scholarly journals Automated Baseline Fluorodeoxyglucose-Positron Emission Tomography Imaging and High BCL2 Expression Provide Orthogonal Prognostic Value in Predicting High-Risk De Novo Diffuse Large B-Cell Lymphoma Patients

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 8-9
Author(s):  
Skander Jemaa ◽  
Samuel Tracy ◽  
Alessia Bottos ◽  
Alex de Crespigny ◽  
Thomas Bengtsson ◽  
...  
Keyword(s):  
High Risk ◽  
Prognostic Value ◽  
De Novo ◽  
B Cell Lymphoma ◽  
Prognostic Models ◽  
Imaging Features ◽  
Publicly Traded ◽  
Private Company ◽  
Positron Emission ◽  
Bcl2 Expression

Introduction: Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma, accounting for 30─40% of cases (Li, et al. Pathology 2017). Although rituximab (R) plus CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) cures approximately 50─60% of patients, clinical outcomes remain poor for those with relapsed or refractory (R/R) disease (Liu and Barta. Am J Hematol 2019). Current prognostic models such as the International Prognostic Index (IPI) have suboptimal sensitivity and specificity to identify these patients at diagnosis. Models that combine biological, clinical and imaging markers may improve prognostication in DLBCL. Methods: We evaluated fluorodeoxyglucose-positron emission tomography (FDG-PET) imaging features alongside clinical and biomarker data in modeling disease prognosis with a primary endpoint of investigator-assessed progression-free survival (PFS) for de novo DLBCL patients from the randomized phase III GOYA study (NCT01287741) comparing R-CHOP versus obinutuzumab (G)-CHOP. Imaging features were derived using a computer-vision modeling algorithm (Jemaa, et al. J Digit Imaging 2020), and included total and by-organ number and volume of lesions. The evaluable population (n=1286) was split into pre-defined training (n=964; PFS events=307) and holdout populations (n=322; PFS events=96). Baseline clinical and imaging features were dichotomized by median or a clinically relevant threshold, and screened with univariate Cox proportional hazard (PH) models (Figure A). Screened variables were further selected to construct a multivariate Cox PH model for risk prognosis utilizing a regularized LASSO Cox regression (Simon, et al. J Statistical Software 2011). Model performance was evaluated by area under the receiver operating characteristic curve (AUC) and C-index on the holdout population. Additional biomarker features were evaluated, including, BCL2 protein expression as determined by Ventana investigational-use only immunohistochemistry (IHC) assay, gene expression quantified by TruSeq® (Illumina) RNAseq, next generation sequencing-based genomic profiling using the FoundationOne HemeTM platform (F1H, Foundation Medicine Inc. [FMI]) and cell of origin (COO) by the Nanostring assay. Results: Total metabolic tumor volume (TMTV), total number of lesions, longest diameter of any lesion, number of kidney lesions, and number of liver lesions were selected as prognostic imaging factors for PFS in de novo DLBCL patients. Strong correlation was observed between corresponding volume and lesion number features, as expected, though collinearity appeared to otherwise be minimal (Figure B). Performance of the resulting model composed of these imaging variables alongside standard clinical features and treatment (AUC=0.66; C-Index=0.64) improved upon a model composed of IPI categories (AUC=0.60; C-Index=0.60). High risk, defined by log-hazard >0 was associated with reduced PFS (Figure C). High BCL2 expression by IHC (score >1) was prognostic for PFS independent of clinical and imaging features (HR, 2.02; CI: 1.36─2.98). High BCL2 was predictive of PFS in patients treated with G-CHOP over R-CHOP in de novo DLBCL patients (HR, 0.55; CI: 0.32─0.97) (Figure D). This trend held when adjusting for COO separate to imaging features. Mutational analysis using the FMI panel also indicated the additional prognostic value of BCL2 and TP53 single-nucleotide variants through selection by LASSO. Conclusions: Automated baseline imaging features and high BCL2 expression demonstrated prognostic value orthogonal to standard clinical features in predicting high-risk de novo DLBCL despite limitations imposed by sample size and multicollinearity among features. These findings support the integration of imaging, genomic and clinical factors in prognostic models to improve the identification of high-risk de novo DLBCL patients. Disclosures Jemaa: F. Hoffmann-La Roche: Current equity holder in publicly-traded company; Genentech, Inc.: Current Employment. Tracy:Genentech, Inc.: Current Employment; F. Hoffmann-La Roche: Current Employment, Current equity holder in publicly-traded company. Bottos:F. Hoffmann-La Roche: Current Employment, Current equity holder in private company. de Crespigny:Genentech, Inc.: Current Employment; F Hoffmann-La Roche: Current equity holder in publicly-traded company. Bengtsson:Genentech, Inc.: Current Employment; F Hoffmann-La Roche: Current equity holder in publicly-traded company. Nielsen:F. Hoffmann-La Roche: Current Employment, Current equity holder in publicly-traded company. Paulson:Genentech, Inc.: Current Employment; F. Hoffmann-Roche: Current equity holder in private company, Current equity holder in publicly-traded company.

