the 3-year event-free survival (EFS) was 51%. The 3-year OS was lower for the DHL group than that for the non-DHL group (43 and 75%, respectively). In the DHL group, both OS and EFS are significantly lower (the risk of poor outcome, including death, is higher) than those in the non-DHL group. It is conceivable that intensified chemotherapy with auto-SCT increases treatment results in patients with BCLU; however, a larger number of observations are needed to obtain valid data.

Plasmablastic Lymphoma: A Review of Current Knowledge and Future Directions.

Plasmablastic lymphoma (PBL) is an aggressive subtype of non-Hodgkin's lymphoma (NHL), which frequently arises in the oral cavity of human immunodeficiency virus (HIV) infected patients. PBL shows diffuse proliferation of large neoplastic cells resembling B-immunoblasts/plasmablasts, or with plasmacytic features and an immunophenotype of plasma cells. PBL remains a diagnostic challenge due to its peculiar morphology and an immunohistochemical profile similar to plasma cell myeloma (PCM). PBL is also a therapeutic challenge with a clinical course characterized by a high rate of relapse and death. There is no standard chemotherapy protocol for treatment of PBL. Cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or CHOP-like regimens have been the backbone while more intensive regimens such as cyclophosphamide, vincristine, doxorubicin, high-dose methotrexate/ifosfamide, etoposide, high-dose cytarabine (CODOX-M/IVAC), or dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (DA-EPOCH) are possible options. Recently, a few studies have reported the potential value of the proteasome inhibitor bortezomib and thalidomide in PBL patients. The introduction of genes encoding artificial receptors called chimeric antigen receptors (CARs) and CAR-modified T cells targeted to the B cell-specific CD19 antigen have demonstrated promising results in multiple early clinical trials. The aim of this paper is to review the recent advances in epidemiology; pathophysiology; clinical, pathologic, and molecular characteristics; therapy; and outcome in patients with PBL.

Overexpression of DNA methyltransferase 1 as a negative independent prognostic factor in primary gastrointestinal diffuse large B-cell lymphoma treated with CHOP-like regimen and rituximab.

The aims of the present study were to elucidate the transcript levels of DNA methyltransferase (DNMT)1, DNMT3a and DNMT3b by quantitative polymerase chain reaction in patients with primary gastrointestinal diffuse large B-cell lymphoma (PGI-DLBCL), and determine the association of their expression with the clinical parameters and prognostic values of the disease. The results revealed that the expression of DNMT1 in patients with PGI-DLBCL was significantly higher than that in healthy controls (P=0.04), while the expression of DNMT3a and DNMT3b were significantly lower (P<0.001 and P=0.001, respectively). The increased expression of DNMT1 was significantly correlated with shorter overall survival and progression-free survival rates (P=0.018 and P=0.008, respectively). The multivariate analysis demonstrated that the level of DNMT1 was an independent prognostic factor. In conclusion, DNMT1 was identified to be an independent prognostic factor for predicting the survival of patients with PGI-DLBCL; this suggests that it could be used as a marker to indicate the prognosis of PGI-DLBCL.

Management and prognosis of 66 patients with B-cell non-Hodgkin lymphoma presenting with initial spinal cord compression: a French retrospective multicenter study

Initial spinal cord compression (ISCC) in B-cell non-Hodgkin lymphoma (NHL) is rarely present at diagnosis. We performed a multicenter retrospective analysis of 66 patients with ISCC, including diffuse large B-cell (DLBCL) (70%), follicular (20%), small lymphocytic (6%), marginal zone (2%) and B-cell unclassified (2%) lymphomas, with the aim of describing their management and outcomes, as well as the occurrence of central nervous system (CNS) relapses. All but two patients received cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) or CHOP-like regimens, with rituximab in 61% of cases. Forty-six patients received CNS prophylaxis. The 5-year overall survival and progression-free survival were 78% and 65% for DLBCL, and 60% and 48% for indolent lymphomas, respectively. CNS relapses occurred in four (6%) patients, all with DLBCL and all in the cerebellum. Initial decompressive procedures, intradural involvement, cerebrospinal fluid infiltration and lack of CNS prophylaxis did not influence survival. Adverse prognostic factors were male sex, poor performance status, elevated lactate dehydrogenase and high age-adjusted international prognostic index.

B-Cell Lymphoma Unclassified, Intermediate Between Diffuse Large B-Cell Lymphoma and Burkitt Lymphoma: A Single Center Experience of Intensive Chemotherapy with and without Auto-SCT

