scholarly journals Follicular Lymphoma Grade 3A Is Different from Grade 1/2 in the Real World

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4524-4524
Author(s):  
Chunyuan Li ◽  
Ping Yang ◽  
Wei Wan ◽  
Shuozi Liu ◽  
Hongmei Jing
Keyword(s):  
Follicular Lymphoma ◽  
De Novo ◽  
Conflicts Of Interest ◽  
Bone Marrow Involvement ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Time Frame ◽  
Clinical Approach ◽  
Ki 67 ◽  
The Difference

Abstract Background: follicular lymphoma (FL) is histologically subdivided into grades 1/2(FL1/2), 3A(FL3A), and 3B(FL3B). FL3B is more like diffuse large B-cell lymphoma (DLBCL), while the clinical approach to FL1/2 and FL3A has been debated. We aim to explore the clinical, biological characteristics and outcomes between them. Methods: A retrospective analysis of 195 de novo FL patients within the same time frame (1999 to 2020) was identified. 141 patients were FL1/2, and 54 patients were FL3A. Results: Comparing with FL1/2, FL3A patients tend to present ECOG≥1, B symptoms, bone marrow involvement, digestive tract involvement, elevated LDH, Ki-67≥30%, CD10 negative, and multiple myeloma oncogene-1(MUM1) positive, while Ann Arbor stage I or II was usually seen in FL1/2. After received CHOP±R (cyclophosphamide, doxorubicin, vincristine and prednisone ±rituximab), the 5-year overall survival (OS) was 89.5% for FL1/2 and 61.1% for FL3A [ HR =3.742(95%CI:1.838-7.620),P <0.0001], the 5-year progression-free survival (PFS) was 62.5 for FL1/2 and 47.6% for FL3A [ HR =2.113(95%CI:1.297-3.443),P =0.003]. Conclusion: FL3A is more aggressive both clinically and biologically compared with FL1/2, and more attention should be paid to the difference of treatment between them. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

R-EPOCH Is Superior to R-CHOP As a First-Line Regimen in De Novo DLBCL Patients with High Ki-67 Expression

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5085-5085
Author(s):  
Jia-Jia Huang ◽  
Wenqi Jiang ◽  
Zhi-Ming Li
Keyword(s):  
De Novo ◽  
Conflicts Of Interest ◽  
Performance Status ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
First Line ◽  
Ki 67 ◽  
Chop Regimen

Abstract Diffuse large B-cell lymphoma (DLBCL) patients with high Ki-67 expression receive limited benefits from R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) therapy. This study aims to compare the R-EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin) and R-CHOP regimens as first-line therapy in DLBCL patients with high Ki-67 expression. Data from 44 untreated DLBCL patients with high Ki-67 expression receiving R-EPOCH therapy were matched with those from 132 untreated DLBCL patients with high Ki-67 expression receiving R-CHOP therapy based on the International Prognostic Index (IPI: age, Ann Arbor stage, performance status, LDH level, number of extranodal sites), gender, and Ki-67 expression. In the R-EPOCH group, 42/44 patients were eligible for response evaluation. A total of 35 patients (83.3%) achieved complete remission (CR); 6 patients (14.3%) achieved partial remission (PR); and one patient (2.4%) exhibited progressive disease (PD) after 2 cycles of therapy. Patients in the R-EPOCH group presented better survival outcomes than those in the R-CHOP group (3-year overall survival [OS]: 89.9% vs. 70.2%, p=0.041; 3-year progression-free survival [PFS]: 86.6% vs. 59.7%, p=0.024). The survival superiority of the R-EPOCH over the R-CHOP regimen persisted when considering only patients of low-to-intermediate IPI risk, but it was not observed in those of high IPI risk. Our data suggest that R-EPOCH is superior to R-CHOP as a first-line regimen in DLBCL patients with high Ki-67 expression, especially in those of low-to-intermediate IPI risk. Disclosures No relevant conflicts of interest to declare.

