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

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

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

scholarly journals Timing of high-dose methotrexate CNS prophylaxis in DLBCL: an analysis of toxicity and impact on R-CHOP delivery

2020 ◽  
Vol 4 (15) ◽  
pp. 3586-3593
Author(s):  
Matthew R. Wilson ◽  
Toby A. Eyre ◽  
Nicolas Martinez-Calle ◽  
Matthew Ahearne ◽  
Katrina E. Parsons ◽  
...  
Keyword(s):  
International Prognostic Index ◽  
Multivariable Analysis ◽  
Prognostic Index ◽  
B Cell Lymphoma ◽  
High Dose ◽  
High Dose Methotrexate ◽  
End Points ◽  
Cns Prophylaxis ◽  
Dose Methotrexate ◽  
Cns Relapse

Abstract High-dose methotrexate (HD-MTX) is increasingly used as prophylaxis for patients with diffuse large B-cell lymphoma (DLBCL) at high risk of central nervous system (CNS) relapse. However, there is limited evidence to guide whether to intercalate HD-MTX (i-HD-MTX) between R-CHOP-21 (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone given at 21-day intervals) or to give it at the end of treatment (EOT) with R-CHOP-21. We conducted a retrospective, multicenter analysis of 334 patients with DLBCL who received CNS prophylaxis with i-HD-MTX (n = 204) or EOT HD-MTX (n = 130). Primary end points were R-CHOP delay rates and HD-MTX toxicity. Secondary end points were CNS relapse rate, progression-free survival, and overall survival. The EOT group had more patients with a high CNS international prognostic index (58% vs 39%; P < .001) and more concurrent intrathecal prophylaxis (56% vs 34%; P < .001). Of the 409 cycles of i-HD-MTX given, 82 (20%) were associated with a delay of next R-CHOP (median, 7 days). Delays were significantly increased when i-HD-MTX was given after day 9 post–R-CHOP (26% vs 16%; P = .01). On multivariable analysis, i-HD-MTX was independently associated with increased R-CHOP delays. Increased mucositis, febrile neutropenia, and longer median inpatient stay were recorded with i-HD-MTX delivery. Three-year cumulative CNS relapse incidence was 5.9%, with no differences between groups. There was no difference in survival between groups. We report increased toxicity and R-CHOP delay with i-HD-MTX compared with EOT delivery but no difference in CNS relapse or survival. Decisions on HD-MTX timing should be individualized and, where i-HD-MTX is favored, we recommend scheduling before day 10 of R-CHOP cycles.

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

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

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

Safety of same day HD-MTX with induction therapy for DLBCL with concurrent CNS disease or as prophylaxis for high risk of CNS relapse.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e19545-e19545
Author(s):  
Brett Barlow ◽  
Haris Hatic ◽  
Charles Douglas Bodine ◽  
Amitkumar Mehta ◽  
Gaurav Goyal ◽  
...  
Keyword(s):  
High Risk ◽  
Induction Chemotherapy ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
B Cell Lymphoma ◽  
High Dose ◽  
Treatment Delays ◽  
Cns Disease ◽  
Cns Relapse ◽  
End Of Treatment

e19545 Background: High-dose methotrexate (HD-MTX) at a dose between 2.5 to 5 gm/m2 is commonly administered in conjunction with standard induction chemotherapy to patients with Diffuse Large B Cell Lymphoma (DLBCL) at high risk of central nervous system (CNS) relapse, as defined by the Lymphoma International Prognostic Index (CNS-IPI). Optimal timing of HD-MTX in relation to induction chemotherapy is unknown. A recent study suggested that HD-MTX intercalated with R-CHOP cycles was associated with increased toxicity and treatment delays without improvement in survival or CNS relapse compared with end of treatment MTX (Wilson et al 2020). This retrospective study evaluates the toxicities and treatment delays associated with HD-MTX administered on day 1 of cycles of chemo-immunotherapy. Methods: This single center retrospective cohort study included 45 patients (pts) with DLBCL with concurrent CNS disease or at high risk of CNS relapse who received HD MTX on day 1 of chemo-immunotherapy at our center. Data was abstracted from chart review and included variables describing clinical and treatment characteristics, time to MTX clearance, toxicities experienced and treatment delays. Results: 31 pts received HD-MTX on the day of R-CHOP chemotherapy, 6 pts received HD-MTX on the day of R-EPOCH (Rituximab, Etoposide, Doxorubicin, Vincristine, Cyclophosphamide, and Prednisone), and 8 pts received HD-MTX with R-MiniCHOP (dose reduced R-CHOP). Same day HD MTX with chemo-immunotherapy was associated with acute kidney injury (AKI; 17-25%), treatment delays >7 days (13-17%), and grade 2 mucositis (11-50%). The burden of toxicities was numerically higher in patients treated with R-EPOCH vs. R-CHOP (Table). Clinical outcomes are summarized in table below. Conclusions: In our heterogeneous population of pts, we describe that the incidence of toxicities and treatment delays experienced with same day HD-MTX are higher with R-EPOCH than with R-CHOP. Comparative studies with intercalated or end of treatment MTX will determine if the incidence of treatment delays, toxicities and de-escalations are higher with same day HD-MTX administration. [Table: see text]

