Analysis of Micro-RNAs Associated to Treatment Failure in Diffuse Large B Cell Lymphoma

Introduction: Micro-RNAs (miRNAs) are 19-24 nucleotide non-coding RNAs that regulate gene expression through the inactivation of their messenger RNA. Previous studies have demonstrated the important role of some miRNAs in the development of cancer. Specifically, in diffuse large B cell lymphoma (DLBCL), miRNAs involved in lymphomagenesis were identified but understanding their biological function continues to be a challenge. Nevertheless, the pathogenesis effects of some miRNAs such as miR-125a, miR-17-92 cluster or mi-R-155 are well characterized. Some studies suggest that miRNAs also possess a prognostic potential role in DLBCL. For this reason, our objective was to analyze the different miRNAs involved in the chemo-sensitivity or resistance to the first line treatment, their correlation with standard prognostic factors at diagnosis and the role of these miRNAs in survival in patients with DLBCL. Material and methods: Patients homogeneously treated with R-CHOP from 1999-2013 were reviewed from 3 Spanish centers. They were retrospectively obtained from Pathology Department registry to avoid selection bias. We included those patients with valid genomic material in formalin-fixed-paraffin-embedded tissue and with available clinical data. Samples were processed using the miRNA 4 Affymetrix microarrays kit in a discovery group that included 2 cohorts (patients with durable complete remission (CR) versus refractory or early relapsing patients). Those miRNAs with differential expression were validated in the whole series with quantitative RT-PCR. We also analyzed the role of these miRNAs as predictors of event-free survival (EFS) and overall survival (OS) and their relationship with standard prognostic factors in DLBCL. Results: We identified 156 patients homogeneously treated with R-CHOP. Finally, 96 samples were obtained with valid material for RNA extraction. To identify those miRNAs with prognostic implication, a discovery cohort of 12 patients was used in which all the cases had poor prognosis with high tumor load and advance disease (III-IV stage and unfavorable R-IPI). On this basis of poor prognosis, 2 groups were defined totally opposed from the point of view of the treatment response and evolution: chemo-resistance group (n=6) including refractory or relapsed (RR) patients (first 12 months) and chemo-sensitive group (n=6) including patients with at least 3 years of CR. A hierarchical clustering was performed in which 26 miRNAs differentially expressed were identified. A screening of miRNAs was carried out based on the fold-change and pathways involved and finally we obtained 10 miRNAs differentially expressed in RR group. The validation of these miRNAs was performed with quantitative RT-PCR in the whole series which finally included 68 samples with valid material. A univariate survival analysis including clinical prognostic factors and the selected 10 miRNAs was performed. We confirmed that 7 of them (miR-20b-5p, miR-1244, miR-6840-3p, miR-1231, miR-193b-5p, miR-6860-5p y miR-199a-5p) significantly influenced EFS and 6 of them (miR-1244, miR-1231, miR-193b-5p, miR-885-3p, miR-182-5p y miR-199a-5p) on OS. From these 10 miRNAs, only 3 had a significant prognosis role not only for EFS but also for OS and progression-free survival (PFS): miR-1244, miR-193b-5p and miR-1231. The overexpression of miR-1244 and miR-193-5p were associated with advance stage and worse clinical prognosis factors (p<0.05). A multivariate analysis was performed including clinical and biological variables and we obtained that the overexpression of miR-1231, high R-IPI and a reduction of relative dose intensity (RDI) >15% were independently associated with worse SG and EFS (Figure 1). In previously reported studies, these 3 miRNAs have been related with proliferative events such as the overexpression of myc or anti-apoptosis. Also, the miR-1231 may be related with new lymphomagenesis pathways associated to viral infections. Conclusions: Through a discovery group focused on progression/refractoriness, a group of new miRNAs differentially expressed on chemo-resistant patients with DLBCL was identified. The overexpression of miR-1244 and miR-193-5p was associated with more extensive disease and worse clinical prognostic factors. The high R-IPI, reduction of >15% RDI and the overexpression of miR-1231 were independently associated with worse EFS and OS. Disclosures Sánchez-González: Amgen: Consultancy, Speakers Bureau; Gilead: Speakers Bureau; Navartis: Consultancy, Speakers Bureau; Shire: Speakers Bureau; Takeda: Consultancy, Speakers Bureau. Salar:Roche: Research Funding, Speakers Bureau; Janssen Pharmaceuticals: Consultancy, Speakers Bureau; Gilead: Consultancy, Speakers Bureau; Celgene: Consultancy.

