incidence

  • Follicular lymphomas are the second most frequent subtype of nodal lymphoid malignancies in Western Europe.

  • The annual incidence of this disease has rapidly increased during recent decades and has risen from 2–3/100 000 during the 1950s to 5–7/100 000 recently.

diagnosis

  • Diagnosis is only based on a surgical specimen/excisional lymph node biopsy. Core biopsies should only be performed in patients without easily accessible lymph nodes (e.g. retroperitoneal bulk), keeping in mind the possible heterogeneity of follicular lymphoma grading difficult to appreciate on core biopsies. Fine needle aspirations are inappropriate for a reliable diagnosis.

  • The histological report should give the diagnosis according to the World Health Organization (WHO) classification. Grading of lymph node biopsies is performed according to the number of blasts/high power field (Table 1). Follicular lymphoma grade 3B (with sheets of blasts) is considered an aggressive lymphoma and treated alike (see clinical recommendation DLBCL) [1].

  • When possible, additional biopsy material should be stored fresh frozen to allow additional molecular (currently still investigational) analyses.

Table 1.

Grading of follicular lymphoma

Grade Description 
≤5 blasts/high power field 
6–15 blasts/high power field 
3A >15 blasts/high power field, centroblasts with intermingled centrocytes 
3B >15 blasts/high power field, pure sheets of blasts 
Grade Description 
≤5 blasts/high power field 
6–15 blasts/high power field 
3A >15 blasts/high power field, centroblasts with intermingled centrocytes 
3B >15 blasts/high power field, pure sheets of blasts 

staging and risk assessment

  • Since treatment substantially depends on the stage of the disease, initial staging should be thorough particularly in the small proportion of patients with early stages I and II (5–10%) (Table 2). Initial work-up should include a computed tomography (CT) scan of the neck, thorax, abdomen and pelvis, and a bone marrow aspirate and biopsy. An additional positron emission tomography (PET) scan is not recommended according to the updated consensus [2]. In rare cases PET scan may be useful to confirm localized stage I/II [IV, C].

  • A complete blood count, routine blood chemistry including lactate dehydrogenase (LDH) and uric acid as well as screening tests for human immunodeficiency virus (HIV) and hepatitis B and C are required.

  • The staging is given according to the Ann Arbor system (Table 2) with mention of bulky disease, when appropriate.

  • For prognostic purposes, a Follicular Lymphoma-specific International Prognostic Index (FLIPI, Table 3: >4 involved nodal sites, elevated LDH, age >60 years, advanced stage III/IV, hemoglobin <12 g/dl) should be determined [I, A] [3, 4]. A revised FLIPI2 (incorporating β2 microglobuline, diameter of largest lymph node, bone marrow involvement and hemoglobin level) has been recently suggested for patients requiring treatment [5].

  • RNA expression analysis suggests a more favorable clinical course in cases with infiltrating T cells in comparison with cases with unspecific macrophage bystander cells [6]. However, this technique is not yet applicable in clinical routine, and immunohistochemistry studies have reported conflicting data recently.

Table 2.

Ann Arbor classification

Stage Area of involvement 
I (IEOne lymph node region or extralymphatic site (IE
II (IIETwo or more lymph node regions or at least one lymph node region plus a single localized extralymphatic site (IIE) on the same side of the diaphragm 
III (IIIE, IIIsLymph node regions or lymphoid structures (e.g. thymus, Waldeyer's ring) on both sides of the diaphragm with optional localized extranodal site (IIIE) or spleen (IIIS
IV Diffuse or disseminated extralymphatic organ involvement 
Stage Area of involvement 
I (IEOne lymph node region or extralymphatic site (IE
II (IIETwo or more lymph node regions or at least one lymph node region plus a single localized extralymphatic site (IIE) on the same side of the diaphragm 
III (IIIE, IIIsLymph node regions or lymphoid structures (e.g. thymus, Waldeyer's ring) on both sides of the diaphragm with optional localized extranodal site (IIIE) or spleen (IIIS
IV Diffuse or disseminated extralymphatic organ involvement 

A, no symptoms.