Single-route CNS prophylaxis for aggressive non-Hodgkin lymphomas: real-world outcomes from 21 US academic institutions

Blood ◽  
2021 ◽  
Author(s):  
Victor Manuel Orellana-Noia ◽  
Daniel Reed ◽  
Ashley Alesia McCook ◽  
Jeremy Michael Sen ◽  
Christian M Barlow ◽  
...  
Keyword(s):  
High Risk ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
B Cell Lymphoma ◽  
Standard Of Care ◽  
High Dose ◽  
Cns Prophylaxis ◽  
Cns Relapse ◽  
Significant Difference ◽  
Relapse Rates

Prophylaxis is commonly used to prevent central nervous system (CNS) relapse in diffuse large B cell lymphoma, with no clear standard of care. We retrospectively evaluated 1162 adult patients across 21 US academic centers with DLBCL or similar histologies who received single-route CNS prophylaxis as part of frontline therapy between 2013-2019. Prophylaxis was administered intrathecally (IT) in 894 (77%) and using systemic high-dose methotrexate (HD-MTX) in 236 (20%); 32 patients (3%) switched route due to toxicity and were assessed separately. By CNS-International Prognostic Index (IPI), 18% were considered low-risk, 51% moderate, and 30% high. Double-hit lymphoma (DHL) was confirmed in 243 of 866 evaluable patients (21%). Sixty-four patients (5.7 %) had CNS relapse, after median 7.1 months from diagnosis, including 15 of 64 (23%) within the first 6 months. There was no significant difference in CNS relapse between IT and HD-MTX recipients (5.4 vs 6.8%, p=0.4), including after propensity score matching to account for differences between respective recipient groups. Weighting by CNS-IPI, expected versus observed CNS relapse rates were nearly identical (5.8 vs 5.7%). Testicular involvement was associated with high risk of CNS relapse (11.3%) despite most having lower CNS-IPI scores. DHL did not significantly predict for CNS relapse after single-route prophylaxis, including with adjustment for treatment regimen and other factors. This large study of CNS prophylaxis recipients with DLBCL found no significant difference in CNS relapse rates between routes of administration. Relapse rates among high-risk subgroups remain elevated and reconsideration of prophylaxis strategies in DLBCL is of critical need.

scholarly journals S5-KL-1 CURRENT TREATMENT FOR DLBCL AND PROPHYLAXIS AND TREATMENT FOR SECONDARY CNS LYMPHOMA

2019 ◽  
Vol 1 (Supplement_2) ◽  
pp. ii4-ii4
Author(s):  
Koji Izutsu
Keyword(s):  
High Risk ◽  
Cell Lymphoma ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
B Cell Lymphoma ◽  
Cns Lymphoma ◽  
High Dose ◽  
Large B Cell Lymphoma ◽  
Cns Relapse ◽  
Large B Cell

Abstract Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of lymphoma, comprising 30% of all lymphoma cases. More than 60% of patients can be cured with current standard treatment, R-CHOP. On the other hand, prognosis of patients with relapsed or refractory DLBCL is disappointing with less than 10% being cured with salvage chemotherapy followed by high-dose chemotherapy with autologous stem cell transplantation. Prognosis of patients with central nervous system (CNS) relapse is especially poor because of a limited treatment option. Thus, evaluating risks of CNS relapse at diagnosis and administering prophylaxis including intrathecal methotrexate (MTX) or systemic high-dose MTX concurrently with R-CHOP or as consolidation therapy in high-risk patients are often-used approach. Clinically, higher risk according to the International Prognostic Index and extranodal involvement in organs such as kidney, adrenal gland, breast, testis, or bone marrow are considered to be high-risk for CNS relapse. Recently, CNS-International Prognostic Index has been proposed to integrate aforementioned risk factors. Moreover, patients with intravascular large B-cell lymphoma, CD5+ DLBCL, double hit lymphoma are reported as high-risk for CNS relapse. Further, the MYD88 L265P mutation, a common mutation in primary CNS DLBCL (PCNSL) is also common in DLBCL of testis or breast, which are the sites associated with CNS relapse. Strategies for CNS prophylaxis have not established yet, and it is still unclear whether intrathecal MTX or high-dose MTX can prevent CNS relapse. Moreover, treatment for secondary CNS relapse have not been established. In particular, for those with both CNS and extra-CNS lesions, effective treatment options are very limited. The role of novel agents such as BTK inhibitors, lenalidomide, and immune check point inhibitors, whose efficacy have been shown for PCNSL, should be investigated further in the management of secondary CNS lymphoma.