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Distinct Expression Patterns of microRNAs in Activated B Cell (ABC) and Germinal Center B (GC) Subtypes of Diffuse Large B Cell Lymphoma (DLBLC).

Blood ◽

10.1182/blood.v110.11.562.562 ◽

2007 ◽

Vol 110 (11) ◽

pp. 562-562

Author(s):

Jean-Noel Bastie ◽

Jean-Philippe Jais ◽

Thierry Molina ◽

Emmanuelle Come ◽

Bertrand Coiffier ◽

...

Keyword(s):

B Cell ◽

Mirna Expression ◽

Germinal Center ◽

Cell Lymphoma ◽

Expression Patterns ◽

B Cell Lymphoma ◽

Rt Pcr ◽

Large B Cell Lymphoma ◽

Micro Rnas ◽

Large B Cell

Abstract The Micro RNAs (miRNAs) are small non-coding, single-stranded RNAs that regulate the expression of genes by hybridizing the mRNA target with complementary sequences that are followed by translational repression, mRNa cleavage or destabilization. There is evidence that miRNA play an important role in carcinogenesis. Aberrant miRNA expression has been found in a variety of human malignancies including B-cell leukemias and lymphomas. The purpose of this study is to determine the miRNA expression patterns in DLBCL and their relationship with clinical characteristics and outcome. We used high throughput quantitative RT-PCR technology (Taqman Low density Arrays) to analyze the expression profile of 365 different mature miRNA in 12 Diffuse Large B-Cell Lymphoma (DLBCL) samples which had been previously characterized at the transcriptional level with Affymetrix HU133A micro-arrays. MiR-155 expression was significantly lower in the 6 samples with a Germinal Center (GC) mRNA profile than in the 6 samples with an Activated B-Cell (ABC) profile. Expression of miR-155 and of different miRNA involved in lymphoid differentiation (miR-181a, miR127) or tumour pathogenesis (cluster miR 17–92) were further evaluated in a series of 64 patients with DLBCL treated with Rituximab associated with chemotherapy (R-CHOP). 28 patients had been enrolled in the LNH98.5 GELA trial between February 1998 and February 2000 and 36 were treated with R-CHOP in GELA centers after the closure of the LNH98-5 trial, between November 2000 and June 2004. The median follow up of these patients is 69 months. Patients median age at diagnosis was 69 years (range 59–82) and 28 patients presented with an International Prognostic Index (IPI) score of more than 3. Mature miRNA expression was determined by quantitative RT-PCR with Applied Biosystems specific miRNA primer and probe sets and normalized to U6 small nuclear RNA expression. MiR-155 expression was significantly higher in patients with a lymphoma of the ABC subtype, defined on the basis of the transcriptional profile (mean delta Ct = − 3.9 in the 41 ABC samples, mean delta Ct = − 1.67 in the 23 GC samples, p<0.00001) and significantly higher in patients with a high (4 or 5) IPI score (p=0.02). A high miR-155 expression was associated with a trend towards a poorer overall survival. The expression of miR-127, miR-181a and the cluster 17–92 were not correlated with clinical outcome. These analyses are currently being extended to a larger series of patients in order to determine whether other miRNA can be used to classify DLBCL samples into ABC and GC subtypes and whether some miRNA have prognostic significance in the era of treatments combining Rituximab and chemotherapy.

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Serum Interleukin-18 Level Determines Clinical Outcome in Patients with Diffuse Large B-Cell Lymphoma in Rituximab Era.

Blood ◽

10.1182/blood.v114.22.1926.1926 ◽

2009 ◽

Vol 114 (22) ◽

pp. 1926-1926

Author(s):

Naoe Goto ◽

Hisashi Tsurumi ◽

Senji Kasahara ◽

Takeshi Hara ◽

Nobuhiro Kanemura ◽

...

