Follicular Lymphoma

Lymphoma Part II

Lymphoma II Part 1

What are the results of the AUGMENT trial in MZL ?

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Superior progression free survival with the addition of lenalidomide to rituximab

Lymphoma II Part 1
Lymphoma

What did the AUGMENT trial assess in MZL ?

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Randomized phase 3 clinical trial, assessing the addition of lenalidomide to rituximab for relapsed or refractory marginal zone lymphoma

Lymphoma
Lymphoma

Has the addition of rituximab to CHOP been shown to improve PFS or TTF in LPL/WM ?

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Yes, Buske et al GLSG trial 2009

Lymphoma
Lymphoma

What is the yearly transformation rate for follicular lymphoma to aggressive lymphoma?

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3% per year

Lymphoma
Lymphoma

How long should progression free survival be before repeat rituximab re-challenge for relapsed
refractory follicular lymphoma?

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At least 6 months

Lymphoma
Lymphoma

Which CD10 positive lymphoma has a BCL-2 positive stain?

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Follicular

Lymphoma
Follicular Lymphoma

What comprises the FLIPI-1 score?

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Age greater than 60, stage III or stage IV disease, hemoglobin less than 12, more than 4 nodal regions,
elevated LDH

Follicular Lymphoma
Follicular Lymphoma

Is there a role for up-front autologous stem cell transplant for stage III and stage IV follicular lymphoma?

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No

Follicular Lymphoma
Follicular Lymphoma

What is the advantage of maintenance rituximab for relapsed refractory follicular lymphoma?

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It improves progression free survival and overall survival

Follicular Lymphoma
Lymphoma II Part 1

Lymphoma II Part 1

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Lymphoma II Part 1

Lymphoma II Part 1
Lymphoma

What dose of radiotherapy is recommended for palliation for follicular lymphoma to a single site?

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4 Gy

Lymphoma
Lymphoma

Which patients are optimal candidates for autologous stem cell transplant with follicular lymphoma?

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Young / fit patients who have progression within 2 years of initial chemotherapy–immunotherapy

Lymphoma
Lymphoma

What is the incidence of the treatment-related mortality with autologous stem cell transplant for follicular lymphoma?

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Between 5 and 20%

Lymphoma
Lymphoma

Is allogeneic stem cell transplantation superior to autologous stem cell transplantation with regards to long-term disease-free remission for follicular lymphoma?

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Yes–but with increased mortality risk

Lymphoma
Lymphoma

What are the major disadvantages of allogeneic stem cell transplant over autologous for follicular lymphoma?

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High risk of secondary malignancies / inferior survival beyond 24 months / inferior progression free survival / higher rates of relapse and progression

Lymphoma
Lymphoma

Which radioimmunotherapy is utilized for follicular lymphoma?

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Ibritumomab Tiuxetan

Lymphoma
Lymphoma

Is Ibritumomab Tiuxetan humanized or Murine?

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Murine

Lymphoma
Lymphoma

What is the target of Ibritumomab Tiuxetan?

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CD20

Lymphoma
Lymphoma

Which isotope was utilized in the manufacture of Ibritumomab Tiuxetan?

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Yttrium-90

Lymphoma
Lymphoma

What is the response rate of ibritumomab the oxygen?

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60 to 80%

Lymphoma
Lymphoma

What are the 2 important complications with Ibritumomab Tiuxetan?

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Secondary malignancies and cytopenias

Lymphoma
Lymphoma

When do the cytopenias occur with ibritumomab tiuxetan ?

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Between 4 to 8 weeks post therapy

Lymphoma
Lymphoma

What are the most common cytopenias seen with Ibritumomab Tiuxetan?

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Thrombocytopenia and leukopenia

Lymphoma
Lymphoma

Which leukocyte is most affected by Ibritumomab Tiuxetan?

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B cells

Lymphoma
Lymphoma

Which patients are ideal candidates for CAR-T with follicular lymphoma?

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Multiply relapsed with remissions shorter than 24 months

Lymphoma
Lymphoma

Which CAR-T therapy is most utilized for relapsed refractory follicular lymphoma?

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Axi-cel

Lymphoma
Lymphoma

Which clinical trial demonstrated the efficacy of CAR-T for follicular lymphoma?

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ZUMA–5

Lymphoma
Lymphoma

What is the overall response rate with axi-cel for relapsed refractory follicular lymphoma?

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94% – 80% complete response and 14% partial response

Lymphoma
Lymphoma

What percentage of patients with relapsed refractory follicular lymphoma treated with axi-cel can expect to see cytokine release syndrome?

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Almost 80%

Lymphoma
Lymphoma

What is the response rate with nivolumab for relapsed refractory follicular lymphoma?

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Less than 5%

Lymphoma
Lymphoma

What is the response rate of venetoclax plus rituximab for relapsed refractory follicular lymphoma?

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Approximately 35%

Lymphoma
Lymphoma

What is the target of tazemetostat?

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EZH2

Lymphoma
Lymphoma

Which biomarker predicts for response with tazemetostat?

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EZH2 mutation

Lymphoma
Lymphoma

Does wild-type EZH2 respond to tazemetostat?