scholarly journals The Distinct Clinical Features and Prognosis of the CD10+MUM1+ and CD10-Bcl6-MUM1- Diffuse Large B-Cell Lymphoma

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3895-3895
Author(s):  
Tingxun Lu ◽  
Yi Miao ◽  
Jia-Zhu Wu ◽  
Qi-Xing Gong ◽  
Jin-Hua Liang ◽  
...  
Keyword(s):  
Clinical Features ◽  
Clinical Characteristics ◽  
Conflicts Of Interest ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Positive Staining ◽  
Double Positive ◽  
Dual Color ◽  
The Difference

Abstract Introduction: Based on combination of the three markers (CD10, Bcl6 and MUM1), Hans algorithm could divide DLBCL into two groups (GCB and non-GCB subtype). Although MUM1 is used as a post GC marker, cases with coexpression of CD10 and MUM1 (CD10+ MUM1+, double positive or DP), which was classified as GCB subtype according to Hans algorithm, do exsit. However, the differences of clinical characteristics and prognosis between DP and other GCB (GCB excluding DP) is unknown. Additionally, DLBCL without any positive staining of these three markers (CD10¨C Bcl6¨C MUM1¨C, triple negative or TN) were also noted. These cases, based on Hans algorithm, are classified as non-GCB subtype. However, little was known about the difference between TN cases with GCB or other non-GCB (non-GCB excluding TN). Patients and methods: Immunohistochemistry was appiled in this study with the antibodies as follows. CD10 (clone 56C6, Dako), CD20 (clone L26, Abcam), Bcl6 (clone LN22, Dako), and MUM1 (clone MUM1p, Dako), FOXP1 (clone JC12, Abcam), GCET1 (clone RAM341, Abcam), LMO2 (clone 1A9-1, Santa Cruz), Myc (clone Y69; Abcam, cut-off: 40%) and Bcl2 (clone 124; Dako, cut-off: 50%). Fluorescence in situ hybridization (FISH) was carried out according to manufacturer¡¯s instructions on with the following probes: MYC dual-color, break apart translocation probe (Vysis LSI) and IGH/BCL2 dual-color, and dual fusion translocation probe (Vysis LSI). For cases with MYC translocation, BCL6 dual-color break apart rearrangement probe (Vysis LSI) wasfurtheranalyzed. A total of 601 cases were included in the study. Among these, 306 cases were treated with rituximab based chemoimmunotherapy and well follow up. The median follow up time was 24.3 months (1 to 115.4 months).We analyzed the clinical features of different groups: GCB vs. non-GCB; DP vs. other GCB (GCB*) or non-GCB; TN vs. other non-GCB (non-GCB*) or GCB. Besides, we further analyzed the survival differences among above groups in patients who were treated with rituximab based chemoimmunotherapy and well followed up. Results: The incidence of the DP patients was 13.3% (80/601, 95%CI: 10.7%-16.3%). The DP phenotype was more likely to occur in elderly patients (P =0.0432) and associated with poor PS status (P =0.0192) than GCB* phenotype. Additionally, although not statistically significant, the DP group showed higher incidence of double hit lymphoma (DHL) than GCB* patients (10.7% vs 2.9%, P =0.139). However, the DP group showed more frequent incidence of double expression lymphoma (DEL, Myc and Bcl2 coexpression) (P =0.044), MYC rearrangement (P =0.016) and DHL (P =0.029) than non-GCB group. The incidence of the TN patients was 8.8% (53/601, 95%CI: 6.7%-11.4%). There was no difference in any of clinical characteristics between the TN and GCB group. However, advanced Ann Arbor stage (III or IV) (P =0.0442), better PS status (P =0.0321), high-risk IPI (P =0.0042) Myc expression as well as BCL2 rearrangement were significantly more common in the non-GCB* group than the TN group. The DP group showed similar overall survival (OS) (median OS: both not reached, P =0.3650) and progression-free survival (PFS) (median PFS: 47.0 vs. 32.7 months, P =0.0878) with the non-GCB group while the TN group showed similar OS (median OS: both not reached, P =0.9278) and PFS (median PFS: both not reached, P =0.9420) with the GCB group (Fig 1-2). Conclusion: Cases in the DP and TE group might hinder the intrinsic power of Hans algorithm in other studies. More detailed classification of DLBCL based on Hans algorithm may help to identify patients with distinct clinical characteristics and prognosis, thereby improving the stratification of patients for risk-adjusted therapies. Disclosures No relevant conflicts of interest to declare.

