Self evaluation 1

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

Histopathologic results

1- The diagnosis is:

1. Follicular Lymphoma

2. Diffuse large B-cell lymphoma

3. Reactive hyperplasia

4. Peripheral-T-lymphoma

5. Mantle cell lymphoma

Follicular lymphoma x Reactive hyperplasia

REACTIVE HYPERPLASIA FOLLICULAR LYMPHOMA

FOLÍCULO REACIONAL FOLÍCULO NEOPLÁSICO REACTIVE HYPERPLASIA FOLLICULAR LYMPHOMA

Ki67

Bcl2

Bcl2

REACTIVE HYPERPLASIA x FOLLICULAR LYMPHOMA

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

CD20+ B-cells in FL

CD20

The follicules are uniformly BCL2 positive

Bcl-2

Follicular lymphoma grading

Grade 1 Grade 2

Grade 3a

Grade 3b

Ki67

Ki67

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)

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.

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.

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

Age >= 60

Stage III-IV

Hb < 12

LDH> normal

Nodal sites>4

Blood, 2004

Blood, 2004

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.

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

Randomized trials demonstrated no difference in OS between the expectant approach of observation and

immediate treatment in advanced FL

Young RC, Lancet, 2003

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.

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 3. 7

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

Salles G, Lancet 2011

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

Indu

ctio

n M

aint

enan

ce

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‡

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

Prog

ress

ion-

free

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