Keyword(s):

Prognostic Factors ◽

Cell Lymphoma ◽

Progression Free Survival ◽

B Cell Lymphoma ◽

Serum Levels ◽

High Serum ◽

Interleukin 18 ◽

Free Survival ◽

Large B Cell Lymphoma ◽

Good Risk

Abstract Abstract 1926 Poster Board I-949 Purpose: Diffuse large B cell lymphoma (DLBCL) is a heterogeneous entity, with patients exhibiting a wide range of outcomes. The introduction of rituximab to CHOP (R-CHOP) has significantly altered improvement in survival. This raises concern regarding the utility of previously identified prognostic factors. Before rituximub era, some investigators have suggested that serum levels of some cytokines and their soluble receptors might reflect tumor growth and host tumor responses. Interleukin-18 (IL-18), originally designated as an interferon (IFN)-gamma inducing factor, is a cytokein which stimulates cytotoxic NK cell activity and T cells to produce IFN-gamma, IL-2, and GM-CSF. Increased IL-18 serum levels have been found in patients with some hematopoietic neoplasms. IL-18 is also immunostimulatory cytokine with antitumor activity in preclinical models, and a phase I study of recombinant human IL-18 was done to patients with advanced cancer. We have previously reported that IL-18 was strong prognostic factor in aggressive lymphoma patients who received CHOP without rituximab (ASH 2004, abstract #4543). The aim of the present study is to re-assess the prognostic significance of serum IL-18 in DLBCL treated with rituximab, and we also assessed IL-18 with subtype of DLBCL, GCB type and non GCB type. Meterials and methods: Consecutive 154 previously untreated patients with DLBCL prospectively participated in this study between 2002 and 2008. The patients were treated with 6-8 cycles of R-CHOP or R-THP (pirarubicin) -COP regimens. There was no difference with CHOP and THP-COP in our recent prospective randomized study (Tsurumi H et. al. JCRCO 2004). Serum IL-18 was determined by ELISA, and we classified subgroups of DLBCL according to Hans et al. Results: In all patients with DLBCL, the mean ± SD of serum IL-18 level was 829.5±1280.8 pg/ml (range 56 - 8697.5) with a median of 415.8 pg/ml. Various poor prognostic features, such as poor PS, many extranodal sites, advanced disease (CS III/IV) increased LDH and elderly people were strongly associated with a high serum IL-18 levels. The median serum IL-18 levels of the different IPI risk groups were as follows: 201pg/ml for the L risk; 361pg/ml for the LI risk; 440pg/ml for the HI risk; 691pg/ml for the H risk, respectively (P<0.0001). A similar result was provided in rivised IPI (219pg/ml for the very good risk; 271 pg/ml for the good risk; 658 pg/ml for the poor risk, respectively P<0.0001). In addition, the serum IL-18 levels were higher in the non-GCB subgroup than in the GCB subgroup (P<0.005). Patients with high IL-18 (500 pg/ml and over) at onset had significantly lower progression free survival (PFS) rates (5-year: 52%), than those with low IL-18 (5-year: 79 %), respectively (P<0.0001). and In both GCB and non-GCB subgroups, patients with high IL-18 had significantly lower progression free survival rates (GCB and low IL-18:5-ys PFS 90%, GCB and high IL-18 %:5-ys PFS 58%, non-GCB and low IL-18:5-ys PFS 65%, non-GCB and high IL-18:5-ys PFS 42% ; P<0.001). Multivariate analysis employing IL-18 and some conventional prognostic factors demonstrated that age, PS and IL-18 for PFS were poor prognostic factors. Conclusion: These results suggest that, in even rituximab era, a high serum IL-18 level predicts a poor prognosis of DLBCL and may be a useful biomarker for selecting appropriate treatment. Upfront high dose chemotherapy might be well indicated for non-GCB type DLBCL patients with serum high IL-18. Disclosures: No relevant conflicts of interest to declare.