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Minimally

Lymphoma
Lymphoma

Which EZH2 mutations will show a response to tazemetostat?

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Y646A 682A 692A

Lymphoma
Lymphoma

What is a common dose and frequency for tazemetostat?

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100 mg orally twice daily

Lymphoma
Lymphoma

What are the 3 most common complications seen with tazemetostat?

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Fatigue/ upper respiratory tract infection/ musculoskeletal pain

Lymphoma
Lymphoma

Is there an increased risk for secondary malignancies with tazemetostat?

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Yes – in particular T-cell lymphoblastic lymphoma

Lymphoma
Lymphoma

What is the overall response rate difference between wild-type and mutated EZH2 follicular lymphoma?

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35 versus 69%

Lymphoma
Lymphoma

How common is alopecia with tazemetostat ?

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17%

Lymphoma
Lymphoma

Which metabolic abnormalities are common with tazemetostat?

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Hyperglycemia which can be seen in more than 50% of patients

Lymphoma
Lymphoma

How common are EZH2 mutations in the follicular lymphoma?

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Approximately 20%

Lymphoma
Lymphoma

Which PI3K inhibitors are commonly utilized with follicular lymphoma?

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Idelalisib / copanlisib / duvelisib / umbralisib

Lymphoma
Lymphoma

Which variant of PI3K does idelalisib target?

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delta variant

Lymphoma
Lymphoma

How common are complete responses with idelalisib in R/R follicular lymphoma?

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Not common at all

Lymphoma
Lymphoma

What are the black box warning for idelalisib?

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hepatotoxicity / diarrhea / colitis / pneumonitis

Lymphoma
Lymphoma

Which endocrine abnormalities can be seen with idelalisib?

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Hyperglycemia and hypertriglyceridemia

Lymphoma
Lymphoma

Which to infectious should be monitored when treating with idelalisib?

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Pneumocystis and cytomegalovirus

Lymphoma
Lymphoma

What is the approximate overall response rate with idelalisib in multiple refractory follicular lymphoma?

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Approximately 60%

Lymphoma
Lymphoma

How commin is diarrhea with idelalisib in r/r follicular lymphoma?

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40%

Lymphoma
Lymphoma

How common are grade 3 / 4 neutropenia with idelalisib?

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Approximately 30%

Lymphoma
Lymphoma

What are the 2 main differences between copanlisib and idelalisib?

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Copanlisib is administered as an intravenous infusion and it targets the alpha isoform of PI3K

Lymphoma
Lymphoma

Which prophylactic therapy should be offered to patients on copanlisib?

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PCP prophylaxis

Lymphoma
Lymphoma

What was copanlisib combined with in the CHRONOS-3 trial ?

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Rituximab

Lymphoma
Lymphoma

How common is grade 3 / 4 hyperglycemia with copanlisib?

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56%

Lymphoma
Lymphoma

Which cardiovascular complication is of concern with copanlisib?

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Hypertension -grade 3 / r 4 can be seen in up to 40%

Lymphoma
Lymphoma

Which isoform of PI3K does duvelisib target?

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Delta and gamma

Lymphoma
Lymphoma

Is duvelisib administered orally or intravenously?

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Orally

Lymphoma
Lymphoma

What are some of the reported causes of death as a result of duvelisib ?

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Diarrhea / opportunistic infection / pneumonitis

Lymphoma
Lymphoma

What are the 2 most common gastrointestinal side effects seen with duvelisib ?

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Diarrhea nausea

Lymphoma
Lymphoma

What percentage of patients can expect a dose reduction or interruption with duvelisib ?

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70%

Lymphoma
Lymphoma

What are the biologic targets of Umbralisib ?

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PI3K delta and CK1-epsilon

Lymphoma
Lymphoma

Is umralisib administered orally or intravenously?

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Orally at 800 mg daily

Lymphoma
Lymphoma

Which clinical trial assessed the efficacy of umralisib in r/r FL ?

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Global Unity–NHL

Lymphoma
Lymphoma

What is the overall response rate with Umralisib in r/r FL ?

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Approximately 50%

Lymphoma
Lymphoma

Which prophylactic therapy is recommended in patients treated with lenalidomide plus rituximab for R/R follicular lymphoma?

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DVT prophylaxis with aspirin

Lymphoma
Lymphoma

What agent did the AUGMENT trial compare lenalidomide plus rituximab to?

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Placebo plus rituximab

Lymphoma
Lymphoma

What has the addition of lenalidomide to single agent rituximab demonstrated for R/R follicular lymphoma?

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Improvement in progression free survival from 14 to 39 months as well as estimated 2-year overall survival from 87 to 93%

Lymphoma
Lymphoma

What is the definition of early treatment failure for follicular lymphoma?

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Progression within 24 months of initial immunochemotherapy or within 12 months of single agent rituximab

Lymphoma
Lymphoma

What are the 3 important variables when organizing a treatment plan for R/R follicular lymphoma?

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Relapse free interval–indications for treatment–histologic transformation

Lymphoma
Lymphoma

What are treatment options for patients with late relapse follicular lymphoma?

