lymphome folliculaire

REFERENTIEL REGIONAL ONCO-LR
Comité Onco-Hématologie
Lymphome Folliculaire
Groupe de travail : Dr Burcheri, Dr Donadio, Dr Garrido, Dr Legouffe, Dr Quinquenet, Dr
Quittet, Dr Rolland, Dr Saad, Dr Vergely, Dr Waultier, Pr Cartron
Version n°1 : avril 2008
Mise à jour le : mai 2013
Page1
LYMPHOME FOLLICULAIRE
Recommandations générales
Tous diagnostic de lymphome folliculaire doit être établi sur l’examen histo-pathologique d’un
ganglion. Le diagnostic de lymphome folliculaire ne peut être retenu sur une seule atteinte extranodale (par exemple envahissement médullaire). Dans certaines situations exceptionnelles, en
l’absence de possibilité de biopsie ganglionnaire (localisation, état général), la suspicion de
lymphome folliculaire devra être confirmée par une étude immuno-phénotypique et cytogénétique
(ou moléculaire).
En cas de rechute, la recherche d’une transformation sera toujours suspecté et au moindre doute
(fièvre, LDH, syndrome compressif,…) une nouvelle biopsie sera réalisée.
Critères histologiques diagnostiques minimaux
Ils sont ceux de la classification OMS international (Harris et al 1999). Il s’agit d’une prolifération
nodulaire de cellules B néoplasiques. La proportion de plage de prolifération diffuse doit être
précisée et quantifiée. La prolifération est constituée essentiellement de petites cellules clivées
(centrocytes) et la proportion de grandes cellules (centroblastes) doit être précisée selon la
classification OMS (Appendix 1). La population tumorale exprime le CD20, le CD10 et bcl-2.
L’analyse de ces trois marqueurs constitue le minimale requis pour poser le diagnostic de
lymphome folliculaire. La recherche de la translocation t(14 ;18) par cytogénétique et/ou la
recherche du réarrangement BCL2-IGH dans le sang, dans la moelle et dans le ganglion est
recommandée au diagnostic.
Bilan d’extension et pré-thérapeutique recommandé
 Clinique
- Age
- Etat général selon l’index ECOG (Appendix 2)
- Aires ganglionnaires envahies et mesure des ganglions
- Co-morbidités
 Biologique
- LDH
- β2-microglobuline
- Sérologie hépatite B, C et HIV-1 et 2
- Protidogramme
- Bilan métabolique rénale et hépatique
- Mesure des β-HCG chez toute femme en âge de procréer
 Biopsie ostéo-médullaire
 Translocation t(14 ;18)
La recherche de la translocation t(14 ;18) par cytogénétique et/ou la recherche du réarrangement
BCL2-IGH dans le sang et dans la moelle est recommandée mais non obligatoire au diagnostic.
 TDM thoraco-abdominal et pelvien
Page2
 Tomographie par émission de positron
La tomographie par émission de positron est recommandée pour évaluer l’extension de la maladie
mais non obligatoire au diagnostic. Elle n’est pas utile à l’évaluation thérapeutique. En fin
d'induction, elle a un caractère pronostique mais ne conditionne pas la thérapeutique ultérieure.
 Mesure de la fraction d’éjection ventriculaire gauche par méthode isotopique ou
échographique
 Prélèvement de gamètes
Un prélèvement de sperme doit est proposé à tous les hommes avant d’initier une chimiothérapie.
Une consultation spécialisée doit être proposée à toutes les femmes pour les informer des risques
de la chimiothérapie sur leur fécondité
Stade et critères pronostiques
Au terme du bilan diagnostic, l’extension de la maladie et les principaux facteurs pronostiques sont
précisés :
- le stade de la maladie est précisé selon la classification Ann Arbor (Appendix 3)
- le pronostic de la maladie est évalué grâce :
 A l’index FLIPI (Appendix 4)
 Aux critères du GELF (Appendix 5)
Ces critères pronostiques (FLIPI, GELF) et d’extension (stade Ann Arbor) devront figurer en clair
dans toute correspondance médicale au sein du réseau (second avis, réunion concertation pluridisciplinaire,…)
Evaluation
L’évaluation de l’efficacité thérapeutique sera réalisée 4 à 6 semaines après la fin du traitement
selon les critères internationaux (Cheson et al 1999) (Appendix 6). La tomographie par émission
de positron n’est pas recommandée pour l’évaluation thérapeutique d’un lymphome folliculaire
Surveillance
Les patients traités pour un lymphome folliculaire justifient d’une surveillance clinique trimestrielle
la première année puis semestrielle pendant deux ans puis annuelle. Après 10 ans les patients
seront revus tous les 2 ans. Un scanner thoraco-abdominal et pelvien est effectuée tous les 6 mois
la première année, puis annuellement pendant 4 ans. La surveillance biologique doit comprendre
un hémogramme, un protidogramme et des LDH. Ces examens sont réalisés sur le même rythme
que la surveillance clinique. Pour les patients recevant des anthracyclines, une mesure de la
fraction d’éjection ventriculaire gauche sera réalisée à la fin du traitement puis à 2 ans puis tous
les 5 ans en l’absence d’anomalie ou tous les ans en cas d’anomalie accompagnée d’un suivi
cardiologique.