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Role Of Interim,-PET In Poor Prognosis Young Patients With Diffuse Large B Cell Lymphoma At Diagnosis: Data From An Ancillary Study Of a Prospective Randomized Phase III Study (DLCL04) From the Fondazione Italiana Linfomi

Blood ◽

10.1182/blood.v122.21.5088.5088 ◽

2013 ◽

Vol 122 (21) ◽

pp. 5088-5088

Author(s):

Luigi Rigacci ◽

Patrizia Pregno ◽

Benedetta Puccini ◽

Andrea Evangelista ◽

Annalisa Chiappella ◽

...

Keyword(s):

Poor Prognosis ◽

Clinical Characteristics ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Phase Iii ◽

Ancillary Study ◽

Interim Pet ◽

Large B Cell Lymphoma ◽

Dose Dense

Abstract Introduction The role of interim-PET (i-PET), after two cycles of chemotherapy, in advanced stage Hodgkin's lymphoma is well defined; the same role in diffuse large B cell lymphoma (DLBCL) is still controversial. The Fondazione Italiana Linfomi planned a prospective randomized phase III trial, addressed to young poor prognosis DLBCL patients at the diagnosis, with a 2x2 factorial design aimed at investigating the possible benefit of intensification with R-HDC+ASCT after R-dose-dense chemotherapy delivered at two different level of dose (R-CHOP14/R-MegaCHOP14). During this study an ancillary study was designed to define the prognostic impact of i-PET on progression free survival (PFS) after two cycles of immunochemotherapy in all treatments arms. Patients and methods As described by Vitolo et al (oral communication, abs 688 ASH 2012), patients were stratified according to aa-IPI and randomized at diagnosis to receive: R-CHOP14 x 8 cycles; R-MegaCHOP14 (1200 mg/sqm Cyclophosphamide, 70 mg/sqm Doxorubicin, standard dose Vincristine and Prednisone) x 6; R-CHOP14 x 4 + R-HDC (Rituximab + High Dose Cytarabine + Mitoxantrone + Dexamethasone) followed by BEAM and ASCT; R-MegaCHOP14 x 4 + R-HDC + BEAM and ASCT. G-CSF support was mandatory. Seventeen centers agreed to participate in the study and enrolled patients. All evaluable patients had performed basal PET and i-PET. A visual dichotomous criteria, according to Deauville Criteria (First Consensus Conference, 2009), was used to define the i-PET result. The final response was identified according to 2007 Cheson response criteria. Results From June 2005 to September 2010, 399 patients were randomized in the overall DLCL04 study and 130 were enrolled for the ancillary PET study , 69 in the R-HDC+ASCT and 61 in R dose dense therapy respectively. The clinical characteristics, as in the overall DLCL04 study, were well balanced among the four arms of therapy excluding a selection bias in the group of patients studied with i-PET. The i-PET result was positive in 74 patients and negative in 56 patients, no differences were observed between negative and positive i-PET results according to clinical characteristics and group of treatment. In particular, in R-dose dense arm 27 were negative and 34 positive, in R-HDC+ASCT 29 were negative and 40 positive, according to immunochemotherapy scheme in R-CHOP14 29 were negative and 40 were positive, in MegaCHOP14 27 were negative and 34 were positive. With a median follow-up of 36 months, 3-year PFS and 3-year Overall Survival (OS) rates for the whole series were: 64% (95% CI:59-69) and 79% (95% CI:74-83) respectively. No differences in PFS was reported according to i-PET result. In particular 3-year PFS were 87%(95% CI:75-94) in i-PET negative patients and 76% (95% CI: 65-85) in i-PET positive patients respectively (p: 0.09 The 3-year PFS according to I- PET results in the different treatment arm were: in the R-HDT+ASCT group i-PET negative or i-PET positive patients had a 3-year PFS of 83% (95% CI:63-92) and 79% (95% CI:63-89) respectively; in the R-dose dense i-PET negative or i-PET positive patients had a 3-year PFS of 92% (95% CI:73-98) and 72% (95% CI:54-85) with a p value near the significance (0.07). According to OS, i-PET negative and i-PET positive patients had a 3-year OS of 89%(95% CI:76-95) and 83%(95% CI:72-90) respectively, p=0.219. Conclusions In our multicenter prospective study, addressed to young poor prognosis DLBCL patients at the diagnosis, i-PET, performed after two immunochemotherapy cycles and analyzed with a visual method, is not able to identify two different risk population. To confirm our data, we are planning in the near future a centralized revision of all evaluable PET. In conclusion, our feeling is that the i-PET after two cycles in poor prognosis DLBCL patients is too early to predict a chemorefractory disease and more parameters must be considered to define clinical response in these patients. Disclosures: No relevant conflicts of interest to declare.