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Single agent rituximab / chemoimmunotherapy / targeted therapy / radio-immunotherapy

Lymphoma
Lymphoma

What is the main advantage of using obinutuzumab rather than rituximab when combined with lenalidomide for R/R follicular lymphoma?

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Improved response rate but at the cost of excess toxicity

Lymphoma
Lymphoma

Which anti-CD20 targeting monoclonal antibody is most commonly utilized for relapsed/refractory follicular lymphoma?

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Rituximab

Lymphoma
Lymphoma

Is there a PFS requested finished utilizing obinutuzumab or rituximab in r/r FL ?

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No

Lymphoma
Lymphoma

What did the HOMER trial demonstrate for rituximab versus obinutuzumab with R/R follicular lymphoma?

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Rituximab offers a similar ORR as well as PFS

Lymphoma
Lymphoma

Which chemotherapy agents are commonly added to an anti-CD20 targeting antibody for R/R follicular lymphoma?

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CHOP/ CVP/ bendamustine/ lenalidomide -depending on first-line therapy

Lymphoma
Lymphoma

How does the addition of fludarabine to rituximab versus bendamustine compare?

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Inferior response rate–PFS and OS

Lymphoma
Lymphoma

What did the GADOLIN trial show for the addition of obinutuzumab to bendamustine versus single agent bendamustine for R/R follicular lymphoma?

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Improvement in PFS and OS

Lymphoma
Lymphoma II Part 1

Lymphoma II Part 1

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Lymphoma II Part 1

Lymphoma II Part 1
Lymphoma II Part 2

What were the results of the BRIGHT trial in MZL ?

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Superior progression free survival compared to RCVP and RCHOP

Lymphoma II Part 2
Lymphoma

What was the purpose of the BRIGHT trial in MZL ?

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BR vs RCHOP or RCVP in first-line indolent non-Hodgkin lymphoma including marginal zone lymphoma

Lymphoma
Lymphoma

What were the results of the RESORT trial in MZL ?

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Maintenance rituximab is superior with regards to time to treatment failure versus retreatment rituximab

Lymphoma
Lymphoma

What was the purpose of the RESORT study in MZL ?

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Randomized phase 3 clinical trial, Retreatment rituximab (weekly ×4) at every progression versus maintenance rituximab (every 3 months)

Lymphoma
Lymphoma

Which HiDAC has shown some efficacy in refractory marginal zone lymphoma ?

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Vorinostat

Lymphoma
Lymphoma II Part 1

What are the results of the AUGMENT trial in MZL ?

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Superior progression free survival with the addition of lenalidomide to rituximab

Lymphoma II Part 1
Lymphoma

What did the AUGMENT trial assess in MZL ?

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Randomized phase 3 clinical trial, assessing the addition of lenalidomide to rituximab for relapsed or refractory marginal zone lymphoma

Lymphoma
Lymphoma II

Is radiotherapy effective for gastric MALT lymphoma if H. pylori treatment does not eradicate the lymphoma?

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Yes

Lymphoma II
Lymphoma

How long can resolution take with antibiotic therapy for H. pylori associated MALT?

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3-18 months

Lymphoma
Lymphoma

What can predict for a lack of response to antibiotic therapy in H pylori associated MALT?

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T(11;18) presence

Lymphoma
Lymphoma

What are 2 common treatments for gastric MALT that are not responsive to H. pylori therapy?

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Radiotherapy and rituximab

Lymphoma
Lymphoma

What is the response rate to H. pylori therapy for gastric MALT lymphoma?

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More than 70%

Lymphoma
Lymphoma

What is the fusion product of t(11;18) in MALT ?

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API2-MALT1

Lymphoma
Lymphoma

Is disseminated MALT more common with gastric or the non-gastric subtype of MALT?

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Gastric

Lymphoma
Lymphoma

What is the incidence of bone marrow involvement with MALT ?

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15-20%

Lymphoma
Lymphoma

Which genetic test can help differentiate marginal zone lymphoma from Waldenström’s/LPL ?

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MYD88 and IGHV

Lymphoma
Lymphoma

Which infectious organisms have been associated with marginal zone lymphoma?

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H. pylori, chlamydia, Campylobacter, Borrelia

Lymphoma
Lymphoma

Where is the most common site for a marginal zone lymphoma?

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Stomach

Lymphoma
Lymphoma

What infectious agent is skin MALT associated with?

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Borrelia

Lymphoma
Lymphoma

Which Lymphoma does Borrelia burgdorferi cause?

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Cutaneous MALT lymphoma

Lymphoma
Lymphoma

What lymphoma does hepatitis C cause?

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Splenic marginal zone lymphoma

Lymphoma
Lymphoma

What are the indolent B-cell lymphomas?

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Follicular lymphoma, marginal zone lymphoma, chronic lymphocytic leukemia, lymphoplasmacytic
lymphoma, hairy cell leukemia, MALT lymphoma

Lymphoma
Lymphoma

Which 5 lymphomas comprise 85% of all cases?

