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Treatments >  ASH 2014 oral abstracts

Last update: 01/13/2015

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MCL | Indolent - MZL, Waldenstrom's  | CLL/SLL | DLBCL  | follicular

ASH 2014 Abstracts


Mantle Cell lymphoma (oral abstracts only)

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Frontline Therapy with the Ribvd Regimen Elicits High Clinical and Molecular Response Rates and Long PFS in Elderly Patients Mantle Cell Lymphoma (MCL); Final Results of a Prospective Phase II Trial By the Lysa Group

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Rituximab Maintenance Versus Wait and Watch after Four Courses of R-DHAP Followed By Autologous Stem Cell transplantation in Previously Untreated Young Patients with Mantle Cell Lymphoma: First Interim Analysis of the Phase III Prospective Lyma Trial, a Lysa Study

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Identification of a First-in-Class PRMT5 Inhibitor with Potent in Vitro and in Vivo Activity in Preclinical Models of Mantle Cell Lymphoma

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Sustained Remission with the Combination Biologic Doublet of Lenalidomide Plus Rituximab As Initial Treatment for Mantle Cell Lymphoma: A Multi-Center Phase II Study Report

SNIP: This study provides the first demonstration that a chemotherapy-free, combination biologic approach is feasible and active as initial therapy for mantle cell lymphoma.  A high proportion of MCL patients can achieve durable remissions while maintaining quality of life with the frontline therapy of lenalidomide up to 25 mg daily given 21 out of 28 days combined with rituximab. 

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Mutational Analysis of Patients with Primary Resistance to Single-Agent Ibrutinib in Relapsed or Refractory Mantle Cell Lymphoma (MCL)

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Phase II Randomized, Multicenter Study of Lenalidomide Vs Best Investigator’s Choice in Relapsed/Refractory Mantle Cell Lymphoma: Results of the MCL-002 (SPRINT) Study

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Ibrutinib and Rituximab Are an Efficacious and Safe Combination in Relapsed Mantle Cell Lymphoma: Preliminary Results from a Phase II Clinical Trial

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Phase II Trial of R-CHOP Plus Bortezomib Induction Therapy Followed By Bortezomib Maintenance for Previously Untreated Mantle Cell Lymphoma: SWOG 0601

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MRD Eradication Should be the Therapeutic Goal in Mantle Cell Lymphoma and May Enable Tailored Treatment Approaches: Results of the Intergroup Trials of the European MCL Network

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The Tumor Microenvironment in Mantle Cell Lymphoma (MCL):  Novel Targets to Overcome Chemo-Resistance in MCL

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Synergistic Cytotoxicity of Ibrutinib and the BCL2 Antagonist, ABT-199(GDC-0199) in Mantle Cell Lymphoma (MCL) and Chronic Lymphocytic Leukemia (CLL):  Molecular Analysis Reveals Mechanisms of Target Interactions

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The Oral Selective Inhibitor of Nuclear Export (SINE) Selinexor (KPT-330) Demonstrates Broad and Durable Clinical Activity in Relapsed / Refractory Non Hodgkin’s Lymphoma (NHL)

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Bendamustine Plus Rituximab Versus Fludarabine Plus Rituximab in Patients with Relapsed Follicular, Indolent, or Mantle Cell Lymphomas – 8-Year Follow-up Results of the Randomized Phase III Study NHL 2-2003 on Behalf of the StiL (Study Group Indolent Lymphomas, Germany)

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623. Lymphoma: Chemotherapy, excluding Pre-Clinical Models: Indolent Lymphoma and Mantle Cell Lymphoma

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Protein Arginine Methyltransferase 5 Directly Targets and Epigenetically Silences microRNAs miR33b and miR96 to Support Constitutive Cyclin D1 Activity in Non-Hodgkin’s Lymphoma



Indolent b-cell lymphoma - marginal zone lymphoma and Waldenstrom (oral abstracts only)  See also follicular

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Deep-Sequencing Reveals the Molecular Landscape of Splenic Marginal Zone Lymphoma: Biological and Clinical Implications