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Improved Progression-Free Survival for Bulky and Non-Bulky Advanced Stage Diffuse Large B-Cell Lymphoma with Consolidative Radiation Therapy: A Bi-Institutional Analysis

10.21203/rs.3.rs-137697/v1 ◽

2021 ◽

Author(s):

Yusef Ali Syed ◽

Cecilia Jiang ◽

Jeffrey Switchenko ◽

Khadija Kirmani ◽

Chris Kelsey ◽

...

Keyword(s):

Systemic Therapy ◽

Cell Lymphoma ◽

Progression Free Survival ◽

B Cell Lymphoma ◽

Complete Response ◽

Stage Iii ◽

Bulky Disease ◽

Free Survival ◽

Large B Cell Lymphoma

Abstract Background: The role of consolidative radiation therapy (RT) for advanced stage diffuse large B-cell lymphoma (DLBCL) is not fully established. Retrospective data provide evidence for the use of consolidative RT in stage III-IV DLBCL and emerging data from randomized studies address the role of RT in bulky disease for these patients.Methods: Patient with stage III-IV DLBCL treated at two institutions who achieved clinical complete response to systemic therapy were included. Kaplan-Meier analysis was performed to determine the impact of consolidative RT. Univariate and multivariable analyses were performed using a Cox proportional hazards model.Results: One hundred eighty-eight patients received systemic therapy consisting of R-CHOP (79%), another Rituximab-based regimen (9%), or chemotherapy alone (12%). Clinical response was assessed using conventional CT or PET-CT. Sixty-eight patients (36%) received consolidative RT (median dose 30 Gy). Consolidative RT conferred a 36.7% absolute benefit in five-year progression-free survival (85.9% vs. 49.2%, log rank p < 0.0001), and a 14.5% absolute benefit in five-year overall survival (87.4% vs. 72.9%, log rank p = 0.0134). On multivariable analysis, consolidative RT was associated with improved PFS (HR 0.23, 95% CI 0.10-0.52, p < 0.001). Patients receiving consolidative RT demonstrated significantly improved PFS for tumors measuring both <5 cm (log rank p = 0.0454) and ³5 cm (log rank p = 0.0003).Conclusions: For patients with stage III-IV DLBCL who achieve clinical complete response after systemic therapy, consolidative RT improves PFS for all patients, including those with non-bulky disease. This benefit persists in the setting of rituximab-based systemic therapy.

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Emerging Role of Consolidative Radiotherapy After Complete Remission Following R-CHOP Immunochemotherapy in Stage III–IV Diffuse Large B-Cell Lymphoma: A Single Institutional and Case-Matched Control Study

Frontiers in Oncology ◽

10.3389/fonc.2021.578865 ◽

2021 ◽

Vol 11 ◽

Author(s):

Ji Hyun Hong ◽

Han Hee Lee ◽

Seung-Eun Jung ◽

Gyeongsin Park ◽

Joo-Hyun O ◽

...

