scholarly journals A Novel Prognostic Index for Patients with EBV-DLBCL NOS: A Study from the Grupo De Estudio Latinoamericano De Linfoproliferativos (GELL)

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1436-1436
Author(s):  
Brady E Beltran ◽  
Denisse Castro ◽  
Luis Villela ◽  
Efreen Montaño Figueroa ◽  
Ana Florencia Ramirez-Ibarguen ◽  
...  
Keyword(s):  
Latin American ◽  
Research Funding ◽  
Cox Regression ◽  
International Prognostic Index ◽  
Eastern Cooperative Oncology Group ◽  
Prognostic Index ◽  
B Cell Lymphoma ◽  
World Health ◽  
Serum Lactate Dehydrogenase ◽  
Latin American Countries

Abstract Introduction: Epstein Barr virus-positive (EBV+) diffuse large B-cell lymphoma (DLBCL), not otherwise specified (NOS) is a newly recognized entity by the World Health Organization. EBV+ DLBCL, NOS is commonly encountered in Latin American countries and carries a dismal prognosis. Current prognostic models such as the Oyama and the International Prognostic Index (IPI) score have limited prognostic value in this patient population. Therefore, we aim to evaluate the ability of these models to risk stratify patients and propose a novel prognostic model in the largest cohort of Latin American patients with EBV+ DLBCL, NOS. Methods: This retrospective cohort study included patients ≥18 years from six Latin American countries diagnosed and treated at tertiary centers from 2010 to 2020. Hematopathologists at each institution reviewed pathological samples to confirm the diagnosis of EBV+ DLBCL, NOS. We collected clinicopathological data by reviewing the medical records of the patients. The primary endpoint was overall survival (OS), defined as the time from the date of diagnosis until death from any cause or last visit. The secondary endpoint, progression-free survival (PFS), was defined as the time from diagnosis until death, progression, or last visit. Our novel model (Grupo de Estudio Latinomericano de Linfoproliferativos [GELL] Score) includes the Eastern Cooperative Oncology Group (ECOG) performance status ≥2, extranodal involvement >1, serum albumin <3.5 g/dL, serum lactate dehydrogenase (LDH) above the upper limit of normal, and platelet-to-lymphocyte ratio >455. We assigned a value of 1 to each of the abovementioned elements in the score and classified the patients as low (0 points), intermediate (1-2 points), and high (3-5) risk. OS and PFS probabilities were computed with the Kaplan-Meier method and compared with the log-rank test. We used Cox regression to evaluate the proportional hazard ratios (HR) of each score for our study outcomes. The C-index was employed to measure discrimination of each model. We used cross-validation to evaluate the model performance. Results: A total of 154 patients with EBV+ DLBCL, NOS were included in this analysis. The median age at diagnosis was 58 years (range 19-86 years) with a slight male predominance (53%). EBER was positive in all cases (range 1-100%). Clinically, 39% presented ECOG ≥2, 57% had B symptoms, 50% had an extranodal disease as a primary tumor, and 71% had Ann Arbor stage III/IV. Fifty-one percent of the patients had an elevated LDH level, and 43% had albumin <3.5 g/dL. Rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) regimen was administered in 79% of individuals as first-line treatment. The overall response rate was 80% (62% complete response and 18% partial response). With a median follow-up of 61 months, the 5-year OS and PFS rates were 61% and 47%, respectively. The 5-year OS rates of patients with low, intermediate, and high-risk disease according to the GELL score was 90%, 59%, and 33%, respectively (Fig 1A). The 5-year PFS rates were 82%, 39%, and 23%, respectively (Fig 2A). Table 1 shows the Cox regression and the discrimination analysis for each of the scores. The GELL score has the highest discriminatory index for OS and PFS compared to the IPI, Revised-IPI, National Comprehensive Cancer Network-IPI, and the Oyama score (Figure 1 and 2). Conclusions: This study proposes a novel score for risk stratification of patients with EBV+ DLBCL, NOS. The GELL score appears to better discriminate OS and PFS than previous scores. Our results should be validated in an independent prospective cohort. Figure 1 Figure 1. Disclosures Ramirez-Ibarguen: Asofarma: Consultancy; MSD: Consultancy; Abbvie: Speakers Bureau; Astra Zeneca: Speakers Bureau; Janssen: Speakers Bureau; Roche: Speakers Bureau; Takeda: Consultancy, Speakers Bureau. Perini: Janssen: Honoraria, Speakers Bureau; Takeda: Honoraria, Speakers Bureau; Astra Zeneca: Honoraria, Speakers Bureau; MSD: Honoraria, Speakers Bureau. Oliver: Roche: Other: conference support and fees ; Abbvie: Other: conference support and fees . Castillo: Abbvie: Consultancy, Research Funding; BeiGene: Consultancy, Research Funding; Pharmacyclics: Consultancy, Research Funding; Janssen: Consultancy; Roche: Consultancy; TG Therapeutics: Research Funding.