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Follicular, large cell, chronic lymphocytic leukemia, MALT lymphoma, mantle cell lymphoma

Lymphoma
Lymphoma

Which cytogenetic translocation is seen with marginal zone lymphoma?

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Trisomy 3 and t(11;18)

Lymphoma
Lymphoma

What is the immunohistochemistry pattern for marginal zone lymphoma?

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CD5 negative, CD10 negative, CD20 positive, CD23 negative

Lymphoma
Lymphoma

Where is the marginal zone relative to the lymph node architecture?

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Very peripheral

Lymphoma
Lymphoma

What are the 3 different types of marginal zone lymphoma?

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Nodal, splenic, MALT

Lymphoma
Lymphoma

What can be seen on a peripheral smear with splenic marginal zone lymphoma?

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Atypical lymphocytes with hairy projections

Lymphoma
Lymphoma

What are the first, second, third and fourth – line treatments for splenic marginal zone lymphoma?

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First-line treatment is hepatitis C treatment
Second line treatment of splenectomy
Third line treatment is rituximab-based chemotherapy
Fourth line treatment is ibrutinib if refractory to CD20 based therapy

Lymphoma
Lymphoma

What is the most important serum laboratory test when splenic marginal zone lymphoma is diagnosed?

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Hepatitis C

Lymphoma
Lymphoma

How do you manage nodal marginal zone lymphoma?

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The same as follicular lymphoma

Lymphoma
Lymphoma

What are the preferred treatment options for MALT lymphoma of the stomach?

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Radiotherapy, rituximab, rituximab-based chemotherapy

Lymphoma
Lymphoma

Where can MALT lymphoma show up?

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Gastrointestinal tract, kidneys, prostate

Lymphoma
Lymphoma

What determines if gastric MALT will respond to triple antibiotic therapy?

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The presence of t(11;18)

Lymphoma
Lymphoma

Which marker is the only one that is positive in marginal zone lymphoma?

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CD20

Lymphoma
Lymphoma

Which 2 markers can distinguish hairy cell leukemia from marginal zone lymphoma?

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CD25 positive, CD103 positive in hairy cell leukemia but negative in marginal zone lymphoma

Lymphoma
Lymphoma

What is a follow-up study if a biopsy for H. pylori in MALT lymphoma is negative?

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Follow-up with urea breath test

Lymphoma
Lymphoma II Part 2

Lymphoma II Part 2

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Lymphoma II Part 2

Lymphoma II Part 2
Lymphoma

Which targeted therapies are most commonly utilized for advanced marginal zone lymphoma treatment?

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PI3K inhibitors/lenalidomide

Lymphoma
Lymphoma

Where targeted therapies preferred for advanced marginal zone lymphoma?

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Early progression i.e. within 2 years of systemic chemoimmunotherapy

Lymphoma
Lymphoma

Is there phase 3 data supporting the use of ibrutinib for marginal zone lymphoma?

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no–only phase 2 data

Lymphoma
Lymphoma

What is the overall response rate of ibrutinib for marginal zone lymphoma?

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48% with a 29% complete response rate

Lymphoma
Lymphoma

Is there phase 3 data supporting the use of lenalidomide plus rituximab for R/R MZL?

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No–only phase 2

Lymphoma
Lymphoma

What is the overall response rate of umbralisib in R/R MZL?

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49%

Lymphoma
Lymphoma

What is the overall response rate with copanlisib in R/R MZL?

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78%

Lymphoma
Lymphoma

What percentage of patients with marginal zone lymphoma may have a histologic transformation?

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Approximately 50%

Lymphoma
Lymphoma

What is the median time to diagnosis of transformation for marginal zone lymphoma?

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Approximately 5 years

Lymphoma
Lymphoma

What is the most common histologic transformation with marginal zone lymphoma?

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Large cell lymphoma

Lymphoma
Lymphoma II Part 2

Lymphoma II Part 2

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Lymphoma II Part 2

Lymphoma II Part 2
Lymphoma II Part 3

What were the results of the GALLIUM trial in FL ?

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Improvement in progression free survival with the Obinutuzumab arm

Lymphoma II Part 3
Follicular Lymphoma

What was the purpose of the GALLIUM trial in FL ?

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Obinutuzumab plus chemo -based therapy versus rituximab–chemotherapy based therapy for first-line treatment of follicular lymphoma followed by maintenance

Follicular Lymphoma
Follicular Lymphoma

What were the final results for median PFS for the PRIMA in iNHL ?

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10 years versus 4 years

Follicular Lymphoma
Follicular Lymphoma

What was the purpose of the PRIMA trial in indolent NHL ?

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Maintenance rituximab versus observation following chemotherapy immunotherapy with rituximab based chemotherapy, R–CHOP or R–CVP or R–B

Follicular Lymphoma
Follicular Lymphoma

What was the outcome of the StiL NHL 2-2003 trial ?

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BR is superior to FR for indolent lymphoma

Follicular Lymphoma
Follicular Lymphoma

What was the purpose of the StiL NHL 2-2003 trial ?

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BR vs FR in iNHL

Follicular Lymphoma
Follicular Lymphoma 111

What did the DELTA trial assess in follicular lymphoma ?