Addition of Rituximab to Chemotherapy Alters the Prognostic Impact of Tumor-Associated Macrophages in Diffuse Large B-Cell Lymphoma

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2650-2650
Author(s):  
Sari Riihijärvi ◽  
Maria Pöyhönen ◽  
Minna Taskinen ◽  
Marja-Liisa Karjalainen-Lindsberg ◽  
Sirpa Leppä
Keyword(s):  
De Novo ◽  
Conflicts Of Interest ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
High Dose Chemotherapy ◽  
Control Group ◽  
High Dose ◽  
Prognostic Impact ◽  
Tumor Associated Macrophages ◽  
Kaplan Meier

Abstract Abstract 2650 Background: Tumor associated macrophages (TAM) have at least two potential roles in promoting tumor growth: suppression of immune responses and potentiation of angiogenesis. In numerous cancer types, including lymphomas, high M2 type TAM content has been associated with worse prognosis. Rarely, high TAM content correlates with better survival. We have recently shown that CD68 positive TAMs in DLBCL contribute to unfavorable survival after high dose chemotherapy. Here we have extended our analyses on M2 type macrophages and questioned how combination of rituximab with chemotherapy influences TAM-associated clinical outcome. Patients and Methods: Expression of CD163 and CCL18, which are primarily expressed in M2 type macrophages, were identified immunohistochemically from samples of 101 de novo DLBCL patients treated with rituximab in combination with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone)-like regimen (immunochemotherapy). With a median follow-up of 65 months, (range 16–114 months), 5-year progression free survival (PFS) was 70% and overall survival (OS) 73%. 29 DLBCL patients previously treated with up front high dose chemotherapy served as a control group. Results: Correlation between CD163 and CCL18 positive TAMs was found (rs=0.427, p<0.001). In the Kaplan-Meier analyses the cutoff level of 67% was found to best discriminate between subgroups with different outcomes. Consistent with previous data, chemotherapy-treated patients with high CD163 or CCL18 positive TAM counts displayed a significantly inferior OS and PFS than the low group (Table). In contrast, after rituximab containing regimen, the patients with high CD163 and CCL18 positive TAM content tended to have favorable survival. Among the patients with low counts in both CD163 and CCL18 positive TAMs, PFS and OS were found to be significantly worse in comparison to others. Conclusions: In contrast to data on chemotherapy treated DLBCL or other lymphoma types, M2 type TAM content is associated with favorable prognosis in DLBCL patients after immunochemotherapy. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Relapses of Diffuse Large B Cell Lymphoma in Rituximab Era Are Limited to the First Two Years after Frontline Therapy

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1307-1307 ◽  
Author(s):  
Tatyana Feldman ◽  
Larysa Gromko ◽  
Ewelina A Protomastro ◽  
Lina Starovoitova ◽  
Anthony R. Mato ◽  
...  
Keyword(s):  
De Novo ◽  
Conflicts Of Interest ◽  
Cohort Analysis ◽  
Community Setting ◽  
B Cell Lymphoma ◽  
Cancer Center ◽  
Cell Transplant ◽  
Ki 67 ◽  
Frontline Therapy