Background: According to current data B-cell lymphoma unclassified (BCLU), intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma represents a highly aggressive type of lymphoma with dramatically bad response for chemotherapy. Cases with translocation of two genes (MYC and BCL2 or BCL6) are divided into double-hit lymphomas (DHL). We need to estimate risk factors to intensify treatment and manage indications for autologous stem cell transplantation (auto-SCT) according to individual characteristics.Aim: To evaluate results of BCLU treatment according to LB-M-04±R protocol in adults younger than 60 years old and CHOP-like regimens in elderly patients (≥60 years old) with auto-SCT in high risk patients group.Patients and Methods: 21 pts observed in National Research Center for Hematology (Moscow) between 2004 and 2014 years were included in a current study. All of them were convenient to BCLU diagnosis criteria according to WHO classification of hematological malignancies (2008). Genetic analysis included: standard karyotyping in 7 pts (6 – lymph nodes samples, 1 sample of cerebrospinal fluid). FISH analysis was performed in 21 pts (in 7 cases on tumor cells; on imprints of tumor in 4 cases, on histologic slides from paraffin blocks - in 10 cases). Taking into account heterogeneity of a common group we divided all pts into 2 subgroups: DHL and non-DHL cases (7 vs. 14 respectively).Pts younger than 60 years old (17 pts) were treated according to LB-M-04±R protocol which included A-C-A-C courses. Course A consisted from dexamethasone 10 mg/m2 i.v. 1-5 ds, methotrexate 1500 mg/m2 12-hours infusion 1st d, ifosfamide 800 mg/m2 1-5 ds, vincristine 1 mg/m2 1st d, doxorubicine 50 mg/m2 3rd d, cytarabine 150 mg/m2 4-5 ds, etoposide 100 mg/m2 4-5 ds; course C included dexamethasone 10 mg/m2 i.v. 1-5 ds, methotrexate 1500 mg/m2 12-hours infusion 1st d, vinblastine 5 mg/m2 1st d, cytarabine 2000 mg/m2 twice a day 2-3 ds, etoposide 150 mg/m2 3-5 ds. Rituximab were indicated before chemotherapy in dosage 375 mg/m2. CNS prophylaxis was made by intrathecal administration of prednisolone 30 mg, cytarabine 30 mg, methotrexate 15 mg in 1st day of each course. When complete remission (CR) was achieved after 2 courses, treatment lasted 4 courses. When tumor regression was diagnosed after 4 courses, treatment continued till 6 courses. 4 pts ˃60 years were managed by CHOP-like regimens ±R. We performed auto-SCT in non-DHL group with signs of poor prognosis (bone marrow involvement, multiple extranodal sites, CR after 6 courses) and in DHL when CR had been achieved after 4 courses. Pts with DHL after auto-SCT received 2 R-EPOCH courses more. As a conditional regimen BEAM was used. An overall survival (OS) as a primary endpoint and event-free survival (EFS) were assessed with using the Kaplan-Meier method (with log-rank test) to estimate an efficacy of treatment. Statistical analysis was performed with SAS 9.3 (SAS Institute Inc. Cary, NC).Results: Studying group included 9 males and 12 females. Comparing pts according DH and non-DH status, DHL group (n=7) consisted of 2 males and 5 females, median age 48 years (30-74), ECOG status was 2.6 (95%CI 1.3-3.9) and non-DH group consisted of 7 male and 7 female, median age was 46 (23-76), ECOG status was 2.4 (95%CI 1.8-3.1). DHL pts had stage II of lymphoma according to Ann-Arbor classification in 1 case, III in 1 case, IV in 5 cases. Non-DHL pts had stage II of lymphoma in 2 cases and IV in 12 cases. Bone marrow involvement was revealed in 2 cases in DHL group and in 5 cases in non-DHL group. More than 1 extranodal site took place in 3 cases of DHL and 8 cases of non-DHL. Survival rates of groups were comparable because they were not significantly different of these characteristics. The 2-year OS and EFS rates were less for DHL pts compared with non-DHL pts: OS: 43 vs. 75%, P=0.24 and EFS: 29 vs. 66%, P=0.09 respectively (Figures 1and 2). Auto-SCT was performed in 2 pts with DHL treated by LB-M-04±R protocol (both pts still be alive) and in 3 pts with non-DHL (1 pt treated by LB-M-04±R and 1 treated by CHOP-like regimen+R are alive in CR and 1 pt treated by LB-M-04±R protocol developed a relapse).Conclusions: Low OS and EFS in BCLU group are caused particularly by DHL cases. We need to enlarge an observation group to confirm benefits of auto-SCT in BCLU pts with signs of poor prognosis. [Display omitted] [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

HLA-G and MHC Class II Protein Expression in Diffuse Large B-Cell Lymphoma

Major histocompatibility complex (MHC) class I and class II are similar in function since they present peptides at the cell surface to CD8+ and CD4+ T cells, respectively. There is mounting evidence indicating that MHC genes play a role in the etiology and clinical course of non-Hodgkin lymphomas (NHL), especially in diffuse large B-cell lymphoma (DLBCL). We investigated the expression of human leukocyte antigen-G (HLA-G) and HLA class II protein in DLBCL among 148 patients and related their expression to the clinical course of the disease. Negative HLA-G expression was associated with a lower probability of achieving a complete remission (P= 0.04). There was no impact of HLA-G or HLA class II expression on the probability of progression-free survival (PFS). Patients with positive HLA-G expression presented a trend towards a higher 3-year overall survival (OS) rate compared to those with negative expression of HLA-G (P= 0.08). The estimated 3-year OS rate of patients with positive HLA class II expression was 59.4% (95%CI 49-69) in comparison to the 37.4% (95%CI 22-56; P= 0.04) in subjects with negative expression. In a multivariate Cox analysis adjusted for the IPI factors, we found that both the intermediate high/high IPI risk group (P= 0.001) and the loss of HLA class II expression (P= 0.05) independently increased the risk of death in the study group. We also investigated whether the impact of HLA class II expression on OS may be related to the subtypes of DLBCL. In the subgroup of 58 patients (39%) with GCB-type pattern, the patients with the loss of HLA class II expression presented a significantly lower 3-year OS rate than those with its positive expression (26% [95% CI 10-53] vs 68.2% [95% CI 51-81], P= 0.02). In contrast, in the subgroup of 90 non-GCB patients (61%), HLA class II expression did not influence OS. To further explore the unexpected favorable effect of positive HLA-G expression on the clinical course of DLBCL, we performed an additional analysis that considered the type of treatment (chemotherapy with or without rituximab). In the group of patients treated with immunochemotherapy, a more pronounced effect of the positive HLA-G expression on OS was revealed. The estimated 3-year OS rate of patients with the positive HLA-G expression was 73.3 % (95% CI 49-88) compared to 47.5% (95% CI 35-60, P= 0.03) in subjects with the negative HLA-G expression. In contrast, in the group treated with CHOP-like regimens, no significant impact of HLA-G expression on OS was observed: the 3-year OS rate for HLA-G positivity was 20% (95% CI 4-62) vs 55.3% (95% CI 37-72; P= 0.08) for the absence of HLA-G. Additionally, the prognostic value of HLA class II expression was also shown to depend on the use of rituximab as a part of first line treatment. In the patients receiving immunochemotherapy, those that had positive HLA class II expression demonstrated a 3-year OS rate of 65.3% (95% CI 52-76) compared to 29.6% (95% CI 13-53, P= 0.04) in subjects with the loss of HLA class II expression. However, HLA class II expression did not have a prognostic impact on OS in the patients treated with chemotherapy alone: the 3-year OS rate was 49.5% (95% CI 32- 67) in the subjects with positive expression in comparison to 50% (95% CI 15-85, P= 0.8) in those with the loss of HLA class II expression.In conclusion, we demonstrated for the first time expression of HLA-G protein in DLBCL and its association with the clinical course of the disease as well as we confirming the association of the loss of HLA class II protein expression with poor survival in patients treated with immunochemotherapy. Although the clinical significance of the loss of HLA class II protein expression seems to be well understood, the contribution of HLA-G to the prognosis of B-cell malignancies deserves further study, especially its immunoregulatory functions in relation to treatment with rituximab, which remains an open question. DisclosuresRobak:MorphoSys AG: Research Funding.

