Consortium For Improving Survival Of Lymphoma Research Articles

17th International Conference on Malignant Lymphoma, Palazzo dei Congressi, Lugano, Switzerland, 13 - 17 June, 2023.

Purpose: Peripheral T-cell lymphomas (PTCLs) are a heterogeneous group of non-Hodgkin lymphomas, and their prognoses are still poor because of frequent relapses and the absence of optimal standard therapy. Cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) has been the backbone of frontline chemotherapy for PTCL for many years. However, it is not clear whether anthracycline-based chemotherapies such as CHOP could be standard induction therapy for PTCL. Thus, we conducted a randomized phase II study to compare the efficacy of CHOP with fractionated ifosfamide, carboplatin, etoposide, and dexamethasone (ICED). Patients and Methods: This study was a phase II, multicenter, open-label randomized trial at 21 hospitals that belonged to the Consortium for Improving Survival of Lymphoma (CISL) in Korea (CISL-1504/ROSE study). Eligible participants were patients aged 20–65 years with previously untreated histologically confirmed PTCLs based on the World Health Organization classification 2008 including PTCL-not otherwise specified (NOS), angioimmunoblastic T-cell lymphoma (AITL), ALK-negative anaplastic large-cell lymphoma (ALCL), enteropathy-associated T-cell lymphoma (EATL), and hepatosplenic T-cell lymphoma (HSTL). Patients with ALK-positive ALCL, extranodal NK/T-cell lymphoma, and mycosis fungoides/sezary syndrome were not included in the study. Patients were randomized at a 1:1 ratio to receive either CHOP or ICED every 3 weeks for 6 cycles. Upfront autologous stem cell transplantation (ASCT) was done for patients achieving complete or partial response and the primary end point was progression-free survival (PFS). Results: Between September 2015 and March 2021, 145 patients were screened, and 138 patients were enrolled. The characteristics were not different between CHOP (n = 69) and ICED (n = 66), and PTCL-NOS (n = 60) and AITL (n = 53) were dominant. The objective response rate was not different between CHOP (41/69, 59.4%) and ICED (37/66, 56.1%), and the 3-year PFS was not different between CHOP (36.7%) and ICED (33.1%, P = 0.709). Around 80% of patients who completed either CHOP or ICED followed by upfront ASCT showed 3-year overall survival (Figure 1). There was no statistically significant difference in PFS between the CHOP and ICED arms for any subgroup analyzed except AITL. CHOP was favored over ICED in AITL patients, whereas ICED was favored over CHOP in EATL/HSTL patients. ICED was associated with more anemia, neutropenia, and thrombocytopenia of all grades and grade 3 or worse, and the frequency of febrile neutropenia was higher in the ICED arm. Keywords: aggressive T-cell non-Hodgkin lymphoma, chemotherapy, stem cell transplant No conflicts of interests pertinent to the abstract.

Impact of BCL2/MYC Protein Dual Expression and Other Clinical Factors on the Risk of Central Nervous System Progression in Patients with Primary Breast Diffuse Large B-Cell Lymphoma

Background Primary breast diffuse large B-cell lymphoma (DLBCL) has poor outcomes with frequent extranodal failures, particularly in the central nervous system (CNS). Recent studies have reported that cell-of-origin (COO), BCL2/MYC dual expression (DE), and MYC and BCL2 and/or BCL6 rearrangements, so-called double hit (DH) and triple hit, are associated with a high risk of CNS progression in DLBCL; however, the impact of these biologic markers in primary breast DLBCL on CNS progression remains unknown. Methods CNS progression was analyzed in newly diagnosed primary breast DLBCL patients identified from 2 sources: the prospective study of the Consortium for Improving Survival of Lymphoma (CISL) study group conducted from January 2012 to July 2017, and the retrospective cohort included patients who were treated outside clinical trial at any CISL institutions between January 2012 and December 2020. Briefly, the prospective study (Yhim HY et al. Cancers 2020;12:2192) included 33 patients (20-75 years of age) with primary breast DLBCL, and treatment consisted of 6 cycles of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) and 4 doses of intrathecal (IT) methotrexate (MTX) at a 3-week interval. The eligibility criteria for the retrospective cohort were virtually the same as the prospective cohort, except for no age limit. 26 patients were screened, 6 of whom were excluded because of incomplete data (n=4) and secondary breast DLBCL (n=2). Thus, the retrospective cohort included 20 patients treated with 6 cycles of R-CHOP ± radiotherapy. CNS prophylaxis was not considered for eligibility in this cohort but was done in 17 patients (4-6 doses of IT MTX [n=14] and systemic high-dose MTX [n=3]). Expert hematopathologists centrally assessed COO and DE status. COO was determined using the Hans algorithm. MYC (≥40%) and BCL2 (≥50%) protein expressions were used to assign DE. Fluorescence in situ hybridization testing was used to determine DH lymphoma. The risk of CNS progression was estimated using the cumulative incidence method. The impact of variables of interest on CNS progression was assessed using a multivariable Cox model. Results We identified 53 patients from 2 data sources. The median age was 55 years (range, 29-78), and all were female. Most patients had unilateral (n=50, 94%), localized-stage (n=48, 91%), and ECOG performance status ≤1 (n=51, 95%). Serum LDH level was elevated in 14 (26%). Hence, IPI and CNS-IPI risks were mainly low (n=45, 85%). No patients had CNS disease at diagnosis. With a median follow-up of 58.8 months (IQR, 30.3-72.9), 7 patients developed CNS progression (parenchymal only, n=4; leptomeningeal only, n=2; parenchymal and leptomeningeal, n=1). The 4-year cumulative incidence of CNS progression was 15.6% (95% CI, 6.7-27.9; Fig A). The Cox analysis revealed bilateral breast involvement (HR, 9.39; 95% CI, 1.69-52.18) was an independent factor for CNS progression in this population. Of the 53 patients, 36 were selected as a histologic data-available population because of a lack of diagnostic materials for COO and DE in 17 patients. Baseline characteristics of the histologic data-available population (n=36) were similar to the overall population (n=53). In the 36 patients with histologic data available, 4 patients had CNS progression (parenchymal only, n=2; leptomeningeal only, n=1; parenchymal and leptomeningeal, n=1), and the 4-year CNS progression rate was 14.2% (95% CI, 0.4-26.3; Fig B). According to the Hans algorithm, 30 (83%) and 6 (17%) were classified as having non-GCB and GCB, respectively. 14 patients (39%) had BCL2/MYC DE, of whom 13 were non-GCB subtype (Fig C). The CNS progression rate of non-GCB did not differ significantly from that of the GCB subtype (4-year, 17.4% vs. 0%; p=0.326), but BCL2/MYC DE had a higher risk of CNS progression than non-DE (4-year, 30.7% vs. 0%, p=0.021; Fig D). 20 patients had sufficient tissue to test DH status, but no DH cases were identified. The multivariable Cox analysis of these 36 patients showed bilateral involvement (HR, 3.73; 95% CI, 1.28-10.86) and BCL2/MYC DE (HR, 2.42×104; 95% CI, 0.51×104-10.60×104) were independent predictors for CNS progression. Conclusion Our data suggested that bilateral breast involvement and BCL2/MYC DE were independent risk factors for CNS events in patients with primary breast DLBCL. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

