scholarly journals Cell-of-Origin (COO) Classification, BCL2 and MYC Expression Associated-Outcome in Younger Patients Treated By RCHOP Front-Line Therapy Versus Intensive Regimen Followed By Autologous Transplant for De Novo Advanced Diffuse Large B Cell Lymphoma (DLBCL) : Results of the French Prospective Multicenter Randomized Trial Goelams -075

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3920-3920
Author(s):  
Gaëlle Labouré ◽  
Marie-Cécile Parrens ◽  
Anjarasoa Tsaranazy ◽  
Magali Bordier ◽  
Steven Le Gouill ◽  
...  
Keyword(s):  
Protein Expression ◽  
B Cell ◽  
Germinal Center ◽  
De Novo ◽  
Free Survival ◽  
Younger Patients ◽  
Interim Pet ◽  
Expression Clone ◽  
Pet Ct ◽  
Intensive Regimen

Abstract Background: The prognostic value of COO classification by immunohistochemistry (IHC) for de novo untreated advanced DLBCL remains controversial after Rituximab-based frontline therapy. Other biomarkers such as BCL2 or MYC protein expression have been proposed to predict survival. IHC characteristics were investigated in a large multicenter randomized study. Methods: Three hundred twenty-three patients (pts) younger than 60 years with de novo untreated advanced DLBCL were randomized in the french prospective multicenter trial GOELAMS-075 to receive either 8 courses of RCHOP14 (n=161) or 2 courses of RCEEP (Rituximab, Cyclophosphamide, Eldisine, Epirubicine, Prednisone) and 1 course of Rituximab-Methotrexate-Cytarabine (RMC) followed by intensive BEAM conditionning with autologous transplant (ASCT) (n=162) upon negative interim PET-CT (visual analysis). In case of positivity, salvage regimen followed by ASCT was applied. Three years Event-free-survival (3y-EFS) was the primary endpoint. Event was defined by interim PET-CT positivity, progression or relapse, or death from any cause. Central pathology review confirmed de novo DLBCL diagnosis for 300 pts (93%). COO determination using Hans algorithm, BCL2 protein expression (clone 124, Dako) and MYC protein expression (clone Y69, Abcam) were recorded. Cut-off values were 70% for BCL2, and 40% for MYC. Results: COO analysis could be performed for 125/161 pts in RCHOP arm and 134/162 pts in intensive regimen arm including 36 and 34 Primary-Mediastinal-B-Cell subtype (PMBL) respectively. Repartition of non-PMBL was: 33/89 (37%) Germinal-Center subtype (GC), 56/89 (63%) Non-Germinal-Center subtype (NGC) in R-CHOP arm; 48/100 (48%) GC, 52/100 (52%) NGC in intensive regimen arm. Of 70 PMBL there were 50 NGC, 4 GC and 16 NE equally distributed in both arms. Clinical characteristics were similar in both GC and NGC subtypes, whereas PMBL presented with more frequent bulky disease