scholarly journals The Prognostic Value of MYC, BCL2 and BCL6 Translocations and Protein Expressions in Young Patients with High-Risk Diffuse Large B-Cell Lymphoma Treated with R-CHOEP

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1694-1694
Author(s):  
Mette Ølgod Pedersen ◽  
Anne Ortved Gang ◽  
Estrid Hoegdall ◽  
Helle Knudsen ◽  
Anne F. Lauritzen ◽  
...  
Keyword(s):  
High Risk ◽  
Protein Expression ◽  
Prognostic Value ◽  
Prognostic Markers ◽  
Cell Lymphoma ◽  
Young Patients ◽  
B Cell Lymphoma ◽  
Large B Cell Lymphoma ◽  
Bcl2 Protein ◽  
Bcl2 Expression

Abstract Background: In young patients with high-risk diffuse large B-cell lymphoma (DLBCL) treatment with R-CHOEP (R-CHOP + etoposide) has been associated with improved outcome. Whether established prognostic markers in R-CHOP treated patients are prognostic in R-CHOEP treated patients remain to be investigated. In addition predictive markers for response to R-CHOEP need to be investigated. Methods: A Danish population based cohort of 140 young (age 18-60) patients with high-risk (2 ≥ additional risk factors including advanced stage, elevated s-LDH, and performance status >1) primary DLBCL diagnosed between 2004 and 2008 was investigated. Patients were treated with R-CHOP (n=84) or R-CHOEP (n=56). Formalin fixed paraffin embedded tumor tissue specimens were analysed for MYC-, BCL2- and BCL6- protein expression by semiquantitative immunohistochemistry (IHC) and genetic translocations by Fluorescence In Situ Hybridization (FISH). Results: MYC protein expression ≥ 40% was seen in 67/106 patients (71%), BCL2 protein expression > 0 and BCL2 protein expression ≥ 70% was seen in 106/138 (77%) and 81/117 patients (69%) respectively. BCL6 expression ≥ 30% was seen in 96/114 patients (84%). Concurrent expression of MYC≥40% and BCL2≥70% (IHC double hit (DH)) was seen in 50/106 patients (47%). Concurrent MYC≥40%, BCL2 >0 or BCL6<30% (Triple hit (TH) score score 2-3) was seen in 61/103 patients (59%). MYC, BCL2 and BCL6 translocation was seen in 14/104 (13%), 31/104 (30%) and 27/104 (26%) patients respectively. Concurrent MYC BCL2/BCL6 translocation (DH) was seen in 8/102 (8%) patients. MYC over-expression was not associated with reduced progression free survival (PFS) in either R-CHOP or R-CHOEP treated patients. BCL2 expression (>0%) and BCL2 overexpression (≥70%) was associated with reduced PFS in R-CHOP (HR: 0.3; 95%CI:0.1-0.9; p=0.03 and HR: 0.4; 95%CI: 0.2-0.9; p=0.02) - but not in R-CHOEP treated patients (HR: 0.9; 95%CI:0.3-3.2; p=0.9 and HR: 0.5; 95%CI: 0.1-1.9; p=0.3). IHC DH was associated with a trend towards reduced PFS in R-CHOP - but not in R-CHOEP treated patients (HR: 0.6; 95%CI:0.3-1.1; p=0.08 and HR: 1.2; 95%CI: 0.4-4.0; p=0.7 respectively). TH score 2-3 was associated with reduced PFS in R-CHOP - but not in R-CHOEP treated patients (HR: 0.4; 95%CI:0.2-0.9; p=0.015 and HR: 0.8; 95%CI: 0.2-2.8; p=0.74). There was no statistical significant interaction between treatment modality and BCL2 expression, IHC DH or TH score 2-3. MYC, BCL2 and BCL6 translocations were not prognostic markers with respect to PFS in either R-CHOP or R-CHOP treated patients. DH translocations were too few to perform meaningful statistical analyses. Conclusions: BCL2 expression, IHC DH and TH score 2-3 had prognostic value in R-CHOP treated patients but this was not seen in R-CHOEP treated patients in this study suggesting the need for novel prognostic markers in R-CHOEP treated patients. Neither BCL2 expression, IHC DH nor TH score 2-3 were however predictive markers for response to treatment with R-CHOEP in this cohort of patients. This could possibly be due to the limited number of patients investigated. MYC BCL2/BCL6 DH translocations were too few to perform meaningful statistical analyses and whether DH translocation will retain a prognostic value in R-CHOEP treated patients also remains to be investigated in larger patient cohorts. A possible predictive value of DH translocation also needs further investigation. Disclosures No relevant conflicts of interest to declare.