524 - Busulfan, Melphalan, and Etoposide (BuME) Showed an Equivalent Effect to Busulfan, Cyclophosphamide, and Etoposide (BuCE) As Conditioning Therapy for Autologous Transplantation in Patients with Relapsed or High Risk Non-Hodgkin Lymphoma: A Multicenter Randomized Phase II Study By the Consortium for Improving Survival of Lymphoma (CISL)

524 - Busulfan, Melphalan, and Etoposide (BuME) Showed an Equivalent Effect to Busulfan, Cyclophosphamide, and Etoposide (BuCE) As Conditioning Therapy for Autologous Transplantation in Patients with Relapsed or High Risk Non-Hodgkin Lymphoma: A Multicenter Randomized Phase II Study By the Consortium for Improving Survival of Lymphoma (CISL)

Open-Labeled, Multicenter Phase II Study of Bortezomib for Maintenance Therapy in Patients with High Risk Diffuse Large B Cell Lymphoma (DLBCL): Borma Trial from Consortium for Improving Survival of Lymphoma (CISL)

Background: High-intermediate or high risk in international prognostic index (IPI) has a long-term chance of cure in the range about 50% in patients with diffuse large B cell lymphoma (DLBCL) treated by R-CHOP. These high risk patients should be considered for additional new treatment to standard R-CHOP or investigational approaches in the context of clinical trials that are designed to ensure that potentially curative therapy. Bortezomib inhibits NF-κB activation through proteasome inhibition, providing rationale for its use in cells that constitutively express NF-κB. Non-germinal center B cell (GCB) DLBCL has a worse survival after upfront chemotherapy and is characterized by constitutive activation of the antiapoptotic NF-κB pathway, which can inhibit chemotherapy. There is no study of bortezomib as maintenance therapy after treated with R-CHOP in high risk patients with DLBCL. So we applied additional bortezomib as maintenance therapy in order to assess improving efficacy and survival rates in high risk patients with non-GCB DLBCL who had been confirmed complete response (CR) after treated with R-CHOP. Methods: Patients with newly diagnosed stage II(bulky)-IV DLBCL with high or high intermediate IPI score of 3 to 5, and patients achieving a CR at the end of 6 or 8 cycles of R-CHOP21 were eligible for enrollment. Non-GCB DLBCL according to Hans criteria confirmed by central review was need before enrollment. Bortezomib maintenance treatment was consisted of bortezomib 1.3mg/m2 subcutaneously administration day 1 and day 15 per 28-day cycle with a total of 12 cycles. The primary endpoint was 3-year progression-free survival (PFS). Secondary endpoints were 3-year overall survival (OS), and toxicites. Toxicity was graded according to the Common Terminology Criteria for Adverse Events v4.0. Results: Fifty-nine patients were enrolled between May 2014 and Oct 2018. The type of Non-GCB DLBCL in all patients was confirmed by the central pathology review. The median age was 65 years (range: 27-86 years), and 60% were > 61 years. The baseline clinical features were as follows: female sex, 45.8%; ECOG >1, 10.2%; stage II bulky (>10cm), 6.8%; stage III/IV, 93.2%. At the time of analysis, 29 patients completed 12-cycles of bortezomib maintenance, and 3 patients is ongoing. Seven patients did not finished maintenance therapy due to toxicities (fatigue, atrial flutter, neuropathy, pleural effusion, thrombocytopenia), and withdrawal of informed consent (n=4). Sixteen patients experienced disease progression during bortezomib maintenance treatment. With a median follow-up of 25.1 months, 3-year PFS rate was 56.9% and 3-year OS rate was 86.4% (Figure 1). Toxicity was assessed in 489 cycles of bortezomib maintenance in all 59 patients. There was no treatment-related death and febrile neutropenia. Conclusion: Bortezomib maintenance showed 3-year PFS rate of 56.9% with acceptable toxicities in patients with high risk DLBCL achieving a CR at the end of 6 or 8 cycles of R-CHOP21. Figure 1 Disclosures Kim: Celltrion: Research Funding; Novartis: Research Funding; J + J: Research Funding; Donga: Research Funding; Kyowa-Kirin: Research Funding; Novartis: Research Funding; F. Hoffmann-La Roche Ltd: Research Funding.

Rituximab-CHOP and Central Nervous System Prophylaxis Using Intrathecal Methotrexate in Primary Breast Diffuse Large B-Cell Lymphoma: A Prospective, Multicenter, Single-Arm Phase II Study