and predominantly female gender. BCL2 ≥70% and MYC ≥40% were found in 147/285 (55%) and 85/185 (46%) of available samples, without difference between two arms. No correlation was found between BCL2 or MYC protein expression and GC or NGC subtype, however there were seen in a significantly lower proportion of PMBL (34% and 17% respectively). Coexpression of BCL2≥70% and MYC≥40% (MYC+/BCL2+) occurred in 52/184 (28%) cases, without difference between two arms or COO subtypes. By contrast, PMBL subtype displayed an extremely low rate of MYC+/BCL2+ cases (1/49, 2%). 3y-EFS rates were 52% ± 6% for GC, 58% ± 5% for NGC and 49% ± 6% for PMBL (p= 0,42) with no significant difference according to treatment arm. Of note, in PMBL, the majority of events was positive interim PET-CT. Worse EFS was seen in BCL2≥70% cases (3y-EFS: 47% ± 4% vs 60% ± 4%, p= 0,05) but this difference was erased in RCHOP arm (3y-EFS: 52% ± 6% vs 58% ± 6%). 3y-Progression Free Survival (PFS) rates were 73% ± 6% for GC, 76% ± 6% for NGC and 94% ± 4% for PMBL (p=0,03) with no difference between the two arms (Fig 1). There was no PFS difference in BCL2≥70% vs <70% cases (3y-PFS: 71% ± 4% vs 82% ± 4%, p= 0,11). EFS and PFS rates were similar between MYC≥40% and <40% cases (3y-EFS: 56% vs 59%; 3y-PFS: 78% vs 84%) without further advantage of one arm compared to another. Same results were obtained for MYC+/BCL2+ vs non MYC+/BCL2+ cases (3y-EFS: 53% vs 58%; 3y-PFS: 78% vs 81%). After a median follow-up of 71 months, PMBL was associated with significant better overall survival (OS) whereas no difference was observed between GC and NGC subtypes (5y-OS : 96% vs 75% and 78% respectively, p= 0,002) (Fig 2). OS rates were similar for BCL2 positive and BCL2 negative cases after exclusion of PMBL (5y-OS: 75% vs 78%, p=0,65). There was no significant impact of IHC MYC positivity (5y-OS : 80% vs 86% for MYC negative cases, p=0,29) or MYC+/BCL2+ coexpression (5y-OS : 80% vs 85% for negative cases, p=0,50) on outcome. There was no significant impact of treatment on OS of MYC and/or BCL2 positive cases. Conclusion: In younger patients, outcome of IHC defined GC and NGC subtype of non-PMBL DLBCL was not different following R-CHOP14 or intensive treatment including ASCT. Similarly, regardless of treatment arm, BCL2 or MYC or both overexpression did not impair significantly the prognosis. IHC defined COO or BCL2/MYC overexpression could not identify DLBCL in need of intensive therapy with ASCT. Finally the good prognosis of PMBL subtype with excellent PFS and OS was confirmed. Disclosures Cartron: Sanofi: Honoraria; Celgene: Honoraria; Gilead: Honoraria; Roche: Consultancy, Honoraria; GSK: Honoraria.