scholarly journals Neoantigens in Patients with De Novo Follicular Lymphoma: Results from the PRIMA Study

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 25-26
Author(s):  
Carsten Henneges ◽  
Dexter X Jin ◽  
Jeffrey M Venstrom ◽  
Sally E Trabucco ◽  
Tina G Nielsen ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
Clinical Outcomes ◽  
Prognostic Value ◽  
De Novo ◽  
Null Model ◽  
B Cell Lymphoma ◽  
Hazard Ratio ◽  
Phase Iii ◽  
Publicly Traded ◽  
The Past

Introduction: Follicular lymphoma (FL) is a slow growing lymphatic cancer characterized by translocations in and overexpression of BCL-2, which inhibits apoptosis. This pathogenesis may generate neoantigens (NAs) that are recognizable by T-cells as part of a patients' immune surveillance and are unique to specific FL mutations. Tumor mutation burden (TMB), and NA prevalence and prognostic nature, have previously been characterized for diffuse large B-cell lymphoma (DLBCL), identifying that TMB correlated with NA burden (NAB). While TMB did not correlate with outcomes, the presence of a NA, especially BCL2 NA, correlated with outcomes in de novo DLBCL. In addition, the majority of patients were predicted to have ≥1 NA (Paulson, EHA 2019). However, to date, the prevalence of NAs in FL, and their association with clinical outcomes, have not been characterized. The aim of our study was to characterize NA prevalence and evaluate the prognostic value of NA biomarkers, assessed by a targeted, comprehensive genomic profiling (CGP) platform, on progression-free survival (PFS) for patients with de novo FL. Methods: CGP data on 465 genes were available from patients with FL who provided biopsy samples at screening for the Phase III PRIMA trial (NCT00140582; intent-to-treat [ITT] population =1018; patients received rituximab [R] maintenance vs observation after response to initial first-line treatment with R-CVP [cyclophosphamide, vincristine, prednisone], R-CHOP [cyclophosphamide, doxorubicin, vincristine, prednisone] or R-FCM [fludarabine, cyclophosphamide, mitoxantrone]). CGP was used to calculate TMB, HLA type (OptiType) and NA prediction (NetMHCpan). The prevalence of NAs at time of screening was analyzed by the number and proportion of patients. The prognostic value of NAs were evaluated against the Cox Proportional Hazards null model for PFS including terms for treatment, country and response to induction treatment. The Akaike Information Criterion (AIC), a likelihood ratio test (LRT) p-value vs the null when including an additional NA term and its associated hazard ratio (95% CI), were calculated. A visualization of the genetic mutational landscape was generated using dimension reduction methods. Results: In total, 247 of the 1202 enrolled patients were assayed with CGP. Baseline characteristics and survival in the biomarker evaluable population (BEP) were consistent with the ITT population. We calculated a median TMB of 6.7 mutations per megabase for the PRIMA cohorts with a median of two predicted NAs per patient. The majority of patients (83%) were predicted to have ≥1 NA. TMB moderately correlated with NAB (0.42 pearson coefficient), Figure A. TMB was not associated with outcomes (hazard ratio [HR] 95% CI: 0.98 [0.94-1.02]) and similarly the presence of a NA was not associated with