Background: Primary breast diffuse large B-cell lymphoma (DLBCL) has poor outcomes with frequent extranodal failures, particularly in the central nervous system (CNS). To prevent CNS recurrence, we designed this phase II trial that addressed feasibility and activity of conventional immunochemotherapy and CNS prophylaxis. Methods: This prospective, multicenter, single-arm phase II study was conducted to evaluate efficacy and safety of 6 cycles of conventional rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone every 21 days (R-CHOP) with the addition of 4 doses of intrathecal methotrexate (IT MTX; 12mg) during the first 4 cycles of R-CHOP in patients with primary breast DLBCL. Primary breast lymphoma was defined as lymphoma involving one or both breasts as a sole extranodal site regardless of specific nodal involvement status. The primary end-point was 2-year progression-free survival (PFS). Secondary end-points included cumulative incidence of CNS recurrence, overall survival (OS), and safety. All patients provided written informed consents and the study was registered at www.clinicaltrials.gov as #NCT01448096. Results: Thirty-three patients with primary breast DLBCL were enrolled between Jan 2012 and Jul 2017 in the Consortium for Improving Survival of Lymphoma (CISL) member institutions. The median age was 50 years at diagnosis (range, 29-75) and all were female. Right breast involvement was more common than left (18 [55%] vs 14 [42%]) and bilateral breast involvement was found in one patient (3%). Nodal involvement was present in 16 patients (49%), primarily in regional nodes (14 patients). Thus, the Ann Arbor stage was IE in 17 (52%), IIE in 13 (39%), IIIE in 2 (6.1%), and IV in 1 (3.0%). ECOG performance status was ≥2 in 1 patient (3%) and serum LDH level was elevated in 9 (27%). Therefore, the IPI and the CNS-IPI risk were mainly low (28 patients, 85%; respectively). No patients had CNS involvement at diagnosis. 32 (97%) of the 33 patients completed R-CHOP as planned, and the remaining patient withdraw a consent after four cycles of R-CHOP because of poor tolerance. CNS prophylaxis using IT MTX was completed as planned in 31 patients (94%), but it was discontinued in 2 patients because of patient's refusal. These 2 patients received two and three IT MTX doses, respectively. 32 patients (97%) were evaluable for treatment response and all these patients achieved a complete response. At the cutoff date of this analysis (10 Jul 2019), all patients who entered a follow-up phase had at least 24.0 months of follow-up. With a median follow-up duration of 46.1 months (IQR 31.1-66.8), 6 patients had experienced treatment failure and 3 of these died. The 2-year PFS and OS were 81.3% (95% CI, 67.7-94.8) and 93.5% (95% CI, 84.9-100.0), respectively (fig 1A and B). Of the 6 patients with treatment failure, diseases involved CNS with or without lymph nodes in 4 patients and breasts in 2 patients (1 ipsilateral and 1 contralateral breast recurrence). 3 of the four patients with CNS recurrence had isolated CNS recurrences (2 brain parenchymal and 1 meningeal disease) and one had a concurrent meningeal and lymph nodal recurrence. All 4 patients with CNS recurrence had received prophylactic IT MTX as planned by protocol. The 2-year cumulative incidence of CNS recurrence, taking into account the competing risk of death, was 12.5% (95% CI, 0.3-23.2, fig 1C). Although the number of patients with intermediate CNS-IPI risk was small (5 patients, 15%), the cumulative incidence of CNS recurrence did not differ significantly according to the CNS-IPI risk group. All CNS recurrences occurred within the first 2 years after enrolment. Toxicities were generally manageable during the R-CHOP and IT MTX treatment. No deaths as a result of toxicity occurred during treatment. Conclusion: Our study shows that conventional R-CHOP with prophylactic IT MTX is feasible in patients with primary breast DLBCL. However, given a substantially high rate of CNS recurrence, further studies to properly define the best strategy for CNS prophylaxis should be needed in patients with primary breast DLBCL. Figure 1 Disclosures Yoon: F. Hoffmann-La Roche Ltd: Research Funding. Kim:Celltrion: Research Funding; Novartis: Research Funding; Donga: Research Funding; Kyowa-Kirin: Research Funding; Novartis: Research Funding; J + J: Research Funding; F. Hoffmann-La Roche Ltd: Research Funding.

Phase II study of R\u2013CVP followed by rituximab maintenance therapy for patients with advanced marginal zone lymphoma: consortium for improving survival of lymphoma (CISL) study

BackgroundThe response rate and survival improvement for rituximab, a CD20-targeting monoclonal antibody, have been demonstrated in marginal zone lymphoma (MZL) as monotherapy and in combination with chemotherapeutic regimens, yet relapses still occur despite treatment completion. Thus, extending the period of remission in MZL patients remains an essential goal. This multicenter, single-arm, open-label phase II study evaluated the survival efficacy of 2 years of rituximab-maintenance therapy in patients with stage III–IV CD20-positive MZL who had responded to first-line R–CVP (rituximab, cyclophosphamide, vincristine, and prednisolone). The objective of this study was to determine whether rituximab maintenance following R–CVP warrants further investigation.MethodsPrior to rituximab-maintenance therapy, patients received 6–8 cycles of first-line R–CVP therapy for stage III–IV MZL. Rituximab (375 mg/m2), cyclophosphamide (750 mg/m2), and vincristine (1.4 mg/m2; maximum 2 mg) were administered via an intravenous infusion on day 1 of each 3-week cycle, while oral prednisolone (100 mg) was given on days 1–5 of each 3-week cycle. The patients who achieved complete response (CR), partial response (PR), or stable disease (SD) to R–CVP treatment, were prescribed rituximab-maintenance therapy which was administered intravenously at a dose of 375 mg/m2 every 8 weeks for up to 12 cycles. The primary endpoint was progression-free survival (PFS). Secondary endpoints were overall survival (OS) and treatment safety.Results47 patients were enrolled, of whom, 45 (96%) received rituximab-maintenance treatment. Fifteen (33%) patients had nodal MZL. Following R–CVP first-line therapy, 20 (44%), 22 (49%), and 3 (7%) patients achieved CR, PR, and SD, respectively. After a median follow-up of 38.2 months, their observed 3-year PFS rate was 81%. During the rituximab-maintenance, 6 PR and 1 SD patients achieved CR following the administration of R–CVP. Elevated LDH and the presence of B symptoms were found to be significant prognostic factors for PFS (P = 0.003) and demonstrated a 3-year OS rate of 90%. Rituximab-maintenance therapy was well tolerated, and the common treatment-emergent adverse events were sensory neuropathy (18%), myalgia (13%), fatigue (9%), and neutropenia (9%).ConclusionRituximab-maintenance therapy following first-line R–CVP demonstrated good PFS in patients with stage III–IV MZL, in addition to a favorable toxicity profile.Trial registration clinicaltrials.gov: NCT01213095

Organ-specific considerations for marginal zone lymphomas in Korea, based on Consortium for Improving Survival of Lymphoma (CISL) and Korean clinical studies.

Organ-specific considerations for marginal zone lymphomas in Korea, based on Consortium for Improving Survival of Lymphoma (CISL) and Korean clinical studies.

Lymphoma epidemiology in Korea and the real clinical field including the Consortium for Improving Survival of Lymphoma (CISL) trial.

Lymphomas are a heterogeneous group of disease entities with well-defined clinical, morphological, immunophenotypic, and cytogenetic characteristics. Moreover, regional and racial differences have been reported in their incidence and subtype compositions. Here, we reviewed the epidemiology of lymphomas and summarized the recent achievements in specific subtypes prevalent in Korean population, focusing on clinical studies conducted by the Consortium for Improving Survival of Lymphoma (CISL) of the Korean Society of Hematology Lymphoma Working Party (KSH-LWP).