Keyword(s):

Local Recurrence ◽

Complete Remission ◽

Head And Neck ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Free Survival ◽

Large B Cell Lymphoma ◽

Consolidative Radiotherapy ◽

Large B Cell

PurposeThe role of consolidative radiotherapy (RT) after complete-remission (CR) following rituximab combined with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in advanced-stage diffuse large B-cell lymphoma (DLBCL) remains unclear. We retrospectively analyzed the survival outcomes and patterns of failure with our institutional experience.Material and MethodsBetween 2009 and 2018, 206 patients with stage III-IV DLBCL achieved CR after receiving R-CHOP. Propensity-score matching was used to analyze the role of consolidative RT. The consolidative RT group (n = 34) and the R-CHOP alone group (n = 68) were matched at a 1:2 ratio. After propensity-score matching, 102 patients were analyzed.ResultsWith a median follow-up of 39.7 months, 26 patients (25.5%) showed local recurrence. Only one patient failed at the previous RT field. RT was delivered to bulky sites, head and neck lesions, testes, and bone with median dose of 30.6 Gy. The most common site of failure was head and neck lesions followed by bulky sites. The 5-year overall survival (OS), progression-free survival (PFS), and isolated-local recurrence free survival (LRFS) were 73.5, 64.0, and 79.9%. In univariate and multivariate analysis, bone marrow involvement and consolidative RT were associated with isolated LRFS (p = 0.006 and 0.032) significantly.ConclusionConsolidative RT improved isolated local control. Based on the pattern of failure, we carefully suggest to radiate on initially involved bulky sites or head and neck lesions. Further studies need to be done to find out the optimal radiation dose and selection of RT site.

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Serum Reactive Oxygen Metabolite Levels Are Associated with Poor Prognosis in Patients with Diffuse Large B-Cell Lymphoma

Blood ◽

10.1182/blood-2018-99-111874 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 1704-1704

Author(s):

Shinji Ogura ◽

Takahiro Kamiya ◽

Kota Mizuno ◽

Chisako Ito ◽

Yuriko Fujita ◽

...

Keyword(s):

Oxidative Stress ◽

Poor Prognosis ◽

Cell Lymphoma ◽

Reactive Oxygen ◽

B Cell Lymphoma ◽

High Serum ◽

Reactive Oxygen Metabolites ◽

Large B Cell Lymphoma ◽

Oxygen Metabolites

Abstract [Introduction] Oxidative stress caused by the increased production of reactive oxygen species (ROS) or decreased efficacy of the antioxidant system is implicated in the pathogenesis of various disease entities, such as atherosclerosis, cardiovascular disease, renal failure, malignant tumors, and autoimmune diseases. Recent observations suggested that oxidative stress is closely related to all aspects of cancer. Oxidative stress markers are prognostically important in various cancers including diffuse large B-cell lymphoma (DLBCL). However, the prognostic role of serum reactive oxygen metabolites (ROMs) in DLBCL is still unknown. The objective of this study is to evaluate the role of serum ROMs in patients with DLBCL. [Methods] We enrolled 52 patients with DLBCL who were treated at our institution between 2012 and 2014. To assess oxidative stress, instead of measuring serum ROS directly, we measured serum d-ROMs (the derivatives of Reactive Oxygen Metabolites) levels. In the present study, serum d-ROMs levels were prospectively examined in 52 patients with DLBCL and 12 healthy subjects by using the Free Radical Analytical System 4 (FRAS 4, Wismerll Co. Ltd., Tokyo, Japan). The d-ROMs test has been successfully used to evaluate oxidative stress in a very large number of studies on humans and animals. The d-ROMs test essentially determines the concentration of hydroperoxides in the blood, which are substances that belong to a broad class of reactive oxygen metabolites. The d-ROMs concentration is expressed in Carratelli Units (1 CARR U = 0.08mg hydrogen peroxide/dl). The study protocol and sampling were approved by the Institutional Review Board of Yokohama Municipal Citizen's Hospital, and it was carried out in accordance with the Declaration of Helsinki. [Results] The median follow-up time was 52 months. Median age at diagnosis was 74 years (range, 39-91 years) and 60% were male. 34 patients (65%) were stage 3-4 and 33 patients (63%) were R-IPI poor risk. The serum d-ROMs levels in patients with DLBCL were significantly elevated compared with normal controls (578.9+/-194.3 vs. 286.8+/-24.2 CARR U, P<0.001). In 52 DLBCL patients, patients with high serum d-ROMs levels (≥513 CARR U) had significantly shorter overall survival (OS) than those with low serum d-ROMs levels (<513 CARR U) (5-year OS, 37.9% versus 77.7%, respectively; P<0.001) (Figure. 1). In multivariate analysis, parameters having independent adverse significance for OS were: high serum d-ROMs levels (≥513 CARR U) (p=0.002, HR 5.17), high LDH levels (p=0.008, HR 4.58), and extranodal involvement >1 (p=0.002, HR 4.57). [Conclusion] In the present study we demonstrated that elevated serum d-ROMs levels are associated with poor prognosis in patients with DLBCL. In particular, our data proved that a high serum d-ROMs level is an independent prognostic factor for survival in patients with DLBCL. These results suggest that oxidative stress may have an important role in DLBCL and may be also a useful prognostic biomarker. Since our results are based on a small-sized analysis, further large prospective studies are warranted to verify this conclusion. Disclosures No relevant conflicts of interest to declare.