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Bendamustine Plus Rituximab Versus Fludarabine Plus Rituximab in Patients with Relapsed Follicular, Indolent, or Mantle Cell Lymphomas – 8-Year Follow-up Results of the Randomized Phase III Study NHL 2-2003 on Behalf of the StiL (Study Group Indolent Lymphomas, Germany)

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The Coding Genome of Nodal Marginal Zone Lymphoma Reveals Recurrent Molecular Alterations of PTPRD and Other Jak/Stat Signaling Genes

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Interim Safety Analysis:  a Phase I Trial of High Dose Therapy and Autologous Stem Cell Transplantation Followed By Infusion of Chimeric Antigen Receptor Modified T-Cells (19-28z CAR-T) Directed Against CD19+ B-Cells for Relapsed and Refractory Aggressive B Cell Non-Hodgkin Lymphoma (B-NHL)  includes one patient with transformed MZL

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Ublituximab, a Novel Glycoengineered Anti-CD20 Monoclonal Antibody (mAb), in Combination with TGR-1202, a Next Generation Once Daily PI3kδ Inhibitor, Demonstrates Activity in Heavily Pre-Treated and High-Risk Chronic Lymphocytic Leukemia (CLL) and B-Cell Lymphoma

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Multiparameter Phosphoprofiling of the B-Cell Receptor Pathway in Waldenström’s Macroglobulinemia

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The Oral Selective Inhibitor of Nuclear Export (SINE) Selinexor (KPT-330) Demonstrates Broad and Durable Clinical Activity in Relapsed / Refractory Non Hodgkin’s Lymphoma (NHL)

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Duvelisib (IPI-145) Inhibits Malignant B-Cell Proliferation and Disrupts Signaling from the Tumor Microenvironment through Mechanisms That Are Dependent on PI3K-δ and PI3K-γ

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624. Lymphoma: Therapy with Biologic Agents, excluding Pre-Clinical Models: Indolent B-cell NHL and T-cell NHL

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623. Lymphoma: Chemotherapy, excluding Pre-Clinical Models: Indolent Lymphoma and Mantle Cell Lymphoma



CLL/SLL (oral abstracts only)

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Frontline Chemoimmunotherapy with Fludarabine (F), Cyclophosphamide (C), and Rituximab (R) (FCR) Shows Superior Efficacy in Comparison to  Bendamustine (B) and Rituximab (BR) in Previously Untreated and Physically Fit Patients (pts) with Advanced Chronic Lymphocytic Leukemia (CLL): Final Analysis of an International, Randomized Study of the German CLL Study Group (GCLLSG) (CLL10 Study)

SNIP Comment: Fitness and age matter.  However, elderly patients have competing options, such as ibrutinib, to consider in addition to B-R:

 The final analysis of the CLL10 study shows that FCR remains the standard therapy in very fit CLL patients, because it yields higher CR rates, more MRD negativity and longer PFS in comparison to BR. However, in elderly fit pts high toxicity rates and infection rates result into dose reductions leading to similar efficacy between both arms. Elderly fit pts or pts with previous infections might benefit from BR as alternative regimen

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Rituximab Maintenance after Chemoimmunotherapy Induction in 1st and 2nd Line Improves Progression Free Survival: Planned Interim Analysis of the International Randomized AGMT-CLL8/a Mabtenance Trial

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Ibrutinib, Single Agent or in Combination with Dexamethasone, in Patients with Relapsed or Relapsed/Refractory Multiple Myeloma (MM): Preliminary Phase 2 Results

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Efficacy and Safety of Ibrutinib in Patients with Relapsed or Refractory Chronic Lymphocytic Leukemia or Small Lymphocytic Leukemia with 17p Deletion: Results from the Phase II RESONATE™-17 Trial

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Value of Minimal Residual Disease (MRD) Negative Status at Response Evaluation in Chronic Lymphocytic Leukemia (CLL): Combined Analysis of Two Phase III Studies of the German CLL Study Group (GCLLSG)

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Second Interim Analysis of a Phase 3 Study of Idelalisib (ZYDELIG®) Plus Rituximab (R) for Relapsed Chronic Lymphocytic Leukemia (CLL): Efficacy Analysis in Patient Subpopulations with Del(17p) and Other Adverse Prognostic Factors

