CC Jan 2016 Chronic Lymphocytic Leukemia

echoecho's version from 2016-03-20 17:24


Question Answer
Chronic lymphocytic leukemia (CLL) is the most prevalent adult leukemia in North America, accounting for approximately ____ to ____% of all adult leukemis in the US?30-35%
In the US, how many new cases of CLL were diagnosed in 2014?15,500
In the US, the male predominance to females is what?3:2
In the US, what was the number of deaths? 5,100
In the US, what is the average age of diagnosis?70 years old
In the US, what % of patients were diagnosed with CLL at < 50 years of age?10-15%
There is a higher incidence of CLL in what ethnic group compared to other ethnic groups?higher in whites compared to AA or asian pacific islanders
True of false? CLL is extremely rare in China, Japan and neighboring countries?true
A significant familal risk of CLL exists, with up to ____% of first-degree family members having a low-level monoclonal B-cell lymphocytosis?15
Having a low-level monoclonal B-cell lymphocytosis can progress to CLL at a rate of < ____% per year?1
There is no evidence that radiation exposure, chemicals (except perhaps _____ ______ ) or drugs are linked to the causation of CLL?agent orange
Variable clinical symptoms are associated with the diagnosis of CLL but the most common presensation is what?an asymptomatic patient with a routine CBC showing significant lymphocytosis, with no other lab abnormality or findings on physical examination
What is the next most common presentation?waxing and waning lymph node enlargement primarily int he neck or supraclavicular areas
List other common compliants?1) fatigue (in part from anemia) 2) bleeding problems due to low platelet counts
List recurrent problems?1) sino-pulomonary infections (can occur larely related to a decrease in immunoglobulin production which is found in up to 80% of patients with CLL) 2) weight loss 3) low-grade fevers 4) night sweats 5) extreme fatigue occurs in < 10% of patients
List autoimmune complications?1) pure red cell aplasia 2) autoimmune hemolytic anemia 3) immune thrombocytopenia
List other reactions seen in CLL?1) exaggerated reactions to insect bites 2) enhanced allergies to medications (especially Ampicillin) 3) enhanced allergies to herpes zoster (shingles)
Can CLL patients be immunizated with live herpes virus? If not, why?1) no 2) because of the risk of disseminated disease related to immunosuppression
*** The diagnosis of CLL is made by what?1) review of peripheral blood smear 2) flow cytometry of the peripheral blood
*** Is a bone marrow biopsy needed to make the diagnosis of CLL?no
When is CT scanning indicated?if symptoms or physical exam suggests the possibility of bulk disease
What does flow cytometry reveal in CLL?1)a distinct pattern in CLL membrane proteins 2) CD5, CD23, and CD19 are overexpressed with dim CD20 expression
What does the peripheral blood smear reveal in CLL?small lymphocytes with limited cytoplasm and a dense nucleus WITHOUT nucleoli
What will be seen in the peripheral blood smear that reflect artifactual disruption of the small lymphocytes as the blood smear is being made?smudge or basket cells
List the 7 lymphoproliferative diseases with circulating lymphocytes that must be distinguished from CLL?1) T-cell prolymphocytic leukemia 2) mantle cell lymphoma 3) hairy cell leukemia 4) follicular lymphoma 5) lymphoplasmacytic lymphoma 6) Sezary syndrome (mycosis fungoides) 7) splenic marginal zone lymphoma with circulating villous lymphocytes
What 3 lab tests will separate the above 7 lymphoproliferative diseases from CLL?1) morphology 2) flow cytometry 3) immunohistochemistry
Patients with lymph node enlargement but < ______ circulating monoclonal B lymphocytes are classifie as small lymphocytic lymphoma (which is treated exactly the same as CLL)?5,000
The ____ Staging System for CLL is the most widely used classification in the US?Rai
Regarding the Rai Staging System, list the stage with % of patients at diagnosis; clinical features; and overall survival in months? 1) stage 0 = 25% of patients at dx; lymphocytosis with > 5,000 monoclonal B lymphocytes in peripheral blood; overall survival is 150 months 2) Stage 1-2 = 50% of patients at diagnosis; lymphadenopathy and/or hepatosplenomegaly; with overall survival of 100 months 3) Stage 3-4 = 25% of patients at diagnosis; non-immune anemia and/or thrombocytopenia; with overall survival of 20 months
Overal survival improving significantly with introduction of what?new therapies