High Incidence of Asian Variant Intravascular Large B-Cell Lymphoma (IVL) among IVL in Japan: Clinicopathologic Study of 95 Patients.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1365-1365
Author(s):  
Takuhei Murase ◽  
Ritsuro Suzuki ◽  
Motoko Yamaguchi ◽  
Masataka Okamoto ◽  
Yumiko Sato ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Prognostic Factors ◽  
B Cell ◽  
Cox Regression ◽  
Cell Lymphoma ◽  
Bone Marrow Involvement ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
B Cell Lymphoma ◽  
Serum Lactate Dehydrogenase

Abstract IVL is a rare form of aggressive B-cell lymphoma characterized by multifocal and predominant growth within vessels. Although its neurologic and dermatologic manifestations at diagnosis have been well documented, clinical courses of IVL are protean by patients. Systematic strategies for diagnosis and treatment of IVL are still to be established. To address these issues, we retrospectively analyzed a series of patients with IVL. This study was conducted by a refractory lymphoma study group, supported by the Ministry of Labor, Health and Welfare of Japan, and approved by the institutional review board of each participating institution. Both histopathological findings of IVL and positive reactions for at least one B-cell antigens (CD20, CD19 or CD79a) were required for inclusion. There were 95 patients (49 males and 46 females), with a median age of 67 years old (range 41–85). Most patients of IVL were associated with poor prognostic factors; i.e., 95% had more than 1 site of extranodal involvement, 91% had stage III/IV disease, 82% showed performance status greater than 1, and 94% had serum lactate dehydrogenase higher than normal level. Eighty-five percent was classified to the high-risk group of the International Prognostic Index (IPI). Therefore, IPI is not useful for the prognostification of IVL. Thirty-five patients (37%) were positive for CD5. Hemophagocytosis in the bone marrow, a key pathologic criterion for Asian variant of IVL (AIVL; Murase et al: Brit J Haematol 2000), was noted in 53 of 79 patients (67%) with available information. All these 53 patients met the clinical and laboratory criteria for AIVL, including anemia, thrombocytopenia, hepatosplenomegaly, and absence of tumor formation. In contrast, no hemophagocytosis was observed in 13 patients who did not meet the criteria. Patients with IVL were further characterized by the presence of B symptoms (76%), neurologic abnormality (27%), skin lesion (13%), and leukocytopenia (<4x109/L; 27%). Bone marrow involvement was identified in 76% of the patients. Leukemic lymphoma cells were noted in 28% of the patients. Since 16 patients were diagnosed at autopsy, and 4 died shortly after the diagnosis or failed to follow, 75 were enrolled for analyses of prognostic factors. Univariate analyses for overall survival showed no use of anthracycline containing regimen (p=0.001), older age (p=0.005), lower platelet count (<100x109/L; p=0.006), and higher serum soluble IL-2 receptor (5x103U/mL or more; p=0.017) as unfavorable prognostic factors. Multivariate analysis using Cox regression model revealed that all these three factors were independent and significant prognostic factors (no anthracycline regimen: p=0.002, Hazard ratio [HR] 3.25, 95% confidence interval [CI] 1.53–6.90; age by 10 years: p=0.014, HR 1.36, 95%CI 1.07–1.66; and platelet <100x109/L: p=0.037, HR 2.12, 95%CI 1.05–4.31). These findings suggest patients with IVL should be treated chemotherapy containing anthracyclines.

Diffuse Large B-Cell Lymphoma (DLBCL) with Central Nervous System (CNS) Relapse: Prognosis and Risk Factors by Retrospective Analysis from Single Center Experience.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3436-3436
Author(s):  
Yutaka Shimazu ◽  
Takeshi Maeda ◽  
Kenji Notohara ◽  
Takeshi Ito ◽  
Satoko Morita ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cox Regression ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
B Cell Lymphoma ◽  
Intrathecal Methotrexate ◽  
Risk Category ◽  
High Dose ◽  
Cox Regression Analysis ◽  
Cns Relapse

