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87 Cards in this Set
- Front
- Back
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CLL comprises what percentage of leukemias?
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30%
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How is CLL different in North America vs. Asia?
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lower incidence in Asia, most cases are T-cell rather than B-cell
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How prevalent is CLL in children?
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Virtually non-existent
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What are risk factors for CLL?
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Familial syndrome (~5-10% of cases). No defined genetic lesions. Increased risk of earlier age dx, female sex, other lymphoproliferative disorders, monoclonal B-cell lymphocytosis
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What is the mechanism of leukocytosis in CLL?
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Mostly failure of apoptosis, smaller component of proliferation
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CLL patients are at increased risk of which solid tumor malignancies? What is the frequency of second malignancies overall?
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Skin is number one, also GI, prostate, lung. Frequency is up to 25% of CLL patients.
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Do male or female CLL patients have a better prognosis?
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Females do better.
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What percentage of CLL cases will show cytogenetic abnormalities on FISH?
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80%
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What is the most common genetic abnormality in CLL? What percentage of patient's have it?
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13q deletion in 55%. Less common abnormalities include trisomy 12, 17p deletion, 11 q deletion
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What is the second most common genetic abnormality in CLL? What percentage of patients have it?
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11q deletion in 18%.
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What is/are the favorable cytogenetic profiles in CLL?
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13 q deletion
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What are the unfavorable cytogenetic profiles in CLL?
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17 p deletion, 11 q deletion
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What is the immunophenotypic pattern for diagnosing CLL?
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CD 5, 19, 20, 23, surface Ig dim
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Of what value is the FMC7 immunophenotypic marker?
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It is positive in mantle cell lymphoma, negative in CLL
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What information does CD 38 positivity convey in CLL?
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May or may not be associated with mutated IgV heavy chain gene, which is of good prognosis.
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What is ZAP-70?
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protein associated with IgV heavy chain mutation, portends indolent course and overall better prognosis in CLL.
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What is level of blood lymphocytes required for a diagnosis of CLL?
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5,000 (clonality confirmed by flow cytometry)
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In what percentage of healthy adults can B-CLL immunophenotype cells be found? What is the significance of this finding?
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3%. These patients have MBL (monoclonal B-cell lymphocytosis) and progress to CLL at 1% per year. Higher abs. lymph count and CD38+ may predict progression.
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What is the incidence of MBL compared to CLL?
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MBL is 100x more common.
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How common is peripheral LAD in CLL? HSM?
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20%, 30-40%
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What are the typical findings on peripheral blood smear in CLL?
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Smudge cells, mature lymphocytes. Smudge cells may be directly proportional to OS.
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What percentage of patients diagnosed with CLL will have a positive Coombs test?
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30%
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What portion of patients with CLL will experience AIHA? ITP?
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10-25% for AIHA
15-20% for ITP |
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What effect does CLL have on gamma globulin levels?
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CLL causes hypogammaglobulinemia in a progressive fashion.
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What is the typical bone marrow involvement in CLL? It is hyper or hypo cellular?
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~30% BM involvement, can be either hypo- or hypercellular.
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What is the main limitation of both the Rai and Binet staging systems for CLL?
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The don't predict which early stage CLL patients are at high risk to progress.
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Are CT scans currently standard in CLL staging.
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No.
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What is Rai stage O (low risk)? What is the median OS for this stage?
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Lymphocytosis only. Median OS is 10 years.
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What is Rai stage I (intermediate risk)? What is the median OS? for this stage?
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Lymphocytosis plus LAD. Median OS is 5-7 years.
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What is Rai stage II (intermediate risk, along with stage I)? What is the median OS for this stage?
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Lymphocytosis, plus HSM or splenomegaly WITH OR WITHOUT LAD. Median OS is between that for stages II-IV.
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What is Rai stage III (high risk)? What is the median OS for this stage?
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Lymphocytosis, LAD or HSM plus Hgb <11. Median OS is 1-3 years.
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What is Rai stage IV? What is the median OS for this stage?
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Lymphocytosis, LAD or HSM, Hgb < 11 plus platelets < 100,000. Median OS is <
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What is the benefit to treating Rai stage 0 CLL patients?
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There is no survival advantage.
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What percentage of early-stage CLL patients will progress?
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~40%.
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What are poor prognostic factors in CLL?
