Non-Hodgkin's Lymphoma Clinical Practice Guidelines

2006 ◽  
Vol 4 (3) ◽  
pp. 258 ◽  
Author(s):  
_ _
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Lymphocytic Leukemia ◽  
Aggressive Lymphoma ◽  
Molecular Characteristics ◽  
Mantle Cell ◽  
Histologic Types ◽  
Hodgkin's Lymphomas ◽  
Natural Histories

Non-Hodgkin's lymphomas (NHLs) may be classified on the basis of morphology, natural history, and immunophenotypic and molecular characteristics. These guidelines were developed for more common NHL histologic types, including chronic lymphocytic leukemia/small lymphocytic lymphoma, follicular lymphoma, and diffuse large B-cell lymphoma, and for less common entities with unique natural histories and therapies, such as marginal zone lymphoma, mantle cell lymphoma, and highly aggressive lymphoma subtypes, including Burkitt's, and lymphoblastic lymphomas and AIDS-related B-cell lymphomas. Certain components of the diagnosis and therapy of the various NHLs are similar. In all cases, an accurate pathologic diagnosis must first be made. For the most recent version of the guidelines, please visit NCCN.org

Safety and Efficacy of Bendamustine with or without Rituximab in the Treatment of Heavily Pretreated Patients with Haematological Malignancies: A Multicenter Retrospective Study

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4945-4945 ◽  
Author(s):  
Luigi Rigacci ◽  
Benedetta Puccini ◽  
Alberto Bosi ◽  
Sergio Cortelazzo ◽  
Sergio Storti ◽  
...  
Keyword(s):  
B Cell ◽  
Mantle Cell Lymphoma ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Lymphocytic Leukemia ◽  
Large B Cell Lymphoma ◽  
Mantle Cell ◽  
Heavily Pretreated ◽  
Pretreated Patients ◽  
Large B Cell

Abstract Bendamustine is an purine analog alkylating agent with marked efficacy in haematological malignancies either when given as monotherapy or in combination with rituximab. The efficacy and safety of this drug was investigated in heavily pretreated patients (pts) with hematological malignancies. A total of 44 patients (median age 63 years ranging from 22–87) from 6 Italian centers treated with bendamustine alone or in combination with rituximab were analyzed in this retrospective study. The diagnoses were multiple myeloma (n=2), chronic lymphocytic leukemia or small lymphocytic lymphoma (n=19), diffuse large B cell lymphoma (n=7), follicular lymphoma (n=8), mantle cell lymphoma (n=4), marginal zone lymphoma (n=2), Hodgkin’s disease (n=1) and peripheral T cell lymphoma (n=1). All pts received bendamustine 60–90 mg/m2 at day 1+2, alone or in combination with rituximab 375 mg/m2 (n=35) at day 1 of each cycle given every 21 or 28 days. The pts were heavily pretreated with a median of 3 previous treatments (range 1–8); 37 pts had previously received rituximab and 9 pts had undergone autologous transplantation. Prior to receiving bendamustine, 14 pts had relapsed disease, 7 had refractory disease and 23 were progressing during therapy. The median number of bendamustine cycles was 3 (range 1–8); 11 pts were still on treatment at the time of this analysis. Patients who completed therapy with at least 1 cycle of chemotherapy were evaluated for response and toxicity; pts in continuous therapy were evaluated for toxicity only. Of 33 pts evaluable for response 7 pts achieved a CR (21%) and 14 a PR (42%) resulting in an ORR of 64%. The remaining 12 pts were non-responders. No differences in the results were observed between groups with different bendamustine doses or scheduling. The best results were obtained in 10 evaluable pts with indolent lymphoma (4 CR, 6 PR) and in 9 pts with chronic lymphocytic leukemia (1 CR, 6 PR). Two evaluable pts with mantle cell lymphoma obtained a response (1 CR, 1 PR). By contrast, only 1 pt with diffuse large B cell lymphoma of 6 patients evaluable for response obtained a CR: the other 5 were non-responders. No pt with myeloma, Hodgkin’s disease or T cell lymphoma achieved a response. After a median follow-up of 4 months, 80% of pts were alive. During 150 treatment cycles, 2 pts experienced grade 4 thrombocytopenia and 1 experienced grade 4 neutropenia; non-hematological toxicity was mild. In conclusion, this retrospective analysis shows that treatment with bendamustine, alone or in combination with rituximab, is a safe and effective regimen in heavily pretreated pts. The best results were obtained in indolent lymphoma: the data in mantle cell lymphoma were also encouraging. No lack of efficacy can be inferred in pts with diffuse large B cell lymphoma, due to the refractory nature of their disease and the advanced age of this particular group (median age 76 years ranging from 67–87).