B, unexplained fever of >38°C, drenching night sweats or loss of <10% body weight within 6 months.

Table 3.

FLIPI risk factors

Parameter Definition of risk factors 
 FLIPI 1 FLIPI 2 
Nodal sites >4 lymph node regions Long diameter of largest lymph node >6 cm 
Age Above 60 years Above 60 years 
Serum marker Elevated lactate dehydrogenase Elevated β2 microglobulin 
stage Advanced (III–IV according to Ann Arbor) Bone marrow involvement 
Hemoglobin <12 g/dl <12 g/dl 
Parameter Definition of risk factors 
 FLIPI 1 FLIPI 2 
Nodal sites >4 lymph node regions Long diameter of largest lymph node >6 cm 
Age Above 60 years Above 60 years 
Serum marker Elevated lactate dehydrogenase Elevated β2 microglobulin 
stage Advanced (III–IV according to Ann Arbor) Bone marrow involvement 
Hemoglobin <12 g/dl <12 g/dl 

With 0–1 risk factors, low risk; 2, intermediate risk; 3–5, high risk.

treatment plan

first line

stage I–II.

  • In the small proportion of patients with limited non-bulky stages I–II, radiotherapy (involved or extended field, 30–36 Gy) is the preferred treatment having a curative potential [II, B] [7]. In selected cases a watchful waiting may be discussed to avoid the side effects of radiation (e.g. cervical, sicca syndrome; abdominal, myeloablative suppression) [8].

  • In patients with large tumor burden or adverse prognostic features, systemic therapy as indicated for advanced stages should be applied and the role of radiation consolidation is not proven [IV, B].

stage III–IV.

induction.

  • In the majority of patients with advanced stage III and IV disease, no curative therapy is yet established. Since the natural course of the disease is characterized by spontaneous regressions in up to 25% of cases and varies significantly from case to case, therapy should be initiated only upon the occurrence of symptoms including B-symptoms, hematopoietic impairment, bulky disease, vital organ compression, ascites, pleural effusion or rapid lymphoma progression [I, A]. In four randomized trials an early initiation of therapy in asymptomatic patients did not result in any improvement of disease-specific survival or overall survival (OS) [9]. In a recent study, early initiation of rituximab resulted in improved progression-free survival (PFS; 80% vs 48%, P <0.001), but the benefit on long-term outcome has to be determined [10].

  • If complete remission and long PFS are to be achieved, rituximab in combination with chemotherapy [such as CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone), CVP (cyclophosphamide, vincristine and prednisone), purine analog-based schemes: FC (fludarabine and cyclophosphamide) or FM (fludarabine and mitoxantrone) or Bendamustine] should be used [I, B] [11]. In cases with (histologically or clinically) suspected transformation to aggressive lymphoma, an anthracycline-based regimen should be preferred. Four prospective first-line trials and two salvage trials as well as a systematic meta-analysis confirmed an improved overall response, PFS and OS when rituximab was added to chemotherapy (Table 4) [12–16].

  • Antibody monotherapy (rituximab, radioimmunotherapy) or chlorambucil plus rituximab remains an alternative in patients with low risk profile or contraindications for a more intensive chemoimmunotherapy [III, B] [17, 18].

  • In hepatitis B patients, specific recommendations (HBV monitoring, antiviral therapy) should be followed [19].

Table 4.