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Diffuse BM involvement, male sex, lymphocyte doubling time of < 1 year, initial lymph count of > 50 K, elevated B2 microglobulin, elelvated LDH, advanced age.
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What percentage of CLL patients have mutated IgV heavy chains, and what is the median survival?
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30-60%, Median OS 10-20 years.
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What is the median OS for CLL patients with unmutated IgV heavy chains?
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5-10 years (about half that of pts. with the mutations)
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In CLL patients treated up-front with fludarabine-containing regimens, unmutated IgV heavy chains predict what?
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decreased OS and PFS.
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What are the problems with using CD 38 as a surrogate for mutated IgV heavy chains?
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Discordance exists in up to a third of cases, and CD 38 positivity may change over time as much as 10%.
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What is the significance of CD49d in CLL?
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High expression of CD49d predicts for decreased survival outcomes.
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What is the discordance rate between ZAP-70 and IgV heavy change mutation status?
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about 20%.
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What can account for the fact that ZAP-70 positive/IgV heavy chain MUTATED patients still have a poor prognosis?
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High rate of adverse cytogenetic abnormalites (del 11q, del 17p) in these patients.
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In what percentage of patients would you expect to see a change in genomic aberrations over the course of their disease?
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~25%.
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Which drug is effective in CLL patients with del 17p (p53) mutations?
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Campath (alemtuzumab).
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Name some alklyating agents.
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Nitrogen mustards (cyclophosphamide, chlorambucil, melphalan), dacarbazine, temozolomide.
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Describe a traditional CLL regimen given to elderly patients.
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Chlorambucil daily (0.1 mg/kg) or q 3-4 weeks 0.4-1.0 mg/kg). Low CR rate, overall response rate of 40-75%, disease advances when tx stopped.
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How does fludarabine compare to alkylator-based regimens in CLL?
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Higher overall response, CR rates, PFS, prolonged remission.
No OS advantage. |
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What is the overall response rate in CLL to single-agent Rituxan?
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50% for previously untreated, 1-20% for previously treated. Remember CLL cells dimly express CD 20.
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What is the role of Pentostatin (a purine analog) in the treatment of CLL?
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When added to cyclophosphamide and Rituxan, OR rates range from 46-94% in both up-front and salvage therapy.
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What is the CC regimen for CLL?
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Cladribine + Cyclophosphamide. In 20 pts with del 17, 80% ORR, 50% CR, 30% PR.
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What are the strengths and weaknesses of Campath in CLL?
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More efficacious than chlorambucil, but better at eradicating peripheral blood and bone marrow disease then in clearing bulky nodal disease. Can be used as a consolidating agent to reduce minimal residual disease.
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Fludarabine may be active in CLL patients with which cytogenetic aberration?
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del 17p
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What is the MOA of bendamustine?
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has both alkylating and purine analog functions.
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Which CLL cytogenetic abnormality can approach 50% prevalence with heavily treated patients?
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del 17p
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What are other causes of cytopenias other than relapsed CLL ?
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autoimmune cytopenias, transformed lymphoma, marrow toxicity or MDS from previous therapy.
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How do you treat the CLL patient who relapses > 12 months after therapy?
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Retreat with the same agents.
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What is the difference in time-to-treatment in CLL patients with mutated vs unmutated IgVh?
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9 years vs. 3.5 years.
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What is the MOA of lenalidomide, and what roles does it have in the treatment of CLL?
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MOA is unknown. Investigational for now.
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What is the "flare reaction" seen in CLL patients treated with lenalidomide? How common is it?
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Flare reaction can include fever, rash, tender enlargement of lymph nodes, leukocytosis and lymphocytosis. Can occur in 50% of patients, 80% severe.
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What can be done to temper the "flare reaction" in CLL patients treated with lenalidomide?
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Low-dose prednisone 10-20 mg/day.
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What is HuMax?
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ofatumumab is an anti-CD 20 antibody that targets a different epitope than Rituxan, and has a higher affinity. May be useful in double-refractory or bulky LAD CLL patients.
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What are the problems with autologous HSCT in CLL?
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1. presence of clonal cells in the stem cell product.
2. preexistent myelosuppression from prior therapy (esp. purine analogs) 3. therapy related MDS or AML (10% incidence) 4. tend to have a pattern of continuing relapse. |
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What is the 100-day transplant mortality rate in most large series of allogeneic HSCT for CLL?