Gemcitabine in Blastic Plasmacytoid Dendritic Cell Neoplasm (CD4+CD56+ hematodermic neoplasm)

Once thought to be a natural killer cell lymphoma, blastic plasmacytoid dendritic cell neoplasm, also termed CD4+CD56+ hematodermic neoplasm, is a rare clinical entity which derives from plasmacytoid dendritic cells. Cutaneous predominant (with better prognosis) and non-cutaneous subtypes (often accompanied by mediastinal involvement and a poorer prognosis) have been described. Many patients are treated with CHOP-like regimens, but the prognosis remains poor. Patients presenting with only skin lesions (median survival 21 months) had a better prognosis than patients presenting with both cutaneous and extra-cutaneous disease.We describe an 86 yo female with a distant history of breast cancer. She noted rapid development of mildly itchy round pink cutaneous nodlues on the arms, buttock, and legs. She was treated with topical steroids without improvement. The CBC, calcium, and LDH were normal. ECOG 0. There was no adenopathy or organomegaly.Skin biopsy demonstrated a dense lymphoid infiltrate involving the upper and mid dermis, as well as adnexal structures, without epidermotropism. The infiltrate was composed predominantly of large to intermediate sized lymphoid cells having moderate amounts of cytoplasm and oval to cleaved nuclei having open chromatin and one or more small nucleoli. Mitotic figures were present. The neoplastic cells expressed CD4, CD56. Ki-67 was expressed by many of the cells. The cells were negative for CD1a, CD3, CD5, CD7, CD8, PAX-5, CD20, CD79a, CD10, CD23, CD30, CD163, bcl-2, bcl-6, myeloperoxidase, kappa/lambda light chains, p63, Tdt, tryptase, chromogranin, MART-1, mammoglobin, CAM 5.2, and AE1/3. The morphology and immunophenotype was consistent with a CD4+/CD56+ hematodermic neoplasm.The patient preferred no additional staging studies or therapy. Based on the available data, cutaneous-only disease was suggested. The disease was observed without intervention for a few weeks, but progressed on her skin. She then requested a gentle therapy that might provide palliative improvement and prevent progression.Gemcitabine (2′,2′-difluorodeoxycytidine) is a well tolerated pyrimidine antimetabolite that impairs DNA synthesis and promotes induction of apoptosis. In patients with relapsed or refractory aggressive non-Hodgkin lymphoma, gemcitabine led to a 20% response rate with median survival of 6 months.Therapy with Gemcitabine was administered at 1000 mg/M2 on days 1, 8, 15 every 28 days. There was rapid and marked improvement of the skin nodules. Treatment was very well tolerated with minimal bilateral leg edema. A 4 week chemotherapy holiday was associated with regrowth. Photographs document the disease progression before therapy and response of disease with ongoing therapy.Gemcitabine may provide palliative benefit in some patients with blastic plasmacytoid dendritic cell neoplasm.TablePre Therapy May 15 2014Day 1 Chemotherapy May 23 2014Day 22 Chemotherapy June 6 2014 [Display omitted] [Display omitted] [Display omitted] DisclosuresOff Label Use: Gemcitabine in blastic plasmacytoid dendritic cell neoplasm (CD4+CD56+ hematodermic neoplasm).

Racial Differences in Treatment Dose Intensity Among Patients with Diffuse Large B-Cell Lymphoma: Analysis of the Veterans Health Administration (VHA) National Database

Introduction: Previous studies in diffuse large B-cell lymphoma (DLBCL) have demonstrated that higher treatment dose intensity is associated with improved survival. Race-based differences in dose intensity may contribute to outcome differences. In order to better understand the relationship between dose intensity and race, we performed a retrospective analysis of veterans examining demographic and clinical factors associated with dose intensity in patients with DLBCL.Methods: Patients diagnosed with DLBCL between October 1, 1998 and December 31, 2008 and treated within the VHA system with CHOP or CHOP-like regimens (+/- rituximab) were identified in the VA Central Cancer Registry. Data on age, sex, race, stage, lactate dehydrogenase (LDH), B-symptoms, body mass index, HIV status, co-morbidities, medications, and socioeconomic status were obtained. Average relative dose intensity (ARDI) was calculated for the use of cyclophosphamide and doxorubicin in patients who received CHOP chemotherapy. Univariate analysis was performed to explore demographic and clinical characteristics dichotomized by ARDI < or ≥ 80%. Additionally, a multivariate logistic regression analysis was used to identify baseline factors associated with receiving treatment with an ARDI ≥ 80%.Results: 1575 DLBCL patients who received doxorubicin and survived more than 5 months after treatment initiation were identified. On univariate analysis, patients who received ARDI <80% were more likely to be older (66.1 vs 61.2, p=<0.001), have advanced stage disease (58.9% vs 52.7%, p=0.015), have systemic B-symptoms (51.7% vs 45.5%, p=0.002), have more co-morbidities (mean co-morbidity score 2.4 vs 1.7, p=<0.0001), have HIV (7.5% vs 3.3%, p=0.0002), less likely to receive rituximab (73.5% vs 79.1%, p=0.008), and were more likely to be from the lowest estimated household income quartile (25.5% vs 21.8%, p=0.03). While not statistically significant on univariate analysis, patients receiving lower ARDI were slightly more likely to be Black (13.8% vs 10.6%, p=0.053). On multivariate logistic regression analysis, factors associated with reduced odds of receiving treatment with an ARDI ≥ 80% included: Black race, (OR 0.62; 95% CI 0.44 – 0.87), age (OR 0.96; 95% CI 0.95 – 0.97), HIV positive status (OR 0.24; 95% CI 0.14 – 0.40), and presence of B-symptoms (OR 0.74; 95% CI 0.59 – 0.93).Conclusion: After controlling for the other identified variables, Black patients were significantly less likely to receive an ARDI of ≥ 80%. The reasons for this finding are unknown from this analysis. Future efforts to reduce racial outcome disparities in NHL could include efforts to understand the underlying causes of chemotherapy dose reductions and delays in racial minority populations, which were present in the VHA, an equal access healthcare system. DisclosuresNo relevant conflicts of interest to declare.