Combined chemoimmunotherapy in follicular lymphoma (first line)

Study Total no. of patients Median follow-up Overall response Time to treatment failure (months) Overall survival 
Marcus 2008 [14] R-CVP 321 53 months 81% (P <0.0001) 27 (P <0.0001) 83% (4 years) (P = 0.029) 
Hiddemann 2005 [12] R-CHOP 428 58 months 96% NR (P <0.001) 90% (2 years) (P = 0.0493) 
Herold 2007 [13] R-MCP 201 48 months 92% (P = 0.0009) NR (P <0.0001) 87% (P = 0.0096) 
Salles 2008 [15] R-CHVP-Ifn 358 60 months 81% (P = 0.035) NR (P <0.0001) (high FPLIPI: P = 0.025) 
Rummel 2009 [11] Bendamustine-R 279 34 months 92.7% NR 84% (4 years) 
Study Total no. of patients Median follow-up Overall response Time to treatment failure (months) Overall survival 
Marcus 2008 [14] R-CVP 321 53 months 81% (P <0.0001) 27 (P <0.0001) 83% (4 years) (P = 0.029) 
Hiddemann 2005 [12] R-CHOP 428 58 months 96% NR (P <0.001) 90% (2 years) (P = 0.0493) 
Herold 2007 [13] R-MCP 201 48 months 92% (P = 0.0009) NR (P <0.0001) 87% (P = 0.0096) 
Salles 2008 [15] R-CHVP-Ifn 358 60 months 81% (P = 0.035) NR (P <0.0001) (high FPLIPI: P = 0.025) 
Rummel 2009 [11] Bendamustine-R 279 34 months 92.7% NR 84% (4 years) 

P, significance levels in comparison with chemotherapy only.

consolidation/maintenance.

  • Meta-analysis of the pre-rituximab era suggests a potential benefit of interferon-α maintenance therapy that has to be balanced against toxicity [20].

  • Rituximab maintenance for 2 years improves PFS (75% vs 58% after 3 years, P <0.0001) [I, B] [21].

  • Radioimmunotherapy consolidation prolongs PFS after chemotherapy but its benefit following rituximab combinations has not been established [I, B] [22].

  • Myeloablative radiochemotherapy followed by autologous stem cell transplantation prolongs PFS but not OS in four randomized trials and therefore represents no standard of care outside of trials [I, A] [23–26]

relapsed disease

  • A repeated biopsy is strongly recommended to rule out a secondary transformation into aggressive lymphoma.

  • Selection of salvage treatment depends on efficacy of prior regimens. In early relapses (<12 months), a non-cross-resistant scheme should be preferred (e.g. Bendamustine after CHOP or vice versa). Rituximab should be added if the previous antibody-containing scheme achieved >6–12 months duration of remission [IV,C].

  • Radioimmunotherapy represents an effective therapeutic approach especially in elderly patients with co-morbidities not appropriate for chemotherapy. Otherwise, it should be applied preferably as consolidation [27].

  • Rituximab maintenance for up to 2 years has a favorable side effect profile and, based on a systematic meta-analysis, substantially prolongs PFS and OS in relapsed disease even after antibody-containing induction in patients who have not received antibody as first-line therapy [I, A] [28].

  • High-dose chemotherapy with autologous stem cell transplantation prolongs PFS and OS and should be especially considered in patients with short-lived first remissions after R-containing regimens, but its role has to be redefined in the rituximab era [I, B] [29, 30].

  • In selected younger patients with high-risk profile, a potentially curative allogeneic stem cell transplantation (preferably with dose-reduced conditioning) may be discussed in relapsed disease [31, 32].

response evaluation

  • Adequate radiological tests should be performed midterm and after completion of chemotherapy. Patients with insufficient or lacking response should be evaluated for early salvage regimens.

  • PET scan-CT to evaluate response quality remains investigational in this disease, until future study confirms its predictive value [33].

  • Minimal residual disease (MRD) analysis at the end of the treatment has some prognostic impact, but should not guide therapeutic strategies outside of clinical studies [34].

follow-up

The following recommendation are based on consensus rather than on evidence:

  • History and physical examination every 3 months for 2 years, every 4–6 months for an additional 3 years, and subsequently once a year with special attention to transformation and secondary malignancies including secondary leukemia [V, D].