Abstract Background: Rituximab has increased the CR rate, improved both PFS and OS and changed the pattern of relapse of DLBCL pts treated with R-CHOP (leading to a > 50% cure). In contrast to the pre rituximab era, the majority of failures occur early (80% of failures occur in the 1st 18 months). The observation made that few relapses (7-8%) occur after 24 months of pts enrolled in clinical trials needs validation in the community setting. We report here a large cohort of pts treated at our institution over a period of 7 years with rituximab-containing chemotherapy regimens. Methods:We performed a retrospective cohort analysis to describe the survival experiences of adult patients with de novo DLBCL treated at our institution between 2007 and 2013. Patients were identified using Hematopathology and John Theurer Cancer Center outcomes databases. Patients who didn’t receive rituximab as part of their initial combination chemotherapy were excluded, as well as transformed DLBCL, primary CNS DLBCL, HIV-related DLBCL pts, those lacking follow up data. Results: A total of 245 patients with DLBCL treated at our institution were identified. Baseline characteristics were as follows: median age was 63 (20-92), 53% males, 75% stage III-IV and 24% stage I-II; IPI score was high in 25% of pts, high-int in 22%, low-int in 45% and low in 7%. Most patients received R-CHOP (66%), while 34% were treated with dose intense regimens based on high risk features such as high IPI, Ki-67 over 80% (R-HyperCVAD, DA-R-EPOCH, R-Magrath), only two patients had frontline planned stem cell transplant. 91% of the patients achieved a CR, 7% were primary refractory (progressed during therapy), 2% PR/SD ). With a median follow up time of 32.5 months, the median OS and PFS have not been reached (75% of patients are alive at 55.9 months). In contrast, the median OS of relapsed patients was only 14.4 months No gender-specific differences in survival were observed. No differences in PFS and OS were observed based on frontline chemotherapy regimen. Achieving CR significantly determines survival (p.<05, LR test). Relapses occurred within first 24 months in 54 out of total of 60 patients who relapsed after frontline therapy. Conclusion: Our series confirm outside clinical trial setting that in contrast to the pre-rituximab era, late relapses are rarely observed in patients treated with rituximab–containing induction therapy. The majority of relapses occur within the first two years of the initial therapy. Our findings validate the data from the Mayo clinic experience (Maurer et al, JCO 2014). This observation not only provides reassurance to patients but also support the current imaging guidelines with no longer a need for routine imaging surveillance for relapse in DLBCL beyond 2 years after frontline therapy. Figure 1 Figure 1. Figure 2 Figure 2. Figure 3 Figure 3. Disclosures No relevant conflicts of interest to declare.

The role of translocations involving c-MYC/8q24, BCL2/18q21 and/or BCL6/3q27 genes in patients with follicular lymphoma. Retrospective analysis of single - centre data

2019 ◽  
Vol 91 (7) ◽  
pp. 52-62
Author(s):  
A E Misyurina ◽  
S K Kravchenko ◽  
A M Kovrigina ◽  
A U Magomedova ◽  
L V Plastinina ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
B Cell ◽  
Clinical Characteristics ◽  
Cell Transformation ◽  
Cell Lymphoma ◽  
Bone Marrow Involvement ◽  
B Cell Lymphoma ◽  
High Grade ◽  
Ki 67 ◽  
Double Hit

Aim of the issue was to compare clinical characteristics and treatment results of patients with follicular lymphoma (FL) with translocations involving loci of c-MYC/8q24, BCL2/18q21 and/or BCL6/3q27 genes and patients with high - grade B-cell lymphoma [High - grade B-cell lymphoma (HGBL), double - hit (DH)]. Materials and methods. Since 2004 to 2017 years in National Research Center for Hematology 12 patients with high - grade B-cell lymphoma double - hit (HGBL DH) and 6 FL patients with translocations involving c-MYC and BCL2 and/or BCL6 had been treated. We performed a comparative analysis of clinical characterisctics in both groups. As primary endpoints was assessed frequency of complete remission (CR) or progressive disease (PD); as secondary endpoints - overall (OS) and event - free survival (EFS). Results. 5 patients with HGBL DH had c-MYC/BCL6, 7 - c-MYC/BCL2 rearrangements; 2 patients with FL had c-MYC/BCL2, 3 - c-MYC/BCL6, 1 - c-MYC/BCL2/BCL6 rearrangements. FL was represented by grade 3A in 2, grade 3B - in 4 cases, 3 of them had large - cell transformation. In HGBL DH and FL patients had no significant differences in clinical characteristics. The majority of patients had a widespread tumour, increased LDH activity, high frequency of extranodal and bone marrow involvement. Ki-67 expression level was lower in patients with FL (p