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The Mevalonate Metabolic Pathway and the CXCL12/CXCR4 Axis Reciprocally Interact and Are Implicated in Fludarabine Resistance of Chronic Lymphocytic Leukemia Cells

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Determination of Recommended Phase 2 Dose of ABT-199 (GDC-0199) Combined with Rituximab (R) in Patients with Relapsed / Refractory (R/R) Chronic Lymphocytic Leukemia (CLL)

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Ublituximab, a Novel Glycoengineered Anti-CD20 Monoclonal Antibody (mAb), in Combination with TGR-1202, a Next Generation Once Daily PI3kδ Inhibitor, Demonstrates Activity in Heavily Pre-Treated and High-Risk Chronic Lymphocytic Leukemia (CLL) and B-Cell Lymphoma

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Adoptive Therapy Using Sleeping Beauty Gene Transfer System and Artificial Antigen Presenting Cells to Manufacture T Cells Expressing CD19-Specific Chimeric Antigen Receptor

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Therapy of B Cell Malignancies with CD19-Specific Chimeric Antigen Receptor-Modified T Cells of Defined Subset Composition

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Clinical Significance of Apoptosis in Chronic Lymphocytic Leukemia (CLL)

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Dinaciclib (SCH 727965) and Ofatumumab for the Treatment of Relapsed and Refractory (R/R) Chronic Lymphocytic Leukemia (CLL) and Small Lymphocytic Lymphoma (SLL): Results of a Phase 1b/2 Study

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IGHV4-34 B-Cell Receptor Immunoglobulins from CLL Stereotyped Subset 4 React with Influenza A Virus: Requirement for IGHV-D-J/Iglv-J Rearrangement and Isotype Switching to IgG

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Ofatumumab (OFA) Maintenance Prolongs PFS in Relapsed CLL: Prolong Study Interim Analysis Results

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IGHV-D-J Ultra-Deep Sequencing Reveals APOBEC and AID Targeted Mutations during Clonal Evolution of CLL in a Xenograft Mouse Model

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Duvelisib (IPI-145) Inhibits Malignant B-Cell Proliferation and Disrupts Signaling from the Tumor Microenvironment through Mechanisms That Are Dependent on PI3K-δ and PI3K-γ

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NFAT2 Regulates Anergy Induction in CLL through Lck

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Complex Karyotype, Rather Than Del(17p), Is Associated with Inferior Outcomes in Relapsed or Refractory CLL Patients Treated with Ibrutinib-Based Regimens

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HLA Ligandome Profiling Identifies a Novel Category of Pathophysiologically Relevant CLL Associated Antigens

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Synergistic Cytotoxicity of Ibrutinib and the BCL2 Antagonist, ABT-199(GDC-0199) in Mantle Cell Lymphoma (MCL) and Chronic Lymphocytic Leukemia (CLL):  Molecular Analysis Reveals Mechanisms of Target Interactions

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Immune Checkpoint Blockade with Anti-PD-L1 Prevents Immune Dysfuntion and CLL Development in the TCL1 Adoptive Transfer Mouse Model

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Aberrant PD-L1 Expression in CLL As a Result of Adaptive Immune Resistance Mediated By Tumor-Secreted Circulating miRNA Binding to Toll-like Receptor 7

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Identification of the Antigenic Targets of the Major CLL-Derived Stereotyped BCRs and First Demonstration of Sub-Subsets

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NOTCH1 Mutations Are Associated with Low CD20 Expression in Chronic Lymphocytic Leukemia: Evidences for a NOTCH1-Mediated Epigenetic Regulatory Mechanism

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Mutations in Chronic Lymphocytic Leukemia, and How They Impact Therapy Choice: Focus on NOTCH1, SF3B1, and TP53

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Questions Regarding: Hematologic malignancy (myeloma, lymphoma, CLL)

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642. CLL: Therapy, excluding Transplantation: Phase 3 Trials and More

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642. CLL: Therapy, excluding Transplantation: Novel Therapies

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Genetics of Chronic Lymphocytic Leukemia and Lymphoplasmacytic Lymphoma

 


Compiled Follicular ASH abstracts (oral presentations only)

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Event-Free Survival at 12 Months (EFS12) from Diagnosis Is a Robust Endpoint for Disease-Related Survival in Patients with Follicular Lymphoma in the Immunochemotherapy Era 

Important milestone at 12 months helps to predict favorable outcomes.