scholarly journals Interim PET/CT based on visual and semiquantitative analysis predicts survival in patients with diffuse large B‐cell lymphoma

2019 ◽  
Vol 8 (11) ◽  
pp. 5012-5022 ◽  
Author(s):  
Xiaoqian Li ◽  
Xun Sun ◽  
Juan Li ◽  
Zijian Liu ◽  
Mi Mi ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Semiquantitative Analysis ◽  
Interim Pet ◽  
Large B Cell Lymphoma ◽  
Pet Ct ◽  
Large B Cell

scholarly journals Hypoxia-Inducible Factor-1 α Expression Predicts Superior Survival in Patients With Diffuse Large B-Cell Lymphoma Treated With R-CHOP

2010 ◽  
Vol 28 (6) ◽  
pp. 1017-1024 ◽  
Author(s):  
Andrew M. Evens ◽  
Laurie H. Sehn ◽  
Pedro Farinha ◽  
Beverly P. Nelson ◽  
Adekunle Raji ◽  
...  
Keyword(s):  
Protein Expression ◽  
B Cell ◽  
Germinal Center ◽  
Cell Lymphoma ◽  
International Prognostic Index ◽  
Hypoxia Inducible Factor ◽  
B Cell Lymphoma ◽  
Large B Cell Lymphoma ◽  
Wide Range ◽  
Large B Cell