The Consortium for Improving Survival of Lymphoma (CISL): recent achievements and future perspective.

The Consortium for Improving Survival of Lymphoma (CISL) of the Korean Society of Hematology Lymphoma Working Party is a multicenter collaborative study group performing prospective clinical studies for lymphoma patients and retrospective analyses. Since 2006, the CISL has performed >35 prospective clinical trials and >30 retrospective studies to investigate the clinical and pathological features of lymphoma subtypes and the outcomes of new therapeutic modalities. The year 2016 is the 10th anniversary of the CISL, and this report aims to commemorate its progress during the past 10 years. The CISL previously reported its achievements between 2006 and 2012, including 32 publications as of the end of 2012 [1]. Herein, we summarize clinical studies conducted by the CISL from 2013 to 2015.

Randomized Phase II Multi-Center Trial of Busulfan, Etoposide, and Cyclophosphamide Versus Busulfan, Etoposide, and Melphalan As Conditioning Therapy for Autologous Transplantation in Patients with Non-Hodgkin's Lymphoma: A Multicenter Study from Consortium for Improving Survival of Lymphoma (CISL)

BackgroundHigh dose chemotherapy followed by autologous stem cell transplantation (ASCT) has become the standard approach for relapsed or high risk non-Hodgkin's lymphoma (NHL). Several different high dose therapy (HDT) conditioning regimens have been used for NHL, such as BEAM(carustine, etoposide, cytosine arabinoside, melphalan), BEAC( carmustine, etoposide, cytosine arabinoside, cyclophosphamide), and CBV(cyclophosphamide, carmustine etoposide). Carmustine is an active drug in the HDT of NHL but the supply of carmustine is limited in some countries. Intravenous busulfan containing regimens as conditioning regimen have been used for both allogeneic and autologous stem cell transplantation in patients with hematologic and non-hematologic malignancies. We and CISL have previously studied that conditioning regimen of i.v. busulfan/melphalan/etoposide was well tolerated and effective in patients with relapsed or high risk NHL. And busulfan/cyclophosphamide/etoposide conditioning regimen has been extensively utilized in ASCT for NHL. Therefore, based on the encouraging results, we conducted a randomized phase II multicenter trial of busulfan/etoposide/cyclophosphamide (BCT) versus busulfan/etoposide/ melphalan/ (BMT) as conditioning therapy for ASCT in patients with NHL.MethodsPatients with chemosensitive high risk NHL or relapsed or primary refractory NHL underwent high dose chemotherapy at 16 centers in Korea. Patients were randomly assigned to receive BCT conditioning chemotherapy or BMT conditioning chemotherapy. BCT regimen consisted of iv busulfan 3.2 mg/kg/day i.v. on days -8,-7, and -6, etoposide 400mg/m2 day i.v. on days -5 and -4 and cyclophosphamide 50mg/kg/day i.v. on days -3 and -2 and BMT regimen were iv busulfan 3.2 mg/kg/day i.v. on days -8,-7, and -6, etoposide 400mg/m2 day i.v. on days -5 and -4 and melphalan 50mg/m2/day i.v. on days -3 and -2. The primary efficacy end points were 2 year progression free survival.ResultsSeventy five patients were enrolled onto the study. Patients randomly assigned to the BCT group (39 patients) or the BMT group (36 patients). Main subgroups were DLBCL (n=42, 56%) and T cell lymphoma (n=27, 36%). Thirteen patients (33.3%) in the BCT group and 11 patients (30.5%) in the BMT group had disease progression or died. 2 year progression free survival rate was 62.5% in the BCT group and 63.1% in the BMT group (p=0.924) (Fig 1). There was no treatment related mortality.ConclusionsNo significant differences were observed in progression free survival between BCT group and BMT group. Accordingly, busulfan based conditioning regimen may be regarded as an important treatment option to substitute for BEAM regimen. Further, considering R-CHOP or CHOP regimes are standard induction regimens, BMT conditioning will be good alternative to patients who can't be used cyclophosphamide. [Display omitted] DisclosuresKim:Celltrion, Inc.: Consultancy, Honoraria.

Phase II Trial of R-CVP Followed By Rituximab Maintenance Therapy for Patients with Advanced Stage Marginal Zone Lymphoma- Consortium for Improving Survival of Lymphoma (CISL) Study

BACKGROUNDAccording to our prior prospective phase II trial, Rituximab in combination with chemotherapy (R-CVP) has been shown to improve response rate (RR) and progression free survival (PFS) in patients with advanced stage marginal zone lymphoma (MZL) compared with chemotherapy alone (CVP). In spite of better RR and PFS, relapses seem to continue after immunotherapeutic treatment in these patients. Thus, eventual relapse remains an important clinical issue for the majority of patients with indolent lymphoma, and defining further ways to extend the period of remission remains an essential goal. But data from clinical trials evaluating rituximab maintenance treatment in these patients are almost limited. We aimed to evaluate the effect of maintenance treatment with rituximab on the PFS of patients with MZL. METHODSHistologically confirmed advanced stage MZL patients who did not progress at the end of 6~8 cycles of 1st line Rituximab-CVP (cyclophosphamide 750 mg/m2 and vincristine 1.4 mg/m2 (maximum 2.0 mg), given intravenously on day 1, and oral prednisolone 100 mg on days 1-5) regimen were enrolled. Patients received 2 years of rituximab maintenance therapy (375 mg/m2 every 8 weeks). Primary objection was three year progression free survival. This trial is registered with ClinicalTrials.gov, number NCT012113095.RESULTSBetween March 2010 and March 2013, a total of 47 patients were enrolled with informed consent at this trial from 17 institutes in Korea. Among these patients, 1 patient withdrew informed consent, 1 patient was screening failure with combined thyroid cancer. The median age of the evaluated 45 (32 males, 13 females) patients is 54 (range 33-77) years. Fifteen patients (33.3%) evidenced nodal MZL, 30 (66.7%) extranodal MZL (10 patients were lung, 6 ocular, and 5 stomach, in order of frequency). The IPI score were 1 in 13 (28.9%), 2 in 21 (46.7%), 3 in 9 (20%), and 4 in 2 (4.4%) patients. The patients received a total of 6 or 8 cycles of 1st line R-CVP chemotherapy were 10 (22.2%) and 35 (77.8%), respectively. There were 20 CR (44.4%), 22 PR (48.9%), and 3 SD (6.7%). Median treated number of rituximab maintenance followed by R-CVP was 12 (range 1-12). Thirty two patients (71.1%) patients completed planned 12 cycles of rituximab maintenance. Disease progression during rituximab maintenance was 8 patients, 2 patients stopped treatment because of side effects (1 abdominal pain, 1 recurrent pneumonia) 2 patients were follow-up loss. Four patients were expired (each 1 pneumonitis, pneumonia, sepsis, and disease progression). PFS and OS rate at 3 years were 78.9% and 90.6%, respectively. CONCLUSION2 years of rituximab maintenance therapy after R-CVP first-line chemotherapy for advanced stage MZL might be improve PFS with tolerable toxicities DisclosuresKim:Celltrion, Inc.: Consultancy, Honoraria. Lee:Amgen: Membership on an entity's Board of Directors or advisory committees.

