Histopathologic results

(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

(3)

(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)

(6)

(7)

FOLÍCULO REACIONAL FOLÍCULO NEOPLÁSICO REACTIVE HYPERPLASIA FOLLICULAR LYMPHOMA

(8)

Ki67 Bcl2

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+ B-cells in FL

(11)

The follicules are uniformly BCL2 positive

(12)

Follicular lymphoma grading

Grade 1 Grade 2 Grade 3a Grade 3b Ki67 Ki67

(13)

Cases with

> 15

centroblasts per high

power field are considered Grade 3 FL

Grade 1: 0-5 centroblasts Grade 2: 6-15 centroblasts Grade 3: > 15 centroblasts 3A - centrocytes present

3B – solid sheets of centroblasts

CRITERIA FOR

CLASSIFICATION

Number of large cells

per high power field

(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-2.

2. 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-B-cell.

(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-B-cell.

(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

(17)

Age >= 60 Stage III-IV Hb < 12 LDH> normal Nodal sites>4 Blood, 2004

(18)

(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

(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)

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

N=334 FL

1.3

(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

Gilles Salles Hospices Civils de Lyon & Université Claude Bernard, Lyon,

France

(25)

R-CHOP N = 885 Randomized N = 769 * 15 pts in 3 sites closed prematurely Patients evaluable (N = 1202)* R-CVP N = 272 Patients registered: N = 1217 R-FCM N = 45 Randomized N = 222 Randomized N = 28 Observation N = 513 Rituximab N = 505

‡ _{1 pt died during the}

randomization process Induc tion M a int e na nc e

 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

Patient disposition

Patients randomized: N = 1018‡

(26)

Primary endpoint (PFS) met at the planned

interim analysis

Rituximab maintenance significantly reduced the risk of progression by 50%

stratified HR=0.50 95% CI 0.39; 0.64 p<.0001 Time (months) Rituximab maintenance N=505 Observation N=513 6 0 12 18 24 30 36 P ro g re s s io n -fr e e rate 0.8 0.6 0.4 0.2 0 1.0 82% 66% Patients at risk 505 513 472 443 336 230 103 18 469 411 289 195 82 15