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The Oral Selective Inhibitor of Nuclear Export (SINE) Selinexor (KPT-330) Demonstrates Broad and Durable Clinical Activity in Relapsed / Refractory Non Hodgkin’s Lymphoma (NHL)

Clinical results reported here.  Background on target: The nuclear export protein, XPO1 is overexpressed in all types of malignant lymphoma. The SINE selinexor (KPT-330) is a slowly reversible XPO1 antagonist that forces the nuclear retention and activation of over 10 tumor suppressor proteins (TSP) such as p53, IkB, FOXO and p21. In addition, selinexor inhibits the nuclear export and the translation of oncogenic mRNAs such as c-myc and Bcl-XL levels. Together these effects result in apoptosis of cancer cells in preclinical models of both T- and B- cell NHL.

Comment:  Very encouraging activity with good safety profile. 
Is there a companion biomarker test that predicts response to this targeted agent?

Selinexor (KPT-330) lymphoma clinical trial query - ClinicalTrials.gov http://1.usa.gov/1xs0cJv 

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Ibrutinib Monotherapy in Relapsed/Refractory Follicular Lymphoma (FL): Preliminary Results of a Phase 2 Consortium (P2C) Trial

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ARID1A Is Recurrently and Significantly Mutated in Follicular Lymphoma (FL) and Impairs DNA Repair Efficiency

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Intratumoral and Peripheral Blood T Cells Recognize Mutated Neo-Antigens in Follicular Lymphoma

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Multiparameter Microscopy Analysis of the Follicular Lymphoma Microenvironment and Normal Germinal Centers: In Vivo evidence That Follicular Helper T Cells Form Synapses with Neoplastic B Cells and Are Associated with Proliferation and Expression of Activation Induced Cytidine Deaminase

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Indolent Lymphoma: Microenvironment

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Csnk2β, the Regulatory Subunit of Protein Kinase CK2, modulates Peripheral B Cell Development Repressing Notch2 Signaling and Promoting a Proper B-Cell Receptor Signal Transmission

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Prosurvival and Chemoprotective Effects of Tumor-Associated Macrophages Reversed By Anti-CSF-1R Monoclonal Antibody in B-Cell Lymphomas

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The IL-15 Superagonist ALT-803 Enhances NK Cell ADCC and in Vivo Clearance of B Cell Lymphomas Directed By an Anti-CD20 Monoclonal Antibody

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Anti-CD19 CAR T Cells Administered after Low-Dose Chemotherapy Can Induce Remissions of Chemotherapy-Refractory Diffuse Large B-Cell Lymphoma

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Interim Safety Analysis:  a Phase I Trial of High Dose Therapy and Autologous Stem Cell Transplantation Followed By Infusion of Chimeric Antigen Receptor Modified T-Cells (19-28z CAR-T) Directed Against CD19+ B-Cells for Relapsed and Refractory Aggressive B Cell Non-Hodgkin Lymphoma (B-NHL)

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Ublituximab, a Novel Glycoengineered Anti-CD20 Monoclonal Antibody (mAb), in Combination with TGR-1202, a Next Generation Once Daily PI3kδ Inhibitor, Demonstrates Activity in Heavily Pre-Treated and High-Risk Chronic Lymphocytic Leukemia (CLL) and B-Cell Lymphoma

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Reduced Intensity Conditioning (RIC) with Rituximab Yields Excellent Outcomes after Allogeneic Hematopoietic Cell Transplantation (alloHCT) for Relapsed Follicuar Lymphoma (FL): A Phase II Multicenter Trial from the Blood and Marrow Transplant Network (BMT CTN 0701)

