Histopathologic results
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1 Self evaluation 1
2 Clinical Case 55-year-old woman Bilateral enlargement of cervical, axillary and inguinal lymph nodes, largest diameter > 6 cm Hepatosplenomegaly. Enlargement of retroperitoneal, mesenteric and para-aortic lymph nodes. B symptoms were absent A biopsy of a left cervical lymph node was perfomed
3 Histopathologic results
4 1- The diagnosis is: 1. Follicular Lymphoma 2. Diffuse large B-cell lymphoma 3. Reactive hyperplasia 4. Peripheral-T-lymphoma 5. Mantle cell lymphoma
5 Follicular lymphoma x Reactive hyperplasia
6 REACTIVE HYPERPLASIA FOLLICULAR LYMPHOMA
7 REACTIVE FOLÍCULO HYPERPLASIA REACIONAL FOLÍCULO FOLLICULAR NEOPLÁSICO LYMPHOMA
8 REACTIVE HYPERPLASIA x FOLLICULAR LYMPHOMA Bcl2 Ki67 Bcl2
9 2- According to the updated WHO classification: 1. The follicules, and not the interfollicular regions, contain CD20+ B- cells 2. The follicules are uniformly BCL2 negative 3. Grade 1 and Grade 2 cases have a marked predominance of centrocytes and only few centroblasts. Since they represent a continuum, distinction between them is not encouraged and a grade 1-2 can be reported 4. Cases with > 50 centroblasts per high power field are considered Grade 3 FL
10 CD20 CD20+ B-cells in FL
11 The follicules are uniformly BCL2 positive Bcl-2
12 Follicular lymphoma grading Ki67 Grade 3a Grade 3b Grade 1 Grade 2 Ki67
13 Cases with > 15 centroblasts per high power field are considered Grade 3 FL CRITERIA FOR CLASSIFICATION Number of large cells per high power field (centroblasts) Grade 1: 0-5 centroblasts Grade 2: 6-15 centroblasts Grade 3: > 15 centroblasts 3A - centrocytes present 3B solid sheets of centroblasts
14 3- Which option is correct regarding the biology of follicular lymphoma: 1. The tumor cells are usually SIg+. They express B-cell associated antigens and also CD10 and CD5, but they are negative for BCL The t(14;18) is present in 50% of patients. 3. This lymphoma usually presents the t(8;14) translocation, associated with bcl2. 4. The postulated normal counterpart is the germinal center-bcell.
15 3- Which option is correct regarding the biology of follicular lymphoma: The t(14;18) is present in 75-85% of patients by cytogenetics and 100% by FISH The postulated normal counterpart is the germinal centre-bcell.
16 4- The Follicular Lymphoma International Prognostic Index (FLIPI), developed by an international consortium, separates patients into three distinct risk categories. Which of these does not belong in FLIPI? 1. Albumin 2. LDH 3. Hemoglobin 4. Age 5. Number of nodal areas
17 Age >= 60 Stage III-IV Hb < 12 LDH> normal Nodal sites>4 Blood, 2004
18 Blood, 2004
19 5- Which choice is correct in regard to treatment of follicular lymphoma: 1. Treatment in early-stage follicular lymphoma is preferentially Rituximab+chemotherapy. 2. Clinical indications for treatment include symptoms arising from progressive local disease, systemic symptoms, threatened end-organ function, significant cytopenia caused by marrow infiltration, and transformation to an aggressive histology. 3. The incorporation of anthracyclines to chemotherapy regimens clearly improved the overall survival in follicular lymphoma. 4. Watch-and-wait strategy is no longer used as a therapy approach for low-tumor burden disease.
20 Treatment in early-stage follicular lymphoma 15%-20% of follicular lymphoma patients presented in Stage I-II. Radiotherapy is the standard of care of these patients
21 Randomized trials demonstrated no difference in OS between the expectant approach of observation and immediate treatment in advanced FL Young RC, Lancet, 2003
22 6- Which would be the best choice in regard to rituximab maintenance for follicular lymphoma 1. Current studies support the role of maintenance with rituximab after treatment of relapsed disease and also after front-line therapy. 2. Rituximab maintenance must be given in a weekly dose every two months for 2 years. 3. The duration of rituximab maintenance in most published studies is more than 5 years. 4. Rituximab is no longer considered for maintenance chemotherapy due to its long-term morbidity.
23 N=334 FL R(375 mg/m2) IV once every 3 months until relapse or for a maximum of 2 years). R maintenance treatment achieves improvement in PFS (median survival 3,7 years vs 1,3 years) after induction treatment with chemotherapy plus rituximab. Update results with 6 years of median FUP JCO, 2010
24 Rituximab Maintenance for 2 Years in Patients with Untreated High Tumor Burden Follicular Lymphoma After Response to Immunochemotherapy G. A. Salles, J. F. Seymour, P. Feugier, F. Offner, A. Lopez-Guillermo, R. Bouabdallah, L. M. Pedersen, P. Brice, D. Belada, L. Xerri on behalf of the PRIMA investigators Salles G, Lancet 2011 Gilles Salles Hospices Civils de Lyon & Université Claude Bernard, Lyon, France
25 Patient disposition Induction Maintenance Patients evaluable (N = 1202)* R-CHOP N = 885 Randomized N = 769 Patients registered: N = 1217 R-CVP N = 272 Randomized N = 222 Patients randomized: N = 1018 R-FCM N = 45 Randomized N = 28 * 15 pts in 3 sites closed prematurely 9 pts did not receive chemo 147 pts withdrew during or at the end of induction (failure to respond; toxicity) 28 pts failed to be randomized 1 pt died during the randomization process Observation N = 513 Rituximab N = 505
26 Primary endpoint (PFS) met at the planned interim analysis Rituximab maintenance significantly reduced the risk of progression by 50% Progression-free rate Patients at risk stratified HR= % CI 0.39; 0.64 p< Time (months) 82% 66% Rituximab maintenance N=505 Observation N=513
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