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

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

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

Timing of high dose methotrexate CNS prophylaxis in DLBCL: a multicenter international analysis of 1,384 patients

Blood ◽  
2022 ◽  
Author(s):  
Matthew R. Wilson ◽  
Toby Andrew Eyre ◽  
Amy A Kirkwood ◽  
Nicole Wong Doo ◽  
Carole Soussain ◽  
...  
Keyword(s):  
High Risk ◽  
International Prognostic Index ◽  
Multivariable Analysis ◽  
B Cell Lymphoma ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Cns Prophylaxis ◽  
Dose Methotrexate ◽  
Cns Relapse ◽  
Increased Risk

Prophylactic high-dose methotrexate (HD-MTX) is often used for diffuse large B-cell lymphoma (DLBCL) patients at high risk of central nervous system (CNS) relapse, despite limited evidence demonstrating efficacy or the optimal delivery method. We conducted a retrospective, international analysis of 1,384 patients receiving HD-MTX CNS prophylaxis either intercalated (i-HD-MTX) (n=749) or at the end (n=635) of R-CHOP/R-CHOP-like therapy (EOT). There were 78 CNS relapses (3-year rate 5.7%), with no difference between i-HD-MTX and EOT; 5.7% vs 5.8%, p=0.98, 3-year difference: 0.04% (-2.0% to 3.1%). Conclusions were unchanged on adjusting for baseline prognostic factors or on 6-month landmark analysis (n=1,253). In patients with high CNS international prognostic index (n=600), 3-year CNS relapse rate was 9.1% with no difference between i-HD-MTX and EOT. On multivariable analysis, increasing age and renal/adrenal involvement were the only independent risk factors for CNS relapse. Concurrent intrathecal prophylaxis was not associated with reduction in CNS relapse. R-CHOP delays of ≥7 days were significantly increased with i-HD-MTX versus EOT, with 308/1573 (19.6%) i-HD-MTX treatments resulting in delay to subsequent R-CHOP (median 8 days). Increased risk of delay occurred in older patients when delivery was later than day 10 in the R-CHOP cycle. In summary, we found no evidence that EOT delivery increases CNS relapse risk versus i-HD-MTX. Findings in high-risk subgroups were unchanged. Rates of CNS relapse in this HD-MTX-treated cohort were similar to comparable cohorts receiving infrequent CNS prophylaxis. If HD-MTX is still considered for certain high-risk patients, delivery could be deferred until R-CHOP completion.

Diffuse Large B-Cell Lymphoma: Risk Stratification and Management of Relapsed Disease

Hematology ◽  
2005 ◽  
Vol 2005 (1) ◽  
pp. 252-259 ◽  
Author(s):  
John W. Sweetenham
Keyword(s):  
Gene Expression ◽  
Risk Stratification ◽  
B Cell ◽  
International Prognostic Index ◽  
Prognostic Significance ◽  
Prognostic Index ◽  
B Cell Lymphoma ◽  
Molecular Techniques ◽  
High Dose ◽  
Large B Cell

Abstract The clinical factors described by the International Prognostic Index (IPI) provide a model for risk stratification in diffuse large B-cell lymphomas (DLBCLs). However, there is variability in outcome within IPI risk groups, indicating the biological and clinical heterogeneity of these diseases. Studies of gene expression profiling (GEP) in DLBCL are uncovering biological heterogeneity with prognostic significance. Various gene expression signatures with predictive value independent of the IPI are now recognized. Immunophenotypic features of DLBCL have also been shown to have prognostic value. The use of fluorodeoxyglucose–positron emission tomography (FDG-PET) scanning may provide additional predictive information when used at diagnosis or soon after initiation of treatment. Future prognostic models in DLBCL are likely to incorporate functional imaging, immunophenotype and GEPs as well as clinical data in risk stratification and choice of treatment. Treatment of relapsed DLBCL remains a major problem. High-dose therapy (HDT) and stem cell transplantation (SCT) has been shown to produce superior overall survival (OS) compared with conventional dose salvage therapy in patients with relapsed, chemosensitive DLBCL. However, only 20% to 30% of patients are cured by this approach, and the effectiveness of HDT and SCT in patients treated with rituximab-based combinations as first-line therapy is unknown. Although new transplant techniques including non-myeloablative allogeneic SCT are being investigated, their role is unclear. New treatment strategies are needed for these patients. The use of molecular techniques such as GEP is identifying many potential new therapeutic targets in DLBCL including histone deacetylase, HLA-DR, bcl-2, bcl-6, mTOR and TRAIL.