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Idelalisib in r/r FL

Follicular Lymphoma 111
Follicular Lymphoma

What did the DAWN trial assess in follicular lymphoma ?

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Ibrutinib in r/r FL

Follicular Lymphoma
Follicular Lymphoma

What was the ORR for FL from duvelisib in the DYNAMO trial ?

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42%

Follicular Lymphoma
Follicular Lymphoma

What was the most common AE with duvelisib in the DYNAMO trial ?

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Diarrhea

Follicular Lymphoma
Follicular Lymphoma

Which NHL subtype had the highest ORR in the DYNAMO trial ?

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SLL

Follicular Lymphoma
Follicular Lymphoma

What was the purpose of the DYNAMO trial ?

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Assess the efficacy of duvelisib in r/r FL

Follicular Lymphoma
Follicular Lymphoma

What was the purpose of the VERTICAL trial in follicular lymphoma ?

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Assess the addition of bortezomib to BR , showed ORR of 88%

Follicular Lymphoma
Follicular Lymphoma

What were the results of the CRONOS-1 trial for follicular lymphoma ?

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45% objective response rate in indolent lymphoma, predominantly follicular histology

Follicular Lymphoma
Follicular Lymphoma

What was the purpose of the CRONOS-1 trial in follicular lymphoma ?

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Single arm study of Copansilib and heavily pretreated lymphoma, 50% follicular lymphoma

Follicular Lymphoma
Follicular Lymphoma

What were the results of the GAUSS trial in follicular lymphoma ?

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Higher overall response rate with obinutuzumab versus rituximab, but no difference in progression free survival

Follicular Lymphoma
Follicular Lymphoma

What was the purpose of the GAUSS trial in follicular lymphoma ?

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Obinutuzumab versus rituximab and relapsed follicular lymphoma

Follicular Lymphoma
Follicular Lymphoma

What was the result of the GADOLIN trial in follicular lymphoma ?

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Improvement in progression free survival in the combination arm

Follicular Lymphoma
Follicular Lymphoma

What was the purpose of the GADOLIN trial in follicular lymphoma ?

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Maintenance obinutuzumab following obinutuzumab plus bendamustine rituximab refractory follicular lymphoma versus bendamustine monotherapy

Follicular Lymphoma
Follicular Lymphoma

How is the lymph node germinal center architecture different in follicular lymphoma versus a non-pathologic lymph node ?

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no gray and light zones present

Follicular Lymphoma
Follicular Lymphoma

Which immunohistochemistry stains can help in the diagnosis of follicular lymphoma?

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CD21 and CD23

Follicular Lymphoma
Follicular Lymphoma

Which growth pattern is common in follicular lymphoma?

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Nodular

Follicular Lymphoma
Follicular Lymphoma

What is the lymph node pattern on clinical exam for follicular lymphoma patients?

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Peripheral lymphadenopathy, commonly cervical, axillary, inguinal and femoral with very little
mediastinal lymphadenopathy

Follicular Lymphoma
Follicular Lymphoma

Which protein is overexpressed in follicular lymphoma?

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Bcl-2

Follicular Lymphoma
Follicular Lymphoma

Which translocation is seen in follicular lymphoma?

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t(14;18)

Follicular Lymphoma
Follicular Lymphoma

In which cells does follicular lymphoma originate?

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Germinal center B cells in centrocytes and centroblasts

Follicular Lymphoma
Follicular Lymphoma

What growth pattern besides a follicular pattern can also be seen in follicular lymphoma?

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Diffuse

Follicular Lymphoma
Follicular Lymphoma

Which 2 rare translocations can also be seen in follicular lymphoma?

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t(2;18)
t(18;22)
Lambda and kappa genes with BCL-2

Follicular Lymphoma
Follicular Lymphoma

Which genes are translocated in follicular lymphoma?

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Immunoglobulin heavy chain and BCL-2

Follicular Lymphoma
Follicular Lymphoma

Which protein is strongly expressed in follicular lymphoma ?

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BCL-2, paradoxically higher expression in low an intermediate grade

Follicular Lymphoma
Follicular Lymphoma

Which cell surface markers are commonly expressed in follicular lymphoma?

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Positive for surface immunoglobulin, CD10, CD19, CD20, CD21, CD23, CD79a, HLA–DR

Negative for CD5, CD43, CD11c

Follicular Lymphoma
Follicular Lymphoma

How is follicular lymphoma graded?

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Grade 1 is less than 6 centroblasts per high power field, grade 2 is 6-15 per high power field
Grade 3 > than 15 per high power field

Follicular Lymphoma
Follicular Lymphoma

Which cell type is the predominate histology for follicular lymphoma?

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Centrocytes are more common and centroblasts

Follicular Lymphoma
Follicular Lymphoma

What are the 2 treatment options for stage I follicular lymphoma?

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Observation versus 24 Gy radiotherapy

Follicular Lymphoma
Follicular Lymphoma

Which follicular lymphoma variant has a different treatment recommendation for early stage I and II
disease?

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Grade 3b, treatment is the same as diffuse large B-cell lymphoma – R-CHOP

Follicular Lymphoma
Follicular Lymphoma

When could you consider chemotherapy and rituximab for early stage follicular lymphoma?