Clinical Outcomes in Patients with Diffuse Large B Cell Lymphoma with Partial Responses to First-Line R-CHOP Chemotherapy: Prognostic Value of Secondary IPI Scores and FDG-PET

Background: Rituximab-containing chemoimmunotherapy (R-CHOP) is a standard treatment for patients with diffuse large B cell lymphoma (DLBCL), with a high response rate. Achievement of only a partial response (PR) was regarded as treatment failure, but data on their prognosis are limited to date. Distinguishing PR from CR is not always clear because of controversies in interpreting 18-fluorodeoxyglucose positron emission tomography (FDG-PET) in rituximab-era. Recent advances have prompted a revision in the response criteria, as recently suggested at the 12th International Conference of Malignant Lymphomas (ICML), emphasizing the prognostic significance of FDG-PET results interpreted using the five-point Deauville score. Based on such changes, the prognosis of PR patients should be re-evaluated.Patients and Methods: We conducted a retrospective multicenter study on behalf of the Consortium for Improving Survival of Lymphoma (CISL), to investigate survival outcomes and to define prognostic factors for PR patients after first-line treatment. A total of 758 patients with histologically proven DLBCL, who received the R-CHOP regimen between January 2005 and December 2013, were assessed. Among them, patients who achieved a PR defined by both computed tomography (CT) and FDG-PET at the end of R-CHOP were included in further analysis. Clinical information at diagnosis and after treatment was collected to determine the prognostic factors affecting the clinical outcome of PR patients. FDG-PET scans were reviewed by physicians and nuclear medicine experts in each institution and interpreted using the Deauville five-point scale. The prognostic role of secondary International Prognostic Index after R-CHOP (IPI2), assessed by restaging, age, performance status, residual multiple extranodal involvements and lactate dehydrogenase (LDH) levels, was evaluated. Progression-free survival (PFS2) and overall survival (OS2), measured from the date of the response assessment after R-CHOP to further progression or death, were determined by Kaplan-Meier methods with log-rank test. We also performed t-tests, χ2 tests, and Cox proportional hazard analysis. Statistical significance was accepted when two-sided p values were <0.05.Results: In total, 88 (11.6%) patients partially responded to R-CHOP with a median age of 53.5 years were searched. Over a median follow-up of 47.8 months, 3-year PFS2 and OS2 rates were 58.8% and 69.4%, respectively. The IPI2 scores were 0-1 (low) in 68.2% and ≥2 (high) in 31.8% of patients. The Deauville scores after R-CHOP were 2-3 (low) in 57.9% and 4 (high) in 42.0% of patients. High (≥2) and low (0-1) IPI2 groups represented 28% and 72% of 3-year PFS2 rates (p <0.001). Patients with Deauville score 4 were also associated with worse 3-year PFS2 rates than those with a lower score (2-3) (40.4% vs. 71.1%, p=0.009). For OS2, IPI2 (47.6% vs. 77.7%, p=0.013) and Deauville score (57.5% vs. 75.3%, p=0.067) were prognostic, although the effect of the Deauville score was not statistically significant. A high-risk group, defined by the IPI2-Deauville index (Table 1), showed significantly lower 3-year rates of PFS2 (17.1% vs. 69.3%, p<0.001) and OS2 (43.4% vs. 75.1%, p=0.006) compared with other groups (Figure 1). In a multivariate analysis, the IPI2-Deauville index was an independent prognostic factor for disease progression (HR 1.76, 95% CI 1.15-2.69, p=0.009), adjusted with initial IPI score and bone marrow involvement at diagnosis. For OS2, the index did not remain significant in a multivariate analysis.Conclusion: Our data shows that patients with DLBCL who achieved a PR to R-CHOP is still a heterogeneous group, and IPI2 and Deauville scores can be useful prognostic factors in addition to initial IPI at diagnosis. Validation through future prospective study would be valuable. [Display omitted] [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Consortium for Improving Survival of Lymphoma (CISL): a model of multicenter collaboration for lymphoma studies in Korea.

Lymphoma is the most common hematologic malignancy, accounting for more than 40% of hematologic malignancies in Korea [1]. However, lymphoma is not a single disorder but a heterogeneous group of subtypes that arise from abnormal B cells or T/NK cells at various stages of development. Although the diagnosis of lymphoma is mainly based on the pathologic findings of lymph node or bone marrow biopsy or both, the number of lymphoma subtypes is expected to increase with advances in molecular and cytogenetic techniques. Besides, the clinical manifestations related to extranodal involvement are also considered for the diagnosis of lymphoma because the involvement of particular extranodal sites can be reflected in the diagnosis of lymphomas. Furthermore, even if patients may have the same subtype of lymphoma, clinical features and treatment outcomes may be different depending on the site involved. Extranodal involvement of lymphomas can be classified as primary or secondary, based on whether the involvement of a certain extranodal organ is a predominant clinical presentation or not. For example, for a case presenting as a lymphoma involving stomach without additional pathologic lesions, it can be designated as primary gastric lymphoma. However, the occurrence of primary extranodal lymphoma is a relatively rare event, especially in those special organs including eyes, thyroid and adrenal glands. In this issue of the Blood Research, Lee et al. [2] reported the results of nationwide retrospective analysis regarding clinical features and treatment outcomes of 20 patients with intraocular lymphoma in Korea. In the study, they summarized clinical features and treatment outcomes of intraocular lymphoma. The intraocular lymphoma is defined as a lymphoma located inside the eye, which arises from the retina, uvea, or the optic nerve. The clinical data were retrospectively collected from eight hospitals, and the number of cases in this study seems to be sufficient for better understanding of intraocular lymphoma due to extreme rarity of the disease. Given that the majority of physicians may not experience such cases in their clinics, even for hemato-oncologists working in a university hospital, this study would provide useful information to the clinicians as well as the pathologists. Therefore, multicenter collaborative study is definitely required for this kind of study focusing on rare subtypes of lymphomas or unusual lymphoma cases. The eight hospitals including Dong-A university hospital belongs to the Consortium for Improving Survival of Lymphoma (CISL). The CISL is a study group for prospective clinical trials for lymphoma patients and various retrospective analyses [3]. Since the first meeting in February of 2006, the CISL performed more than 35 prospective clinical trials and comprised of 68 centers under the Korean Society of Hematology Lymphoma Working Party. In addition, the CISL reported many results of retrospective analyses like the article by Lee et al. in Blood Research. The CISL addressed many issues related to primary extranodal lymphomas including those that involved Waldeyer's ring, breast, adrenal and thyroid glands [4,5,6,7,8,9]. The information they reported is expected to provide an evidence for the management of unusual lymphoma cases as well as to help physicians to improve the understanding of those rare extranodal lymphoma cases. Taken together, this report is a good example of multicenter collaborative study for the rare occasions of lymphoid malignancies as well as the outstanding performance of the CISL as a study group for lymphomas. Considering there are many other rare hematologic disorders besides lymphomas, the establishment of study groups for multicenter collaboration should be encouraged more in the field of hematology in the future.