PFS (HR [95% CI]: 0.90 [0.56-1.44]). The most prevalent predicted NAs (n [patients]; %) were in BCL2 (54; 21.9%), CREBBP (49; 19.8%), EZH2 (14; 5.7%), KMT2D (13; 5.3%), and CARD11 (10; 4.0%). In a pooled analysis of patients from both arms, only presence of EZH2 NA improved the AIC of the null model (AIC=1135.6) to 1134.7 (LRT p=0.09 better than 0.1), Table. The HR (95% CI) of EZH2 NA in this model was 0.46 (0.17-1.25), indicating better survival for the EZH2 NA-negative group. Within each treatment group, HR (95% CI) for EZH2 was 0.27 (0.07-1.13) in the observation group and 1.05 (0.25-4.44) in the R group, Figure B. Inspecting the tSNE mutations by gene, a neighborhood pattern could be seen between EZH2 and BCL2 connected by KMT2D and flanked by CARD11 and CREBBP, Figure C. Conclusions: We observed that similarly to de novo DLBCL, TMB and NAB were also correlated in patients with de novo FL. While NAB was associated with clinical outcomes in de novo DLBCL, we did not observe these associations in FL. In patients with de novo FL,who discontinued R after initial treatment response, the absence of EZH2 predicted neoantigens were associated with PFS. This is consistent with results on EZH2 mutation status reported by Huet, et al.(Blood Cancer J 2017). A caveat to this hypothesis generating analysis is the small number of PFS events in the EZH2 neoantigen group. These insights may inform future personalized strategies in FL. Disclosures Henneges: Genentech (via Syneos Health): Current Employment; University of Wurzburg: Ended employment in the past 24 months. Jin:F. Hoffmann-La Roche: Current equity holder in publicly-traded company; Foundation Medicine Inc: Current Employment. Venstrom:Foundation Medicine, Inc.: Current Employment; F. Hoffmann-La Roche: Current equity holder in publicly-traded company. Trabucco:F. Hoffmann-La Roche, Bristol-Myers Squibb Co., BioNTech: Current equity holder in publicly-traded company; Bristol-Myers Squibb Co: Current equity holder in publicly-traded company; BioNTech: Current equity holder in publicly-traded company; Loxo Oncology: Divested equity in a private or publicly-traded company in the past 24 months; Foundation Medicine, Inc.: Current Employment; Patent pending with Foundation Medicine and Genentech: Patents & Royalties: Patent pending. Nielsen:F. Hoffmann-La Roche: Current Employment, Current equity holder in publicly-traded company. Penuel:Genentech, Inc./ F. Hoffmann-La Roche: Current Employment; F. Hoffmann-La Roche: Current equity holder in publicly-traded company. Salles:Abbvie, Amgen, Celgene, Gilead, Janssen, Kite, Morphosys, Novartis, Roche, Takeda: Other: Participation to educational events; Abbvie, Autolus, BMS/Celgene, Debiopharm, Genmab, Kite/Gilead, Epizyme, Janssen, Karyopharm, Morphosys, Novartis, Roche, Takeda: Membership on an entity's Board of Directors or advisory committees; Abbvie, Amgen, Celgene, Gilead, Janssen, Kite, Morphosys, Novartis, F. Hoffmann-La Roche, Takeda: Honoraria; Abbvie, Autolus, BMS/Celgene, Debiopharm, Genmab, Kite/Gilead, Epizyme, Janssen, Karyopharm, Morphosys, Novartis, F. Hoffmann-La Roche, Takeda: Consultancy. Paulson:Genentech, Inc.: Current Employment; F. Hoffmann-La Roche: Current equity holder in private company, Current equity holder in publicly-traded company.