Page3
Recommandations Thérapeutiques
Lymphome folliculaire au diagnostic
Stade I
Stade II, III, IV
Au choix :
- Abstention (10)
- Radiothérapie (36 gy)
- 4xR
- Entretien :
- R / 2 mois pendant 2 ans
- Ou R M5 M7 M9 M12
Forte masse
tumorale
(GELF)
Faible masse
tumorale
(GELF)
Essai RELEVANCE
(R Chimio vs R Revlimid)
Protocole
LYSA
- 6 x CHOP21 + 2R
Option : 8 x R-CVP
Abstention
Option 6 R Benda + 2 R en cas de comorbidités
Cardiovasculaires
- puis entretien : R/2 mois
pendant 2 ans
4xR
+/6 R / 2mois
pendant 2 ans
Brice P, Bastion Y, Lepage E et al. Comparison in low tumour-burden follicular lymphomas between an initial
no-treatment policy, prednisolone or interferon alpha: a randomised study from GELF. J. Clin Oncol 1997; 5:
1110-1117
Buske C, Kneba M, Lengfelder E, Pfreundschuh M, Ludwig WD, Graeven U, Hallek M, Dreyling M, Unterhalt
M, Hiddemann W: Front-line combined immuno-chemotherapy (R-CHOP) significantly improves the time to
treatment failure and overall survival in elderly patients with advanced stage follicular lymphoma - Results of
a prospective randomized tria of the German Low Grade Lymphoma Study Group (GLSG). Blood 2006,
108:482a
Colombat P, Brousse N, Morschhauser F et al. Single treatment with rituximab monotherapy for low-tumor
burden follicular lymphoma (FL): survival analyses with extended follow-up of 7 years. Blood 2006, 108:486a
Page4
Colombat P, Salles G, Brousse N et al. Rituximab (anti-CD20 monoclonal antibody) as single first-line
therapy for patients with follicular lymphoma with a low tumor burden: clinical and molecular evaluation.
Blood 2001, 97:101-106
Foussard N, Mounier N, van Hoof A, Delwail V, Casasnovas E, Deconninck E, Tilly H, Fitoussi O,
Gressin R, Salles G: Update of the FL2000 randomized trial combining rituximab to CHVPInterferon in follicular lymphoma (FL) patients. J Clin Oncol 2006, 24:7508a
Ghielmini M, Schmitz SF, Cogliatti SB, Pichert G, Hummerjohann J, Waltzer U, Fey MF, Betticher DC,
Martinelli G, Peccatori F, et al.: Prolonged treatment with rituximab in patients with follicular lymphoma
significantly increases event-free survival and response duration compared with the standard weekly x 4
schedule. Blood 2004, 103:4416-4423
Herold M, Haas R, Srock S, Neser S, Al Ali KH, Neubauer A, Doelken G, Naumann R, Fietz T, Freund M, et
al.: Addition of rituximab to first-line MCP (Mitoxantrone, Cnlorambucil, Prednisolone) cemotherapy prolongs
survival in advanced follicular lymphoma - 4 years follow-up results of a phase III trial of the East German
Study Group Hematology and Oncology (OSHO#39). Blood 2006, 108:484a.
Marcus RE, Solal-Celigny P, Imrie K, Catalano JV, Dmoszynska A, Raposo JC, Offner FC, Gomez-Codina J:
MabThera (Rituximab) plus cyclophosphamide, vincristine and prednisone (R-CVP) chemotherapy improves
survival in previously untreated patients with advanced follicular non-Hodgkin's lymphoma (NHL). Blood
2006, 108:481a.