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Plasma Microrna Predicts  B-Cell Lymphoma up to 12 Months before Diagnosis –  Data from the Danish Blood Donor Study

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Quality of Life at Diagnosis Independently Predicts Survival in Patients with Aggressive Lymphoma

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Predictors of Hospice Utilization Among Patients with Lymphoma

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Lymphoma: Therapy with Biologic Agents, excluding Pre-Clinical Models: Indolent B-cell NHL and T-cell NHL

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a Phase 1 Evaluation of Duvelisib (IPI-145), a PI3K-δ,γ Inhibitor, in Patients with Relapsed/Refractory iNHL

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Preliminary Results of a Phase I Study of Nivolumab (BMS-936558) in Patients with Relapsed or Refractory Lymphoid Malignancies

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Rituximab Plus Lenalidomide Improves the Complete Remission Rate in Comparison with Rituximab Monotherapy in Untreated Follicular Lymphoma Patients in Need of Therapy. Primary Endpoint Analysis of the Randomized Phase-2 Trial SAKK 35/10

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Rituximab Maintenance after Chemoimmunotherapy Induction in 1st and 2nd Line Improves Progression Free Survival: Planned Interim Analysis of the International Randomized AGMT-CLL8/a Mabtenance Trial

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Bendamustine Plus Rituximab Versus Fludarabine Plus Rituximab in Patients with Relapsed Follicular, Indolent, or Mantle Cell Lymphomas – 8-Year Follow-up Results of the Randomized Phase III Study NHL 2-2003 on Behalf of the StiL (Study Group Indolent Lymphomas, Germany)

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High Dose Therapy with Autologous Stem Cell Transplantation (HDT/ASCT) Support in Follicular Lymphoma (FL) a Very Long Follow-up  Analysis of 640 Patients of Geltamo Spanish Group Suggests That FL Might be Cured, Even in High-Risk Patients

Comment:  As reported appears to be proof of principle that FL can be cured.

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Autologous Stem Cell Transplantation (ASCT) for the Treatment of Patients with Waldenstrom’s Macroglobulinemia / Lymphoplasmacytic Lymphoma (WM/LPL). a Risk Factor Analysis By the European Society for Blood and Marrow Transplantation (EBMT) Lymphoma Working Party

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731. Clinical Autologous Transplantation: Results: Clinical Results in Lymphoid Malignancies

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Unrelated Donor KIR B/X Genotype Reduces Relapse and Improves Progression-Free Survival after HLA-Matched Allogeneic Transplantation for Relapsed/Refractory Non-Hodgkin Lymphoma

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To be continued soon.

DLBCL

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Clinical Implications of the New Molecular Knowledge for Treatment of Diffuse Large B-Cell Lymphoma

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Quality of Life at Diagnosis Independently Predicts Survival in Patients with Aggressive Lymphoma

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Racial Differences in Treatment Dose Intensity Among Patients with Diffuse Large B-Cell Lymphoma:  Analysis of the Veterans Health Administration (VHA) National Database

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Anti-CD19 CAR T Cells Administered after Low-Dose Chemotherapy Can Induce Remissions of Chemotherapy-Refractory Diffuse Large B-Cell Lymphoma

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Interim Safety Analysis:  a Phase I Trial of High Dose Therapy and Autologous Stem Cell Transplantation Followed By Infusion of Chimeric Antigen Receptor Modified T-Cells (19-28z CAR-T) Directed Against CD19+ B-Cells for Relapsed and Refractory Aggressive B Cell Non-Hodgkin Lymphoma (B-NHL)

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Monitoring of Circulating Tumor DNA As Minimal Residual Disease in Diffuse Large B-Cell Lymphoma

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Clinical Significance of Genetic Aberrations in Diffuse Large B Cell Lymphoma

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The Oral Selective Inhibitor of Nuclear Export (SINE) Selinexor (KPT-330) Demonstrates Broad and Durable Clinical Activity in Relapsed / Refractory Non Hodgkin’s Lymphoma (NHL)

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Preliminary Results of a Phase I Study of Nivolumab (BMS-936558) in Patients with Relapsed or Refractory Lymphoid Malignancies