Purpose Hypoxia-inducible factor (HIF) controls the expression of genes in response to hypoxia, as well as a wide range of other cellular processes. We previously showed constitutive stabilization of HIF-1α in the majority of patients with diffuse large B-cell lymphoma (DLBCL). To our knowledge, the prognostic significance of HIF in lymphoma has never been investigated. Patients and Methods We studied the immunohistochemical protein expression of HIF-1α on tissue microarrays from 153 patients with DLBCL treated in sequential cohorts with cyclophosphamide, doxorubicin, oncovin, and prednisone (CHOP) or rituximab-CHOP (R-CHOP) from 1999 to 2002. Results were correlated with patient outcome. Results Median follow-up for all patients was 80 months. Among all patients, HIF-1α was expressed in 62% of germinal center and 59% of non–germinal center patients. With HIF-1α analyzed as a dependent variable, there were no survival differences in CHOP-treated patients. In the R-CHOP group, however, HIF-1α protein expression correlated with significantly improved progression-free survival (PFS) and overall survival (OS). Five-year PFS for HIF-1α–positive patients was 71% v 43% for HIF-1α–negative patients (P = .0187), whereas 5-year OS was 75% and 54%, respectively (P = .025). In multivariate analysis with International Prognostic Index criteria, HIF-1α remained a significant predictor for PFS (P = .026) and OS (P = .043). Compared with other biomarkers, HIF-1α correlated only with BCL6 (P = .004). In terms of gene expression, we found several common gene associations of HIF-1α and the stromal-1 signature with genes predominantly involved in regulation of the extracellular matrix (eg, BGN, COL1A2, COL5A1, and PLOD2). Conclusion The expression of HIF-1α protein is an important independent favorable prognostic factor for survival in patients with DLBCL treated with R-CHOP.

The Peripheral Cannabinoid Receptor CB2 and CD40 Are Novel Biological Markers That Predict Outcome in Diffuse Large B-Cell Lymphoma of Elderly Patients.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3256-3256
Author(s):  
Nazik Rayman ◽  
King H. Lam ◽  
Dries A.H Mulder ◽  
Ronnie B. van der Holt ◽  
Jeanette Doorduijn ◽  
...  
Keyword(s):  
Clinical Outcome ◽  
Elderly Patients ◽  
B Cell ◽  
Germinal Center ◽  
Outcome Prediction ◽  
Cannabinoid Receptor ◽  
Prognostic Significance ◽  
B Cell Lymphoma ◽  
Free Survival ◽  
Large B Cell

Abstract Since diffuse large B-cell lymphomas (DLBCL) are biologically and clinically heterogeneous, various attempts have been made to distinguish subtypes of DLBCL. Using gene expression profiling two main subtypes have previously been identified, i.e germinal center B-cell like (GCB) with a favorable prognosis and non-GCB-cell like DLBCL with an unfavorable outcome (Alizadeh et al. Nature403, 503–511, 2000). Applying immunohistochemical analysis, using antibodies directed against CD10, BCL-6 and MUM1, the same investigators were capable of identifying the same subclasses of favorable (GCB) and non-favorable (Non-GCB) DLBCL phenotypes (Hans et al. Blood103, 275–282, 2004). To investigate the applicability of these three markers in de novo DLBCL patients at an age of 65 years or older with advanced stage disease, a cohort of 138 cases was studied. All patients were included in a multicenter clinical trial setting and received uniform treatment. Using the markers CD10, BCL-6 and MUM1, we assigned 40 cases (29%) into the GCB (CD10+ and/or BCL6+, MUM1−) and 98 cases (71%) into the non-GCB-like (CD10−, BCL6+, Mum1+ or CD10−, BCL6−, MUM1+) DLBCL group. In contrast to previous reports, no clinical significance was observed between the two subtypes (overall survival (OS), event-free survival (EFS), progression-free survival (PFS) and disease-free survival (DFS) P-values >0.2), indicating that the prognostic significance of this classification was not evident in this cohort of elderly patients. We previously identified a novel combination of markers that could discriminate between GCB and non-GCB in normal lymphoid tissue, i.e. CB2 and the activation protein CD40. B-cells present in the germinal center (GC) of healthy individuals appeared highly positive for both CD40 and CB2, a previously identified proto-oncogene that encodes for the peripheral cannabinoid receptor. Non-GCB-lymphocytes were mainly CB2 and CD40 negative or weakly positive. We used these two markers for immunohistochemical analyses in the same cohort of novo DLBCL. Single expression of CB2 (PFS (P<0.04) and DFS (P=0.02)) and CD40 (P<0.04) was associated with a favorable clinical outcome. A combined immunophenotypic profile of N-CB2 and CD40 resulted in improved outcome prediction (PFS, P=0.02). Moreover, our data show that CB2 and CD40 are novel markers that recognize DLBCL with a particular GC-like phenotype and have impact on the clinical outcome in a cohort of elderly DLBCL patients. We suggest that CB2 and CD40 may serve as novel markers in DLBCL outcome prediction.