Salles G.A, Seymour J.F. Feugier P et al : Rituximab maintenance for 2 years in patients with untreated high
tumor burden follicular lymphoma after response to immuno-chemotherapy
J. Clin Oncol 2010 ; 28 : 15 s Abst 8004
Ghielmini ME, Schmitz SH, Martinelli G et al.Long term follow-up of patients with follicular lymphoma (FL)
receiving single agent Rituximab at two different schedules in study SAKK 35/98.
J. Clin Oncol 2009; 27 ; 15 s Abst. 8512.
Rummel MJ, Al-Batran SE, Kim SZ, Welslau M, Hecker R, Kofahl-Krause D, Josten KM, Dürk H, Rost A,
Neise M, von Grünhagen U, Chow KU, Hansmann ML, Hoelzer D, Mitrou PS. Bendamustine plus rituximab
is effective and has a favorable toxicity profile in the treatment of mantle cell and low-grade non-Hodgkin's
lymphoma.
J Clin Oncol. 2005 May 20;23(15):3383-9
Page5
LYMPHOME FOLLICULAIRE A LA RECHUTE
OU REGRACTAIRE
Eligibilité pour intensification :
Age (+/- 65 ans)
Délai rechute
Transformation
Inclusion dans un protocole
Patient non éligible pour
intensification
Patient éligible pour
intensification
Options :
- Chimiothérapie* + Rituximab +
entretien Rituximab/ 3mois, 2 ans
- R-DHAP x 2 Option : R- Bendamustine
- Si réponse > 50% : mobilisation CSP
(CPM 4g/m²)
- Zevalin
- R4-DHAP ( ou R DHAX ou R DHAC) x 2
Option ; R- Bendamustine
- Rituximab monothérapie + entretien
- Intensification par BEAM
- Chimiothérapie* + Rituximab +
Consolidation par Zevalin
- Entretien par Rituximab :
R/3 mois pendant 2 ans
*Chimiothérapie : CVP, CHOP, FCM, DHA (P, C ou X), VID, Bendamustine
Forstpointner R, Unterhalt M, Dreyling M, Bock HP, Repp R, Wandt H, Pott C, Seymour JF, Metzner B,
Hanel A, et al.: Maintenance therapy with rituximab leads to a significant prolongation of response duration
after salvage therapy with a combination of rituximab, fludarabine, cyclophosphamide, and mitoxantrone (RFCM) in patients with recurring and refractory follicular and mantle cell lymphomas: Results of a prospective
randomized study of the German Low Grade Lymphoma Study Group (GLSG). Blood 2006, 108:4003-4008.
Ghielmini M, Schmitz SF, Cogliatti SB, Pichert G, Hummerjohann J, Waltzer U, Fey MF, Betticher DC,
Martinelli G, Peccatori F, et al.: Prolonged treatment with rituximab in patients with follicular lymphoma
significantly increases event-free survival and response duration compared with the standard weekly x 4
schedule. Blood 2004, 103:4416-4423.
Hochster HS, Weller E, Gascoyne RD, Ryan TS, Habermann TS, Gordon LI, Frankel SR, Horning SJ:
Maintenance rituximab after CVP results in superior outcome in advanced follicular lymphoma: results of the
E1496 phase III trial from the Eastern Cooperative Oncology Group and the Cancer and Leukemia Group B.
Blood 2005, 106:349a.
Page6
Hainsworth JD, Litchy S, Shaffer DW, Lackey VL, Grimaldi M, Greco FA: Maximizing therapeutic benefit of
rituximab: maintenance therapy versus re-treatment at progression in patients with indolent non-Hodgkin's
lymphoma--a randomized phase II trial of the Minnie Pearl Cancer Research Network. J Clin Oncol 2005,
23:1088-1095.
Radford JA, Ketterer N, Sebban C, Zinzani PL, Delaloye AB, Rohatiner AZ et al. (2003). Ibritumomab
tiuxetan (Zevalin) therapy is feasible and safe for the treatment of patients with advanced B-cell follicular
NHL in first remission: interim analysis for safety of a multicenter, phase III clinical trial. Blood 102 (Abstract
1484).
Shipley DL, Greco FA, Spigek DR, Edwards D, Mayfield M, Yost K et al. (2005). Rituximab withsh ort
duration chemotherapy followed by 90Y ibritumomab tiuxetan as first-line treatment for patients withfollicular
lymphoma: Update of a Minnie Pearl Cancer ResearchNetwork phase II trial. J Clin Oncol 23 (Abstract
6577).
van Oers MH, Klasa R, Marcus RE, Wolf M, Kimby E, Gascoyne RD, Jack A, Van't Veer M, Vranovsky A,
Holte H, et al.: Rituximab maintenance improves clinical outcome of relapsed/resistant follicular non-Hodgkin
lymphoma in patients both with and without rituximab during induction: results of a prospective randomized
phase 3 intergroup trial. Blood 2006, 108:3295-3301.