***More important than staging is what two important procedures?1) stratification of CLL by mutation status 2) identification of cytogenetic abnormalities by fluorescent in situ hybridization (FISH)
Mutation in the heavy chain occurs when?lymphocytes interact with an antigen and are programmed to make specific antibodies
The presence of a mutated heavy chain almost doubles the median survival compared to unmutated CLL, from ___ years to ___ years?10; 20
A ____ deletion (found in 50% of CLL patients) is very favorable?13q
Deletions in ____ and ___ predict poor outcome?17p; 11q
List the German CLL Study Group Prognostic Score as to predictive factors; points; survival predictions?1) Del (17p) = 6 points; low risk (0-2 points) with 95% 5 year survival 2) serum beta-2 microglobulin > 3.5 ng/L = 2 points and low risk (0-2 points) of 95% 5 year survival 3) serum beta-2 micro globulin 1.7 to 3.5 ng/L = 1 point and intermediate risk (3-5 ponts) of 82% 5 year survival rate 4) unmutated IGHV = 1 point and intermediate risk (3-5 points) with 82% 5 year survival rate 5)ECOG performance status > 0 = 1 point with high risk (6-10 points) of 68% 5 year survival rate 6) Del (11q) = 1 point and high risk (6-10 points) of 68% 5 year survival rate 7) male gender = 1 point and very high risk (11-14 points) of 19% of 5 year survival rate 8) age > 60 = 1 point and very high risk (11-14 points) of 19% of 5 year survival rate
What careful evaluation is important to determine which treatment option is right for the patient?1) evaluation of a patient's performance status 2) patient's cormobidities
What is the treatment for asymptomatic patients?followed without active treatment
____ to ____% of patients with CLL will never require therapy?15-20
List the indications for active treatment of CLL?1) cytopenias related to bone marrow infiltration (not immune mediated) 2) lymphocyte doubling time < 6 months 3) enlarging or symptomatic lymph nodes 4) liver or spleen enlargement 5) night sweats 6) fever 7) fatigue 8) immune related cytopenias not responding to steroids
Lymphocytosis as high as 300,000/mm3 is NOT an indication for therapy if the patient is what?asymptomatic
True or false?Additionally, patients who are asymptomatic and do not meet criteria for therapy are not treated even if they have unfavorable prognostic clinical and molecular features?true
Before therapy is started, all patients should be screened for what? Why?1) HIV, hepatitis B and C 2) these infections can be reactivated with the use of rituximab (Rituxan) which may lead to liver failure, especially in patients with dormant hepatitis B
In healthy patients < 65 years old, a combination of what 3 drugs is the regimen of choice?1) fludarabine 2) cyclophosphamide 3) rituximab
What are the response rates in the above regimen of choice?> 90% with 70% achieving complete remission with no evidence of residual disease
What is the only curative approach to CLL, but very few patients are healthy enough to be eligible?allogenic hermatopoietic stem cell transplantation
What regimen is commonly used in older patients, with high response rates and prolongation of survival without major toxicity?1) Bendamustine (Treandal) and 2) Rituximab
What regimen is recommended in patients > 70 years old that has resulted in durable remissions with minimal side effects?1) Chlorambucil and 2) Obinatuzimab (an anti-CD20 antibody)
List two novel agents that have been recently approved for use in CLL that are oral drugs that block the B lymphocyte maturation pathway?1) Bruton's tyrosine kinase inhibitor (ibrutinib [Imbruvica] and 2) P13-kinase inhibitor (idelalisib [Zydelig])
Which of the above novel agents is very active in the difficult 17p mutated CLL and is approved for first-line therapy in this subset of patients (8-10% at initial diagnosis)?Ibrutinib (Imbruvica)
*** What is the Richter's syndrome?a devastating complication of CLL when here is transformation to aggressive diffuse large B cell lymphoma
*** Richter's syndrome occurs in what % of patients with CLL and is not related to previous chemotherapy?5-8%
*** What is the median survival after Richter's syndrome is diagnosed?12-14 months
*** SUMMARY = What is the most prevalent adult leukemia? What is the average age at diagnosis?CLL ; 70
*** SUMMARY = What is the most common initial presentation of CLL?an asymptomatic patient with a routine CBC showing significant lymphocytosis with no other lab abnormality or findings on physical examination
*** SUMMARY = Asymptomatic patients are most commonly treated by what?following WITHOUT active treatment