Abstract Background: The introduction of rituximab into the therapy of DLBCL has improved the prognosis dramatically. However, relapse in CNS is still the issue. We studied the prognosis and risk factors of CNS recurrence in DLBCL. Method: Between Jan. 1996 and Apr. 2007, 441 patients were diagnosed to have DLBCL in our institute, of whom 31 patients were excluded due to CNS involvement at the time of initial diagnosis. We have analyzed 410 cases, in which 37 cases had relapsed in CNS. Before Sep. 2003, 168 patients were treated with the regimen based on CHOP, and after Sep. 2003, 242 patients were treated with the regimen based on CHOP plus rituximab. Once relapsing in CNS, the patients were treated with systemic chemotherapy plus high-dose methotrexate or radiation with intrathecal methotrexate. The risk category by the international prognostic index of these 411 cases was assessed as low: 36%, low-intermediate: 15%, high-intermediate: 23%, and high: 26%. Results: The median age was 71 years old (range: 17–92). Median follow-up period was 507 days, and the median period free from relapsing in CNS was 331 days. The mean survival period of the cases with CNS relapse, of the cases relapsed outside the CNS, and of the non-relapsed cases was 1328 days, 2290 days, and 2817days, respectively. The overall survival rate of cases with CNS relapse was significantly lower than that of the cases relapsed outside the CNS, or than that of the non-relapsed cases (p=0.0233, p=0.0003, respectively). Multivariate Cox regression analysis identified the increased lactate dehydrogenase (p=0.014), the involvement of more than one extranodal site (p=0.006), and not using rituximab before CNS relapse (p=0.040) as an independent predictor of CNS recurrence. Conclusion: CNS relapse has extremely poor prognosis than relapse outside the CNS in DLBCL. Rituximab may be effective in preventing CNS relapse. Since rituximab poorly penetrates into CNS, this may partly due to the reduction of all recurrence by rituximab. According to the risk assessment in CNS relapse, an effective CNS prophylaxis strategy should be determined.

Safety and Efficacy Of Bendamustine In Patients With Aggressive Non-Hodgkin Lymphomas (NHL)

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4371-4371 ◽  
Author(s):  
Jakob Hammersen ◽  
Michael Sommer ◽  
Christin Gössel ◽  
Ulf Teichgräber ◽  
Sabine Hahnfeld ◽  
...  
Keyword(s):  
Cox Regression ◽  
Cell Lymphoma ◽  
Univariate Analysis ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
B Cell Lymphoma ◽  
Disease Stage ◽  
Sustained Remission ◽  
Cox Regression Analysis ◽  
Line Therapy

Abstract Introduction Frail patients with aggressive NHL frequently do not qualify for CHOP-based chemotherapy. Alternatives are required urgently. Bendamustine has been well established as a standard treatment of indolent lymphomas. Its use in high grade lymphoma has been suggested as a promising option. However, which patients benefit most effectively requires further clarification. Methods We retrospectively characterized 51 unselected consecutive patients (39,2% female, 60,8% male, median age 70 years, range 32 - 92 years) with aggressive NHL treated with bendamustine +/- rituximab. They were analyzed for baseline characteristics (histological type, IPI, ABC/GCB-subtypes, age, ECOG, comorbidity (CIRS-G), outcome (ORR, PFS, OS), and toxicity (CTCAE)). Results 21 patients with aggressive NHL received Bendamustin as 1st-line therapy and 30 patients beyond 1st-line. Of the 1st line patients 14 suffered from diffuse large cell B cell lymphoma (DLCBL), 5 from mantle cell lymphoma (MCL), and 2 from other subtypes. In 1st line patients median age was 82 years, ECOG-status was ≥ 2 in 38%. Median international prognostic index (IPI) was 3 (range 1-4). Comorbidity assessment by CIRS-G revealed median 3 (range 1 to 5) severely or very severely affected organs. The overall response rate (ORR) in 1st line treatment was 91%, with a median progression free survival (PFS) of 6 months and a median overall survival (OS) of 15 month. In DLBCL 5 GCB- and 6 ABC-lymphomas were differentiated. GCB-patients showed an ORR of 80% (2 complete remission (CR), 2 partial remission PR)), a median PFS 8 month and OS of 15 months, respectively. ABC-patients had an ORR 67% (no CR, 4 PR, 2 SD), a median PFS of 6 month and OS of 8 months, respectively (n.s.). 7 patients achieved a long term-remission >5 years. Univariate analysis of prognostic variables showed significance for ECOG (p<0.0001) and CIRS-G (p=0.002) for OS, Cox-regression analysis showed significance for ECOG (p=0.016). No significance was shown for disease stage or LDH activities. The ORR in patients beyond 1st-line therapy (median age 64 years, ECOG-status ≥ 2 in 17%) was 66% with a median PFS of 8 month and OS of 24 month. Median cumulative dose was 540 mg/m2 in median 4 cycles. Toxicity in the 1st-line cohort was moderate, mainly grade 1 & 2. Three patients showed grade 3 leukocytopenia. Other side effects primarily were: inappetence, weight-loss, fever. Conclusion Bendamustine shows high efficacy in aggressive NHL, even sustained remission was achieved by a subgroup, which requires further definition. Toxicity was well manageable. Defining prognostic parameters we showed GCB-subtype of DLBCL might predict a better outcome in bendamustine treated patients. Remarkably, performance and comorbidity assessment is of crucial prognostic value with a greater impact on outcome compared to classic parameters. Currently, the BRENDA trial (NCT01686321) prospectively investigates the role of bendamustine in aggressive NHL. Disclosures: Off Label Use: Use of Bendamustine in aggressive NHL. Wedding:Roche: Speakers Bureau; Amgen: Speakers Bureau; Chugai: Speakers Bureau; Janssen-Cilag: Speakers Bureau; Novartis: Speakers Bureau; Cephalon: Speakers Bureau; Prostarkan: Speakers Bureau; Pfizer: Speakers Bureau. La Rosée:Mundi Pharma: Honoraria.