  • Blood count and routine chemistry every 6 months for 2 years, then only as needed for evaluation of suspicious symptoms.

  • Evaluation of thyroid function in patients with irradiation of the neck at 1, 2 and 5 years.

  • Minimal adequate radiological or ultrasound examinations every 6 months for 2 years and annually thereafter. Regular CT scans are not mandatory outside of clinical trials.

  • MRD screening may be performed in clinical studies but should not guide therapeutic strategies.

Table 5.

Recommended treatment strategies outside of clinical studies

Low tumor burden High tumor burden 
Stage I/II Stage III/IV Stage III/IV (<65 years) Stage III/IV (>65 years) 
Radiotherapy (involved field) 30–36 GyIn selected cases: watchful waiting Watch and waitIn symptomatic cases: consider rituximab monotherapy Chemoimmunotherapy (e.g. R-CHOP, R-CVP, BR)In selected cases: rituximab monotherapy Chemoimmunotherapy (e.g. R-CVP, BR, R-CHOP)In selected cases: R-chlorambucil Rituximab monotherapy 
  CR/PR:Rituximab maintenance (single application every 2 months up to 2 years) CR/PR:Rituximab maintenance (single application every 2 months up to 2 years) 
  Insufficient response: consider radioimmunotherapy consider ASCT after salvage Insufficient response: consider radioimmunotherapy 
Relapse/progress 
ChemoimmunotherapyIn selected cases: palliative radiation (e.g. 2×2 Gray) Chemoimmunotherapy (e.g.. R-CHOP, R-CVP, BR)In selected cases: Rituximab monotherapy Dependent on first-line regimen and remission duration: Chemoimmunotherapy: e.g. BR, R-CHOP, R-FCDiscuss high dose consolidation with autologous ASCTRituximab maintenance (single application every 3 months, up to 2 years)Alternatively radioimmuntherapy In selected cases: discuss allogeneic transplantation Dependent on first-line regimen and remission duration: Chemoimmunotherapy: e.g.. BR, R-CHOP, R-FCRituximab maintenance (single application every 3 months, up to 2 years)Alternatively radioimmuntherapy 
Low tumor burden High tumor burden 
Stage I/II Stage III/IV Stage III/IV (<65 years) Stage III/IV (>65 years) 
Radiotherapy (involved field) 30–36 GyIn selected cases: watchful waiting Watch and waitIn symptomatic cases: consider rituximab monotherapy Chemoimmunotherapy (e.g. R-CHOP, R-CVP, BR)In selected cases: rituximab monotherapy Chemoimmunotherapy (e.g. R-CVP, BR, R-CHOP)In selected cases: R-chlorambucil Rituximab monotherapy 
  CR/PR:Rituximab maintenance (single application every 2 months up to 2 years) CR/PR:Rituximab maintenance (single application every 2 months up to 2 years) 
  Insufficient response: consider radioimmunotherapy consider ASCT after salvage Insufficient response: consider radioimmunotherapy 
Relapse/progress 
ChemoimmunotherapyIn selected cases: palliative radiation (e.g. 2×2 Gray) Chemoimmunotherapy (e.g.. R-CHOP, R-CVP, BR)In selected cases: Rituximab monotherapy Dependent on first-line regimen and remission duration: Chemoimmunotherapy: e.g. BR, R-CHOP, R-FCDiscuss high dose consolidation with autologous ASCTRituximab maintenance (single application every 3 months, up to 2 years)Alternatively radioimmuntherapy In selected cases: discuss allogeneic transplantation Dependent on first-line regimen and remission duration: Chemoimmunotherapy: e.g.. BR, R-CHOP, R-FCRituximab maintenance (single application every 3 months, up to 2 years)Alternatively radioimmuntherapy 

Levels of Evidence [I–V] and Grades of Recommendation [A–D] as used by the American Society of Clinical Oncology are given in square brackets. Statements without grading were considered justified standard clinical practice by the expert authors and the ESMO faculty.