Velasquez WS et al. Effective salvage therapy for lymphoma with cisplatin in combination with high dose
AraC and dexamethasone (DHAP). Blood 1988 ; 71(1) : 117-122.
Witzig TE et al. Randomized controlled trial of yttrium-90-labeled ibritumomab tiuxetan radioimmunotherapy
versus rituximab immunotherapy for patients with relapsed or refractory low grade, follicular or transformed
B-cell non hodgkin’s lymphoma. J Clin Oncol. 2002;20(10):2453-63
Pettengell R, Schmitz N, Gisselbrecht C et al. Randomized study of Rituximab in patients with relapsed or
resistant follicular lymphoma prior to high dose therapy as in vivo purging and to mantain remission follow
high dose therapy.
J. Clin Oncol; 28 : 15 s Abst 8005.
Rummel MJ, Niederle N, Maschmeger G et al. : Bendamustine + Rituximab is superior in respect of
progression free survival and CR ratio when compared to CHOP plus Rituximab as first line treatment of
patients with advanced follicular, indolent, and mantle cell lymphoma. Final results of a randomized phase III
study of STIL- Blood 2009 ; 114 : 405.
Page7
LYMPHOME FOLLICULAIRE ≥ 2 RECHUTES
OU REFRACTAIRE
Options :
- Protocole phase I/II
- Greffe allogénique
- Intensification thérapeutique
- Chimiothérapie* + Rituximab
- Zevalin
- Rituximab monothérapie +/- entretien
- Chimiothérapie* + Rituximab + consolidation par Zevalin
*Chimiothérapie CVP, CHCP, FCM, DHAP, VD, F, CPM, Chl, Bendamustine
Forstpointner R, Unterhalt M, Dreyling M, Bock HP, Repp R, Wandt H, Pott C, Seymour JF, Metzner B,
Hanel A, et al.: Maintenance therapy with rituximab leads to a significant prolongation of response duration
after salvage therapy with a combination of rituximab, fludarabine, cyclophosphamide, and mitoxantrone (RFCM) in patients with recurring and refractory follicular and mantle cell lymphomas: Results of a prospective
randomized study of the German Low Grade Lymphoma Study Group (GLSG). Blood 2006, 108:4003-4008.
Ghielmini M, Schmitz SF, Cogliatti SB, Pichert G, Hummerjohann J, Waltzer U, Fey MF, Betticher DC,
Martinelli G, Peccatori F, et al.: Prolonged treatment with rituximab in patients with follicular lymphoma
significantly increases event-free survival and response duration compared with the standard weekly x 4
schedule. Blood 2004, 103:4416-4423.
Hochster HS, Weller E, Gascoyne RD, Ryan TS, Habermann TS, Gordon LI, Frankel SR, Horning SJ:
Maintenance rituximab after CVP results in superior outcome in advanced follicular lymphoma: results of the
E1496 phase III trial from the Eastern Cooperative Oncology Group and the Cancer and Leukemia Group B.
Blood 2005, 106:349a.
Hainsworth JD, Litchy S, Shaffer DW, Lackey VL, Grimaldi M, Greco FA: Maximizing therapeutic benefit of
rituximab: maintenance therapy versus re-treatment at progression in patients with indolent non-Hodgkin's
lymphoma--a randomized phase II trial of the Minnie Pearl Cancer Research Network. J Clin Oncol 2005,
23:1088-1095.
Radford JA, Ketterer N, Sebban C, Zinzani PL, Delaloye AB, Rohatiner AZ et al. (2003). Ibritumomab
tiuxetan (Zevalin) therapy is feasible and safe for the treatment of patients with advanced B-cell follicular
NHL in first remission: interim analysis for safety of a multicenter, phase III clinical trial. Blood 102 (Abstract
1484).
Shipley DL, Greco FA, Spigek DR, Edwards D, Mayfield M, Yost K et al. (2005). Rituximab withsh ort
duration chemotherapy followed by 90Y ibritumomab tiuxetan as first-line treatment for patients withfollicular
lymphoma: Update of a Minnie Pearl Cancer ResearchNetwork phase II trial. J Clin Oncol 23 (Abstract
6577).