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Novel Approach to the Potential Treatment of Patients with B-Cell Lymphomas Harboring the MYD88 L265P Mutation:  Combination Treatment with TLR Antagonist and Rituximab

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The B-Cell Receptor Is Required for Optimal Viability, Growth, and Chemotherapy Resistance of Diffuse Large B-Cell Lymphoma Cell Lines of the Germinal Center B-Cell Subtype

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Genomic Profiling Combining DNA and RNA Analysis of 112 Formalin-Fixed Paraffin-Embedded Diffuse Large B Cell Lymphoma Specimens Identifies a High Frequency of Clinically Relevant Genomic Alterations

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Preliminary Report of a Multicenter Prospective Phase II Study of DA-EPOCH-R in MYC-Rearranged Aggressive B-Cell Lymphoma

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Combination of Ibrutinib and BCL-2 or SYK Inhibitors in Ibrutinib Resistant ABC-Subtype of Diffuse Large B-Cell Lymphoma

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Potent Efficacy of BCL2 Inhibition with ABT-199 in High-Risk Aggressive B-Lymphoma Models When Combined with Knockdown of MCL1

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Brentuximab Vedotin Monotherapy in DLBCL Patients with Undetectable CD30:  Preliminary Results from a Phase 2 Study

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The Impact of Concurrent MYC BCL2 Protein Expression on the Risk of Secondary Central Nervous System Relapse in Diffuse Large B-Cell Lymphoma (DLBCL)

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Akt Activation Confers an Inferior Survival in Patients with Activated B-Cell Subtype of Diffuse Large B-Cell Lymphoma: A Report from the International DLBCL Rituximab-CHOP Consortium Program

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Phase 2 Trial of Interim PET Scan-Tailored Therapy in Patients with Advanced Stage Diffuse Large B-Cell Lymphoma (DLBCL) in British Columbia (BC)

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R-CHOP with or without Radiotherapy in Non-Bulky Limited-Stage Diffuse Large B Cell Lymphoma (DLBCL):  Preliminary Results of the Prospective Randomized Phase III 02-03 Trial from the Lysa/Goelams Group

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A Phase 2/3 Multicenter, Randomized Study Comparing the Efficacy and Safety of Lenalidomide Versus Investigator’s Choice in Relapsed/Refractory DLBCL

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Ofatumumab Versus Rituximab Salvage Chemoimmunotherapy in Relapsed or Refractory Diffuse Large B-Cell Lymphoma: The Orcharrd Study (OMB110928)

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Positron Emission Tomography (PET) Guided Therapy of Aggressive Lymphomas – a Randomized Controlled Trial Comparing Different Treatment Approaches Based on Interim PET Results (PETAL Trial)

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Plasma Microrna Predicts  B-Cell Lymphoma up to 12 Months before Diagnosis –  Data from the Danish Blood Donor Study

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Molecular Dissection of Diffuse Large B-Cell Lymphoma

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Double Hit Diffuse Large B-Cell Lymphoma

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Validation of a Prognostic Model to Assess the Risk of CNS Disease in Patients with Aggressive B-Cell Lymphoma

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Clonal Evolution in Relapsed or Refractory Diffuse Large B Cell Lymphoma

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Ublituximab, a Novel Glycoengineered Anti-CD20 Monoclonal Antibody (mAb), in Combination with TGR-1202, a Next Generation Once Daily PI3kδ Inhibitor, Demonstrates Activity in Heavily Pre-Treated and High-Risk Chronic Lymphocytic Leukemia (CLL) and B-Cell Lymphoma

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Chemical Genomics Reveals JAK STAT Activation As a Mechanism of Resistance to HDAC Inhibitors in B Cell Lymphomas

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Targeted Therapy of B Cell Lymphoma with a Direct Inhibitor of the NF-κB Subunit c-Rel

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Global Commentary - advocate's perspective

Given the high number of emerging agents for lymphoma there's a need for companion biomarker tests that may predict response to the targeted agent.  Response outcomes as percentages without such tests are not likely to be interpretable (relative to other standard and investigational options).      Karl Schwartz




 
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