scholarly journals Apoptotic Blocks in Primary Non-Hodgkin B Cell Lymphomas Identified by BH3 Profiling

Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1002
Author(s):  
Ryan N. Rys ◽  
Claudia M. Wever ◽  
Dominique Geoffrion ◽  
Christophe Goncalves ◽  
Artin Ghassemian ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Poor Response ◽  
Lymphocytic Leukemia ◽  
Low Grade ◽  
High Grade ◽  
Microtubule Inhibitors ◽  
Mantle Cell ◽  
Induced Apoptosis

To determine causes of apoptotic resistance, we analyzed 124 primary B cell NHL samples using BH3 profiling, a technique that measures the mitochondrial permeabilization upon exposure to synthetic BH3 peptides. Our cohort included samples from chronic lymphocytic leukemia (CLL), follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), high-grade B cell lymphoma with translocations in MYC and BCL2 (HGBL-DH), mantle cell lymphoma (MCL) and marginal zone lymphoma (MZL). While a large number of our samples displayed appropriate responses to apoptosis-inducing peptides, pro-apoptotic functional defects, implicating BAX, BAK, BIM or BID, were seen in 32.4% of high-grade NHLs (12/37) and in 3.4% of low-grade NHLs (3/87, p < 0.0001). The inhibition of single anti-apoptotic proteins induced apoptosis in only a few samples, however, the dual inhibition of BCL2 and MCL1 was effective in 83% of samples, indicating MCL1 was the most common cause of lack of response to the BCL2 inhibitor, venetoclax. We then profiled Toledo and OCI-Ly8 high-grade lymphoma cell lines to determine which drugs could reduce MCL1 expression and potentiate venetoclax responses. Doxorubicin and vincristine decreased levels of MCL1 and increased venetoclax-induced apoptosis (all p < 0.05). Overall, in primary NHLs expressing BCL2 that have no defects in pro-apoptotic signaling, a poor response to venetoclax is primarily due to the presence of MCL1, which may be overcome by combining venetoclax with doxorubicin and vincristine-based chemotherapy or with other anti-microtubule inhibitors.

Pattern of Mir-155 and PU.1 Expression in CLL/SLL and Aggressive Lymphomas

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4600-4600
Author(s):  
Tomas Stopka ◽  
Karin Vargova ◽  
Hana Huskova ◽  
Pavel Burda ◽  
Nikola Curik ◽  
...  
Keyword(s):  
B Cell ◽  
Conflicts Of Interest ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Lymphocytic Leukemia ◽  
Peripheral T Cell Lymphoma ◽  
Lymphoid Malignancies ◽  
Mantle Cell ◽  
Prognostic Groups ◽  
Nfkb Pathway