A Proposal for a New Staging System of Extranodal Natural Killer T-cell Lymphoma, Nasal-Type: a Multicenter Study of Chinese Southwest Oncology Group (CSWOG)

Purpose: Extranodal NK/T-cell lymphoma, nasal type (ENKTL), is a rare and highly aggressive disease. The Ann Arbor staging system had been unsuitable to proper staging of ENKTL. This study was conducted to establish a new staging system specified for ENKTL, which can identify poor prognostic patients.Patients and Methods: Patients with untreated, centrally reviewed diagnosis of ENKTL were included in our study. The new staging system was established based on the study of single center consecutive patients treated with CHOP-like regimens with or without involved field radiotherapy (IFRT), then we initinated a multicenter confirmation study and conducted a multicenter prospective study to validate the new staging system.Results: From Jan 1997 to June 2006, 134 consecutive patients treated in the cancer center of Sun Yat-sen University were analyzed. The following was a summary of the classification system developed: stage I: lesions confined within nasal cavity or nasopharynx without local invasiveness (paranasal sinuses or bony or skin invasion); stage II: localized disease with local invasiveness; stage III: localized disease with regional lymph node involvement (cervical lymph nodes); and stage IV: disseminated disease (lymph nodes on both sides of diaphragm, multiple extranodal site). The distribution of stage I to IV using the new system and Ann Arbor system were 39.6%, 23.9%, 23.1%, 13.4% and 63.4%, 23.1%, 5.2%, 8.2%, respectively. The 5-year OS rate of stage I to IV using the new system were 29.5%, 23.4%, 21.3% and 0.07% compared with 23.8%, 21.3%, 0.0% and 0.0% using the Ann Arbor system. In the multicenter confirmation study conducted in 18 centers in China, 722 patients were analyzed. The results showed that the distribution of the new system compared with Ann Arbor system from stage I to IV were 24.1%, 34.9%, 18.3%, 22.7% vs 59.1%, 19.0%, 6.9%, 15.0%, respectively, and the 5-year OS rate of stage I to IV were 56.0%, 48.3%, 33.8%, 26.1% vs 50.7%, 39.1%, 10.8%, 28.0%, respectively. For the multicenter prospective study, 233 newly diagnosed ENKTL patients treated with non-CHOP-like regimens were enrolled and showed a balanced distribution of 17.2%, 39.9%, 19.3%, 23.6% vs 53.6%, 25.3%, 6.9%, 14.2% from stage I to IV and superior 5-year OS rate: 82%, 73%, 67%, 54% vs 75.2%, 65.6%, 46.9%, 73.8% from stage I to IV using the new system in compared with the Ann Arbor system.Conclusions: The new staging system with a more balanced distribution and a superior prognostic discrimination as compared with Ann Arbor staging system no matter for CHOP-like or non-CHOP-like regimens, is more suitable for ENKTL and can be recommended used in the future. DisclosuresNo relevant conflicts of interest to declare.

Risk Stratification of DLBCL Patients According to NCCN-IPI in Our Hospital

TitleRisk stratification of DLBCL patients according to NCCN-IPI in our hospitalBackgroundRecently, a robust prognostic tool termed enhanced International Prognostic Index (NCCN-IPI) for the rituximab era was reported. The aim of this study was to assess the usefulness of NCCN-IPI in risk discrimination and its suitability in clinical applications.Patients and MethodsWe retrospectively analyzed consecutive patients with de novo diffuse large B cell lymphoma (DLBCL) who were diagnosed and treated with R-CHOP or CHOP-like regimens between January 2004 and December 2013. Patients were required to be cancer-free for 5 years before diagnosis and had to have no prior documented history of indolent lymphoma. We stratified DLBCL patients using IPI and NCCN-IPI, and estimated overall survival (OS) in each risk group. The unadjusted probabilities of OS were estimated using the Kaplan-Meier(K-M) method. The log-lank test and multivariate Cox regression analysis were used to assess the prognostic values of each clinical variable.ResultsThree-hundred and seventy one patients were identified. The median age was 69 (20–93) years. The median follow-up time was 41 months. The numbers of patients with NCCN-IPI-defined low (L), low-intermediate (L-I), high-intermediate (H-I), and high (H) risk were 35 (9.4%), 125 (33%), 139 (37%), and 72(19%), respectively. The 3-year OS in each risk group was 93%, 89%, 70%, and 52%, respectively. NCCN-IPI was better for the discrimination of low- and high-risk groups (3-year OS, 93% vs 52%) than IPI (3-year OS, 87% vs 56%), and NCCN-IPI gave a better concordance index than IPI (c-Harrel = 0.678 vs 0.665). However, the discriminating power of NCCN-IPI was not as good as previously reported. In the multivariate analysis using the five independent variables of NCCN-IPI as covariates, age was not a significant factor in the <40, 40-60, and 61-75 age groups, and LDH ratio was not a significant factor between≤1 and >1-3 groups. Ann Arbor stage was not a significant factor either. Next, we examined extranodal involvement, which was a significant prognostic factor (HR, 2.3; p<0.001). Multivariate analysis, using age, LDH, performance status, stage, and extranodal involvement in major organs as covariates, lung (HR, 3.5; p<0.001) and bone marrow (HR, 1.8; p=0.048) involvement were significantly poor prognostic factors, and CNS (HR, 2.5; p=0.066) or GI tract (HR, 1.4; p=0.13) involvement adversely affected OS, although they were not significant factors. In contrast, liver involvement did not affect OS (HR, 0.87; p=0.70). We simplified the NCCN-IPI method by using a maximum of four scoring points for age (>75, 1pt), LDH ratio (>3, 1pt), extranodal disease (bone marrow, lung, CNS, or GI tract, but not liver, 1pt), and ECOG PS (≥2, 1pt) and not using Ann Arbor stage as a prognostic factor. Four distinct groups were formed based on K-M curves for OS: low (L, 0 pt), low-intermediate (L-I, 1pt), high-intermediate (H-I, 2pt), and high (H, 3-4 pt). Simplified NCCN-IPI better discriminated low- and high-risk groups (3-year OS, 93% vs 34%; c-Harrel = 0.705) than NCCN-IPI. When patient age was compared in each scoring system, high-risk patients were older in the NCCN-IPI (median age, 79 years old) and its simplified version (median age, 79 years old) than in IPI (median age, 72 years old).ConclusionNCCN-IPI showed better discrimination in our cohort than IPI. However, we found that the enhancement in predicting outcomes by including age and LDH was not as useful as previously reported, and stage and liver involvement was not an independent prognostic factor in our cohort. In the rituximab era, Ann Arbor stage is not a useful prognostic factor. Further validation and optimization of cut-off in each variable could improve the NCCN-IPI. The majority of the high risk patients evaluated by both NCCN-IPI and simplified NCCN-IPI were elderly, so innovative therapeutic approaches adjusted for age are required to improve the outcome of the high-risk group. To identify high-risk groups especially among younger patients, a refined scoring system including not only conventional clinical factors but also other factors such as biological markers will be required. [Display omitted] [Display omitted] [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Efficacy and Safety of Biosimilar Epoetin Alpha in Patients with Chronic Lymphoproliferative Syndromes and Chemotherapy-Induced Anemia: An Observational, Retrospective, Monocentric Analysis