Validation of the NCCN-IPI for Diffuse Large B-Cell Lymphoma (DLBCL) in a Nation-Wide Spanish Series of 1885 Patients. the Geltamo-IPI Project

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3955-3955
Author(s):  
Carlos Montalbán ◽  
Antonio Díaz-López ◽  
Heidys Garrote Santana ◽  
Julián Matias Freue ◽  
Lourdes López ◽  
...  
Keyword(s):  
Research Funding ◽  
De Novo ◽  
International Prognostic Index ◽  
Geographical Area ◽  
Prognostic Index ◽  
B Cell Lymphoma ◽  
Risk Groups ◽  
Rank Test ◽  
Published Data ◽  
Pairwise Comparisons

Abstract The development of the NCCN International Prognostic Index (NCCN-IPI) for patients with DLBCL treated in the rituximab era improves discrimination when compared to the original IPI model. The aim of the present study is to validate the results of the NCCN-IPI in a large independent series of patients in a different geographical area. Materials & Methods. This nation-wide retrospective study includes 2156 patients with de novo DLBCL diagnosed in 20 (mostly) large academic Spanish centers within the Grupo Español de Linfomas y Transplante de Médula Osea (GELTAMO) network between 1998 to July 2014. Patients had to be ≥ 18 years-old, treated with rituximab plus chemotherapy (R-CHOP or variants and also more intense treatments) and a minimum of 1 year of follow-up; all histological subtypes of DLBCL and primary extranodal cases were acceptable, with the only exclusion of primary testicular or CNS sites. In the whole series the scoring of the IPI and NCCN-IPI indexes were used and 5-year Overall Survival (5y-OS) estimated with the Kaplan-Meier method and compared with the log-rank test. Results. Debugging the database resulted in a final working series that included 1885 patients. The demographics of the series were comparable to the NCCN series: NCCN/GELTAMO male gender(%) 54 vs 50.4, Age(y) 57 vs 60, LDH>1(%) 50 vs 54.7, Ann Arbor stage III-IV (%) 59 vs 62.5, ECOG PS≥2(%) 11 vs 30, extranodal disease(%) 36 vs 40.7. The IPI scoring (1760 patients) significantly separated the four risk groups, low (LR, 33.6% of the patients), low/intermediate (LI, 22.7%), intermediate/high (HI, 25.1%) and high (HR, 18.6%) with significantly different (p<0.001 in the global and pairwise comparisons) 5y-OS 5 (88, 77, 68 and 51%, respectively) (Figure 1). The NCCN-IPI (1773 patients) also significantly (p<0.001 in the global and pairwise comparisons) separated the four risk groups (L 12,7%, LI 34.5%, HI 37% and H 15.8%) with 5y-OS (%) of 93, 84, 67 and 49, respectively (Figure 2), comparably to the published data (Table 1). Conclusions. NCCN-IPI for the prognosis of DLBC lymphoma treated with chemo-immunotherapy has been validated in a large independent Spanish series. However, in our population the NCCN-IPI is not more powerful than the IPI for predicting survival. Figure 1. Figure 1. Figure 2. Figure 2. Figure 3. Figure 3. Disclosures López-Guillermo: Roche, Celgene, Mundipharma, Gilead, Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding. Dlouhi:Gilead: Equity Ownership. Martín García:Servier, Gilead: Consultancy. Sancho:CELLTRION, Inc.: Research Funding.

CHOP-R + bortezomib as initial therapy for diffuse large B-cell lymphoma (DLBCL)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 8031-8031 ◽  
Author(s):  
J. P. Leonard ◽  
R. R. Furman ◽  
Y. K. Cheung ◽  
J. M. Vose ◽  
P. W. Glynn ◽  
...  
Keyword(s):  
High Risk ◽  
Phase I ◽  
B Cell ◽  
International Prognostic Index ◽  
Elevated Serum ◽  
Prognostic Index ◽  
B Cell Lymphoma ◽  
Serum Lactate Dehydrogenase ◽  
Hematologic Toxicity ◽  
Combination Regimen