Abstract Abstract 4600 MicroRNA miR-155 represents a candidate pathogenic factor in chronic lymphocytic leukemia (CLL) and lymphomas (Eis PS, et al. 2005, Fulci V, et al. 2007, Calin GA, et al. 2005, Kluiver J, et al. 2005, Metzler M, et al. 2004, van den Berg A, et al. 2003., Vargova K. et al 2011). In diffuse large B-cell lymphoma (DLBCL) expression of miR-155 was associated with NFkB pathway (Rai et al., 2008). In addition, increased miR-155 levels were associated with more aggressive (Activated B-cell like) DLBCL (Eis et al. 2005). The targets of up-regulated miR-155 apparently include a key hematopoietic transcription factor PU.1. Down-regulation of PU.1 represents an important and critical step for both myeloid as well as lymphoid tumorigenesis. We herein found the increased levels of miR-155 coupled with downregulation of its target PU.1 are frequent events in B cells of a vast majority of CLL patients (N=169). To advance understanding of miR-155 and PU.1 in lymphoid malignancies we studied lymph node biopsies derived from patients with lymphomas. We show that increased miR-155 levels are also found in DLBCL (N=31, P < 0.0001), Hodgkin lymphoma (HL, N=22, P < 0.0001), follicular lymphoma (FL, N=23, P < 0.001), small lymphocytic lymphoma (SLL, N=12, P < 0.01), and marginal zone lymphoma (MZL, N=11, P < 0.01). The miR-155-overexpressing tumors display downregulation of PU.1. In contrast, peripheral T cell lymphoma (T-NHL, N=6) and mantle cell lymphoma (MCL, N=7) expressed miR-155 and PU.1 comparably as control lymph nodes. Our data indicate that expression pattern of miR-155 and its target PU.1 represents a hallmark of some but not all lymphoid malignancies. Interestingly, the miR-155/PU1 levels vary substantially within each diagnosis, therefore, our aim is to further analyze the occurrence of this relationship in different prognostic groups and analyze the clinical outcome as well. (Grants: NT10310-3/2009 & NT11218-6/2010, MPO FR-TI2/509, GAUK251135 82210 & 251070 45410, SVV-2011-262507) Disclosures: No relevant conflicts of interest to declare.

scholarly journals Richter transformation in the era of novel agents

Hematology ◽  
2018 ◽  
Vol 2018 (1) ◽  
pp. 256-263 ◽  
Author(s):  
Wei Ding
Keyword(s):  
B Cell ◽  
De Novo ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Lymphocytic Leukemia ◽  
Novel Agents ◽  
Aggressive Lymphoma ◽  
Management Approach ◽  
Large B Cell Lymphoma ◽  
Large B Cell

AbstractRecent approvals of several oral targeted agents have revolutionized chronic lymphocytic leukemia (CLL) therapy. However, CLL patients continue to progress; particularly, 4% to 20% of previously treated CLL patients undergo transformation into high-grade lymphoma. Richter transformation is defined as a transformation of CLL into aggressive lymphoma, most commonly diffuse large B-cell lymphoma. These patients typically have poor response to traditional chemotherapy used to treat de novo diffuse large B-cell lymphoma and similar or shorter overall survival (median 3-11 months) in the era of novel agents. Here, I review the contemporary literature on Richter transformation, particularly in the context of novel agents used in CLL, and discuss the management approach for these patients.

Diffuse Aggressive Lymphoma

Hematology ◽  
2004 ◽  
Vol 2004 (1) ◽  
pp. 221-236 ◽  
Author(s):  
Richard I. Fisher ◽  
Thomas P. Miller ◽  
Owen A. O'Connor
Keyword(s):  
B Cell ◽  
Mantle Cell Lymphoma ◽  
Phase Ii ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Standard Of Care ◽  
Large B Cell Lymphoma ◽  
Mantle Cell ◽  
Hodgkin's Lymphomas ◽  
Large B Cell