References

1.
Ott
G
Katzenberger
T
Lohr
A
, et al.  . 
Cytomorphologic, immunhisto-chemical, and cytogenetic profiles of follicular lymphoma: 2 types of follicular lymphoma grade 3
Blood
 , 
2002
, vol. 
99
 (pg. 
3806
-
3812
)
2.
Cheson
B
Pfistner
B
Juweid
ME
, et al.  . 
Revised response criteria for malignant lymphoma
J Clin Oncol
 , 
2007
, vol. 
25
 (pg. 
579
-
586
)
3.
Solal-Celigny
P
Roy
P
Colombat
P
, et al.  . 
Follicular lymphoma international prognostic index
Blood
 , 
2004
, vol. 
104
 (pg. 
1258
-
1265
)
4.
Buske
C
Hoster
E
Dreyling
M
Hasford
J
, et al.  . 
The Follicular Lymphoma International Prognostic Index (FLIPI) separates high risk from intermediate or low risk patients with advanced stage follicular lymphoma treated front-line with Rituximab and the combination of Cyclophosphamide, Doxorubicin, Vincristine and Prednisone (R-CHOP) with respect to treatment outcome
Blood
 , 
2006
, vol. 
108
 (pg. 
1504
-
1508
)
5.
Federico
M
Bellei
M
Marcheselli
L
, et al.  . 
Follicular lymphoma international prognostic index 2: a new prognostic index for follicular lymphoma developed by the international follicular lymphoma prognostic factor project
J Clin Oncol
 , 
2009
, vol. 
27
 (pg. 
4555
-
4652
)
6.
Dave
SS
Wright
G
Tan
B
, et al.  . 
Prediction of survival in follicular lymphoma based on molecular features of tumor-infiltrating immune cells
N Engl J Med
 , 
2004
, vol. 
351
 (pg. 
2159
-
2169
)
7.
MacManus
PM
Hoppe
RT
Is radiotherapy curative for stage I and II low grade follicular lymphoma? Results of a long term follow-up study of patients treated at Stanford University
J Clin Oncol
 , 
1996
, vol. 
14
 (pg. 
1282
-
1290
)
8.
Advani
R
Rosenberg
SA
Horning
SJ
Stage I and II follicular non-Hodgkin's lymphoma: long-term follow-up of no initial therapy
J Clin Oncol
 , 
2004
, vol. 
22
 (pg. 
1454
-
1459
)
9.
Ardeshna
KM
Smith
P
Norton
A
, et al.  . 
Long-term effect of a watch and wait policy versus immediate systemic treatment for asymptomatic advanced-stage non-Hodgkin lymphoma: a randomised controlled trial
Lancet
 , 
2003
, vol. 
362
 (pg. 
516
-
522
)
10.
Ardeshna
KM
Smith
P
Qian
W
 
An intergroup randomised trial of rituximab vs a watch & wait approach in patients with advanced stage, asymptomatic, non-bulky follicular lymphoma. ASH 2010 Congress, December 2010; abstract 6
11.
Rummel
MJ
Niederle
N
Maschmeyer
G
, et al.  . 
Bendamustin plus ritxuiamb is superior in respect of progression free survival and CR rate when compared to CHOP plus rituximab as first-line treatment of patients with advanced follicular, indolent, and mantle cell lymphomas: final results of a randomized phase III study of the STIL
Blood
 , 
2009
, vol. 
110
 