8031 Background: Bortezomib is a proteasome inhibitor with anti-tumor activity in B cell malignancies. These effects, which may relate to NF-kappaB associated pathways, could sensitize tumor cells to standard chemotherapy-based regimens and enhance efficacy. We report findings of a phase I/II trial of dose-escalated bortezomib + standard CHOP-rituximab in DLBCL patients (accrual of the MCL cohort of this study remains ongoing). Methods: Patients with previously untreated DLBCL (n=40) received CHOP-21 + rituximab (375 mg/m2 each cycle) plus bortezomib at 0.7 mg/m2 (Arm 0, n=4), 1.0 mg/m2 (Arm 1, n=8) or 1.3 mg/m2 (Arm 2, n=28 including phase I and all phase II) on days 1 and 4 of each cycle Results: Median age (n=40) was 58 years (range 21–86), thirty-five subjects (88%) had stage III/IV disease at study entry, and 29 (73%) had elevated serum lactate dehydrogenase (LDH). Patients generally had unfavorable baseline international prognostic index (IPI) scores of 2 in 16 subjects (40%) and 3–5 in 19 subjects (48%). Median follow-up is 21 months (range 9 - 35 months). Treatment was generally well tolerated. Peripheral neuropathy occurred in 22 subjects (55%), with 45% grade 1, 5% grade 2 and 5% grade 3. Grade 4 hematologic toxicity included thrombocytopenia (15%) and leukopenia (15%). Four subjects (3 over age 75 and all with high risk IPI) died prior to first response assessment. Intent to treat (ITT) overall response rate (n=40) is 90% with 68% CR/CRu. For the evaluable subset (n=36), ORR was 100% with CR/CRu 75%. Kaplan-Meier estimate (n=40) of 2-year progression-free survival is 72%. Of all 19 enrolled (ITT) patients in the high-intermediate or high-risk IPI groups, 14 (74%) were alive without progression at last assessment. Correlation of outcome with cell of origin type (activated B cell vs germinal center) is ongoing. Conclusions: Bortezomib can be administered with acceptable toxicity in conjunction with CHOP-R chemotherapy. Efficacy findings with this combination regimen in newly-diagnosed DLBCL are encouraging and warrant further study. No significant financial relationships to disclose.

Clinicopathologic Correlations of Genomic Gains and Losses in Follicular Lymphoma

2002 ◽  
Vol 20 (23) ◽  
pp. 4523-4530 ◽  
Author(s):  
Andreas Viardot ◽  
Peter Möller ◽  
Josef Högel ◽  
Kirsten Werner ◽  
Gunhild Mechtersheimer ◽  
...  
Keyword(s):  
International Prognostic Index ◽  
Elevated Serum ◽  
Prognostic Index ◽  
Hazard Ratio ◽  
Prognostic Scores ◽  
World Health ◽  
Serum Lactate Dehydrogenase ◽  
Comparative Genomic ◽  
Data Set ◽  
Genomic Aberrations

PURPOSE: To evaluate the clinical relevance of genomic aberrations in follicular lymphomas (FLs). PATIENTS AND METHODS: In this study, we analyzed 124 biopsy samples of patients with FL using comparative genomic hybridization. RESULTS: In 87 cases (70%), genomic imbalances were detectable. The most frequent aberrations were gains of chromosome arms 7p (21 patients), 7q (21 patients), Xp (16 patients), 12q (15 patients), and 18q (14 patients) as well as losses on 6q (21 patients). Grades 2 and 3 according to the World Health Organization classification correlated with a more complex karyotype (P < .0001). In a subset of 82 patients, a comprehensive clinical data set was available. In a multivariate analysis including all clinical risk factors of the International Prognostic Index as well as genomic aberrations, the loss of material on chromosomal bands 6q25q27 was the strongest predictor of a shorter survival (P = .0001; hazard ratio, 6.5), followed by elevated serum lactate dehydrogenase level (P = .0009; hazard ratio, 4.9), the presence of more than one extranodal manifestation (P = .017; hazard ratio, 4.2), and age greater than 60 years (P = .022; hazard ratio, 2.6). CONCLUSION: These data indicate that genomic aberrations may contribute significantly to risk assessment in patients with FL, the majority of whom are included in low-risk groups using established clinical prognostic scores.

Does An Anthracycline Make a Difference for Follicular Lymphoma (FL) Grade 3? Patterns of Care and Treatment Outcomes of Grade 3 FL From the National LymphoCare Study (NLCS)

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1768-1768 ◽  
Author(s):  
Christopher R Flowers ◽  
Michael Taylor ◽  
Michelle Byrtek ◽  
Jamie H. Hirata ◽  
James Cerhan ◽  
...  
Keyword(s):  
Research Funding ◽  
Cox Regression ◽  
Combined Modality Therapy ◽  
International Prognostic Index ◽  
Single Agent ◽  
Prognostic Index ◽  
The United States ◽  
Categorical Variables ◽  
Stock Ownership ◽  
Grade 3