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30-40%. That's why non-myeloablative regimens are gaining popularity, although these have problems as well, including acute and chroni GVHD.
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AIHA and ITP are common complications of CLL (5-10%). What are the more rare complications?
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pure red cell aplasia and autoimmune granulocytopenia.
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What is the first line treatment for autoimmune mediated cytopenias in CLL?
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Prednisone 1 mg/kg/day
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What is the second-line treatment for autoimmune mediated cytopenias in CLL?
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cyclosporine, azathioprine, rituximab. Splenectomy is appropriate for some patients.
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Should chemotherapy be used as the first approach to autoimmune cytopenias in CLL?
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The cytopenias should be controlled with immunosuppression prior to initiating chemotherapy.
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Which class of chemotherapy agents should be avoided in CLL patients with autoimmune cytopenias?
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Purine analogs (fludarabine).
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How are the infectious complications different for CLL patients treated with alkylators vs purine analogs?
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Alkylators - bacterial infections.
Purine analogs - T-cell mediated problems such as HSV. |
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What is Richter's tranformation? How common is it? What is the median survival?
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CLL changes to a high-grade lymphoproliferative disorder, usually but not always DLBCL.
Occurs in 10-15% of CLL patients. Median survival is < 6 months. |
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What is the cutoff for diagnosing prolymphocytic leukemia? How common is this transformation from CLL? How is it commonly treated?
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55% peripheral blood prolymphocytes. Occurs in 2-5% of CLL pts. Commonly treated with Campath.
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What is an underecognized aspect of CLL patients' QOL?
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Understanding their disease, worrying about it daily. Euphemisms such as "you have a good leukemia" are not helpful.
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What are some immunophenotypic markers that point AWAY from CLL?
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CD10, CD79b, FMC7; bright expression of CD20, CD11, CD25.
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What characterizes a prolymphocyte histologically?
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Prominent Nucleolus.
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What physical findings are characteristic of PLL?
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Massive splenomegaly without much LAD.
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What are the characteristic immunophenotypic findings of PLL?
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dense surface IgM positivity, FMC7 positive, CD 23 negative.
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What is the typical clinical presentation of hairy cell leukemia?
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Male age 50-60 with pancytpenia, splenomegaly, infections. Dry tap marrow.
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What are the characteristic histologic and immunophenotypic findings in hairy cell leukemia?
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Positive tartrate-resistant acid phosphatase (TRAP) stain. Positive for CD 19, 20, 22, 11c, 25, 103.
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What is the usual therapy for hairy cell leukemia?
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pentostatin or cladribine.
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How can mantle cell lymphoma be differentiated from CLL?
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Mantle cell lymphoma will be positive for t11:14, express cyclin D1
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What is the mechanism of action of fludarabine? What are the main adverse effects?
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MOA = antimetabolite, induces apoptosis. Adverse effects are mainly myelosuppression (including AIHA and aplastic anemia), immunosuppression with increased risk of infections including HSV, fungi, PCP. Counts may take a year to normalize.
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What is the mechanism of action of cyclophosphamide? What are the main adverse effects?
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Alkylator. Main adverse effects are myelosuppression, bladder toxicity
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What is the mechanism of action of fludarabine? What are the main adverse effects?
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MOA = antimetabolite, induces apoptosis. Adverse effects are mainly myelosuppression (including AIHA and aplastic anemia), immunosuppression with increased risk of infections including HSV, fungi, PCP. Counts may take a year to normalize.
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What is the mechanism of action of cyclophosphamide? What are the main adverse effects?
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Alkylator. Main adverse effects are myelosuppression, bladder toxicity, nausea and vomiting. Also causes alopecia, possibly permanent amenorrhea with ovarian failure, SIADH.
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Describe the bladder toxicity associated with cyclophosphamide.
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Hemorrhagic cystitis, dysuria and frequency. 5-10% incidence. May occur within 24 hours or several weeks later.
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Other than infusion reactions and TLS, what are less commonly seen reactions to Rituxan?
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Multiple skin reactions including TEN, Stevens-Johnson, pemphigus. Arrythmias and chest pain.
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What are the adverse reactions to alemtuzumab (Campath)?
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Infusion-related symptoms. Immunosuppression with increased risk of: CMV, HSV, PCP, Candida, Crypto, Listeria
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