INTRODUCTION. Chemotherapy (CHT)-induced anemia is a consequence of the myelosuppressive effect of CHT, delivered for solid or hematologic malignancies, and tends to worsen over the course of repeated cycles of therapy. Erythropoietic agents have shown their efficacy in correcting CHT-induced anemia in cancer patients, in reducing the need of blood transfusion and in improving patients’ quality of life. Epoetin (EPO) biosimilars have emerged as an alternative to originator products, sharing an equivalent mechanism of action, efficacy and safety, as a result of a rigorously conducted comparability exercise.PATIENTS AND METHODS. This study was aimed at evaluating the response to EPO alpha biosimilar (Binocrit®, Sandoz, 40,000 IU/week subcutaneously) after a 4-weeks (and 8-weeks, when applicable) treatment period, as well as the rate of CHT cycles delays or interruptions due to anemia, in 49 consecutive adult patients, affected by chronic lymphoproliferative disorders, undergoing CHT, either as a first-line induction (35 patients) or second-line or salvage treatment (14 patients), and presenting with CHT-induced anemia. The median age was 69 (range 21-90) years, with 49% of the patients older than 70. Fourteen had diffuse large B-cell lymphoma, 14 an indolent non-Hodgkin’s lymphoma, 6 had chronic lymphocytic leukemia, 5 mantle cell lymphoma, 4 T-cell lymphoma, 2 hairy cell leukemia and 1 had histiocytosis. Response to EPO was defined as an increase in hemoglobin (Hb) levels after 4 (ΔHb4) and 8 weeks (ΔHb8) of treatment of at least +1 g/dL, or as the achievement of Hb > 11 g/dL independently of ΔHb, with a complete transfusion-independence. Hb stability was regarded as a ΔHb comprised between -1 and +1 g/dL. A ΔHb < -1 g/dL or an acquired transfusion dependence was judged as a lack of response. Treatment with EPO was started at the first occurrence of Hb < 10 g/dL during chemotherapy, when anemia was not due to any different concomitant cause (e.g. hemolysis, iron deficiency, malabsorption, etc). Treatment duration was established by the treating physician; however, treatment was stopped when Hb reached at least 11 g/dL, in patients whose chemotherapy programme had reached its completion and in those who became transfusion dependent.RESULTS. Mean Hb (± standard deviation) at presentation was 11.0 ± 1.6 g/dL, with 49% of patients being anemic mostly as a consequence of their disease. Nine patients had grade 2 anemia, while one presented with grade 3 anemia. Twenty-one were treated with a cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) every 21 days or with a weekly CHOP-like regimen; 10 received a fludarabine-based regimen; 6 underwent a bendamustine-based second-line treatment. The remaining 12 patients were treated with various regimens (lenalidomide, rituximab, cladribine, temsirolimus, gemcitabine). Mean Hb level at EPO treatment start was 9.3 ± 0.5 g/dL. After 4 weeks of treatment, the reached mean Hb level was 10.8 ± 1.4 g/dL for patients receiving a first-line CHT, and 11.4 ± 1.6 g/dL for those on a second or later CHT line, with a mean ΔHb4 of 1.4 ± 1.4 g/dL and 2.1 ± 1.6 g/dL for each group of patients, respectively. Sixteen patients had their Hb level measured after 8 weeks of treatment, achieving a mean Hb level of 11.0 ± 1.7 g/dL and 9.8 ± 1.4 g/dL for each treatment subgroup, with a ΔHb8 of 1.7 ± 1.6 g/dL and 0.5 ± 1.3 g/dL, respectively. Overall, 36 patients responded to the treatment, yielding to a 73.4% hematological improvement rate. Eleven patients (22.5%) showed a stable Hb level throughout their treatment course, and 2 (4.1%) were considered non-responders (figure). Among responders, 2 patients required a new biosimilar EPO alpha treatment, again with response; 2 patients showed a late recurrence of anemia, and were managed with blood transfusions. Overall, 22 patients (44.9%; 61.1% of responders) had an Hb increase of at least 2 g/dL. CHT cycles were delayed in 9 cases (18.4%) because of anemia; interruptions of the planned CHT programme occurred in 6 cases (12.2%). No adverse events were documented; in particular, no thromboembolic or pure red-cell aplasia episodes have been demonstrated.CONCLUSION. The treatment of CHT-induced anemia with biosimilar EPO alpha in patient with chronic lymphoproliferative disorders is correlated with a high rate of responses and allows a safe completion of the planned CHT programme in most of the cases, both in induction and salvage treatment settings. [Display omitted] DisclosuresBroccoli:Sandoz: Membership on an entity’s Board of Directors or advisory committees. Zinzani:Sandoz: Membership on an entity’s Board of Directors or advisory committees.