Van Oers MH, Klasa R, Marcus RE, Wolf M, Kimby E, Gascoyne RD, Jack A, Van't Veer M, Vranovsky A,
Holte H, et al.: Rituximab maintenance improves clinical outcome of relapsed/resistant follicular non-Hodgkin
lymphoma in patients both with and without rituximab during induction: results of a prospective randomized
phase 3 intergroup trial. Blood 2006, 108:3295-3301.
Page8
Velasquez WS et al. Effective salvage therapy for lymphoma with cisplatin in combination with high dose
AraC and dexamethasone (DHAP). Blood 1988 ; 71(1) : 117-122.
Witzig TE et al. Randomized controlled trial of yttrium-90-labeled ibritumomab tiuxetan radioimmunotherapy
versus rituximab immunotherapy for patients with relapsed or refractory low grade, follicular or transformed
B-cell non hodgkin’s lymphoma. J. Clin Oncol. 2002; 20 (10) : 2453-63
Page9
APPENDIX 1
FOLLICULAR LYMPHOMA GRADING SYSTEM
(WHO classification)
Follicular Cell Lymphomas : Grading
Grade 1
Grade 2
Grade 3
3a
3b
0-5 centroblasts/hpf
6-15 centroblasts/hpf
15 centroblasts/hpf
15 centroblasts, but centrocytes are still present
Centroblasts form solid sheets with no residual centrocytes
Harris LH, Jaffe ES, Kiebold J, et al. World Health Organization classification of neoplastic diseases of
the hematopoietic and lymphoid tissues: report of the Clinical Advisory Committee Meeting-Airlie
House, Virginia, November 1997. J. Clin Oncol. 1999;17: 3835-3849.
Page10
APPENDIX 2
ECOG PERFORMANCE STATUS
GRADE
0
1
2
3
4
Page11
PERFORMANCE STATUS – WHO CLASSIFICATION
Able to carry out all normal activity without restriction
Restricted in physically strenuous activity but ambulatory and able to
to carry out light work
Ambulatory and capable of all self-care but unable to carry out any
work; up and about more 50% of waking hours
Capable of only limited self-care confined to bed or chair more than
50% of waking hours.
Completely disabled; cannot carry out any self-care; totally confined
to bed and chair.
APPENDIX 3
ANN ARBOR STAGE
 Stage I :
- I : Involvement of a single lymph node region.
- IE : Localized involvement of a single extralymphatic organ or site.
 Stage II :
- II Involvement of 2 or lymph node regions on the same side of the diaphragm.
- IIE: Localized involvement of a single associated extralymphatic organ or site and its
regional lymph nodes with or without other lymph node regions on the same side of
the diaphragm.
 Stage III :
- III: Involvement of lymph node regions on both sides of the diaphragm.
- IIIE: Involvement of lymph node regions on both sides of the diaphragm accompanied
by localized involvement of an extralymphatic organ or site.
- IIIS: Involvement of lymph node regions on both sides of the diaphragm accompanied
by involvement of the spleen.
- IIIS+E: Both IIIS+IIIE.
(Of note, in FLIPPI, spleen involvement is categorized as stage IV)
 Stage IV :
- IV: Disseminated (multifocal) involvement of 1 or more extralymphatic sites with or
without associated lymph node involvement or isolated extralymphatic organ
involvement with distant ( non regional) nodal involvement.
- IVE: Extranodal lymphoid malignancies arise in tissues separate from, but near, the
major lymphatic aggregates.
Page12
APPENDIX 4
FLIPI NODAL AREAS
FLIPI - 1
 Adverse prognostic factors
- 1. Age
- 2. Ann Arbor satge
- 3. Hemoglobin level
- 4. Number of nodal areas
- 5. Serum LDH level
≤ 60 y :
I-II :
≥ 120 g/L:
≤ 4:
≤ normal
0
0
0
0
0
> 60 y :
II-IV:
< 120 g/L
>4
> normal
1
1
1
1
1
FLIPI index = sum of values
 Risk groups
- 1. Low risk: 0 to 1
- 2. Intermediate risk: 2
- 3. Poor risk: ≥ 3
Solal-Celigny P, Roy P, Colombat P et al.Follicular lymphoma international prognostic index.Blood.