Abstract The aggressive non-Hodgkin’s lymphomas can be cured in more than half of the cases. However, there has been great variation in the results reported from individual clinical Phase II trials. This variation in result can be attributed to unrecognized heterogeneity in this group of diseases. Recent clinical and molecular studies have enabled us to define more homogenous population in which new therapies can be studied. For patients with advanced stages of diffuse large B cell lymphoma, a new standard of therapy exists. For patients with localized aggressive non-Hodgkin’s lymphomas, heterogeneity in patient selection prevents us from defining a new standard of care. Finally, in mantle cell lymphoma, new opportunities in drug discovery may permit advances in the treatment of this uniformly fatal malignancy. In Section I, Dr. Richard Fisher reviews the development of combination chemotherapy for patients with advanced stage diffuse large B cell lymphoma. Because of great heterogeneity in patients enrolled in Phase II studies, large randomized Phase III studies were required in the 1980s to define CHOP has the standard of care. This heterogeneity has now been defined carefully in the international prognostic factor index and more recently by gene array studies. It will now need to be incorporated prospectively into studies or retrospectively analyzed to understand clinical trial results. The addition of rituximab to CHOP has now been demonstrated to improve survival in two large Phase III studies in elderly patients. A recently presented study in younger patients suggests a similar benefit. Thus CHOP/rituximab has become the established standard of care for all patients with advanced stage diffuse large B cell lymphoma. Other concepts being evaluated to further improve on these results include: dose intensification; initial treatment with chemotherapy plus allogeneic stem cell transplantation; and infusional chemotherapy. Finally, the status of the treatment for relapsed patients will be defined. In Section II, Dr. Thomas Miller defines the treatment for limited stage aggressive non-Hodgkin’s lymphoma. Randomized trials have demonstrated the critical importance of initial chemotherapy for treatment of these patients. The amount of chemotherapy given needs to be increased for patients with bulky tumors. In most circumstances radiotherapy after the completion of chemotherapy has been shown to be advantageous. A modification of the international prognostic factor index for patients with early stage disease is presented to permit comparisons among different populations. Recently reported early-stage studies need to be analyzed in terms of the heterogeneity of the patients involved to understand the reported results. The addition of monoclonal antibodies, as well as radioimmunotherapy, are being tested in an effort to improve on the results for the poor prognosis patients. In Section III, Dr. Owen O’Connor describes the pathology immunophenotype and natural history of mantle cell lymphoma. Conventional treatment strategies with combination chemotherapy achieved objective responses in approximately half of the patients but no significant impact on survival. The addition to rituximab to CHOP chemotherapy or other treatment strategies appears to improve the remission rate; however, no major changes in survival have also been reported. Excellent single institution results have been reported with HyperCVAD plus rituximab regimen, which is currently being tested in a national cooperative group trial. The most excitement in this field currently relates to the variety of new agents which appear to have significant activity in relapsed patients with mantle cell lymphoma. This includes the proteosome inhibitor, bortezomib, which is shown to have approximately a 50% response rate with some CRs and reasonable durability in early single institution Phase II studies. Larger national multi-center trials are ongoing. In addition, agents such as thalidomide, flavopiridol, and piroxantrone will be reviewed.

scholarly journals Flavopiridol, Fludarabine, and Rituximab in Mantle Cell Lymphoma and Indolent B-Cell Lymphoproliferative Disorders

2010 ◽  
Vol 28 (3) ◽  
pp. 418-423 ◽  
Author(s):  
Thomas S. Lin ◽  
Kristie A. Blum ◽  
Diane Beth Fischer ◽  
Sarah M. Mitchell ◽  
Amy S. Ruppert ◽  
...  
Keyword(s):  
Partial Response ◽  
B Cell ◽  
Mantle Cell Lymphoma ◽  
Cell Lymphoma ◽  
Progression Free Survival ◽  
Complete Response ◽  
Median Number ◽  
Lymphocytic Leukemia ◽  
Mantle Cell ◽  
Hodgkin's Lymphomas