Abstract Abstract 1768 Background: Although advances in therapy have improved outcomes for patients (pts) with FL, no optimal patient management strategy for pts with FL grade 3 has been identified largely due to debate regarding the benefits of anthracyclines for this subtype. Methods: The NLCS is a multi-center, longitudinal, observational study that collects data on treatment and outcomes for pts with FL diagnosed at 265 community (80%) and academic practices in the United States from 2004–2007. Pts enrolled in NLCS with a diagnosis of FL grade 3 as recorded by the treating physicians were examined to compare patterns of presentation, treatment strategies, and outcomes. No central pathology review was required. Data from pts who received watchful waiting (WW), single agent rituximab (R), R with cyclophosphamide, adriamycin, vincristine, and prednisone (R-CHOP), or R with cyclophosphamide, vincristine, and prednisone (R-CVP) as initial therapy were summarized using median and range for continuous variables and frequencies for categorical variables. Univariate associations between demographic, baseline disease characteristics, treatment setting, and initial treatment strategy, were tested using a standard χ2 test where sample size allowed. Relationship and hazard ratios for progression free survival (PFS) were estimated using Cox regression models adjusted for FL International Prognostic Index (FLIPI). Results: Of 2736 pts enrolled in NLCS, 500 had grade 3 FL. FL grade 3 pts had a median age of 64 years (range 26–97 years), 53% were female, and 67% had stage 3/4 disease. Pts were evenly distributed across FLIPI categories (30% good, 33% intermediate and 37% poor risk). Initial therapies for pts with FL grade 3 were WW (n=48), R alone (n=41), R-CVP (n=30), R-CHOP (n=245), R with another anthracycline (n=26), R with other chemotherapy (n=28), radiation alone (n=14), combined modality therapy (n=26), and regimens without R (n=42). Pts with FL grade 3 who received R-CHOP were younger than those who received R-CVP but similar in other FLIPI factors (Table). Events, defined as death or disease progression, occurred for 58% of patients who watched and waited and 33% of those who received treatment. Treated patients had improved PFS (median not reached [NR] 95% CI 66 months-NR) versus WW (median 29 months; 95% CI 19–43 months). Pts who received R-CHOP had improved PFS compared with WW (hazard ratio [HR] 3.09 95% CI 1.97– 4.86) but not R-CVP (HR 1.06 95% CI 0.52–2.14; Figure) Conclusions: In this large observational dataset of FL grade 3 patients, R-CHOP was the most commonly used first-line regimen. These results suggest that R with chemotherapy provides meaningful PFS benefits over WW for this population. Prospective randomized trials in pathologically identified pts are needed to evaluate the benefit of R-CHOP versus non-anthracycline regimens. Disclosures: Flowers: Millenium: Research Funding; Prescription Solutions: Consultancy; Genentech: Consultancy; Biogen/Idec: Consultancy; Celgene: Consultancy. Taylor:Genentech: Consultancy; Roche: Stock Ownership. Byrtek:Genetech: Consultancy; Roche: Stock Ownership. Hirata:Genentech: Employment; Roche: Stock Ownership. Cerhan:Genentech: Consultancy, Honoraria, Research Funding. Hainsworth:Genentech: Consultancy, Research Funding. Link:Genentech: Consultancy, Research Funding; Biogen Idec: Consultancy, Research Funding; Millennium Pharm: Consultancy, Research Funding; GlaxoSmithKline: Research Funding. Friedberg:Genentech: Consultancy.

Prognostic Value of cMYC Gene Abnormalities in Diffuse Large B Cell Lymphoma Treated with Chemo-Immunotherapy

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2664-2664 ◽  
Author(s):  
Ana Batlle López ◽  
Sonia Glez de Villambrosia ◽  
Santiago Montes-Moreno ◽  
Francisco Mazorra ◽  
Andrés Insunza ◽  
...  
Keyword(s):  
Cancer Research ◽  
B Cell ◽  
Research Funding ◽  
Cell Lymphoma ◽  
Univariate Analysis ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
B Cell Lymphoma ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Abstract 2664 Diffuse large B cell lymphoma (DLBCL) is a heterogeneous group of aggressive lymphomas. Despite improvements in diagnostic and therapeutic procedures, DLBCL still represents a significant cause of morbidity and mortality. Two molecularly defined types of DLBCL have been recently described: the germinal center B-cell (GCB) and the activated B-cell (ABC) subtype. GCB type DLBCL has been shown to have a better OS and PFS than ABC-type in multiple series of DLBCL patients treated with chemoimmunotherapy. The processes involved in lymphomagenesis in both subtypes are not fully understood, but deregulated expression of various proto-oncogenes is observed, often as the result of chromosomal translocations leading to constitutive gene expression. The specific role of the cMYC gene abnormalities in the pathogenesis of these lymphomas is still a matter of debate. To address this question, the status of the cMYC gene was analyzed by interphase fluorescence in situ hybridization (FISH) using a break apart probe, in TMA arranged tissue samples from 241 patients with de novo DLBCL treated with chemoimmunotherapy (R-CHOP and R-CHOP-like regimens). cMYC was rearranged in 15 cases out of 166 evaluable (9.26%). We did not find differences in the incidence of cMYC rearrangements between GCB and ABC-DLBCL subtypes (9/74 GCB and 6/82 ABC type) as classified according to extended immunohistochemical algorithms (Choi et al in Cancer Res. 2009). In our series, patients with DLBCL and cMYC rearrangements presented more frequently extranodal disease (p=0.007), higher IPI (p=0.037) and tended to have less than 60 years (p=0.053). cMYC gains were observed in 33 cases (21.85%). In the univariate analysis, cMYC abnormalities (gains and rearrangements) had no impact on the clinical outcome in the ABC subtype. However, whilst the cMYC gains did not identify a risk group in terms of OS or PFS the presence of cMYC rearrangements showed a significantly inferior progression-free survival (PFS) in the GCB-type group (p<0.006). However, the multivariate analysis showed that the only independent adverse predictors in these series of DLBCL cases were the presence of a high International Prognostic Index score (p=0.0028; RR=2.59 95% CI 1,34–4,99) and the ABC phenotype (p=0.0182; RR=2.16 95% CI 1,1–4,21). In summary, although cMYC rearrangements apparently do not provide additional prognostic information to the IPI score and/or GC-ABC classification in the whole DLBCL population, it identifies a subgroup of GCB-type DLBCL with very poor outcome. Disclosures: Montalban: Red Temática de Investigación Cooperativa en Cancer (RETICC): Research Funding; Asociación Española contra el Cancer: Research Funding. Mollejo:Red Temática de Investigación Cooperativa en Cancer (RETICC): Research Funding; Asociación Española contra el Cancer: Research Funding.