scholarly journals A Prognostic Model Incorporating Tumor Lesion Morphology and Texture Features Identifies High-Risk Patient Subpopulations in De Novo DLBCL and FL

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 28-28
Author(s):  
Xiao Li ◽  
Skander Jemaa ◽  
Richard AD Carano ◽  
Thomas Bengtsson ◽  
Joseph N Paulson ◽  
...  
Keyword(s):  
High Risk ◽  
Fdg Pet ◽  
De Novo ◽  
Risk Group ◽  
Low Risk ◽  
Phase Iii ◽  
Publicly Traded ◽  
Prognostic Performance ◽  
Pet Scans ◽  
Worse Prognosis

Background: Despite effective first-line (1L) treatment options for patients with NHL almost 40% of patients with diffuse large B cell lymphoma (DLBCL) will have a poor response or disease progression after 1L treatment. In follicular lymphoma (FL) 15-20% of patients experience early relapse, and almost 8% may develop transformation to more aggressive forms of the disease (such as DLBCL) after 1L treatment. More accurate identification of patients at high-risk for a poor prognosis with the standard of care could lead to improved outcomes. Although the International Prognostic Index (IPI) and its FL extension (FLIPI) are often used to stratify patients by prognosis, they have relatively modest sensitivity and specificity for predicting individualized risk. Radiomics is a promising approach to improve upon existing prognostic models because it provides a comprehensive quantification of tumor lesion morphology and texture derived from FDG-PET scans and may provide new and important information about disease biology and progression risk on an individual level. Methods: A collection of 107 radiomics features [pyradiomics v2.20] that describe shape, size or volume and texture of tumor lesions, including complex features that are believed to reflect the underlying biological tumor phenotype and microenvironment, were derived for n=1093 de novo DLBCL patients with available baseline FDG-PET scans from the Phase III GOYA study (NCT01287741) evaluating obinutuzumab plus CHOP chemotherapy (G-CHOP) versus rituximab plus CHOP chemotherapy (R-CHOP) (Vitolo, et al. J Clin Oncol 2017). The same set of features were also extracted from n=451 de novo FL patients with available baseline FDG-PET scans from the Phase III GALLIUM study (NCT01332968) comparing obinutuzumab plus chemotherapy with rituximab plus chemotherapy [Marcus, et al. N Engl J Med 2017]. To investigate the association between the derived radiomics features along with baseline clinical variables and progression-free survival (PFS), a Cox proportional hazard model with L1 regularization was trained and internally validated using the GOYA study. We used a nested Monte Carlo Cross Validation (nMCCV) strategy to train our model and provide high- and low-risk group predictions on held-out samples of data. This modeling strategy allows us to make a group prediction on all GOYA patients while reducing overfitting. To evaluate prognostic performance, we ported the final model trained using the GOYA study (called the Li prognostic model) to the fully independent GALLIUM study. Results: Using our nMCCV approach we identified 11 factors, with an inclusion probability of &gt;50%, that are associated with PFS of DLBCL patients (Figure A). Included within the top features are several image-derived morphometric (i.e. metabolic tumor volume, surface area) and radiomics features (i.e. tumor elongation, NGTDM contrast, GLCM inverse variance). When stratifying patients on the predicted (via majority vote) low-risk vs high-risk groupings we found that our high-risk group had significantly worse prognosis vs the low-risk group (Figure B). In comparison, the high-risk group from the IPI model (defined as IPI &gt; 2) had significantly worse prognosis vs the low-risk group, but the performance was slightly worse than our model (Figure C). PFS probability estimates at 2 and 5 years for predicted high-risk patients was 72.7% [70.0-76.6] and 59.8% [54.8-65.2] (vs 74% [70.0-78.2] and 60.4% [55.1-66.2] for the IPI model). After training and testing in the DLBCL population, we evaluated the prognostic performance of our model in an independent set of FL patients. We found that high-risk FL patients had a significantly worse prognosis than the low-risk group (Figure D). PFS probability estimates at 2 and 5 years for predicted high-risk patients was 77.4% [69.8-85.8] and 48.9% [39.5-60.5] (vs. 80% [0.748-0.856] and 58.3% [51.6-65.9] in the full group). Conclusions: Radiomics features are prognostic in DLBCL and provide a modest improvement in prognostic performance when combined with traditional IPI scores, clinical features, and lab values (vs IPI alone). Our prognostic signature, developed in DLBCL, has significant prognostic performance in an independent dataset of patients with FL. While these results are promising, our FL validation dataset was relatively small and further evidence is required to confirm our findings. Disclosures Li: Genentech, Inc.: Current Employment; F. Hoffmann-La Roche: Current Employment, Current equity holder in publicly-traded company. Jemaa:F. Hoffmann-La Roche: Current equity holder in publicly-traded company; Genentech, Inc.: Current Employment. Carano:F. Hoffmann-La Roche: Current equity holder in publicly-traded company; Genentech, Inc.: Current Employment. Bengtsson:Genentech, Inc.: Current Employment; F. Hoffmann-La Roche: Current equity holder in publicly-traded company. Paulson:F. Hoffmann-La Roche: Current equity holder in private company, Current equity holder in publicly-traded company; Genentech, Inc.: Current Employment. Jansen:F. Hoffmann-La Roche: Current Employment; Molecular Health GmbH: Ended employment in the past 24 months; F. Hoffmann-La Roche, Abbvie, Alphabet, other (non-healthcare), indexed funds and ETFs: Current equity holder in publicly-traded company. Nielsen:F. Hoffmann-La Roche: Current Employment, Current equity holder in publicly-traded company. Hibar:Genentech, Inc.: Current Employment; F. Hoffmann-La Roche: Current equity holder in publicly-traded company.

