|
Useful in select circumstances:
Factors that may determine treatment timing and approach:The characteristics of the lymphoma at diagnosis as determined by pathology tests, and it's actual clinical behavior, and other factors determine the type of treatment and the timing of treatment you and your doctor will consider. According to NCCN guidelines, the most appropriate treatment can depend on age and clinical trials are recommended.
Staging (Rai | Binet) of CLL/SLL
|
![]() |
Overview LLS | PDQ® | CLLTopics.org | Wikipedia.org |
![]() |
CLL diagnosis and prognosis: implications of the IWCLL guidelines 2009 lymphomaforum.org.uk
|
![]() |
Biology and Treatment of CLL asheducationbook.org |
![]() |
Novel Insights into the Biology of CLL
|
![]() |
Chronic Lymphocytic Leukemia asheducationbook.org
|
![]() |
CLL Question & Answers acor.org |
![]() |
Genetics Cancer Genetics Web |
![]() |
Management Strategies for Chronic Lymphocytic Leukemia CME Author: Michael J. Keating, MB, BS Medscape (free login req.) |
![]() |
Richter’s transformation (DLBCL) can arise from CLL
|
![]() |
Signs and Symptoms of CLL ACS |
![]() |
Treatment: A New World of Possibilities, Levine Medscape free login req. |
![]() |
Flow Cytometry and Polymerase Chain Reaction-Based Analyses of Minimal Residual Disease in Chronic Lymphocytic Leukemia hindawi.com |
"Small lymphocytic lymphoma (SLL), which accounts for approximately 5% of non-Hodgkin's lymphomas in adults, is almost identical to chronic lymphocytic leukemia (CLL) both morphologically and clinically.
A somewhat arbitrary distinction is drawn between them based on the relative degree of marrow and nodal involvement and the numbers of circulating lymphoma cells." LymphomaInfo.Net
![]() |
About Small Lymphocytic Lymphoma (SLL) LymphomaInfo.Net
|
![]() |
SLL - Low number of DNA copy number changes in small lymphocytic lymphoma Haematologica 1998 Aug;83(8):690-2 |
Cytogenetic
factors that may
predict survival or the clinical behavior
or response to specific therapies
Telomere "is an enzyme that adds telomere repeat sequences to the 3' end of DNA strands.
Most cancers arise from somatic cells (from the body; not germline - from parents).
But one of the crucial features that distinguishes a cancer cell from a normal somatic cell is its ability to divide indefinitely.
It turns out that most (85–90%) cancer cells have regained the ability to synthesize high levels of telomerase throughout the cell cycle, and thus are able to prevent further shortening of their telomeres."
"Oncology does not need more prognostic factors, it needs
predictive factors that are treatment-regimen specific. Prognostic factors
are unlikely to be used unless they are therapeutically relevant ... "
~ Richard Simon, DSc
![]() |
NOTABLE QUOTE ON LIMITATIONS OF PROGNOSTIC MARKERS:
|
![]() |
How I treat CLL up front http://bit.ly/favAVV (2010)
|
Prognostic factors are features of the disease that are associated with the clinical behavior, response to treatment and survival.
The many interrelated factors that influence survival have NOT been defined definitively at this time.
See also Chromosomal abnormalities by fluorescent in situ hybridization
(FISH) - PubMed Topic Search
![]() |
Stage (see Rai staging system (Most reliable according to some experts) |
![]() |
Mutated (more favorable) versus non-mutated (less favorable) |
![]() |
ZAP-70 (less favorable) |
![]() |
CD38+ immunophenotype (has cd38 protein on cell surface). |
![]() |
Lymphocyte doubling time (unfavorable) |
![]() |
High Beta-2-microglobulin (unfavorable) |
* Telomere and mutation status:
Mutation status is correlated with Telomere lengths, which
can vary based on the cellular derivation of B-cells
Factors that May Help to Predict Treatment Response
(notes from presentation)
Response predictors may help to
(1) spare patients from ineffective treatments
(2) select patients most likely to respond to a given therapy
(Example: alemtuzumab in p53 cases* ),
(3) investigate new treatments targeting specific biologic abnormalities.