Clinicopathologic Analysis of Follicular Lymphoma (FL) Patients with Coexisting Diffuse Large B-Cell Lymphoma (DLBCL) Undergoing Rituximab-Containing Chemotherapy

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3693-3693 ◽  
Author(s):  
Suguru Fukuhara ◽  
Dai Maruyama ◽  
Ken-ichi Miyamoto ◽  
Sung-Won Kim ◽  
Takashi Watanabe ◽  
...  
Keyword(s):  
Research Funding ◽  
De Novo ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
B Cell Lymphoma ◽  
Initial Diagnosis ◽  
The Other ◽  
Low Grade ◽  
Other Hand ◽  
Significant Difference

Abstract Abstract 3693 Background: Histopathologically, some FLs have components of DLBCL at diagnosis. In the pre-rituximab era, there were two reports regarding the characteristics and prognosis of patients (pts) with these particular FLs1,2). Hans et al. reported that the overall survival (OS) of pts with FL grade 3 having a predominant (> 50%) DLBCL component is similar to that of pts with DLBCL1). Ghesquières et al. concluded that pts with DLBCL presenting with a low-grade component have a similar OS to those with de novo DLBCL2). However, the clinical implications and prognosis of FL pts with coexisting DLBCL at diagnosis undergoing rituximab-containing chemotherapy remain unclear. Patients and Methods: We retrospectively analyzed the clinicopathologic features of 59 FL pts with coexisting DLBCL (FL/DLBCL) initially undergoing rituximab-containing chemotherapy. Furthermore, the prognosis of FL/DLBCL pts was compared with that of 223 FL pts without DLBCL as well as 285 DLBCL pts without FL3). All pts received a rituximab-containing regimen as the initial chemotherapy. These pts with FL/DLBCL or FL were diagnosed and treated at our institution between 2001 and 2010, and DLBCL pts between 2003 and 2010. Results: The median age of the 59 pts with FL/DLBCL was 54 years (range: 22–83). Among them, 41 (69%) pts had FL grade 1–3a and the remaining 18 (31%) had FL grade 3b components. Thirty (51%) pts had a predominant (> 50%) DLBCL component. With regard to treatment, all pts except one received the R-CHOP regimen. Forty-nine (83%) pts achieved CR, but 22 of them (37%) relapsed. With a median follow-up of 5.4 years, the estimated 5-year OS and progression-free survival (PFS) for all 59 pts were 83 and 64%, respectively. The International Prognostic Index (IPI) and FLIPI were not correlated with OS and PFS, whereas the revised-IPI (R-IPI) and FLIPI2 were significantly correlated with PFS. A predominant DLBCL component was predictive of neither OS nor PFS. In the 41 pts with FL grade 1–3a with DLBCL, %CR, 5-year OS, and PFS rates were 80, 84, and 60%, respectively. On the other hand, in the 18 pts with FL grade 3b with DLBCL, they were 89, 82, and 72%, respectively. The %CR and PFS rates of the latter cohort showed superior tendencies to those of the former cohort, with no statistically significant difference. Among 22 relapses, 10 were confirmed histologically: 5 DLBCL, 4 FL, and 1 HL. In 16 relapsed pts with FL grade 1–3a at initial diagnosis, 4 relapsed as FL, one each as DLBCL and HL. Two pts who had relapsed as FL and HL subsequently developed DLBCL. On the other hand, 4 out of 5 relapsed pts with FL grade 3b at the initial diagnosis relapsed as DLBCL. Additionally, the prognosis of FL/DLBCL pts was compared with that of FL and DLBCL pts. The 5-year OS rate of FL/DLBCL pts (83%) was significantly worse than that of DLBCL pts (91%, p=0.039) as well as FL pts (97%, p=0.001) (Fig 1). The 5-year PFS rate of FL/DLBCL pts (64%) was not significantly different from that of DLBCL pts (72%, p=0.120). The PFS curves (Fig 2) suggested a slight increase in progression or mortality in FL/DLBCL pts during the first 2 years. However, the FL/DLBCL pts had a low incidence of events after 2 years. The PFS curve of FL/DLBCL pts was similar to that of DLBCL pts. By multivariate analysis of pts with FL/DLBCL and DLBCL, coexisting FL components was a significant predictor of inferior OS, but not PFS. Conclusions: The PFS curve of FL/DLBCL pts was similar to that of DLBCL pts, although pts with FL/DLBCL had poorer prognosis than DLBCL pts in the rituximab era. Furthermore, in our present analysis, predominant DLBCL component was predictive of neither OS nor PFS. Disclosures: Kobayashi: Nippon Shinyaku: Research Funding; Ariad: Research Funding; Ohtsuka: Research Funding; Celgene: Research Funding; Behringer : Research Funding. Tobinai:Grant Support: Zenyaku, Chugai/Roche, GSK, Biomedics Other.