Intraocular lymphoma in Korea: the Consortium for Improving Survival of Lymphoma (CISL) study.

BackgroundIntraocular lymphoma (IOL) is a rare malignant lymphoma that most closely resembles a diffuse large B-cell lymphoma, and it is a subtype of primary central nervous system lymphoma (PCNSL). IOL is located inside the eye in the retina, uvea, and/or optic nerve. We retrospectively analyzed IOL patient data to identify treatment patterns and survival rates in Korea.MethodsCytological confirmation for a diagnosis of IOL was performed for all patients. The clinical data collected from medical records included Ann Arbor stage, International Prognostic Index, performance status, date of diagnosis, treatment modality and response, date of relapse, and date of last follow-up.ResultsTwenty patients who were diagnosed with IOL, between December 2007 and June 2014 at multiple centers in Korea, were included in the analysis. Four patients were diagnosed with IOL alone, not involving the CNS. Two patients with isolated IOL later developed PCNSL. Nine patients developed CNS lesions before the onset of ocular lymphoma. Five patients had simultaneous onset in the eye and CNS. Twelve patients were treated by intravitreal injection of methotrexate for IOL. The median progression-free survival (PFS) for patients was 19.7 months (95% CI, 8.7-30.7 mo). The estimated 3-year overall survival (OS) for all patients was 75.1%.ConclusionTreatment for IOL patients included radiotherapy and intraocular chemotherapy. IOL patients showed favorable PFS and OS. These patients would require long-term follow-up to identify relapse and adverse effects of radiotherapy or intraocular chemotherapy.

Clinical Outcomes of R-CHOP Chemotherapy Alone Compared with R-CHOP Plus Radiotherapy in Patients with Localized, Non-Bulky Diffuse Large B-Cell Lymphoma

IntroductionAlthough several previous studies addressed the role of radiation in treating localized diffuse large B-cell lymphoma (DLBCL), chemotherapy alone has shown promising efficacy with the emergence of Rituximab. Thus, we evaluated the clinical efficacy outcomes and failure patterns of patients with localized DLBCL according to two different treatment strategies, either 6 or more cycles of R-CHOP chemotherapy alone or 3 or 4 cycles of R-CHOP followed by involved field radiotherapy (IFRT).MethodsA prospectively collected database from 21 tertiary centers participating the Consortium for Improving Survival of Lymphoma (CISL), built up for PROCESS study (NCT01202448) for secondary central nervous system involvement in DLBCL, was recruited for current study in addition to the Asan Medical Center (AMC) Lymphoma Registry. CISL database and AMC lymphoma registry consisted of data from patients with newly diagnosed DLBCL between August 2010 and August 2012, and between February 2004 and February 2012, respectively. Inclusion criteria were localized (stage I or II), non-bulky (<10cm in longest diameter) DLBCL treated with R-CHOP as 1st line chemotherapy, and patients either who received 6 or more cycles of R-CHOP chemotherapy only (R-CHOP alone group) or received 3 or 4 cycles of R-CHOP chemotherapy followed by IFRT (R-CHOP plus RT group). Comparisons of clinicopathologic parameters, clinical outcomes and the patterns of relapse were performed between two groups. The types of relapse were classified as either locoregional or distant, according to whether it involves any separate region from primary sites. Efficacy outcomes included complete response (CR) rate, 2-year overall survival (OS) rate, and 2-year event-free survival (EFS) rate.ResultsA total of 357 patients (CISL prospective cohort: 161 patients, AMC registry: 196 patients) were eligible for the analyses. Two hundred ninety nine patients (83.5%) received 6 or more cycles of R-CHOP chemotherapy alone, and 58 patients (16.2%) underwent 3 or 4 cycles of R-CHOP followed by IFRT. Median age was 54 years (range, 16-87). During the median follow-up of 24 months (range, 4-116 months), 35 patients (9.8%) experienced relapse, and 22 patients (6.1%) died. Two-year OS and EFS rate was 94.7% and 89.9%, respectively, and 345 out of 357 patients (96.6%) achieved CR. Comparing R-CHOP alone to R-CHOP plus RT group, there was no significant difference in clinicopathologic parameters. R-CHOP alone could achieve significantly higher CR rate of 97.7 % than 91.4% of R-CHOP plus RT group (p = 0.030). Two-year OS and EFS were significantly longer in R-CHOP alone group than R-CHOP plus RT group (96.1 vs 89.9 %, p = 0.029 and 91.7% vs 81.8%, p= 0.028) (Figure 1). Relapse rate was significantly lower in R-CHOP alone group compared with R-CHOP plus RT group than group (7.4% vs 22.4%, p=0.001), and distant relapses were also significantly lower (15.5% vs 2.7%, p<0.001). In addition, even only in relapsed patients, R-CHOP alone group showed lower incidence of distant relapses with marginal statistical significance (36.4% vs 69.2 %, p=0.062) (Table 1).ConclusionIn our cohort, R-CHOP alone for six to eight cycles without IFRT could achieve significantly higher 2-year OS and EFS rate as well as CR compared with R-CHOP plus RT group. In addition, the rate of relapse and systemic failure were significantly lower in R-CHOP alone group, which altogether warrant further validation in prospective trial.Table 1Explorative comparison of overall clinical outcomes and patterns of relapse between two subgroups: patients who underwent six or more cycles of R-CHOP chemotherapy alone and who underwent 3 or 4 cycles of R-CHOP followed by IFRTTotal (%)R-CHOP alone group (%)R-CHOP plus RT group (%)P -valueNumber of patients357 (100)299 (83.5)58 (16.2)Treatment responseComplete response345 (96.6)292 (97.7)53 (91.4)0.030Overall response351 (98.3)294 (98.3)57 (98.3)1.000Rate of relapse35 (9.8%)14 (7.4)11 (22.4)< 0.001Median time to relapse (95% CI)11 (7-15)11 (8-14)10 (5-14)0.346Pattern of relapse< 0.001 (0.062)Locoregional14 (4.7) (63.6)4 (6.9) (30.8)Distant8 (2.7) (36.4)9 (15.5) (69.2) [Display omitted] [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Review of the clinical research conducted by the Consortium for Improving Survival of Lymphoma of the Korean Society of Hematology Lymphoma Working Party