The Treatment of Primary Mediastinal Large B-Cell Lymphoma: A Two Decades Monocentric Experience on 98 Patients

The first line treatment for primary mediastinal large B-cell lymphoma (PMLBCL) still remains a matter of debate even if the literature confirms that an anthracycline-containing regimen should be the main choice. The European experience shows the superiority of “third-generation” dose-dense regimen like MACOP-B (methotrexate, doxurubicin, cyclophosphamide, vincristine, bleomycin, prednisone) or VACOP-B (same as MACOP-B, with etoposide instead of methotrexate) over CHOP (cyclophosphamide, adriamycin, vincristine and prednisone) or CHOP-like regimen. The addition of rituximab to third-generation regimen does not seem to cause any advantages in terms of overall survival (OS) and progression free-survival (PFS), while external radiotherapy (RT) has shown a good efficacy as a consolidation strategy at the end of induction chemotherapy, especially in converting partial responses (PR) into complete responses (CR).Between October 1989 and April 2010, 98 (58 females and 40 males) previously untreated PMLBCL patients were diagnosed and subsequently treated at our Institution. All patients were treated with MACOP-B regimen, concurrent rituximab was administered in 57 patients (58.2%) and 67 patients (68.4%) received mediastinal RT. Among 57 patients who received rituximab, 37 (64.9%) underwent RT whereas, among 41 who did not receive rituximab, RT was delivered in 30 (group 4, 73.2%) patients. 11 patients (group 1, 11.2%) received chemotherapy alone and 37 (group 3, 37.8%) received besides immunotherapy and RT (Table 1). All patients were assessed at the diagnosis and after the treatment with computed tomography and positron emission tomography (after 2001) scan.Main aims of our study were the effectiveness of the regimen measured as overall response rate (ORR) and patients survival. Sixty-one (62.2%) out of 98 patients achieved a CR and 27 (27.6%) were in PR after 12 cycles of MACOP-B regimen (with or without rituximab). Twenty-one patients in PR after (immuno)chemotherapy converted the response into CR with mediastinal RT. At the end of the scheduled treatment, 82 patients (83.7%) achieved a CR and 6 a PR (6.1%), yielding an ORR of 89.8%. At a median follow-up of 5.6 years, 9 patients relapsed within the first 2 years of treatment. During the follow-up 15 patients died, of whom 13 as a consequence of disease relapse or progression. The projected OS at 17 years is 72% with a PFS and a disease free survival (DSF) of 86.8% and 88.4% respectively (Figure 1 A-C). The subgroup analysis shows a statistically significant difference in term of OS (p=0.0003) but not in term of PSF and DFS among the four groups of treatment (Figure 1 D-F). All the patients receiving consolidation RT obtained a CR without differences between subgroup 3 and 4. RT seems to have a small consolidative potential in patients who obtained CR after chemo-immunotherapy alone: there are no differences in term of DFS between subgroup 2 and 3. No statistically significant differences in terms of OS, PFS and DSF occurred among patients received rituximab or not, regardless of a subsequent RT. Our monocentric experience spans a period of 20 years and indicates that a third-generation regimen like MACOP-B is feasible and could be a standard of first line treatment for PMLBCL. In agreement with the literature, adding rituximab doesn’t improve the outcome. Mediastinal RT, delivered as a consolidative strategy, impacts on global survival and on CR rates. In particular, RT after third-generation regimen remains a good strategy to convert PR into CR, but it may be avoided in patients obtaining CR after (immuno)chemotherapy.Table 1GroupMACOP-BRituximabRadiotherapyN (%)1YesNoNo11 (11.2%)2YesYesNo20 (20.4%)3YesYesYes37 (37.8%)4YesNoYes30 (30.6%)TOTALN (%)98 (100%)57 (58.2%)67 (68.4%)98 (100%) [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Brentuximab Vedotin in Combination with RCHOP As Front-Line Therapy in Patients with DLBCL: Interim Results from a Phase 2 Study

Brentuximab Vedotin in Combination with RCHOP As Front-Line Therapy in Patients with DLBCL: Interim Results from a Phase 2 Study

Less Toxic Gemcitabine-Oxaliplatin Based Induction Regimen (R-GIDIOX) Prior to Autologous SCT Produces Outcomes Similar to High-Dose Cytarabine Containing Intensive Induction Regimen in Mantle Cell Lymphoma – a Follow up Report of the Multicenter Study

Abstract Background: MCL is B-cell neoplasm diagnosed predominantly among older men. (R)CHOP-like regimens demonstrated high response rate, but the event-free survival (EFS) and overall survival (OS) are disappointingly short - 16-20 months and 3-4 years, respectively. An addition of high-dose AraC (12 g/m2) to the upfront therapy and autoSCT have significantly improved outcomes but remain feasible largely for younger and medically fit patients. Based on the activity and good tolerance of gemcitabine-oxaliplatin combinations in relapsed and refractory MCL patients, we developed an alternative first-line regimen for patients who are not candidates for R-HD-MTX-AraC (R-HMA). We presented an initial data of our pilot protocol at ASH 2012 (#2043). According to the protocol patients who had renal insufficiency and/or experience prohibitive toxicity following the first course of R-EPOCH, were assigned to receive R-EPOCH/R-GIDIOX regimen, while others were treated with R-EPOCH/R-HMA regimen. Both arms received consolidative autoSCT followed by R-maintenance. Aim: Assess toxicity and efficacy of R-DA-EPOCH/R-HMA and R-DA-EPOCH/R-GIDIOX in untreated MCL patients eligible for autoSCT. Patients and Methods: 47 untreated MCL patients from 6 centers were enrolled in prospective study between May 2008 - Sep. 2013; stage II-IV; ECOG 0-3; median age 55 years (29-64); M/F 76%/24%; MIPIb: 28% low, 33% intermediate and 39% high risk. Following 1st R-EPOCH patients were assigned to receive either R-DA-EPOCH/R-HMA or R-DA-EPOCH/R-GIDIOX regimen. In the absence of hematological toxicity gr. 4, severe infections and renal failure patients received R-HMA (R 375 mg/m2 d1, MTX 1000 mg/m2/24 hours d 2, AraC 3000 mg/m2 q 12 hrs d 3-4). Patients who experienced at least one of the complications above received R-GIDIOX (R 375 mg/m2 d 1, gemcitabine 800 mg/m2 d 2 and 5, oxaliplatin 120 mg/m2 d 3, irinotecan 100 mg/m2 d 4, dexamethasone 10 mg/m2 IV d 2-6, ifosfamide 1000 mg/m2 d 2-6). Subsequently these courses were alternating with R-DA-EPOCH in each arm of the protocol. Patients who achieved CR after the first cycle (2 courses), received additional 2 cycles, (for a total 6 courses). Patients without CR after 2 cycles of therapy received 2 more cycles, for total of 8 courses, unless they progressed on therapy. Those patients who achieved PR/CR/CRu underwent autoSCT (BEAM-R). Response the therapy was assessed by Cheson's criteria (2007). Patients with residual PET+ tumor after autoSCT were consolidated with local radiotherapy. Post-transplant R- maintenance was administered for 3 years (R-375 mg/m2 every 3 months). Patients were analyzed on an intent-to-treat basis. Results: 29/47 patients were treated on R-HMA arm (Arm1) (median 51years; MIPIb: 35,7% low, 28,6% intermediate and 35,7% high risk) and 18/47 patients were on R-GIDIOX arm (Arm2) (median 60 years; MIPIb: 16,7% low, 38,9% intermediate and 44,4% high risk). There was 1/29 induction death after first R-HMA course (acute renal failure and septic shock). 1 of 18 patients had disease progression before autoSCT in Arm2. 28/29 patients from Arm1 achieved CR/CRu (96,6%). In Arm 2 OR and CR/CRu rates were 94,4% (17/18) and 77,8% (14/18), respectively. Main non-hematological toxicity of R-GIDIOX was asymptomatic elevation of transaminases (gr. 1-2 and 3-4 in 65,5% and 6,9% of courses respectively), while leukopenia gr. 4 occurred in 74,1% of courses (median 5 days, range 1-13), thrombocytopenia gr. 4 -39,7% courses. 45/47 patients underwent autoSCT: 28/29 in Arm1 and 17/18 in Arm2. The sources of stem cells were PBSC in 39/45 patients (86,7%) and BM in 6/45 (13,3%) patients with PBSC collection failure following R-HMA (3/28) or R-GIDIOX (3/17). With median follow-up of 31 months (range 11-76), the estimated 4-year OS and EFS remain identical in both groups: 78% (SE 12%) and 72% (SE 18%), respectively. Conclusions: Combination of R-DA-EPOCH/R-GIDIOX followed autoSCT and R-maintenance is well tolerated and produces EFS/OS similar to those seen with more toxic regimen utilizing R-HD-MTX-AraC. Equal outcomes were observed despite higher proportion of high risk patients treated with non-HD-AraC regimen. We conclude that R-GIDIOX can be an alternative component of induction regimen for those patient with MCL who are not candidates for intensification with high-dose AraC and MTX. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures No relevant conflicts of interest to declare.