RhoF GTPase Transcription Is Upregulated in Germinal Center B-Cells, Shows Altered Expression in Malignant B-Cells, and Interacts with the ATM Pathway.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 285-285
Author(s):  
Launce G. Gouw ◽  
N. Scott Reading ◽  
David K. Crockett ◽  
Philippe Szankasi ◽  
Megan S. Lim ◽  
...  
Keyword(s):  
T Cells ◽  
B Cells ◽  
B Cell ◽  
Germinal Center ◽  
De Novo ◽  
Cell Lymphoma ◽  
Lymphocyte Subpopulations ◽  
Interacting Proteins ◽  
Tissue Samples

Abstract Follicular lymphoma (FL) is the most common low-grade B-cell non Hodgkin lymphoma in the Western hemisphere. A significant proportion of FL undergo histologic transformation to diffuse large B-cell lymphoma (DLBCL). Using cDNA microarray analysis, we identified an expressed sequence tag GI#10952525 consistently differentially expressed in transformed follicular lymphomas (tFL). This was characterized as RhoF, a novel member of the Rho family. Rho GTPases play central roles in cytoskeletal dynamics, cell-cell interactions, and intracellular signaling pathways involved in migration, proliferation and survival. Dysregulation of Rho proteins are key events implicated in tumorigenesis. To define the role of RhoF in lymphocyte physiology and lymphoma transformation, we assessed its expression across phenotypically defined lymphocyte subpopulations, using quantitative real-time PCR. We determined relative RhoF levels in immunomagnetic bead purified normal lymphoid subpopulations [naïve B-cells, memory B-cells, germinal center B-cells and T-cells], reactive lymphoid tissues (n=5), cell lines [derived from t(14;18) tFL (n =3), de novo DLBCL (n=7), and T-cell malignancy (n=3)] and tissue from primary human lymphoid neoplasms [FL (n=5), de novo DLBCL (n=5), tFL (n=5), CLL/SLL (n=4), anaplastic large cell lymphoma (n=8), mantle cell lymphoma (n=5), and T-cell acute lymphoblastic leukemia (n=5)]. RhoF was expressed at significantly higher levels in B-cells relative to T-cells. We saw this pattern in purified lymphocyte subpopulations, in cell lines, and in primary lymphoma tissue samples. Notably, we detected elevated levels of RhoF transcript in B-cells of germinal center (GC) origin, both in the reactive and neoplastic samples of GC-derived B-cells. The highest transcriptional levels of RhoF were in malignant B-cells of GC origin; both in heterogeneous primary tissue samples and in homogeneous tissue culture preparations. To investigate its functional role, we cloned RhoF into a vector coding for a C-terminal polyhistidine- and V5 epitope-tag. We expressed the constructs in HEK 293T cells, and purified the RhoF-containing complexes using a tandem affinity purification approach. We ran cell lysates through a nickel column; non-interacting proteins were washed off under native conditions and the bound RhoF complexes eluted with imidazole. Eluate was immunoprecipitated with sepharose-bound anti-V5 antibody. Immunoprecipitated complexes were denatured and resolved by 1D-PAGE. Unique bands representing RhoF interacting proteins were isolated and enzymatically cleaved with trypsin. Resultant peptides underwent liquid chromatography and tandem mass spectrometry. Data were searched against the NCBI nr.FASTA nonredundant protein database using the SEQUEST algorithm and false positive rates determined with INTERACT and ProteinProphet. Among several putative RhoF interactors, we identified ATM as an important RhoF binding partner. In conclusion, our demonstration of the differential expression of RhoF in GC-derived cells and its upregulation in tFL provide evidence for a connection between the role of this novel protein in B-cell development and malignancy. In addition, evidence of an association between RhoF and ATM may provide a link between DNA repair, cell cycle control and morphological dynamics.