no 11
12.
Hiddemann
W
Kneba
M
Dreyling
M
, et al.  . 
Front-line therapy with rituximab added to the combination of cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) significantly improves the outcome of patients with advanced stage follicular lymphomas as compared to CHOP alone—results of a prospective randomized study of the German Low Grade Lymphoma Study Group (GLSG)
Blood
 , 
2005
, vol. 
106
 (pg. 
3725
-
3732
)
13.
Herold
M
Haas
A
Srock
S
Rituximab added to first-line mitoxantrone, chlorambucil, and prednisolone chemotherapy followed by interferon maintenance prolongs survival in patients with advanced follicular lymphoma: an East German Study Group Hematology and Oncology Study
J Clin Oncol
 , 
2007
, vol. 
25
 (pg. 
1986
-
1992
)
14.
Marcus
R
Imrie
K
Solal-Celigny
P
, et al.  . 
Phase III study of R-CVP compared with cyclophosphamide, vincristine, and prednisolone alone in patients with previously untreated advanced follicular lymphoma
J Clin Oncol
 , 
2008
, vol. 
28
 (pg. 
4579
-
4586
)
15.
Salles
G
Mounier
N
de Guibert
S
, et al.  . 
Rituximab combined with chemotherapy and interferon in follicular lymphoma patients: results of the GELA-GOELAMS FL2000 study
Blood
 , 
2008
, vol. 
112
 (pg. 
4824
-
4831
)
16.
Schulz
H
Bohlius
JF
Trelle
S
, et al.  . 
Immunochemotherapy with rituximab and overall survival in patients with indolent or mantle cell lymphoma: a systematic review and meta-analysis
J Natl Cancer Inst
 , 
2007
, vol. 
99
 (pg. 
706
-
714
)
17.
Kaminski
MS
Tuck
M
Estes
J
, et al.  . 
131I-Tositumomab therapy as initial treatment for follicular lymphoma
N Engl J Med
 , 
2005
, vol. 
352
 (pg. 
441
-
449
)
18.
Martinelli
G
Schmitz
SF
Utiger
U
, et al.  . 
Long-term follow-up of patients with follicular lymphoma receiving single-agent rituximab at two different schedules in trial SAKK 35/98 J Clin Oncol
 , 
2010
, vol. 
28
 (pg. 
4480
-
4484
)
19.
Ziakas
PD
Karsaliakos
P
Mylonakis
E
Effect of prophylactic lamivudine for chemotherapy-associated hepatitis B reactivation in lymphoma: a meta-analysis of published clinical trials and a decision tree addressing prolonged prophylaxis and maintenance
Haematologica
 , 
2009
, vol. 
94
 (pg. 
998
-
1005
)
20.
Rohatiner
AZ
Gregory
WM
Peterson
B
, et al.  . 
Meta-analysis to evaluate the role of interferon in follicular lymphoma
J Clin Oncol
 , 
2005
, vol. 
23
 (pg. 
2215
-
2223
)
21.
Salles
G
Seymour
J-F
Offner
F
, et al.  . 
Rituximab maintenance for 2 years in patients with high tumour burden follicular lymphoma responding to rituximab plus chemotherapy (PRIMA): a phase 3, randomised controlled trial
Lancet
 , 
2010
, vol. 
377
 (pg. 
42
-
51
)
22.
Morschhauser
F
Radford
J
van Hoof
A
, et al.  . 
Phase III trial of consolidation therapy with yttrium-90-ibritumomab tiuxetan compared with no additional therapy after first remission in advanced follicular lymphoma
J Clin Oncol
 , 
2008
, vol. 
26
 (pg. 
5156
-
5163
)
23.
Lenz
G
Dreyling
M
Schiegnitz
E
, et al.  . 
Myeloablative radiochemotherapy followed by autologous stem cell transplantation in first remission prolongs progression-free survival in follicular lymphoma—results of a prospective randomized trial of the German Low-Grade Lymphoma Study Group (GLSG)
Blood
 , 
2004
, vol. 
104
 (pg. 
2667
-
2674
)
24.
Sebban
C
Mounier
N
Brousse
N
, et al.  . 