Tissue Microarray Is a Useful Tool in the Evaluation of Genes Implicated in Transformation of Follicular Lymphoma.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2267-2267 ◽  
Author(s):  
Abigail Lee ◽  
Andrew Davies ◽  
Andrew Clear ◽  
Maria Calaminici ◽  
Janet Matthews ◽  
...  
Keyword(s):  
Gene Expression ◽  
Follicular Lymphoma ◽  
Tissue Microarray ◽  
Molecular Mechanisms ◽  
De Novo ◽  
B Cell Lymphoma ◽  
Follicular Dendritic Cell ◽  
Response To Therapy ◽  
Aurora Kinase B ◽  
General Response

Abstract A subset of patients (pts.) with follicular lymphoma (FL) will transform to a more aggressive histological sub-type, most typically diffuse large B-cell lymphoma (DLBCL). In general response to therapy is poor and survival short. Paired analysis of samples pre- and post transformation suggest that the molecular mechanisms underlying transformation (Tx) are heterogeneous. In order to independently validate recurring changes in gene/protein expression at transformation (GC phenotype of TxDLBCL, Davies et al., 2002; loss of follicular dendritic Cell (FDC) markers, Shiozawa et al., 2003) a Tx-tissue microarray (Tx-TMA) was created comprising serial samples from 35 pts. (median age 54yrs (22–81) at the time of transformation). In these pts. transformation occurred a median of 3.1years from diagnosis (range 0–15.4) and for each pt. ‘set’ at least 1 pre-Tx FL sample (1–3; n=56), and 1 (1–4; n=44) post transformation sample were represented on the array. To ensure that the Tx-TMA cores accurately represented the corresponding full tissue sections a panel of routine immunohistochemical (IHC) diagnostic markers (n=9) were scored. The concordance between Tx-TMA and full sections (n=10) was >90%. The Tx-TMA was then used to investigate the phenotype of transformed DLBCL, according to the germinal centre (GC)/non-GC like model of de novo DLBCL. Using CD10, BCL6 and MUM1 expression to discriminate between the two subclasses of DLBCL the methodology was first validated on a de novo DLBCL TMA (n=31; 20/31 (65%) non-GC, 11/31 (35%) GC phenotype; 5-yr survival for non-GC pts. 51% and for GC pts., 73%). IHC confirmed the results of gene expression profiling indicating that in 31/35 (89%) pts. transformed DLBCL was of GC phenotype (28/35 (80%) CD10+ and 3/35 (9%) CD10-, BCL6+, MUM1-). Of the remainder, 4/35 were CD10-, BCL6+, of which 3/4 were MUM1+ (3/35 (9%) non-GC phenotype; 1/4 MUM1 was not assessable). Similarly the Tx-TMA confirmed loss of FDC markers (CD21 and CD23) on transformation. Samples from 28 pts were evaluable for CD21 and CD23 IHC expression. In 71% (20/28) of pts. the FDC meshwork was lost or became more sparse on transformation (CD21 loss 15/28 (54%); CD23 loss 17/28 (61%)). The most discriminating changes in gene expression on transformation are now being assessed by IHC. Aurora kinase B (ARKB) is an attractive therapeutic target given that disruption of ARK function results in the induction of apoptosis in RL, a t(14:18) positive DLBCL cell line (Harrington et al. 2004). The observed elevation in ARKB transcription on transformation was confirmed by IHC in this series. The Tx-TMA showed ARKB expression increased on Tx in 13/33 (40%) pts., potentially defining a subset of pts. who might be considered for ARKB directed therapies. Expression of ARKB was low throughout in 18/33 (55%) pts and decreased in 2/33 (6%) pts.; difference in ARKB expression was not significantly associated with survival. These preliminary studies suggest that the availability of TMA of serial biopsies from pts. with transformed FL will provide a powerful means of assessing the relevance of gene expression, both within the tumour and the microenvironment while facilitating the selection of patients most likely to benefit from directed therapeutic approaches.