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Bulky disease with high collateral tissue injury from radiotherapy, high-grade, IIIB follicular lymphoma,
patient declines radiotherapy

Follicular Lymphoma
Follicular Lymphoma

In what situation would you add rituximab and/or chemotherapy for stage I follicular lymphoma?

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Never unless radiotherapy is not an option

Follicular Lymphoma
Follicular Lymphoma

What dose of radiotherapy is delivered for early stage follicular lymphoma?

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24 Gy

Follicular Lymphoma
Follicular Lymphoma

If a patient with follicular lymphoma requires immune radiotherapy, what must be done immediately
prior?

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Bilateral bone marrow biopsy to assess bone marrow reserve

Follicular Lymphoma
Follicular Lymphoma

What bone marrow biopsy is required to properly stage follicular lymphoma?

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Yes

Follicular Lymphoma
Lymphoma II Part 4

What defines stage III follicular lymphoma ?

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lymphadenopathy above and below the diaphragm or above the diaphragm with splenomegaly

Lymphoma II Part 4
Follicular Lymphoma

What are the findings of stage II follicular lymphoma?

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2 or more lymph node groups on the same side of the diaphragm

Follicular Lymphoma
Follicular Lymphoma

How can you treat stage I follicular lymphoma?

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Radiotherapy

Follicular Lymphoma
Follicular Lymphoma

What comprises the FLIPI-1 score?

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Age greater than 60, stage III or stage IV disease, hemoglobin less than 12, more than 4 nodal regions,
elevated LDH

Follicular Lymphoma
Follicular Lymphoma

What comprises the FLIPI-2 score?

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age greater than 60, bone marrow involvement, hemoglobin less than 12, at least one lymph node
larger than 6 cm, beta 2 microglobulin elevated above upper limit or normal

Follicular Lymphoma
Follicular Lymphoma

What are some prognostication tools for determining relapse rates in follicular lymphoma?

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Tumor grade, FLIPI score, time to relapse, histologic changes

Follicular Lymphoma
Follicular Lymphoma

How can you distinguish reactive follicular hyperplasia from follicular lymphoma?

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Reactive follicular hypo-aplasia lacks a BCL-2 translocation

Follicular Lymphoma
Follicular Lymphoma

What agents are approved following rituximab chemotherapy treatment for stage III and stage IV
follicular lymphoma?

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Ibritumaamb and Tositumumab

Follicular Lymphoma
Follicular Lymphoma

What is a major adverse event with radio-immunotherapy use in stage III and stage IV follicular
lymphoma?

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myelodysplastic syndrome / leukemia at 15 years is roughly 15%

Follicular Lymphoma
Follicular Lymphoma

If follicular lymphoma patients with stage III or IV disease are poor candidates for chemotherapy, which
treatment is an option?

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Single agent rituximab

Follicular Lymphoma
Follicular Lymphoma

What 2 chemotherapy regimens besides bendamustine + rituximab are acceptable for stage III and stage
IV follicular lymphoma?

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R – CHOP and R – CVP

Follicular Lymphoma
Follicular Lymphoma

What is the recommended chemotherapy regimen for stage III and stage IV, non-grade IIIb follicular
lymphoma?

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Bendamustine plus rituximab, unless it is high-grade then consider rituximab plus CHOP

Follicular Lymphoma
Follicular Lymphoma

What is the treatment of choice for symptomatic stage III and stage IV follicular lymphoma ?

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Rituximab plus chemotherapy

Follicular Lymphoma
Follicular Lymphoma

What is rate of progression of follicular lymphoma to aggressive lymphoma per year?

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3% per year

Follicular Lymphoma
Follicular Lymphoma

How can you treat patient with stage III and stage IV follicular lymphoma without any symptoms?

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Observation then treatment if there is progression

Follicular Lymphoma
Follicular Lymphoma

What is the treatment for interfollicular hyperplasia?

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Surgery

Follicular Lymphoma
Follicular Lymphoma

What can determine failure of radiotherapy for early stage I and stage II follicular lymphoma?

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Tumor bulk

Follicular Lymphoma
Follicular Lymphoma

What are two treatment options for stage II follicular lymphoma?

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Radiotherapy versus rituximab plus chemotherapy

Follicular Lymphoma
Follicular Lymphoma

Which relapsed follicular lymphoma patients are ideal candidates for autologous stem cell transplant ?

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Patients who have a history of chemosensitive disease, relapse within the first couple of years of
treatment

Follicular Lymphoma
Follicular Lymphoma

Which chemotherapy regimens should be used for relapse of refractory follicular lymphoma?

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R-CHOP versus R-CVP versus BR, depending on what first-line therapy was used

Follicular Lymphoma
Follicular Lymphoma

What is the frequency of maintenance rituximab in follicular lymphoma?

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Weekly for 4 infusions then every 8 weeks for 2 years total

Follicular Lymphoma
Follicular Lymphoma

How long is maintenance rituximab in stage III and stage IV follicular lymphoma given?