The Consortium for Improving Survival of Lymphoma (CISL) in Korean Society of Hematology Lymphoma Working Party had first meeting in February, 2006 with 10 institutions and 12 members. Now CISL comprised of 64 centers. CISL has concentrated research activity on lymphomas which are relatively frequent in Korea and has tried to give favors for the Korean lymphoma patients. CISL has conducted more than 30 retrospective studies to evaluate Korean peculiar lymphoma subtypes. More than 30 prospective trials have been being performed for diffuse large B-cell lymphoma, marginal zone lymphoma, extra-nodal NK/T-cell lymphoma, and so on. The first prospective trial for advanced marginal zone lymphoma has led to use Rituximab containing chemotherapy with the re-imbursement of health insurance in Korea. The multi-center trials of the CISL with new therapeutic modalities will improve further the survival of lymphoma patients not only quantitatively but also qualitatively.

Plerixafor use for peripheral blood stem cell mobilization in Korea

Peripheral blood stem cell (PBSC) mobilization is a prerequisite for the success of autologous stem cell transplantation (ASCT), and the infusion of adequate number of CD34+ hematopoietic progenitor cells is correlated with successful engraftment [1]. Traditionally, chemotherapeutic agents such as cyclophosphamide in combination with granulocyte-colony stimulating factor (G-CSF) have been used for mobilization of hematopoietic stem cells from bone marrow into peripheral blood. However, approximately 10-30% of patients who are at risk of mobilization failure are unable to mobilize minimum required number of PBSCs (≥2.0×106 CD34+ cells/kg) for the success of ASCT [2], and consequently fail to undergo ASCT. Plerixafor (AMD3100), a small molecule inhibitor of stromal cell-derived factor-1α binding to the CXCR4 receptor, was introduced as a solution for patients who show inadequate mobilization of CD34+ PBSCs. Results of Phase I/II trials demonstrated the efficacy of plerixafor, and a subsequent Phase III study showed that the use of plerixafor in combination with G-CSF significantly increased the number of CD34+ PBSCs, compared to G-CSF alone [3]. Plerixafor has been approved for patients with lymphoma and multiple myeloma who show poor PBSC mobilization, and its use is expected to increase the likelihood of successful ASCT. However, it is still difficult to define 'poor' mobilization because the total number of CD34+ cells can be influenced by the number of apheresis. There have been variable parameters to evaluate the extent of mobilization, such as cumulative apheresis yield as well as the number of CD34+ cells per apheresis. In addition, the total yield of CD34+ cells depends on the number of courses of apheresis, which is, in turn contingent on physicians' discretion. Recently, the Italian Group for Stem Cell Transplantation (GITMO) proposed consensus criteria for 'proven poor mobilizers' as follows: (a) circulating CD34+ cell peak of less than 20/µL up to 6 days after mobilization with G-CSF or up to 20 days after adequate mobilization such as using G-CSF 10 µg/kg if used alone or 5 µg/kg after chemotherapy, (b) less than 2.0×106 CD34+ cells per kg after fewer than three apheresis [4]. In Korea, use of plerixafor in combination with G-CSF is approved in patients with non-Hodgkin lymphoma and multiple myeloma for PBSC mobilization, and reimbursement is provided to those who have failed previous mobilization attempts with chemotherapy and G-CSF. However, the appropriate time for the initiation of plerixafor is still subject to ambiguity due to the lack of consensus on usable criteria for determining mobilization failure. Despite CD34+ PBSC count being considered the most powerful predictive factor of mobilization failure, the measurement of circulating CD34+ cells is not feasible in a majority of institutes in Korea. Therefore, at the recent meeting of the Consortium for Improving Survival of Lymphoma (CISL), the board members adopted a consensus definition of 'mobilization failure' as a count of less than 2.0×106 CD34+ cells/kg after three courses of apheresis. Thus, if the total number of CD34+ cells does not reach the minimum requirement for ASCT, the use of plerixafor should be considered, rather than continuation of apheresis with G-CSF. Furthermore, in specific patient populations which are expected to have low possibility of adequate cell yield such as elderly and heavily-pretreated patients, the board members of CISL discussed early administration of plerixafor. While the risk factors of mobilization failure have not yet been clearly identified, the recent GITMO working group proposed consensus criteria to define 'predicted poor mobilizers' as follows: (1) they failed a previous collection attempt (not otherwise specified); (2) they previously received extensive radiotherapy or full courses of therapy affecting PBSC mobilization; and (3) they met two of the following criteria: advanced disease (≥two lines of chemotherapy), refractory disease, extensive bone marrow involvement or cellularity <30% at the time of mobilization; age ≥65 years (4). A recent study on identifying prognostic factors for prescribing plerixafor-based PBSC mobilization showed that an age of 65 years, a diagnosis of non-Hodgkin's lymphoma, and treatment with four chemotherapy regimens were significantly associated with mobilization failure. Given the congruence between these prognostic factors and GITMO criteria of 'predicted poor mobilizers', it is evident that PBSC mobilization is impacted by the existence of risk factors and hence, the early use of plerixafor for high-risk groups should be carefully considered [5]. Further study is warranted to prevent mobilization failure by maximizing the benefit of plerixafor in Korean clinical setting. Plerixafor is a new class agent with a novel mechanism of action and has the potential to lead to a paradigm shift in PBSC mobilization and success of ASCT. In the era of plerixafor, considerable changes in clinical practices associated with PBSC mobilization can be expected in Korea.

Prospective Cohort Study with Risk-Adapted Central Nervous System (CNS) Evaluation in Diffuse Large B-Cell Lymphoma Patients Treated with Rituximab-CHOP: Analysis of Incidence and Risk Factors for Secondary CNS Involvement.