MYC Translocations and Expression Are Clinically Important in R-CHOP Treated Patients with De Novo DLBCL.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1100-1100
Author(s):  
Nathalie A. Johnson ◽  
Susanna Ben-Neriah ◽  
Kerry J. Savage ◽  
Tang Lee ◽  
Douglas E. Horsman ◽  
...  
Keyword(s):  
Protein Expression ◽  
B Cell ◽  
Research Funding ◽  
De Novo ◽  
Cell Lymphoma ◽  
Molecular Subtype ◽  
B Cell Lymphoma ◽  
Prognostic Impact ◽  
Statistical Software ◽  
Bcl2 Protein

Abstract Abstract 1100 Poster Board I-122 Background MYC, an oncogene associated with cellular proliferation, is deregulated as a result of chromosomal translocation in Burkitt lymphoma (BL), and in 8-12% of diffuse large B cell lymphomas (DLBCL). In 2006, 2 studies defined the molecular features of BL and DLBCL by gene expression profiling (GEP) (Dave, NEJM 2006; Hummel, NEJM 2006) and identified a subset of cases that resembled DLBCL by morphology, but by GEP, expressed MYC and MYC target genes similar to classical BL, i.e. molecular BL (mBL) signature. The clinical outcome of these cases is poorly defined. More recently, MYC expression and MYC translocations (MYC tr+) have been associated with an inferior overall survival (OS) in de novo DLBCL patients (pts) treated with R-CHOP (Rimsza, Blood 2008; Savage, Blood 2009) but the prognostic impact of BCL2 protein expression and concurrent BCL2 translocations (BCL2 tr+) is poorly understood. We investigated the prognostic impact of the presence of a mBL signature by GEP, high MYC mRNA expression, and the presence of a MYC tr+ with or without a concurrent BCL2 tr+ in DLBCL pts treated uniformly with R-CHOP. Methods 315 samples were reviewed by a panel of expert hematopathologists and classified according to the WHO 2008 criteria. Pts with high grade B cell lymphoma otherwise unclassifiable, BL, primary mediastinal B cell lymphoma (PMBCL), T-cell-rich B cell lymphoma and pts that were not treated with R-CHOP were excluded from this analysis. The remaining 259 DLBCL samples were subjected to GEP as previously described (Lenz, NEJM 2008). Tissue microarrays (TMA) were constructed in cases with available paraffin material. 184 had successful GEP arrays, 186 were included on a TMA and 151 cases were assessed on both platforms. Presence of a mBL signature was determined according to the method described by Dave (NEJM 2006). MYC expression was determined using log normalized expression values from Affymetrix U133 Plus 2.0 probe set id 202431_s_at and dichotomized into high versus low expression using a cut off threshold determined by the statistical software X-Tile (http://www.tissuearray.org/rimmlab/). The presence of MYC tr+ or BCL2 tr+ was determined by fluorescence in situ hybridization (FISH) using MYC and BCL2 breakapart probes (Abbott) on TMAs. BCL2 protein expression was determined by immunohistochemistry (IHC) using clone 124 (Dako). Correlation between variables and association with OS was performed by Pearson Chi-Square, Kaplan-Meier and Cox regression analysis using SPSS statistical software. Results A mBL signature was found in 4/184 samples (2%). One case was MYC tr+, one was MYC tr-, and the MYC translocation status was unknown in the remaining 2 cases. All 4 pts with a mBL had a complete response to R-CHOP lasting >2 years after diagnosis. MYC tr+, BCL2 tr+ or concurrent MYC tr+/ BCL2 tr+ were present in 12%, 20% and 4% of 186 DLBCL cases, respectively. BCL2 tr+ were predominately found in the germinal center B cell (GCB) molecular subtype (36%) compared to the activated B cell (ABC) or unclassifiable (U) subtypes (4% and 19%, p=0.0001) but were not associated with an inferior OS. In contrast, MYC tr+ were not associated with a specific molecular subtype (GCB 15%, ABC 8%, U 19%, p=0.2) but were associated with an inferior OS (p=0.0078). When dichotomizing patients with MYC tr+ according to the BCL2 status, pts with concurrent MYC tr+/ BCL2 tr+ (4%) and pts with MYC tr+ and BCL2 protein-positive biopsies (7%) had a markedly inferior OS compared to pts with MYC tr+ and BCL2 protein-negative biopsies or pts with no MYC tr (median OS 7 months vs. not reached, both p < 0.00001). The presence of MYC tr+ correlated with high MYC expression in 6/16 (38%) MYC tr+ cases whereas high MYC expression was present in 5/111 (5%) MYC tr- cases (p=0.0001). High MYC expression alone was also associated with an inferior OS (p<0.00001). In multivariate analysis, high MYC mRNA expression, concurrent MYC tr+/ BCL2 tr+, and the IPI were independent predictors of OS (p=0.04, p=0.05, p=0.007, respectively). Conclusion MYC expression, as prognostic marker in DLBCL, should be investigated in routine clinical practice. Cytogenetic analysis to determine MYC and BCL2 translocation status by FISH and/or karyotype of de novo DLBCL samples, and BCL2 protein expression by IHC are clinically indicated to identify a group of high-risk pts that may benefit from up-front intensified therapy. Disclosures Connors: Roche Canada: Research Funding. Gascoyne:Roche Canada: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.