Peripheral T-cell lymphomas in a large US multicenter cohort: prognostication in the modern era including impact of frontline therapy

Optimal frontline therapy for peripheral T-cell lymphoma (PTCL) in the modern era remains unclear. We examined patient characteristics, treatment, and outcomes among 341 newly diagnosed PTCL patients from 2000 to 2011. Outcome was compared with a matched cohort of diffuse large B-cell lymphoma (DLBCL) patients, and prognostic factors were assessed using univariate and multivariate analyses. PTCL subtypes included PTCL, not otherwise specified (PTCL-NOS) (31%), anaplastic large T-cell lymphoma (ALCL) (26%), angioimmunoblastic T-cell lymphoma (23%), NK/T-cell lymphoma (7%), acute T-cell leukemia/lymphoma (6%), and other (7%). Median age was 62 years (range 18-95 years), and 74% had stage III-IV disease. Twenty-three (7%) patients received only palliative care whereas 318 received chemotherapy: CHOP-like regimens (70%), hyperCVAD/MA (6%), or other (18%). Thirty-three patients (10%) underwent stem-cell transplantation (SCT) in first remission. The overall response rate was 73% (61% complete); 24% had primary refractory disease. With 39-month median follow-up, 3-year progression-free survival (PFS) and overall survival (OS) were 32% and 52%. PFS and OS for PTCL patients were significantly inferior to matched patients with DLBCL. On multivariate analysis, stage I-II disease was the only significant pretreatment prognostic factor [PFS: hazard ratio (HR) 0.54, 95% confidence interval (CI) 0.34-0.85, P = 0.007; OS: HR 0.42, 95% CI 0.22-0.78, P = 0.006]. ALK positivity in ALCL was prognostic on univariate analysis, but lost significance on multivariate analysis. The most dominant prognostic factor was response to initial therapy (complete response versus other), including adjustment for stage and SCT [PFS: HR 0.19, 95% CI 0.14-0.28, P < 0.0001; OS: HR 0.26, 95% CI 0.17-0.40, P < 0.0001]. No overall survival difference was observed based on choice of upfront regimen or SCT in first remission. This analysis identifies early-stage disease and initial treatment response as dominant prognostic factors in PTCL. No clear benefit was observed for patients undergoing consolidative SCT. Novel therapeutic approaches for PTCL are critically needed.

Current knowledge on HIV-associated Plasmablastic Lymphoma.

HIV-associated PBL is an AIDS-defining cancer, classified by WHO as a distinct entity of aggressive DLBCL. To date less than 250 cases have been published, of them 17 are pediatric. The pathogenesis of this rare disease is related to immunodeficiency, chronic immune stimulation and EBV. Clinically is a rapid growing destructive disease mainly involving the oral cavity even if extraoral and extranodal sites are not infrequent. The diagnosis requires tissue mass or lymph node biopsy and core needle or fine needle biopsy is acceptable only for difficult access sites. Classically immunophenotype is CD45, CD20, CD79a negative and CD38, CD138, MUM1 positive, EBER and KI67 is >80%. Regarding the therapy, standard treatment is, usually, CHOP or CHOP-like regimens while more intensive regimens as CODOX-M/IVAC or DA-EPOCH are possible options. Use of cART is recommended during chemotherapy, keeping in mind the possible overlapping toxicities. Rituximab is not useful for this CD20 negative disease and CNS prophylaxis is mandatory. Intensification with ABMT in CR1 may be considered for fit patients. For refractory/relapsed patients, therapy is, usually, considered palliative, however, in chemo-sensitive disease, intensification + ABMT or new drugs as Bortezomib may be considered. Factors affecting outcome are achieving complete remission, PS, clinical stage, MYC, IPI score. Reported median PFS ranges between 6–7 months and median OS ranges between 11–13 months. Long term survivors are reported but mostly in pediatric patients. Finally, due to the scarcity of data on this subtype of NHL we suggest that the diagnosis and the management of HIV-positive PBL patients should be performed in specialized centers.