~ Dr. Emillio Montserrat, MD presentation L&M conference 2007
Weak Predictors
Clinical stage, Bone marrow infiltration,
Doubling time, Morphology (appearance)Strong Predictors
Genetics
chromosomal translocations
17p- resistance to Fludarabine, alkylators, Rituxan
11q- lower response rate to fludarabine (vs. FC)
early relapse from autologous Stem Cell Transplantp53 mutations and deletions
predicts response to Alemtuzumab
See BloodJournal.hematologyli pdfResponse to Therapy
Questionable predictor:
CD38+, Zap 70+, Un-mutated (either alone or combined)
Stronger predictors
High Beta-2-microglobulin -
poor response to chemo-immunotherapyCLLU1 gene -
poor response to chemo-immunotherapy
See also http://bloodjournal.hematologylibrary.orgPatients achieving response have longer survival
Minimal Residual Disease (MRD) after treatment correlates
with better outcome (Progression Free Survival and Overall Survival)
MRD-positivity - particularly increasing MRD levels, anticipates
clinical relapse (exception: after allotransplantation)Question: Does treatment timing correlate with MRD negativity?
Source: Dr. Emillio Montserrat, MD presentation L&M conference 2007
New topic placeholder
Untreated | Previously treated | Ritcher's
Tip: Click the Result on Map tab to locate studies in your region of the USA or the World.
![]() |
inhibitors of apoptosis |
![]() |
micro-RNAs |
![]() |
microenvironment (e.g., Lenalidomide) |
![]() |
telomeres inhibitor (GRN163L) |
See also Pipeline and Clinical Trials
"The clinical and morphologic transformation is very low -- 3 to 5% of chronic lymphocytic leukemia (CLL) to diffuse large-cell lymphoma (DLCL) is commonly referred to as Richter's syndrome.
Richter's syndrome occurs mostly in lymph nodes and may represent a second neoplasm or a transformation from the same clonal population." 1
![]() |
Follows CLL from 1.3 to 5 years |
![]() |
Increasing splenomegaly (enlarged spleen) |
![]() |
Lymphadenopathy (enlarged lymph nodes) |
![]() |
Increased prolymphocytes (abnormal lymphocytes) in the blood |
Source: thedoctorsdoctor
![]() |
About Prolymphocytic transformation Terry Hamblin |
Combination therapy, often including purine analogs, are being explored, and are more effective than single agents, often inducing complete responses. There is more toxicity with this approach, however.
Quality of response (minimal residual disease status) might be key to improving outcomes. Age and fitness are important clinical factors that guide clinical practice as is the stage and behavior of the disease.
Newly approved and investigational targeted agents (such as ibrutinib) with better toxicity profiles are expected to change practice rapidly. See for example, Jain, Rai: Overview of recent developments in chronic lymphocytic leukemia http://1.usa.gov/1fsLkSw and related farticles: ncbi.nlm.nih.gov
![]() |
Obinutuzumab Gains Role in CLL NCCN Guidelines http://bit.ly/Qn5K6G In recent outcome reports, Obinutuzumab (first-in-class glycoengineered type-2 anti-cd20 antibody) has shown superior outcomes in combination with chlorambucil to both Rituxan plus chlorambucil and to chlorambucil alone. COMMENT: This is big news for CLL. It’s not yet clear to me that the superiority of this cd20 antibody in CLL will translate to other types of b-cell lymphomas. As always, the study reports from well designed trials will tell us that (requiring our participation) … not opinions and theories. |
![]() |
What Is the Optimal Initial Treatment for CLL? cancernetwork.com |
![]() |
NCCN recommends Clinical Trials for the treatment of CLL/SLL:
|
![]() |
ACOR.org | Cancer.gov | LLS | Research Reports_LLS |
![]() |
CLL Treatment: A New World of Possibilities, Levine
|
![]() |
Eradication of Minimal Residual Disease in B-Cell Chronic Lymphocytic Leukemia After Alemtuzumab Therapy Is Associated With Prolonged Survival. J Clin Oncol. 2005 Feb 28; PMID: 15738539 |
![]() |
Improving the Complete Remission Rate in CLL
|
![]() |
Setting the Stage for Stem Cell Transplantation for CLL
|
![]() |
Protocols for Refractory Disease PAL |
![]() |
How I treat CLL up front, 2010 John G. Gribben Full text: http://bloodjournal.hematologylibrary.org
|
![]() |
Chlorambucil Is Still an Appropriate First-Line Therapy for Chronic Lymphocytic
|
||||||||||
![]() |
Campath / Alemtuzumab / anti-cd52 (humanized IgG1 kappa antibody)Campath Available For First Line Treatment Of B-Cell Chronic Lymphocytic Leukaemia (CLL) For Whom Fludarabine Chemotherapy Is Not Appropriate medicalnewstoday.com/articles/97739.php
|
![]() |
Alone or combined with Rituxan for refractory CLL mdanderson.org |
![]() |
Campath + Rituxan in high risk CLL PubMed articles |
![]() |
Campath data for CLL PubMed articles |
![]() |
Lumiliximab / anti-cd23 Related articles | ClinicalTrials.gov
|
![]() |
Ofatumumab / Humax cd20 Related articles | ClinicalTrials.gov
|
![]() |
Fludarabine as frontline? - Cheson HealthTalk |
![]() |
Rituximab dose-escalation trial in chronic lymphocytic leukemia. J Clin Oncol. 2001 Apr 15;19(8):2165-70. PMID: 11304768 PubMed | Related Abstracts |
![]() |
Preliminary Positive Data from Rituxan Multi-Center Trial in First-Line and Maintenance Therapy in Patients With Chronic Lymphocytic Leukemia Buswire |
![]() |
Standard-dose anti-CD20 antibody rituximab has efficacy in chronic lymphocytic leukaemia: results from a Nordic multicentre study.