2005; 104: 1258-1265
Page13
FLIPI - 2
 Adverse prognostic factors
- 1. Age
- 2. Atteinte médullaire
- 3. β2Microglobuline
- 4. Hemoglobin level
- 5. Bulky
≤ 60 y :
non :
≤N:
≥ 120 g/L :
≤ 6 cm :
0
0
0
0
0
> 60 y :
oui :
>N :
< 120 g/L
> 6 cm :
1
1
1
1
1
 Risk groups
- 1. Low risk: 0
- 2. Intermediate risk: 1-2
- 3. High risk: ≥ 3
Frederico M, Bellei M, Marsheselli 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; 27; 4555-4562
Page14
APPENDIX 5
GELF CRITERIA
 Low - tumor burden criteria
None of the following criteria
-
B symptoms (fever > 38°C, weight loss > 10% or sweat)
nodal or extranodal mass >7cm in its greater diameter
involvement of at least 3 nodal sites, each with a diameter greater than 3 cm
splenic enlargement reaching ombilic
compressive syndrome
pleural/peritoneal effusion.
increase LDH and 2microglobulinemia
 High - tumor burden criteria
At least one of the following criteria
-
B symptoms (fever > 38°C, weight loss > 10% or sweat)
nodal or extranodal mass >7cm in its greater diameter
involvement of at least 3 nodal sites, each with a diameter greater than 3 cm
splenic enlargement reaching ombilic
compressive syndrome
pleural/peritoneal effusion
increase LDH and 2microglobulinemia
Brice P, Bastion Y, Lepage E et al. Comparison in low tumour-burden follicular lymphomas between
an initial no-treatment policy, prednisolone or interferon alpha: a randomised study from GELF. J. Clin
Oncol 1997; 5: 1110-1117
Page15
APPENDIX 6
CRITERIA FOR EVALUATION OF RESPONSE
IN NON-HODGKIN’S LYMPHOMA
 Complete Response (CR)
A complete response requires the following:
- Complete disappearance of all detectable clinical and radiographic evidence of disease and
disappearance of all disease-related symptoms if present before therapy, and normalization
of those biochemical abnormalities [e.g., lactate dehydrogenase (LDH)] definitely
assignable to NHL
- All lymph nodes and nodal masses must have regressed to normal size (≤1.5 cm in their
greatest transverse diameter for nodes ≥1.5 cm before therapy). Previously involved nodes
that were 1.1 to 1.5 cm in their greatest transverse diameter before treatment must have
decreased to < 1 cm in their greatest transverse diameter after treatment, or by more than
75% in the sum of the products of the greatest diameters (SPD).
- The spleen, if considered to be enlarged before therapy on the basis of a CT scan, must
have regressed in size and must not be palpable on physical examination. Similarly, other
organs considered to be enlarged before therapy due to involvement by lymphoma, such as
liver and kidneys, must have decreased in size.
- Bone marrow, if positive at baseline, must be histologically negative for lymphoma.
 Complete Response, unconfirmed (CRu)
CRu includes those patients who fulfill criteria 1 and 3 above, but with one or more of the following
features:
- A residual lymph node mass greater than 1.5 cm in greatest transverse diameter that has
regressed by more than 75% in the SPD. Individual nodes that were previously confluent
must have regressed by more than 75% in their SPD compared with the size of the original
mass.
- Indeterminate bone marrow (increased number or size of aggregates without cytologic or
architectural atypia).
 Partial Response (PR)
A partial response requires the following:
- ≥50% decrease in SPD of the six largest dominant nodes or nodal masses. These nodes or
masses should be selected according to the following features: (a) they should be clearly
measurable in at least two perpendicular dimensions, (b) they should be from as disparate
regions of the body as possible, and (c) they should include mediastinal and retroperitoneal
areas of disease whenever these sites are involved.
- No increase in the size of the other nodes, liver, or spleen
- Splenic and hepatic nodules must regress by at least 50% in the SPD.
- With the exception of splenic and hepatic nodules, involvement of other organs is
considered assessable and not measurable disease.
Page16
- No new sites of disease
 Stable Disease (SD)
Stable disease is defined as less than a PR (as described above) but not progressive disease (see
below).
 Progressive Disease (PD)
Progressive Disease is defined as follows:
- ≥50% increase from nadir in the SPD of any previously identified abnormal node
- Appearance of any new lesion during or at the end of therapy
Cheson BD, Horning SJ, Coiffier B, Shipp MA, Fisher RI, Connors JM, et al. Report of an international
workshop to standardize response criteria for non-Hodgkin’s lymphomas. J Clin Oncol 1999;17:1244–53.
Page17