Abstract 2683▪▪This icon denotes a clinically relevant abstract BackgroundSecondary central nervous system (CNS) involvement in diffuse large B-cell lymphoma (DLBCL) includes CNS relapse or CNS involvement with systemic disease progression. Although many publications have provided information regarding the incidence and risk factors for CNS involvement in DLBCL, its incidence reported across those studies varies widely. It might be related with that the majority of data were from retrospective analyses. Furthermore, the role of CNS prophylaxis for DLBCL has been challenged, especially in the era of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone). As a result, this rare but fatal clinical problem still remains a therapeutic dilemma in the management of DLBCL. In this study, we prospectively explored the risk factors of CNS involvement and the clinical impact of screening evaluation for CNS involvement. MethodsWe analyzed the incidence of secondary CNS involvement in pathologically confirmed DLBCL patients enrolled in the Prospective Cohort Study with Risk-adapted Central Nervous System Evaluation in Diffuse Large B-cell Lymphoma (PROCESS study, NCT01202448). Patients should be treated with at least one cycle of R-CHOP, and provide written informed consents. We assessed the risk of CNS involvement based on previously reported risk factors: serum LDH elevation, the number of extranodal involvements, serum albumin, bone marrow invasion, HIV positivity, the involvement of testis, breast, paranasal sinus, bone, retroperitoneal lymph nodes, orbit, and epidural space. If patients had any of these risk factors, they underwent CSF study to screen the CNS involvement at diagnosis. If the results were abnormal, additional studies including brain MRI could be done depending on physicians' decision. CNS prophylaxis was done with intrathecal chemotherapy with methotrexate for patients who had positive findings of screening evaluation or were determined to have a risk of CNS involvement based on physicians' decision. Results564 patients were enrolled between 2010 and 2012 from 26 institutions belonged to the Consortium for Improving Survival of Lymphoma (CISL). They were prospectively monitored with the median follow-up duration of 10.5 months. The median age was 59.5 years old (range 20–89 years), and approximately a half of patients had Ann Arbor stage III/IV (n = 276, 48.9%) and 193 patients involved two or more than two extranodal sites (34.2%). Based on the International Prognostic Index (IPI) risk, 192 patients belonged to high or high-intermediate risk (34%). Among patients (n = 368) who had at least one of risk factors for CNS involvement, 243 patients underwent CNS evaluation, and the evidence of CNS involvement was found in16 patients including positive cytology (n = 11), and brain parenchyma lesion (n = 5). The other 78 patients showed equivocal results of CSF analysis including the presence of atypical cells (n = 17). Intrathecal prophylaxis was done for 51 patients whereas high dose methotrexate chemotherapy was combined with R-CHOP for patients with brain lesion. During follow-up, 14 cases of additional CNS involvement including brain parenchyma (n = 8), leptomeningeal (n = 5), and ocular invasion (n = 1) were observed. The median time to CNS event in these 14 patients was 7.5 months (range 1.2 – 15.9 months). Thus, 30 cases of secondary CNS involvement were documented in our study population at the time of analysis (5.3%) including 16 cases at diagnosis and 14 cases during follow-up. The univariate analysis for evaluation of risk factors demonstrated serum LDH, the number of extranodal involvements, bone marrow invasion, and the involvement of retroperitoneal lymph nodes, breast, paranasal sinus and orbit were significantly associated with CNS involvement. The high/high-intermediate risk of IPI was also predictive of CNS involvement (P < 0.05). However, in the multivariate analysis, bone marrow invasion and the involvement of breast, paranasal sinus and orbit were independently predictive for CNS involvement. ConclusionsThe incidence of secondary CNS involvement in DLBCL patients treated with R-CHOP was around 5%, and a half of cases had the evidence of CNS involvement at diagnosis. Considering a particular risk of CNS involvement of disease-related factors, risk-adapted active screening against CNS involvement may help to improve treatment outcome of patients with DLBCL. Disclosures:No relevant conflicts of interest to declare.

Waldeyer’s ring marginal zone B cell lymphoma: are the clinical and prognostic features nodal or extranodal? A study by the Consortium for Improving Survival of Lymphoma (CISL)

There has been controversy surrounding Waldeyer's ring (WR), especially focused on the question of whether it should be regarded as a nodal or an extranodal site. We conducted retrospective analyses of marginal zone B cell lymphomas involving WR (WR-MZLs) to observe their clinical features and prognosis, with specific regard to the nodal-or-extranodal question. A total of 52 patients with histological diagnosis of WR-MZL were retrospectively analyzed. The most common involvement site was the tonsil (40.4 %). Ann Arbor stage III/VI disease was present in 48.1 % (25 of 52). The response rate of the 27 stage I/II patients was 88.9 %, with 21 complete remissions and three partial remissions. The median time to progression (TTP) was 3.7 years (95 % CI 2.5-4.9 years). The estimated 5-year TTP and overall survival rates were 39.4 and 90.5 %, respectively. In a comparison with the historical data regarding extra-WR MALT lymphoma and nodal MZL (N-MZL), MALT lymphoma showed better TTP results than did WR-MZL and N-MZL (P < 0.001).

Prognostic factors in primary diffuse large B-cell lymphoma of adrenal gland treated with rituximab-CHOP chemotherapy from the Consortium for Improving Survival of Lymphoma (CISL)

BackgroundThe objective of this study was to identify prognostic factors for survival in patients with primary diffuse large B-cell lymphoma (DLBCL) of the adrenal gland.MethodsThirty one patients diagnosed with primary adrenal DLBCL from 14 Korean institutions and treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone) were analyzed.ResultsComplete remission (CR) and overall response rate after R-CHOP chemotherapy were 54.8% and 87.0%. The 2-year estimates of overall survival (OS) and progression-free survival (PFS) were 68.3% and 51.1%. In patients achieving CR, significant prolongations of OS (P = 0.029) and PFS (P = 0.005) were observed. Ann Arbor stage had no influence on OS. There was no significant difference in OS between patients with unilateral involvement of adrenal gland and those with bilateral involvement. When staging was modified to include bilateral adrenal involvement as one extranodal site, early stage (I or II) significantly correlated with longer OS (P = 0.021) and PFS (P <0.001).ConclusionsContrary to prior reports, our data suggests that outcomes of primary adrenal DLBCL are encouraging using a regimen of R-CHOP, and that achieving CR after R-CHOP is predictive of survival. Likewise, our modified staging system may have prognostic value.