|
![]() |
Adding fresh frozen plasma to Rituxan for the treatment of patients with refractory advanced CLL oxfordjournals.org
|
![]() |
Serum globulins as marker of immune restoration after treatment with high-dose Rituxan for CLL PubMed
|
![]() |
Mini Allogeneic Stem Cell Transplants Effective in Advanced Chronic Lymphocytic Leukemia cancerconsultants.com |
![]() |
F+R - fludarabine + Rituxan PubMed articles |
![]() |
F+C+R - fludarabine + Cytoxan + Rituxan (OR 95%; CR 70%)
|
![]() |
P+C+R - pentostatin + Cytoxan + RituxanPCR therapy for CLL - comparing it to FCR: medscape.com/ |
![]() |
Thalidomide + Fludarabine PubMed articles | ClinicalTrials.gov |
![]() |
Rituxan Combo For CLL: Rituximab and methylprednisolone for therapy of CLL www.haematologica.org |
![]() |
GM-CSF & Rituxan for CLL: Rituximab reduces the number of peripheral blood B-cells in vitro mainly by effector cell-mediated mechanisms. Haematologica. 2002 |
![]() |
For Untreated CLL/SLL
|
![]() |
State or Country |
![]() |
Other criteria such as age, stage, phase, refractory |
![]() |
Weill Cornell Clinical Trials | |
![]() |
Venetoclax Achieves Durable and Deep "treatment free" Remissions in CLL - The ASCO Post http://bit.ly/2tuyRcD |
![]() |
Background and video on Selective BCL-2 Inhibitor (venetoclax) | BioOncology http://bit.ly/1O122KO |
![]() |
Farrukh T. Awan, MD
|
![]() |
CLL - Weill Cornell 2015:
|
![]() |
Obinutuzumab Gains Role in CLL NCCN Guidelines http://bit.ly/Qn5K6G In recent outcome reports, Obinutuzumab (first-in-class glycoengineered type-2 anti-cd20 antibody) has shown superior outcomes in combination with chlorambucil to both Rituxan plus chlorambucil and to chlorambucil alone. COMMENT: This is big news for CLL. It’s not yet clear to me that the superiority of this cd20 antibody in CLL will translate to other types of b-cell lymphomas. As always, the study reports from well designed trials will tell us that (requiring our participation) … not opinions and theories : ) NCCN Guidelines for Obinutuzumab in CLL1 Frail patient with significant comorbidity Obinutuzumab + chlorambucil as 1st preference First-line therapy for patients without del 11q or 17p Obinutuzumab + chlorambucil as 1st preference for patients aged ≥70 y, or younger with comorbidities |
![]() |
* ASCO Post:
|
![]() |
Imedex 2014:
|
![]() |
Ibrutinib in the News!