The Follicular Lymphoma International Prognostic Index (FLIPI) as Part of a Proposed Prognostic Model for Follicular Lymphoma Patients Undergoing Autologous Hematopoietic Stem Cell Transplantation (ASCT).

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 12-12 ◽  
Author(s):  
Grant E. Keeney ◽  
Theodore A. Gooley ◽  
Oliver W. Press ◽  
John M. Pagel ◽  
Stephen H. Petersdorf ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Median Number ◽  
Hematopoietic Stem ◽  
Prior Chemotherapy ◽  
Five Factors ◽  
Grade 3

Abstract The FLIPI has recently been demonstrated to correlate with survival in patients (pts) with newly diagnosed follicular lymphoma (FL). No such index has been developed or evaluated to predict outcome for FL pts in the setting of myeloablative therapy and ASCT, despite data suggesting that ASCT may improve overall and progression-free survival (PFS). We examined the factors that contribute to the FLIPI as well as other factors assessed at time of transplant for their association with overall survival (OS) in 189 pts undergoing ASCT for FL. Baseline characteristics included: median age = 47 years (range, 24 – 64), stage III–IV = 94%, &gt;4 nodal areas = 7.7%, elevated LDH = 30%, &gt;5 cm maximal bulk of disease = 18%, chemoresistant disease = 13%, median number of prior chemotherapy regimens = 2. The FL histologies included: Grade 1 (49%), Grade 2 (31%), Grade 3 (13%), and transformation to diffuse large B-cell lymphoma (6%). Patients were conditioned with chemotherapy-only (21%), chemo+TBI (45%), or radioimmunotherapy +/− chemo (34%). Among all pts, the five-year estimated OS and PFS are 58% and 39%, respectively, with a median follow-up among surviving pts of 8 years (range, 1 – 18). The five factors that were found to be most significantly associated with OS include two FLIPI factors [age, hazard ratio for death (HR) = 1.37 per ten-year increase in age; elevated LDH, HR = 1.57] and three other clinical factors [&gt;1 maximal extranodal site of disease, HR = 1.67; ≥2 prior chemotherapy regimens, HR = 1.99; chemoresistant disease, HR = 2.8]. Patients with 0 – 1 adverse factors (with age dichotomized as &lt; 45 vs. ≥ 45) had an estimated 5-year OS of 79%, those with 2 factors 50%, 3 factors 41%, 4 or 5 factors 13% (Figure). Although prospective validation of this proposed model is required, this approach may be used to counsel FL pts regarding expected outcome following ASCT, to compare data between trials, and to design future studies. Figure Figure

The Efficacy of R-ICE Therapy as a Salvage Treatment for Relapse and Refractory Diffuse Large B-Cell Lymphoma.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4441-4441
Author(s):  
Makoto Kodaira ◽  
Masahiro Yokoyama ◽  
Hiroaki Asai ◽  
Shuhei Yamada ◽  
Kyoko Ueda ◽  
...  
Keyword(s):  
B Cell ◽  
De Novo ◽  
Cell Lymphoma ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Salvage Chemotherapy ◽  
Salvage Treatment ◽  
Large B Cell Lymphoma ◽  
Grade 3 ◽  
Large B Cell