Purpose Flavopiridol downmodulates antiapoptotic proteins associated with resistance to fludarabine and rituximab and is effective against p53-mutated chronic lymphocytic leukemia (CLL). We conducted a phase I study of flavopiridol, fludarabine, and rituximab (FFR) in patients with mantle-cell lymphoma (MCL), indolent B-cell non-Hodgkin's lymphomas (B-NHL), and CLL to determine the activity of FFR. Patients and Methods Therapy included fludarabine 25 mg/m2 intravenously (IV) days 1 to 5 and rituximab 375 mg/m2 day 1 every 28 days for 6 cycles. We administered flavopiridol 50 mg/m2 by 1-hour IV bolus (IVB) day 1 (n = 15); day 1 to 2 (n = 6); 20 mg/m2 30-minute IVB + 20 mg/m2 4-hour IV infusion (n = 3); or 30 mg/m2 + 30 mg/m2 (n = 14). Results Thirty-eight patients (median age, 62 years) with MCL (n = 10); indolent B-NHL including follicular (n = 9), marginal zone (n = 4), lymphoplasmacytic (n = 1), or small lymphocytic lymphoma (n = 3); and CLL (n = 11), were enrolled. Twenty-two patients were previously untreated; 16 had received one to two prior therapies. Two patients in cohort 2 developed grade 3 dose-limiting toxicity (seizures, renal insufficiency). The median number of treatment cycles was 4, with cytopenias (n = 10) and fatigue (n = 3) the most common reasons for early discontinuation. Overall response rate was 82% (complete response, 50%; unconfirmed complete response, 5%; partial response, 26%), including 80% of patients with MCL (median age, 68; seven complete responses, one partial response). Median progression-free survival (PFS) was 25.6 months. Median PFS of patients with nonblastoid variant MCL (n = 8) was 35.9 months. Conclusion FFR was active in MCL, indolent B-NHL, and CLL and should be studied for older patients with MCL who are not candidates for aggressive chemotherapy.

Homeostatic chemokines drive migration of malignant B cells in patients with non-Hodgkin lymphomas

Blood ◽  
2004 ◽  
Vol 104 (2) ◽  
pp. 502-508 ◽  
Author(s):  
Livio Trentin ◽  
Anna Cabrelle ◽  
Monica Facco ◽  
Davide Carollo ◽  
Marta Miorin ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
B Lymphocytes ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Lymphocytic Leukemia ◽  
Receptor Expression ◽  
Mantle Cell ◽  
B Cell Subsets ◽  
Almost All

Abstract This study investigated the role of several chemokines and their receptors on malignant B lymphocytes recovered from 13 patients with chronic lymphocytic leukemia (CLL), 9 with hairy cell leukemia (HCL), 5 with mantle cell lymphoma (MCL), 5 with marginal zone B-cell lymphoma (MZL), 6 with small lymphocytic lymphoma (SLL), and 5 with follicular cell lymphoma (FCL). Flow cytometry analysis demonstrated that CXCR4 and CXCR5 were expressed on all malignant and normal B cells. Considering CC receptors, CCR1 was expressed in 70% of patients with CLL and 40% of those with HCL but was lacking in patients with MCL, MZL, SLL, and normal B cells. CCR2 showed a heterogeneous pattern of expression. CCR3 was found in almost all patients with CLL and in the majority of those with HCL, whereas it was usually lacking in patients with MZL and SLL and in healthy subjects. CCR5 was expressed in patients with HCL and MCL. Migration assays showed that different chemokines, mainly CXCL12 and CXCL13, are able to trigger migration of malignant B lymphocytes. Some of these chemokines induce calcium mobilization. These data indicate that different patterns of chemokine receptor expression identify different malignant B-cell subsets and that these receptors are functional and might play a role in malignant B-cell circulation. (Blood. 2004;104:502-508)

scholarly journals PAK4 and NAMPT as Novel Therapeutic Targets in Diffuse Large B-Cell Lymphoma, Follicular Lymphoma, and Mantle Cell Lymphoma