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Primary Mediastinal Large B-Cell Lymphoma: Investigation On The Role Of Rituximab and PET During Treatment

Blood ◽

10.1182/blood.v122.21.3046.3046 ◽

2013 ◽

Vol 122 (21) ◽

pp. 3046-3046 ◽

Cited By ~ 1

Author(s):

Pier Luigi Zinzani ◽

Cinzia Pellegrini ◽

Beatrice Casadei ◽

Enrico Derenzini ◽

Alessandro Broccoli ◽

...

Keyword(s):

Cell Lymphoma ◽

Disease Free Survival ◽

B Cell Lymphoma ◽

Additional Treatment ◽

Free Survival ◽

Large B Cell Lymphoma ◽

Disease Free ◽

Large B Cell

Abstract Due to limited prospective studies, the optimal treatment of primary mediastinal large B-cell lymphoma (PMLBCL) is still a matter of debate. Third-generation MACOP-B (adriamycin, cyclophosphamide, vincristine, bleomycin, methotrexate and prednisone) regimen in combination with mediastinal radiotherapy (RT) seems to improve disease free survival of patients. In addition, the impact of additional treatment with rituximab and the role of PET are still under investigation due to controversial reported results. As per institutional guidelines, MACOP-B plus RT was recommended in all PMLBCL patients until 2002. Aim of this report was evaluate the outcome of PMBCL patients diagnosed and treated with MACOP-B plus rituximab and consolidative mediastinal RT (30-36 Gy) after 2002. PET role was also investigated. Seventy-four patients were deemed eligible for this study (follow up of at least 2 years). Fifty patients had stage II and 24 stage IIE-IV, bulky disease was documented in 93% of patients. Median age was 34 years (range, 17-62) and 59.5% were females. All patients were evaluated by both CT and PET scan. After the final PET evaluation, PET-negative patients were observed while PET-positive patients underwent mediastinal RT. At the end of treatment, 61 (82.4%) patients achieved a complete response (CR); 51 (68.9%) presented a positive final PET and were treated with local RT, while the other 23 (31.1%) had a negative PET. Five patients relapsed within 12 months. At 10 years, estimated overall survival was 82%, progression-free survival was 87.6% and disease-free survival (DFS) for the 61 CR patients was 90.5% (median follow-up 4 years). Regarding the DFS curve (figure 1), no statistically significant differences were observed between patients who underwent also RT (PET-positive, group 1) and patients who remained under observation (PET-negative, group 2): 90.7% (4/51 relapses) vs 90% (1/23 relapse) (p= 0.85), respectively. Comparing these results with our institutional historical series when the front-line for PMLBCL patients included only MACOP-B plus RT without any decision related to PET results (before 2002), the 10-year DFS resulted lower, i.e. 82.8%. Although with the limitations of an observational retrospective study, the present report underlines that the additional treatment with rituximab does not change the final results in terms of CRs and DFS utilizing third-generation regimens. Moreover, the introduction of the PET-guided RT approach after MACOP-B plus rituximab allows a patient tailored strategy which reduces the use of RT and preserves clinical outcomes. Figure 1 Figure 1. Disclosures: No relevant conflicts of interest to declare.

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