Abstract <Background> Patients with relapsed and refractory diffuse large B-cell lymphoma are usually treated with platinum-based salvage chemotherapy. We retrospectively analyzed the efficacy of adding rituximab with ICE as a salvage treatment for relapsed and refractory diffuse large B-cell lymphoma. <Method>From November 2003 to December 2006, patients with relapsed or refractory de novo diffuse large B-cell lymphoma represented CD20 positivty who received R-ICE (rituximab375mg/m2, Ifosfamide 1200mg/m2, calboplatin 400mg/m2 and etopside100mg/m2 ), were analyzed retrospectively. <Result>23 patients (19 relapse and 4 reflactory) (M:F=14:9) (median age 69, 28–77) were included. At starting treatment, twelve patients received rituximab and 11 patients were rituximab naive. In all 23 patients, responses were 11 Complete remission (CR), and 6 partial response (PR), resulting in overall response (ORR) was 74.9%. With median follow up of 10.5 months, estimated 1yr-progression free survival (PFS) was 49% and 1yr-overall survival (OS) was 70%.In patients received rituximab, ORR was 66.7% and 5 patiets achieved CR (41.7%).In the without rituximab, ORR was 90.9% and 7 patiets achieved CR (63.6%). No statistical differences were observed in response even with retuximab pretreatment. Estimated 1yr-PFS was 23% and 70% (p=0.0752) and 1yr-OS was 59% and83% (P=0.0049),respectively. NCI-CTC grade 3/4 neutropenia and thrombocytopenia were reported 100% and 91%, For non-hematological adverse event, there were grade 3 liver dysfunction (2/23) and grade 3 arrythmia (1/23). No toxic death was reported in this study. <Conclusion> R-ICE showed promising efficacy with tolelable toxicity. Available date suggested adding rituximab to ICE is more effective for patients not received rituximab in the pretreament.

Radioimmunotherapy (RIT) with 90Y-Ibritumomab Tiuxetan (Zevalin) for the Treatment of Relapsed or Resistant Aggressive Diffuse Large B-Cell Lymphoma (DLBCL) Heavily Pretreated with Rituximab + Chemotherapy: A GIMURELL Experience.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4478-4478 ◽  
Author(s):  
Barbara Botto ◽  
Marilena Bellò ◽  
Giulia Benevolo ◽  
Maria Giuseppina Cabras ◽  
Claudia Castellino ◽  
...  
Keyword(s):  
De Novo ◽  
Cell Lymphoma ◽  
Bone Marrow Involvement ◽  
B Cell Lymphoma ◽  
Aggressive Lymphoma ◽  
Ibritumomab Tiuxetan ◽  
Large B Cell Lymphoma ◽  
Heavily Pretreated ◽  
Previously Treated ◽  
Grade Iii

Abstract Introduction: The addition of antibody monoclonal anti CD20 Rituximab to CHOP chemotherapy has resulted in improved CR, progression free survival and overall survival rates for patients affected by diffuse large B cell lymphoma. Recently, RIT with Zevalin has been shown effective in the treatment of relapsed refractory elderly DLBCL. We report the results of a study to evaluate the efficacy and safety of Zevalin in relapsed or chemoresistant aggressive lymphoma previously treated with Rituximab. Patients and methods: Elegibility criteria were as follows: age over 18 years, refractory or chemoresistant CD20+ aggressive lymphoma (grade III follicular, PML or DLBCL de novo) WHO performance status of 0 to 2, stage II bulky, III or IV, bone marrow involvement < 25%, written informed consent in accordance with institutional guidelines. All patients were previously treated with Rituximab and almost two lines of chemotherapy. Patients with pre-treatment platelet counts of > 150.000/mm3 received Zevalin at 0.4 mCi/kg whereas those with platelets < 150.000/mm3 received 0.3 mCi/kg. Results: Fourteen patients were treated with RIT: 5 patients were stage II, 3 stage III, 6 stage IV (5 with bone marrow involvement). Six patients had grade III follicular, 4 primary mediastinal and 4 DLBCL de novo. Ten patients received 0.4 mCi/kg and 4 patients 0.3 mCi/kg. Five chemoresistant patients after 2 or more lines chemoimmunotherapy received RIT in combination with BEAM and subsequent autologous stem cell transplantation (ASCT) and 9 patients were treated with Zevalin alone. Two months after RIT we reported CR 4 patients, PR 5 patients and no response/progression 5 patients (ORR 9/14 patients 64%). All 5 patients treated with RIT + BEAM + ASCT achieved a response (CR 2 patients and PR 3 patients ORR 100%). ORR in 9 patients treated with RIT alone was 46% (CR 2 patients and PR 2 patients). No toxic deaths were observed, two patients died of lymphoma (one patients 1 year after Zevalin infusion and the second progressed and died 5 months after RIT). The most common grade 3–4 AE were neutropenia and thrombocytopenia. Discussion: RIT with 90Y-Ibritumomab Tiuxetan is a safe and effective approach for patients affected by aggressive lymphoma and heavily pretreated with Rituximab + chemotherapy. The effective role of RIT alone or in combination with high dose chemotherapy + ASCT as salvage therapy has to be studied in this subset of patients.