Cancers ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 160
Author(s):  
Husain Yar Khan ◽  
Md. Hafiz Uddin ◽  
Suresh Kumar Balasubramanian ◽  
Noor Sulaiman ◽  
Marium Iqbal ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Follicular Lymphoma ◽  
B Cell ◽  
Mantle Cell Lymphoma ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Large B Cell Lymphoma ◽  
Mantle Cell ◽  
Hodgkin's Lymphomas ◽  
Large B Cell

Diffuse large B-cell lymphoma (DLBCL), grade 3b follicular lymphoma (FL), and mantle cell lymphoma (MCL) are aggressive non-Hodgkin’s lymphomas (NHL). Cure rates are suboptimal and novel treatment strategies are needed to improve outcomes. Here, we show that p21-activated kinase 4 (PAK4) and nicotinamide phosphoribosyl transferase (NAMPT) is critical for lymphoma subsistence. Dual targeting of PAK4-NAMPT by the Phase I small molecule KPT-9274 suppressed cell proliferation in DLBCL, FL, and MCL. Growth inhibition was concurrent with apoptosis induction alongside activation of pro-apoptotic proteins and reduced pro-survival markers. We observed NAD suppression, ATP reduction, and consequent cellular metabolic collapse in lymphoma cells due to KPT-9274 treatment. KPT-9274 in combination with standard-of-care chemotherapeutics led to superior inhibition of cell proliferation. In vivo, KPT-9274 could markedly suppress the growth of WSU-DLCL2 (DLBCL), Z-138, and JeKo-1 (MCL) sub-cutaneous xenografts, and a remarkable increase in host life span was shown, with a 50% cure of a systemic WSU-FSCCL (FL) model. Residual tumor analysis confirmed a reduction in total and phosphorylated PAK4 and activation of the pro-apoptotic cascade. This study, using various preclinical experimental models, demonstrates the therapeutic potential of targeting PAK4-NAMPT in DLBCL, FL, and MCL. The orally bioavailable, safe, and efficacious PAK4-NAMPT dual inhibitor KPT-9274 warrants further clinical investigation.

Gastrointestinal lymphomas

2020 ◽  
pp. 2892-2902
Author(s):  
Kikkeri N. Naresh
Keyword(s):  
B Cell ◽  
Lymphoid Tissue ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Aggressive Lymphoma ◽  
Gastrointestinal Lymphoma ◽  
Mantle Cell ◽  
Gastrointestinal Lymphomas ◽  
Large B Cell ◽  
Aggressive B Cell Lymphoma

Primary gastrointestinal lymphoma is the most common extranodal lymphoma and is almost exclusively of non-Hodgkin type. It is defined as lymphoma that has presented with the main bulk of disease in the gastrointestinal tract, with or without involvement of contiguous lymph nodes. MALT lymphoma is an indolent B-cell lymphoma whose histology recapitulates the features of mucosa-associated lymphoid tissue (MALT). It most commonly affects the stomach, presenting with nonspecific dyspepsia. Most cases appear to be driven by Helicobacter pylori, with 75% regressing following eradication of the organism with appropriate antibiotics. Deeply invasive lymphomas and those with adverse histological or cytogenetic features are unlikely to respond. Mantle cell lymphoma and follicular lymphoma are adult B-cell lymphomas that can present as gastrointestinal lymphomas. Diffuse large B-cell lymphoma is an aggressive lymphoma that is relatively frequently encountered in gastrointestinal locations. Burkitt’s lymphoma is also an aggressive B-cell lymphoma, and is the most frequent childhood gastrointestinal lymphoma. Enteropathy-associated T-cell lymphoma is an intestinal lymphoma of intraepithelial T lymphocytes that occurs most commonly in the jejunum or ileum and is associated with coeliac disease. It presents with abdominal pain, often due to intestinal perforation. The prognosis is usually poor, with death frequently resulting from abdominal complications in patients already weakened by uncontrolled malabsorption.

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