scholarly journals High-grade B-cell lymphoma relapse presenting as neurolymphomatosis of the median nerve

2019 ◽  
Vol 12 (3) ◽  
pp. e228742
Author(s):  
Rebecca Tai ◽  
Julian Maingard ◽  
Mithun Nambiar ◽  
Kelvin Lim
Keyword(s):  
Median Nerve ◽  
Cell Lymphoma ◽  
Haematological Malignancy ◽  
B Cell Lymphoma ◽  
Imaging Features ◽  
Imaging Diagnosis ◽  
Colour Doppler ◽  
Surgical Biopsy ◽  
Positron Emission ◽  
Ultrasound Findings

Neurolymphomatosis (NL) is the infiltration of lymphocytes into the peripheral nervous system in a haematological malignancy. We describe the imaging features of NL in a patient with relapsed Burkitt-like non-Hodgkin’s lymphoma on positron emission tomography (PET) and ultrasound. Imaging features on ultrasound are infrequently described and provide useful information in helping to establish an imaging diagnosis of NL. Features of NL in our patient included intense linear fluorodeoxyglucose-18 (18FDG) uptake on PET along the affected median nerve. B-mode ultrasound demonstrated concentric tubular thickening and loss of fascicular architecture. Perineural and intraneural vascularity was present on colour Doppler ultrasound. It is important to be able to correlate ultrasound findings to features observed on 18FDG-PET as this aids in diagnosis and in guiding potential surgical biopsy.