Thymidylate Synthase (TS) Expression In Diffuse Large B-Cell Lymphoma (DLBCL): Identification of a Potential Therapeutic Target

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 5107-5107
Author(s):  
Emilian Racila ◽  
Sergei I Syrbu ◽  
Michel Nasr ◽  
Malik E. Juweid
Keyword(s):  
Cell Proliferation ◽  
Therapeutic Target ◽  
De Novo ◽  
Conflicts Of Interest ◽  
Cell Lymphoma ◽  
Pearson Correlation ◽  
B Cell Lymphoma ◽  
P Values ◽  
Cell Staining ◽  
The Mean

Abstract Abstract 5107 Purpose: TS is critical for the de novo synthesis of thymidine needed for tumor cell proliferation and DNA damage repair, whereas thymidine kinase 1 (TK1) is key to the salvage pathway providing thymidine recovered from plasma. While TK1 expression has been previously shown to correlate with proliferation in DLBCL, little is known about TS levels in these neoplasms. We hypothesized that, similarly to TK1, TS expression levels associate with increased proliferation and thus may represent a novel therapeutic target in large cell lymphoma. Methods: To address this hypothesis, we determined the expression of TS in lymph node biopsies from 43 DLBCL patients sequentially enrolled in the study with no pre-selection criteria other than the primary histological diagnosis of lymphoma, and then compared it to TK1 expression. In addition, Ki-67 (MIB1) was included as an established marker of cell proliferation. Pearson correlation along with the correlation coefficient and two-tailed P values were calculated to measure the extent of covariation. Results: TS expression and both MIB1 and TK1 were significantly correlated with correlation coefficients of 0.43 and 0.65, respectively (95% CI 0.13 to 0.65 and 0.44 to 0.8; P values = 0.006 and <0.0001, respectively). The correlation between TS and MIB1 expression was in fact stronger than between MIB1 and TK1 (P values 0.006 and 0.04, respectively). Mean percent positive cells and standard deviations for MIB1, TS and TK1 were 44.5% (SD=35), 51.8% (SD=33.4), and 44% (SD=28.5), respectively. Despite the general good correlation, however, six patients had relatively high TS levels (defined as % cell staining above the mean for TS) and relatively low TK1 levels (% cell staining below the mean for TK1), while the reverse was true in seven patients. Eight patients had high levels of TK1 and TS with ≥ 70% cells positive for both; seven patients had low levels of both proteins (≤30% of cells stained). Conclusion and Significance: This is the first report of TS expression in DLBCL. TS is frequently expressed in DLBCL and there is a significant correlation between TS and TK1 or MIB1 expression. Further studies are warranted to determine the correlation between TS or TK1 expression and patient prognosis in comparison to MIB1. Importantly, the common expression of TS in patients with DLBCL indicates that TS may be a suitable target for TS inhibitors (TSIs) in these neoplasms. Preclinical studies are underway to test this hypothesis. Disclosures: No relevant conflicts of interest to declare.

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