|
![]() |
April 2013: Pharmacyclics Completes Enrollment of Phase III Ibrutinib CLL Study
|
![]() |
CLL Abstracts - ASH 2012 - grouped by PAL |
![]() |
Dr. Sharman's CLL & Lymphoma Blog: Choosing first therapy in CLL http://bit.ly/13vDKTa
|
![]() |
Dr. Sharman's CLL & Lymphoma Blog: What is FCR? http://bit.ly/PBQkI6
|
![]() |
CLL - ASCO 2012 abstracts |
![]() |
OncLive: Dr. Wierda Discusses Watchful Waiting in CLL |
![]() |
Two reports on same study: Chronic Lymphocytic Leukemia - Aggressive Drug Combo Restores Quality Of Life and http://bit.ly/xJitXk |
![]() |
Medscape (login required):
|
![]() |
ASH Education Book Dec 2011: Alemtuzumab Use In Relapsed and Refractory CLL/SLL |
![]() |
ASH Education Book Dec 201: Nurture versus Nature: The Microenvironment in Chronic Lymphocytic Leukemia |
![]() |
ASH Education Book Dec 2011: Using the Biology of CLL to Choose Treatment |
![]() |
ASH Education Book Dec 2011: The Treatment of Relapsed Refractory CLL/SLL |
![]() |
Medscape, Dr. Cheson - ASH review: A Dickensian CLL Story |
![]() |
Medical News Today: Chronic Lymphocytic Leukemia Patients' Lives Extended By New Combination Treatment |
![]() |
NCCN: Advances in CLL Therapy Offer Prolonged Survival; Toxicities Continue to Plague Elderly Patients |
![]() |
Jennifer R. Brown, MD, PhD
|
![]() |
2015: Experts discuss Initiation and Discontinuation of Ibrutinib From http://bit.ly/1uYT1EH |
![]() |
Ofatumumab in Refractory Chronic Lymphocytic Leukemia: Experience ... - PubMed - NCBI http://1.usa.gov/1Dx2IxZ
|
![]() |
Dr Sharman 2014:
|
![]() |
Autologous stem cell transplantation as a first-line treatment strategy for CLL: a multicenter, randomized, controlled trial http://bit.ly/je7iRh
|
![]() |
Treatment options for high-risk CLL http://bit.ly/kTWK01
|
![]() |
How I treat CLL up front http://bit.ly/favAVV (2010)
|
![]() |
Positive Phase I/IIa Results With Acadra (Acadesine) in CLL prnewswire.com
|
![]() |
Relapsed CLL: Does adding lumiliximab (anti-cd23) improve on FCR? ncbi.nlm.nih.gov
|
![]() |
Tumor Flare Reaction Associated With Lenalidomide Treatment in Patients With CLL Predicts Clinical Response
|
![]() |
Fludarabine Provides OS Advantage vs Chlorambucil in Previously Untreated CLL http://bit.ly/5LgDhj |
![]() |
CLL Aggressiveness May Be Predicted By New Biomarker medicalnewstoday.com
|
![]() |
Comprehensive review: Treating CLL ncbi.nlm.nih.gov/books
|
![]() |
FCR Versus FC Improves Response Rates and Progression-Free Survival of Previously Untreated [and fit] Patients with Advanced CLL
|
![]() |
Flavopiridol (Alvocidib) Induces Durable Responses in Relapsed Chronic Lymphocytic Leukemia (CLL) Patients with High-Risk Cytogenetic Abnormalities
|
![]() |
Adding fresh frozen plasma to Rituxan for the treatment of patients with refractory advanced CLL oxfordjournals.org
|
![]() |
Fludara (Fludarabine) Not Superior to Cytoxan (Chlorambucil) for Elderly with CLL cancerconsultants.com
|
![]() |
What Is the Optimal Initial Treatment for Chronic Lymphocytic Leukemia? cancernetwork.com |
![]() |
Assessment of CLL and SLL by absolute lymphocyte counts in 2,126 patients: 20 years of experience at the University of Texas M.D. Anderson Cancer Center.J Clin Oncol. 2007 Oct 10;25(29):4648-56. PMID: 17925562
|
![]() |
First line Campath for CLL: FDA Approves Expanded Labeling For Campath® To Include First Line Treatment For CLL medicalnewstoday.com
|
![]() |
Big news for CLL: 70% of complete responders remain in continuous remission: Five-year follow-up of 300 patients treated with FCR as initial therapy of CLL
|
![]() |
New agents in chronic lymphocytic leukemia.
|
![]() |
Gene expression signatures separate B-cell chronic lymphocytic leukaemia prognostic subgroups defined by ZAP-70 and CD38 expression statusA Hüttmann1, L Klein-Hitpass2, J Thomale2, R Deenen2, A Carpinteiro1,3, H Nückel1, P Ebeling4, A Führer1, J Edelmann1, L Sellmann1,2, U Dührsen1 and J Dürig1"Remarkably, the microarray experiments described herein revealed relative overexpression of additional BCR pathway components such as CD5, IGHD, IGL, IGLJ3 and IGLC2. These findings are in accordance with a recent flow cytometry study showing higher IgM surface levels on IgVH unmutated as compared to mutated B-CLL cells.36 Furthermore, the present microarray analysis showed that FcRH2/IRTA4 was significantly downmodulated in ZAP-70+CD38+ B-CLL, results which were subsequently confirmed at the protein level using flow cytometry in a series of 26 B-CLL patients." |
![]() |
Potential protein markers in diagnosis and treatment of B-CLL cancerprev.org |
![]() |
Therapy-related myeloid leukemias are observed in patients with chronic lymphocytic leukemia after treatment with fludarabine and chlorambucil: results of an intergroup study, cancer and leukemia group B 9011. J Clin Oncol. 2002 Sep 15;20(18):3878-84. PMID: 12228208 PubMed |