scholarly journals Follicular lymphoma patients with a high FLIPI score and a high tumor burden: A risk stratification model

2015 ◽  
Vol 72 (1) ◽  
pp. 26-32 ◽  
Author(s):  
Bosko Andjelic ◽  
Milena Todorovic-Balint ◽  
Darko Antic ◽  
Jelena Bila ◽  
Vladislava Djurasinovic ◽  
...  
Keyword(s):  
Risk Factors ◽  
Overall Survival ◽  
Prognostic Factors ◽  
Follicular Lymphoma ◽  
Histological Grade ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
Tumor Burden ◽  
Cox Regression Analysis ◽  
High Tumor Burden

Background/Aim. The widely accepted Follicular Lymphoma International Prognostic Index (FLIPI) divides patients into three risk groups based on the score of adverse prognostic factors. The estimated 5-year survival in patients with a high FLIPI score is around 50%. The aim of this study was to analyse the prognostic value of clinical and laboratory parameters that are not included in the FLIPI and the New Prognostic Index for Follicular Lymphoma developed by the International Follicular Lymphoma Prognostic Factor Project (FLIPI2) indices, in follicular lymphoma (FL) patients with a high FLIPI score and high tumor burden. Methods. The retrospective analysis included 57 newly diagnosed patients with FL, a high FLIPI score and a high tumor burden. All the patients were diagnosed and treated between April 2000 and June 2007 at the Clinic for Hematology, Clinical Center of Serbia, Belgrade. Results. The patients with a histological grade > 1, erythrocyte sedimentation rate (ESR) ? 45 mm/h and hypoalbuminemia had a significantly worse overall survival (p = 0.015; p = 0.001; p = 0.008, respectively), while there was a tendency toward worse overall survival in the patients with an Eastern Cooperative Oncology Group (ECOG) > 1 (p = 0.075). Multivariate Cox regression analysis identified a histological grade > 1, ESR ? 45 mm/h and hypoalbuminemia as independent risk factors for a poor outcome. Based on a cumulative score of unfavourable prognostic factors, patients who had 0 or 1 unfavourable factors had a significantly better 5-year overall survival compared to patients with 2 or 3 risk factors (75% vs 24.1%, p = 0.000). Conclusion. The obtained results suggest that from the examined prognostic parameters histological grade > 1, ESR ? 45 mm/h and hypoalbuminemia can contribute in defining patients who need more aggressive initial treatment approach, if two or three of these parameters are present on presentation.

Cell of origin, germinal center versus nongerminal center, determined by immunohistochemistry on tissue microarray, does not correlate with outcome in patients with relapsed and refractory DLBCL

Blood ◽  
2005 ◽  
Vol 106 (10) ◽  
pp. 3383-3385 ◽  
Author(s):  
Craig H. Moskowitz ◽  
Andrew D. Zelenetz ◽  
Tarun Kewalramani ◽  
Paul Hamlin ◽  
Simone Lessac-Chenen ◽  
...  
Keyword(s):  
De Novo ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
B Cell Lymphoma ◽  
High Dose ◽  
Second Line ◽  
Cell Of Origin ◽  
Free Survival ◽  
Significant Difference ◽  
The Common

AbstractA number of prognostic factors affect outcome in patients with relapsed or primary refractory diffuse large B-cell lymphoma (DLBCL), including refractory disease and the second-line age-adjusted international prognostic index. In de novo DLBCL, the cell of orgin, as determined by expression microarray analysis or immunohistochemistry (IHC), predicts event-free survival (EFS). We evaluated the cell of origin, as well as other pathologic markers of outcome, on the repeat biopsy specimen of 88 transplantation-eligible patients undergoing ifosfamide, carboplatin, etoposide (ICE) second-line chemotherapy (SLT) followed by high-dose therapy (HDT) and autologous stem cell transplantation (ASCT) to see if were they prognostic in the salvage setting. Pretreatment clinical factors were well balanced between the cohorts. There was no significant difference in response to SLT, HDT, event-free or overall survival based on the cell of origin or any of the common pathologic markers examined. The cell of origin as determined by IHC does not predict outcome in transplantation-eligible patients with relapsed or primary refractory DLBCL.

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