Respective PROGNOSTIC Value of the International Harmonization PROJECT (IHP), Gallamini and London Criteria for Interim FDG PET-CT Performed AFTER 4 Courses of ABVD IN HODGKIN'S LYMPHOMA

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3889-3889
Author(s):  
Thomas Gastinne ◽  
Pierre-yves Le roux ◽  
Caroline bodet-Milin ◽  
Beatrice Mahe ◽  
Viviane Dubruille ◽  
...  
Keyword(s):  
Treatment Outcome ◽  
Fdg Pet ◽  
Prognostic Value ◽  
Point Scale ◽  
Bulky Disease ◽  
Free Survival ◽  
Scale Method ◽  
Interim Pet ◽  
Pet Ct ◽  
Fdg Pet Ct

Abstract Abstract 3889 During the last decade, the role of Interim 2-[18F]fluoro-2-deoxy-D-glucose emission positron tomography (FDG PET-CT) has increased for Hodgkin's lymphoma (HL) evaluation and it is strongly recommended for both staging and post treatment evaluation. Early treatment response assessment is a challenge for risk-adapted therapy and interim PET-CT has emerged as a powerful prognostic tool to predict treatment outcome, a negative exam predicting a favorable disease-free survival while a positive study a worse prognosis. However, FDG PET response criteria are a matter of ongoing debate. So, the aim of our study was to confirm the prognostic value of interim FDG PET-CT performed after 4 courses of chemotherapy (ABVD) but also to compare the respective performances of the different published criteria: International Harmonization Project (IHP), Gallamini criteria, 5-point scale (Gallamini A et al. Haematologica 2006; 91: 475–481; Juweid ME et al. J Clin Oncol 25:571-578, 2007; Barrington SF et al. Eur J Nucl Med Mol Imaging 2009;36(Suppl. 2):S252; Meignan M et al. Leukemia & Lymphoma, August 2009; 50(8): 1257–1260; Gallamini A, et al. Leuk Lymphoma. 2009 Nov;50(11):1761-4.) Design and methods: From 2002 to 2006, newly diagnosed patients with HL who underwent interim PET-CT after 4 courses of ABVD were eligible for the purpose of the present study. Treatment strategy after 4 courses of ABVD was then adapted according to prognostic factors at diagnosis and interim PET-CT result. PET images were interpreted prospectively visually by at least two nuclear medicine physicians with expertise in lymphoma imaging with the criteria used before 2005: negative result was defined as no residual uptake above local background. All other findings were considered as positive. Using these evaluation criteria, interim PET positive patients who were not in CR on CT underwent autologous stem cell transplantation. Interim PET positive patients who reached CR on CT and interim PET negative patients received additional courses of ABVD (patients with advanced HD or bulky disease at diagnosis) or radiotherapy alone (stage I or II without bulky disease). Retrospectively and for the purpose of the present study, interim PET results were interpreted using the more recent criteria (Gallamini criteria, IHP criteria and 5-point scale method) Results: 90 patients were included. Median age at diagnosis was 34.4 (16-71). 49% of the patients presented with B-symptoms and 50% had stage III-IV disease. According to initial criteria, 31 patients had a positive interim PET result. Among these patients, 28 underwent ASCT. Fifty-nine patients had a negative interim PET-CT. Six of 31 patients with positive interim PET-CT and 7 of 59 patients with negative interim result presented treatment failure. Thus, the negative predictive value (NPV) and positive predictive value (PPV) for predicting 2 years progression free survival (PFS) was 95% and 16%, respectively. Retrospectively, interim PET-CT was analyzed according to different recent published criteria using mediastinum and liver background as threshold for positivity. With these criteria, NPV remained very high (from 95% to 96%). However, the PPV increased from 25% to 55% according to the threshold used. Taken together, the statistical analysis revealed that Interim PET-CT was significantly correlated with PFS only for two methods: the Gallamini criteria and the 5-point scale method. Conclusion: The first part of our study using the criteria used before 2005 shows the high NPV of interim PET-CT for predicting treatment outcome in HL. However, better prognostic values are obtained by using higher threshold for positivity such as liver background even after 4 cycles of ABVD. Indeed, our analysis underscores the better results reached by the Gallamini criteria and 5-point scale methods. The better method to predict PFS was obtained by the 5-point scale (scores 1, 2, 3 and 4 were classified as negative while only score 5 was classified as positive) showing a PPV and NPV of 55% and 96%, respectively. Disclosures: No relevant conflicts of interest to declare.

Dose-Adjusted EPOCH Plus Rituximab in Untreated Patients with Poor Prognosis Large B-Cell, with Analysis of Germinal Center and Activated B-Cell Biomarkers. A Phase IV Study Conducted by the Spanish PETHEMA Group

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 593-593
Author(s):  
Noelia Purroy ◽  
Juan Bergua ◽  
Laura Gallur ◽  
Julio Prieto ◽  
Juan-Manuel Sancho ◽  
...  
Keyword(s):  
B Cell ◽  
Germinal Center ◽  
Poor Prognosis ◽  
Cellular Differentiation ◽  
Tumor Proliferation ◽  
Bulky Disease ◽  
Free Survival ◽  
Grade 3 ◽  
Large B Cell ◽  
Patients With Poor Prognosis