P1-20-4 - Outcome of Relapse of Diffuse Large B-Cell Lymphoma After Autologous Stem Cell Transplantation

Introduction: Usefulness of autologous stem cell transplantation (ASCT) for diffuse large B-cell lymphoma (DLBCL) has been established. However, relapse after ASCT even at complete remission (CR) remains to be crucial. We evaluated outcome of such patients concerning the intervals from ASCT to relapse.Patients and methods: Among 77 patients who received ASCT at CR between 1997 and 2013, 26 relapsed. Their age ranged from 39 to 74 with a median of 58. They included 23 at first CR and 3 second CR. We retrospectively analyzed clinical records to investigate survival outcome.Results: Induction chemotherapy was CHOP-like regimen with or without rituximab (R). 3 patients with second CR had received MECP as re-induction therapy. Stem cells were mobilized by high-dose etoposide and MCVC was used as a conditioning regimen. Most patients had nodal relapse, but 4 patients (15.4%) at central nervous system and one (3.8%) at testis. Patients had received 1 to 4 regimens of salvage therapy, i. e., MECP, CHASE, or DHAP. CR was achieved in 3 patients (11.5%) and PR in 2 (7.7%), resulting in overall response rate of 19.2%. With observation periods of 4 to 198 months (median 22), 1-year overall survival (OS) was 50%. Although OS was significantly poor in patients who relapsed within a year after ASCT, survival from relapse was not different.Discussion: These results suggest that relapse rate after ASCT should be reduced since highly refractory disease might emerge after myeloablative therapy. Deeper remission is required and prophylaxis of sanctuary region appears to be more widely considerable in first-line therapy.

Rate of primary refractory disease in B and T-cell non-Hodgkin's lymphoma: correlation with long-term survival.

BackgroundPrimary refractory disease is a main challenge in the management of non-Hodgkin’s Lymphoma (NHL). This survey was performed to define the rate of refractory disease to first-line therapy in B and T-cell NHL subtypes and the long-term survival of primary refractory compared to primary responsive patients.MethodsMedical records were reviewed of 3,106 patients who had undergone primary treatment for NHL between 1982 and 2012, at the Hematology Centers of Torino and Bergamo, Italy. Primary treatment included CHOP or CHOP-like regimens (63.2%), intensive therapy with autograft (16.9%), or other therapies (19.9%). Among B-cell NHL, 1,356 (47.8%) received first-line chemotherapy with rituximab. Refractory disease was defined as stable/progressive disease, or transient response with disease progression within six months.ResultsOverall, 690 (22.2%) patients showed primary refractory disease, with a higher incidence amongst T-cell compared to B-cell NHL (41.9% vs. 20.5%, respectively, p<0.001). Several other clinico-pathological factors at presentation were variably associated with refractory disease, including histological aggressive disease, unfavorable clinical presentation, Bone Marrow involvement, low lymphocyte/monocyte ration and male gender. Amongst B-cell NHL, the addition of rituximab was associated with a marked reduction of refractory disease (13.6% vs. 26.7% for non-supplemented chemotherapy, p<0.001). Overall, primary responsive patients had a median survival of 19.8 years, compared to 1.3 yr. for refractory patients. A prolonged survival was consistently observed in all primary responsive patients regardless of the histology. The long life expectancy of primary responsive patients was documented in both series managed before and after 2.000. Response to first line therapy resulted by far the most predictive factor for long-term outcome (HR for primary refractory disease: 16.52, p<0.001).ConclusionChemosensitivity to primary treatment is crucial for the long-term survival in NHL. This supports the necessity of studies aimed to early identify refractory disease and to develop different treatment strategies for responsive and refractory patients.

Downregulated expression of Dicer1 predicts inferior survival in primary gastrointestinal diffuse large B-cell lymphoma treated with CHOP-like regimen and rituximab

The aim of this study was to detect the expression levels of Dicer1, Drosha, DGCR8, and Ago2 messenger ribonucleic acids (mRNAs) in patients with primary gastrointestinal diffuse large B-cell lymphoma (PGI-DLBCL) and determine their associations with clinical parameters and prognostic significance. The mRNA level expressions of Dicer1, Drosha, DGCR8, and Ago2 were detected by real-time quantitative polymerase chain reaction. Immunohistochemical staining of CD10, BCL6, and MUM1 was performed using EnVision™ system. The clinicopathologic features and follow-up data were analyzed using Kaplan-Meier estimator. The results show that the expression of Dicer1 (P=0.001), Drosha (P=0.01), DGCR8 (P=0.02), and Ago2 (P=0.002) mRNAs in cancer tissues of patients with PGI-DLBCL was significantly lower than those in normal tissues of healthy controls. Among the expression of CD10, BCL6, and MUM1, 27.4% (17/62) of the patients belonged to the germinal center B-cell (GCB) subtype and 72.6% (45/62) belonged to the non-GCB subtype. Dicer1 expression was significantly decreased in the non-GCB subgroup (P=0.02) and in the high International Prognostic Index (3-5 score) subgroup (P=0.03). Kaplan-Meier analysis showed that the low-Dicer1 subgroup had a shorter overall survival (P=0.02) and shorter progression-free survival (P=0.015) than the high-Dicer1 subgroup. Multivariate analysis identified Dicer1 as an independent prognostic factor in PGI-DLBCL. In Conclusion, Dicer1, Drosha, DGCR8, and Ago2 play key roles in the pathogenesis of PGI-DLBCL. Dicer1, an independent prognostic factor for predicting shortened survival of patients with PGI-DLBCL, can be used as a biomarker to guide the prognosis.

Rituximab plus a CHOP-like regimen, central nervous system prophylaxis, and contralateral testicular irradiation for localized primary testicular diffuse large B-cell lymphoma lead to prolonged progression-free survival.

We retrospectively evaluated the clinical features, management, and survival of 12 patients (age 51-84years) with localized primary testicular diffuse large B-cell lymphoma (PTL). All 12 PTL patients underwent orchiectomy. Seven of the 12 patients were treated with strategy A, which consisted of at least six cycles of rituximab (R) plus a CHOP-like regimen, central nervous system (CNS) prophylaxis involving intrathecal chemotherapy (IT) and/or high-dose intravenous methotrexate, and contralateral scrotal irradiation (cRT). The other five patients were treated with strategy B, which included three regimens: orchiectomy alone, orchiectomy plus cRT and IT, and orchiectomy plus 3-4 cycles of R-CHOP plus cRT with or without IT. The median follow-up period was 48months (range 19-123months). The 4-year progression-free survival (PFS) rate for the seven patients treated with strategy A was 85.7%, whereas that for the five patients treated with strategy B was 20%. The patients treated with strategy A exhibited a significantly higher 4-year PFS rate than those treated with strategy B (P=0.017). These results confirmed that the administration of a sufficient number of cycles of an R-containing chemotherapy regimen plus cRT plus CNS prophylaxis should be considered as a treatment for localized PTL.