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2 years

Follicular Lymphoma
Follicular Lymphoma

How many cycles of bendamustine + rituximab should be given for follicular lymphoma?

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6

Follicular Lymphoma
Follicular Lymphoma

Does maintenance rituximab improve progression free survival and overall survival in follicular lymphoma after first line treatment ?

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No, only progression free survival

Follicular Lymphoma
Follicular Lymphoma

Which chemotherapy regimen should receive maintenance rituximab versus observation for stage III
and stage IV follicular lymphoma?

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R-CHOP

Follicular Lymphoma
Follicular Lymphoma

How should you manage patients with hepatitis C and follicular lymphoma?

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Treat underlying hepatitis C first

Follicular Lymphoma
Follicular Lymphoma

Is there a role for up-front autologous stem cell transplant for stage III and stage IV follicular lymphoma?

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No

Follicular Lymphoma
Follicular Lymphoma

What is the advantage and disadvantage of using a radio immunotherapy CD20 antibody conjugate for
stage III and stage IV disease?

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Increases the complete response rate but unfortunately at the expense of developing leukemia

Follicular Lymphoma
Follicular Lymphoma

In which setting can you use idelaisib for follicular lymphoma?

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Third line setting

Follicular Lymphoma
Follicular Lymphoma

What is the advantage of maintenance rituximab for relapsed refractory follicular lymphoma?

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It improves progression free survival and overall survival

Follicular Lymphoma
Follicular Lymphoma

Which radioisotope is used in Tositumumab?

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Iodine-131

Follicular Lymphoma
Follicular Lymphoma

Which radioisotope is used in Ibritumumab ?

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Yttrium-90

Follicular Lymphoma
Follicular Lymphoma

What is a major disadvantage of using autologous stem cell transplant for relapsed follicular lymphoma?

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Significant bone marrow suppression, hence there may be no future role for radio immunotherapy

Follicular Lymphoma
Follicular Lymphoma

What defines progressive disease for refractory follicular lymphoma?

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New LN, hepatosplenomegaly no, more than 50% growth in each lesion

Follicular Lymphoma
Lymphoma II Part 5

What is the product of the t(14;18) translocation in follicular lymphoma ?

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Fusion of BCL-2 and immunoglobulin heavy chain which increases cell survival

Lymphoma II Part 5
Lymphoma

What is the immunohistochemistry pattern for follicular lymphoma?

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CD5 negative, CD10 positive, CD20 positive, CD23 negative

Lymphoma
Lymphoma

How do you treat transformed diffuse large B-cell lymphoma with evidence of follicular lymphoma in the
background?

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RCHOP

Lymphoma
Lymphoma

What is the yearly transformation rate for follicular lymphoma to aggressive lymphoma?

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3% per year

Lymphoma
Lymphoma

What did the RCVP/FCR/RCHOP trial show in follicular lymphoma?

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No difference in overall survival between any of the regimens, but increased progression free survival
with RCHOP and RCVP

Lymphoma
Lymphoma

What did the BR vs RCHOP study show for follicular lymphoma?

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Similar efficacy with lower toxicity

Lymphoma
Lymphoma

What is the overall response rate with single agent rituximab and follicular lymphoma and the duration
of response?

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70% overall response rate with a 1-2 year duration

Lymphoma
Lymphoma

What are the GELF criteria to consider treatment for follicular lymphoma?

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At least 3 lymph node sites, the presence of constitutional symptoms, a spleen larger than 16 cm, single
lymph node larger than 7 cm, notable cytopenias, notable malignant effusions

Lymphoma
Lymphoma

What is the treatment for stage I and 2 follicular lymphoma?

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Observation or radiotherapy

Lymphoma
Lymphoma

What percentage of follicular lymphomas are diagnosed as stage I and 2?

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15% are stage I and 2 and 85% or stage 3 and 4

Lymphoma
Lymphoma

Which cytoreductive therapies are seen with follicular lymphoma?

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t(14;18)

Lymphoma
Lymphoma

What is the FISH pattern for follicular lymphoma?

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BCL-2 positive in 85%, BCL 6 positive in 100%

Lymphoma
Lymphoma

Which type of allogeneic stem cell transplant should be considered for follicular lymphoma?

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Non-myeloablative from a primary related donor

Lymphoma
Lymphoma

Which follicular lymphoma patients are good candidates for allogeneic stem cell transplant?

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Those without a response to autologous stem cell transplant or CART

Lymphoma
Lymphoma

How long should progression free survival be before repeat rituximab re-challenge for relapsed
refractory follicular lymphoma?

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At least 6 months

Lymphoma
Lymphoma

How is rituximab administered in the relapse refractory setting of follicular lymphoma?

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Weekly for 4 weeks

Lymphoma
Lymphoma

What is required before proceeding with autologous or allogeneic stem cell transplant for transformed
follicular lymphoma ?

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Patients must be in a complete remission

Lymphoma
Lymphoma

What is a common presentation for diffuse large B-cell lymphoma transformation from an underlying follicular lymphoma ?

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single enlarged lymph node

Lymphoma
Lymphoma

Which study showed the value of maintenance rituximab for follicular lymphoma?