Abstract Abstract 593 Objectives . This prospective multi-institutional phase IV study was designed within the Spanish PETHEMA Group to assess the efficacy and safety of dose adjusted EPOCH plus Rituximab (DA-EPOCH-R) infusional therapy (as previously reported*) in untreated patients with poor prognosis large B-cell lymphomas. All cycles were supported with G-CSF. Additional analysis of the clinical outcome and the influence of biomarkers associated with tumor proliferation (Ki67) and cellular differentiation was performed. Patients and Methods. Eighty-one untreated patients diagnosed of DLBCL (68), PMLBL (6) and FL grade 3 (7), with an age-adjusted IPI higher than 1 (or equal to 1 plus bulky disease), were enrolled and evaluable. Radiation consolidation was permitted to patients with bulky disease at diagnosis. Histology was centrally reviewed. Fifty tumor tissue samples (61.7% of patients) were analyzed by immunohistochemistry for biomarkers of proliferation (Ki67) and cellular differentiation (CD10, Bcl6, GCET1, MUM1 and FOXP1). Results. The median age was 52 (range, 21–77) years, with 52% older than 60. 92.5% had intermediate-high or high risk score according to aaIPI criteria. The median number of cycles administered was 6 (range, 1–8). Treatment was discontinued in 7 patients: disease progression (2) and death (5: 2 unrelated and 3 for disease progression). Radiotherapy (30 Gy maximum) was given to 37 patients (45.7%). A median of 3 escalation level (range, 0–6) was achieved. Toxicity was assessed during 470 cycles administered. Grade 3–4 anaemia was reported in 240 cycles (51%) and in 84% of patients; and grade 3–4 thrombocytopenia in 176 cycles (37%) and in 71.6% of patients. There were 54 episodes of neutropenic fever (11.5% of cycles) in 37 patients (45.7%). On an intention-to-treat basis, 64 (79.1%) patients achieved a complete response (CR or uCR) and 8 (9.9%) a partial response (PR) with an overall response rate (ORR) of 89%. 19.8% (16) of patients who achieved CR (or uCR) relapsed between 6 to 12 months after the beginning of EPOCH-R therapy. With a median follow-up of 55 months (range, 23–100 months), overall survival (OS), progression-free survival (PFS), and event-free survival (EFS) were 63.1% (95% CI 50.1%–76.1%), 62.01% (95% CI 50.8%–73.2%), and 59.7% (95% CI 48.5%–70.9%) respectively; and disease-free survival for patients who achieved CR or uCR was 72.1% (95% CI 60.95%–83.3%). Neither aaIPI risk factors nor IPI were associated with poorer response, PFS (p=0.418 and p=0.099 respectively) or OS (p=0.458 and p=0.141 respectively). There was only a slight association between ß2 microglobulin levels (>3.5mg/L) and OS (p=0.015). High tumor proliferation (Ki67>75%) was not associated with neither poorer OS (p= 0.461) nor poorer PFS (p=0.769). After having ruled out other non-DLBCL histologies, 39 patients were analyzed for germinal center (GC) or activated B-cell (ABC) biomarkers using Hans and Choi algorithms. No differences were found neither in OS (p=0.972 and p=0.673, respectively) nor PFS (p=0.215 and p=0.433, respectively). Conclusion. DA-EPOCH-R shows a promising outcome in Intermediate-High and High risk aaIPI subgroups of large B-cell lymphoma patients with an acceptable toxicity profile. Further studies (some of them are now in process) are needed to verify its actual role in the ABC subtype of DLBCL. DA-EPOCH-R outcome was no affected by high tumor proliferation. * Wilson WH et al. JCO 2008: 26:2717-24. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Bone marrow biopsy superiority over PET/CT in predicting progression-free survival in a homogeneously-treated cohort of diffuse large B-cell lymphoma

2017 ◽  
Vol 6 (11) ◽  
pp. 2507-2514 ◽  
Author(s):  
Tzu-Hua Chen-Liang ◽  
Taida Martín-Santos ◽  
Andrés Jerez ◽  
Guillermo Rodríguez-García ◽  
Leonor Senent ◽  
...  
Keyword(s):  
Bone Marrow ◽  
B Cell ◽  
Bone Marrow Biopsy ◽  
Cell Lymphoma ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Free Survival ◽  
Large B Cell Lymphoma ◽  
Pet Ct ◽  
Large B Cell
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