A New Prognostic Disease Specific Model To Predict Survival after Intensive Antileukemic Treatment for Young Patients with Poor-Risk MDS and AML: Results of the CRIANT and AML-10 Studies Conducted by the EORTC/GIMEMA/SAKK/HOVON/EBMT Groups.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2020-2020
Author(s):  
M. Oosterveld ◽  
S. Suciu ◽  
P. Muus ◽  
M. Delforge ◽  
A. Belhabri ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
High Risk ◽  
Prognostic Value ◽  
De Novo ◽  
Survival Rates ◽  
White Blood Count ◽  
Poor Risk ◽  
Prognostic Importance ◽  
De Novo Aml ◽  
Disease Specific

Abstract The use of intensive antileukemic treatment is less widely accepted in high-risk MDS pts compared to de novo AML, due to the reported inferior results. It is questionable whether the poorer outcome reflects an intrinsic property of the involved stem cell or a higher frequency of poor prognostic factors. The purpose of this analysis is to identify disease-specific prognostic factors for outcome of young (aged <56 years) MDS and AML pts. This analysis combines the data of 591 pts in the AML-10 study and 203 pts with high-risk MDS or secondary AML (sAML) in the CRIANT study. Both groups received identical remission-induction therapy (idarubicin, cytarabine and etoposide), followed by one consolidation course with intermediate dose of cytarabine and idarubicin (IDIA). In both studies post-consolidation therapy consisted of alloSCT if an HLA-identical sibling donor was available. The remaining pts received autoSCT (ASCT) in AML-10 or were randomized between ASCT and a 2nd consolidation course in CRIANT. The CR rate was 68% (AML-10) vs. 59% (CRIANT) (p=0.02). The 4-year survival rates were 35% vs. 33% (p=0.80). DFS at 4 years was 43% (AML-10) vs. 35% (CRIANT) (p=0.18). For overall survival (OS) in both studies, study was not of importance (HR=1.09, p=0.45), but the following variables showed independent prognostic value: cytogenetic risk group (the HR for poor vs intermediate risk was 1.68, 95% CI 1.24–2.27, p=0.0008), white blood count (WBC) ≥ 100 x 109/l (HR=2.02, 95% CI 1.53–2.68, p<0.0001), age 46–55 yrs (HR=1.39, 95% CI 1.16–1.67, p=0.0004) and performance status (PS) (HR=1.32, 95% CI 1.17–1.49, p <0.0001). For DFS, the following factors were of an independent prognostic importance: cytogenetics (p<0.0001), age 46–55 (HR=1.23, p=0.05), WBC >100 (HR=1.67, p=0.02) and donor availability (HR=0.77, p=0.04). Some variables were of prognostic value for OS in only one of the studies: in the CRIANT study number of cytopenias (3 vs 0–2) and AHD >6 months appeared of prognostic importance for OS, wherease FAB subtype M2/M4 and cytogenetics inv(16)/t(8;21) were prognostic in AML-10. Therefore a specific prognostic score for OS was established for each study, AML-10 (based on cytogenetics, PS, FAB, WBC and age) and CRIANT (based on cytogenetics, nr of cytopenias, age, AHD and WBC). The AML-10 study distinguished 5 groups with an estimated 4-year survival rate of 69%, 40%, 45%, 26% and 17%, resp. The prognostic value of this score has been validated on patients treated in the AML-10 study with mitoxantrone instead of idarubicin: the 4-year survival were 76%, 46%, 41%, 33% and 18%, resp. The CRIANT study distinguished 5 groups with a 4-year survival rates of 72%, 44%, 39%, 12% and 0%, resp. In conclusion: the prognostic scores identify a group of 26% AML and 42% MDS pts, with a 4-year survival less than 20%. Apparently current treatment modalities are unsatisfactory for these poor-risk pts and novel treatment strategies should be offered to these pts in the context of clinical trials. Our finding that different variables are of prognostic importance in MDS/sAML and de novo AML pts supports the hypothesis that these are intrinsically different disorders. The CRIANT-derived score is a valuable alternative for the IPSS in intensively treated high-risk MDS pts.