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PRIMA

Lymphoma
Lymphoma

Which immunohistochemistry stains and cytogenetics are different for grade 3b follicular lymphoma
versus low and intermediate grade follicular lymphoma?

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CD10 negative, BCL-2 negative, t(14;18) negative

Lymphoma
Lymphoma

What defines a high-grade follicular lymphoma?

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More than 15 centroblasts per high-powered field, grade 3b

Lymphoma
Lymphoma

What are treatment options for stage I follicular lymphoma?

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Observation versus radiotherapy versus rituximab-based chemotherapy

Lymphoma
Lymphoma

What studies support single agent rituximab for follicular lymphoma?

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RESORT study, R-Chemo followed by rituximab maintenance versus rituximab on progression showed a
significant improvement in progression free survival

Lymphoma
Lymphoma

Which genes are transposed in t(14;18) follicular lymphoma?

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Immunoglobulin heavy chain and BCL-2

Lymphoma
Lymphoma

Which stains can distinguish CD19 positive CD20 positive CD23 positive follicular lymphoma from
chronic lymphocytic leukemia?

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CD10 negative in CLL

Lymphoma
Lymphoma II Part 6

What is the advantage of weekly cladribine over the 5-day regimen besides convenience for hairy cell leukemia ?

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None, no change in efficacy or toxicity

Lymphoma II Part 6
Lymphoma

What are the main AE expected with BR or FR with first line Waldenstrom’s treatment ?

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Myelosuppression and infection

Lymphoma
Lymphoma

Is there randomized data supporting the use of BR vs FR in newly diagnosed Waldenstrom’s ?

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Yes, BR appears has superior PFS

Lymphoma
Lymphoma

What were the results of the iNNOVATE trial in Waldenstrom’s ?

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Ibrutinib added to rituximab in newly diagnosed and previously treated Waldenstrom’s improved PFS

Lymphoma
Lymphoma

What did the iNNOVATE trial assess in Waldenstrom’s ?

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Ibrutinib versus placebo added to rituximab to newly diagnosed and previously treated Waldenstrom’s

Lymphoma
Lymphoma

Which regimens have randomized data supporting their use in r/r Waldenstrom’s ?

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Bendamustine + rituximab, ibrutinib + rituximab, Fludarabine + rituximab

Lymphoma
Lymphoma

Which genetic test can help differentiate marginal zone lymphoma from Waldenström’s/LPL ?

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MYD88 and IGHV

Lymphoma
Lymphoma

What dose of radiation can be given for nasal type natural killer cell lymphoma concurrent with
cisplatin?

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Concurrent radiotherapy with cis-platinum and a total radiation dose of 4000-5210 centigray followed
by adjuvant ICE for 3 cycles
SMILE regimen

Lymphoma
Lymphoma

What are the indolent B-cell lymphomas?

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Follicular lymphoma, marginal zone lymphoma, chronic lymphocytic leukemia, lymphoplasmacytic
lymphoma, hairy cell leukemia, MALT lymphoma

Lymphoma
Lymphoma

What is the precursor to Waldenström’s macroglobulinemia ?

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Lymphoplasmacytic lymphoma

Lymphoma
Lymphoma

What percentage of lymphoplasmacytic lymphoma and Waldenström’s are transformed to diffuse large B-
cell lymphoma ?

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25%

Lymphoma
Lymphoma

What are 2 indications to treat Waldenström’s ?

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Hyperviscosity and positive organomegaly

Lymphoma
Lymphoma

What mutation is seen in 90% of Waldenström’s?

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L265P in MYD88

Lymphoma
Lymphoma

What other diseases can complicate Waldenström’s?

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Neuropathy, cryoglobulins, amyloidosis, cold agglutinins

Lymphoma
Lymphoma

Which lymphoma underlies Waldenström?

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Lymphoplasmacytic lymphoma

Lymphoma
Lymphoma

What can be seen on a peripheral smear with splenic marginal zone lymphoma?

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Atypical lymphocytes with hairy projections

Lymphoma
Lymphoma

Which chemotherapy regimen is recommended for nasal type natural killer cell lymphoma?

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SMILE

Lymphoma
Lymphoma

Which cell surface cluster differentiation marker is seen in nasal type natural killer cell lymphoma?

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CD2 positive, CD 56 positive, CD3cytoplasm positive, CD8 negative

Lymphoma
Lymphoma

Which 2 markers can distinguish hairy cell leukemia from marginal zone lymphoma?

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CD25 positive, CD103 positive in hairy cell leukemia but negative in marginal zone lymphoma

Lymphoma
Lymphoma

Which cell surface marker distinguishes natural killer cells?

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CD 56

Lymphoma
Lymphoma

Which regimens can be used for nasal type natural killer cell lymphoma?

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Concurrent chemotherapy and radiotherapy, SMILE, SHAP regimens

Lymphoma
Lymphoma

Which cell surface markers can distinguish a T-cell from a natural killer cell?

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CD5

Lymphoma
Lymphoma

What part of a complete blood count with differential can help make a diagnosis of hairy cell leukemia?

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Monocytopenia

Lymphoma
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