Double Hit Lymphomas: Role of Immunohistochemistry in the Era of Florescent in-Situ Hybridization

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5405-5405
Author(s):  
Vineela Kasireddy
Keyword(s):  
In Situ Hybridization ◽  
Screening Test ◽  
Conflicts Of Interest ◽  
International Prognostic Index ◽  
Elevated Serum ◽  
Prognostic Index ◽  
B Cell Lymphoma ◽  
Serum Lactate Dehydrogenase ◽  
Double Hit

Background Diffuse large B-cell lymphoma (DLBCL) is a clinically and biologically heterogeneous disease. A subset of DLBCL patients with translocations involving MYC and BCL2 genes, called "Double-hit" lymphoma (DHL), are being identified to have poor prognosis after standard chemotherapy. Fluorescent in situ hybridization (FISH) technique which can identify these gene mutations is the gold standard for diagnosis of DHL. Immunohistochemistry (IHC) is a rapid and inexpensive test that can identify abnormal protein expression of these mutated genes. Two studies thus far have shown that MYC IHC can be used as a screening test to identify DHL cases with sensitivities of 74% and 100%, both multi-center studies conducted at university hospitals. We conducted this study at a single large community hospital to determine if these results can be generalized to our institution. Objective Our primary objective was to determine the association between protein and genetic expression of MYC and BCL2 in cases of de novo DLBCL by comparing the results of IHC and FISH. Our secondary objectives were to determine if MYC IHC could be used as a screening test to determine DHL status, to determine if the double hit biology is associated with any clinic-pathological features which might allow for risk stratification of patients and to determine the prevalence of DHL in our cohort of DLBCL patients. Methods Twenty-two patients who were diagnosed with primary DLBCL from February 2015 to February 2016 at Abington Hospital (AH) Jefferson Health were identified after applying exclusion and inclusion criteria. Clinico-pathological data was obtained by review of electronic medical records and biopsy specimens for IHC and FISH were obtained from the Department of Pathology at AH. The FISH test was performed by Quest Diagnostics™ and IHC was performed by the Chair of the Department of Pathology at our institution. Statistical analysis was performed using IBM SPSS Statistics for Windows, version 20.0 (Armonk, NY: IBM Corp). Results Double hit gene rearrangements by FISH were detected in 3/22 (13.6%) patients. MYC IHC was positive in 8/22 (36.3%) cases, and 3 of these 8 cases (37.5%) were FISH positive. Sensitivity, specificity and concordance of MYC IHC as a screening tool were 100%,73.6% and 72.27%, respectively. BCL2 staining was positive in 19/22 (86.3%) cases, and only 3 of the 19 cases (15.7%) were FISH positive. 5/22 (22.7%) cases were positive for both MYC and BCL2 by IHC (double protein expresser status) and 3 of these 5 (60%) cases were positive for DHL status by FISH. DHL biology did not show an association with any clinico-pathological parameters including age, elevated serum Lactate dehydrogenase, R-IPI (Revised International Prognostic Index) score, ECOG performance status, extra-nodal disease and cell-of-origin sub-type. Conclusion The association between MYC IHC and FISH in our study was not statistically significant but showed a trend towards association. Given that sensitivity of MYC in our study was 100%, we propose that it can be used as an effective screening test if similar results can be validated in larger studies. Our study supports the practice of routinely testing for MYC and BCL2 status in all cases of DLBCL, irrespective of clinical features of the disease, to identify the high-risk DHL subset of patients, who can be candidates for more intense newer chemotherapy regimens and for prognostic purposes Disclosures No relevant conflicts of interest to declare.

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