Interim [18F]Fluorodeoxyglucose Positron Emission Tomography Scan in Diffuse Large B-Cell Lymphoma Treated With Anthracycline-Based Chemotherapy Plus Rituximab

2012 ◽  
Vol 30 (2) ◽  
pp. 184-190 ◽  
Author(s):  
Violaine Safar ◽  
Jehan Dupuis ◽  
Emmanuel Itti ◽  
Fabrice Jardin ◽  
Christophe Fruchart ◽  
...  
Keyword(s):  
Prognostic Value ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Emission Tomography ◽  
Negative Results ◽  
Large B Cell Lymphoma ◽  
Positron Emission ◽  
Positive Results ◽  
Large B Cell ◽  
Fluorodeoxyglucose Positron Emission

Purpose The prognostic value of [18F]fluorodeoxyglucose–positron emission tomography (PET), interpreted according to visual criteria, is a matter of debate for diffuse large B-cell lymphoma (DLBCL). Moreover, most published studies do not differentiate between patients treated with or without rituximab. We retrospectively investigated the prognostic value of PET performed in patients with DLBCL receiving chemotherapy plus rituximab. Images were interpreted both visually and by computing maximum standardized uptake value (SUVmax) between PET performed at baseline and after two cycles of chemotherapy. Patients and Methods One hundred twelve patients newly diagnosed with DLBCL were treated with an anthracycline-based regimen plus rituximab. A PET was performed after two cycles of treatment. PET positivity or negativity was related to progression-free survival (PFS) and overall survival (OS) using Kaplan-Meier analysis. Results Visual analysis showed that 70 patients (62.5%) presented with a negative PET scan after two cycles of treatment. The 3-year PFS and OS rates were 84% and 88%, respectively, in patients with PET-negative results versus 47% and 62%, respectively, in patients with PET-positive results (P < .0001 and P < .003, respectively). A second analysis was performed on 85 patients by using interim PET in a quantitative approach on the basis of a ΔSUVmax evaluation of more than 66%. The 3-year PFS was 77% for patients with PET-negative results and 37.5% for patients with PET-positive results (P = .002). Conclusion An early PET scan after two cycles of treatment can effectively predict the outcome in patients with DLBCL treated with rituximab and anthracycline-based chemotherapy by using either a visual or quantitative approach.

scholarly journals Imaging features of skeletal muscle lymphoma: a case report and literature review

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Shuxi Gao ◽  
Hong Shu ◽  
Hua Yang
Keyword(s):  
Skeletal Muscle ◽  
Lower Extremity ◽  
B Cell Lymphoma ◽  
Imaging Features ◽  
Left Lower Extremity ◽  
Non Hodgkin Lymphoma ◽  
Guided Biopsy ◽  
Mri Features ◽  
Positron Emission ◽  
Magnetic Resonance Imaging Mri

Abstract Background Diffuse large B cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma (NHL), occurring predominantly in older people. Skeletal muscle lymphoma is a rare form of DLBCL, most frequently affecting the thigh, upper extremities, calf, and pelvis. Case presentation We report a case of skeletal muscle DLBCL that was diagnosed using ultrasound (US)-guided biopsy. A 70-year-old man presented with progressive swelling and pain in the left lower extremity and an elevated erythrocyte sedimentation rate (ESR) and serum C-reactive protein (CRP), ferritin, and CA125 levels. US, magnetic resonance imaging (MRI), and computed tomography (CT) showed diffuse lesions in several muscles of the left lower extremity. Positron emission tomography/CT (PET/CT) showed FDG-uptake in the affected muscles. The patient was treated with chemotherapy and achieved a good response. A systematic review of the literature published between 1992 and 2019 was conducted to investigate the role of imaging, including imaging-guided biopsy, in the diagnosis of skeletal muscle lymphoma. Conclusions Skeletal muscle lymphoma is rare. US and MRI features include enlargement of muscular structures, with preservation of the architecture of the tissue and surrounding anatomical structures. Definitive diagnosis relies on histological and immunohistological analysis of a sample obtained through imaging-guided biopsy.

Sign in / Sign up

Export Citation Format

Share Document