Standard chemotherapy with interferon compared with CHOP followed by high-dose therapy with autologous stem cell transplantation in untreated patients with advanced follicular lymphoma: the GELF-94 randomized study from the Groupe d'Etude des Lymphomes de l'Adulte (GELA)
Blood
 , 
2006
, vol. 
108
 (pg. 
2540
-
2544
)
25.
Ladetto
M
Ed Marco
F
Benedetti
F
, et al.  . 
Prospective, multicenter randomized GITMO/IIL trial comparing intensive (R-HDS) versus conventional (CHOP-R) chemoimmunotherapy in high-risk follicular lymphoma at diagnosis: the superior disease control of R-HDS does not translate into an overall survival advantage
Blood
 , 
2008
, vol. 
111
 (pg. 
4004
-
4013
)
26.
Gyan
E
Foussard
C
Bertrand
P
, et al.  . 
High dose therapy followed by autologous purged stem cell transplantation and doxorubicin-based chemotherapy in patients with advanced follicular lymphoma: a randomized multicenter study by the GOELAMS. Final results with a median follow-up of nine years
Blood
 , 
2009
, vol. 
113
 (pg. 
995
-
1001
)
27.
Dreyling
M
Trumper
L
von Schilling
C
, et al.  . 
Results of a national consensus workshop: therapeutic algorithm in patients with follicular lymphoma—role of radioimmunotherapy
Ann Hematol
 , 
2007
, vol. 
86
 (pg. 
81
-
87
)
28.
Vidal
L
Gafter-Gvili
A
Leibovici
L
, et al.  . 
Rituximab maintenance for the treatment of patients with follicular lymphoma: systematic review and meta-analysis of randomized trials
J Natl Cancer Inst
 , 
2009
, vol. 
101
 (pg. 
248
-
255
)
29.
Schouten
HC
Qian
W
Kvaloy
S
, et al.  . 
High-dose therapy improves progression-free survival and survival in relapsed follicular non-Hodgkin's lymphoma: results from the randomized European CUP trial
J Clin Oncol
 , 
2003
, vol. 
21
 (pg. 
3918
-
3927
)
30.
Sebban
C
Brice
P
Delarue
R
, et al.  . 
Impact of rituximab and/or high-dose therapy with autotransplant at time of relapse in patients with follicular lymphoma: a GELA study
J Clin Oncol
 , 
2008
, vol. 
26
 (pg. 
3614
-
3620
)
31.
Van Besnien
K
Loberiza
FR
Bajorunaite
R
, et al.  . 
Comparison of autologous and allogeneic hematopoietic stem cell transplantation for follicular lymphoma
Blood
 , 
2003
, vol. 
102
 (pg. 
3521
-
3529
)
32.
Khouri
IS
McLaughlin
P
Saliba
RM
, et al.  . 
Eight-year experience with allogeneic stem cell transplantation for relapsed follicular lymphoma after nonmyeloablative conditioning with fludarabine, cyclophosphamide, and rituximab
Blood
 , 
2008
, vol. 
111
 (pg. 
5530
-
5536
)
33.
Trotman
J
Fournier
M
Lamy
T
, et al.  . 
Result of FDG PET-CT imaging after immunochemotherapy induction is a powerful and independent progsnotic indicator of outcome for patients with follicular lymphoma
Blood
 , 
2010
, vol. 
116
 pg. 
372
  
(#855)
34.
Rambaldi
A
Carlotti
E
Oldani
E
, et al.  . 
Quantitative PCR of bone marrow BCL2/IgH+ cells at diagnosis predicts treatment response and long-term outcome in follicular non-Hodgkin lymphoma
Blood
 , 
2005
, vol. 
105
 (pg. 
3428
-
3433
)

Author notes

Approved by the ESMO Guidelines Working Group: August 2002, last update April 2011. This publication supersedes the previously published version—Ann Oncol 2010; 21 (Suppl 5): v181–v183.
Conflict of interest: Professor Dreyling has reported that he has received support for research from Bayer, Mundipharma and Roche, and that he is a member of the advisory board of Roche. Professor Ghielmini, Professor Marcus, Professor Salles and Professor Vitolo have reported no conflicts of interest.