High numbers of tumor-associated macrophages have an adverse prognostic value that can be circumvented by rituximab in patients with follicular lymphoma enrolled onto the GELA-GOELAMS FL-2000 trial.
OBJECTIVE
High amounts of intratumoral macrophages have been shown to correlate with poor prognosis in patients with follicular lymphoma (FL) treated with chemotherapy without rituximab. We tried to establish whether intratumoral macrophage count (MC) definitely is able to predict the outcome of FL patients in the rituximab era.


METHODS
We analyzed immunohistochemical CD68 expression in 194 FL patients from the FL-2000 trial, randomly assigned to receive cyclophosphamide, doxorubicin, etoposide, prednisolone, and interferon (CHVP-I) or rituximab plus CHVP-I. Immunohistochemistry was performed on paraffin sections using anti-CD68 KP1 antibody, and stained macrophages were scored on high-power field (hpf) in either intrafollicular (IF) or extrafollicular (EF) areas.


RESULTS
For IF MC, the best cutoff point was estimated at 10 macrophages/hpf. Low IF MC was significantly associated with a better event-free survival (EFS; P = .011). However, this effect was observed only in the CHVP-I arm (P = .012) and not in the rituximab plus CHVP-I arm. Using a cutoff of 15 IF MC, we found no significant association with EFS. For EF MC, fewer than 22 macrophages/hpf were associated with better EFS in the CHVP-I arm (P = .02) but not in the rituximab plus CHVP-I arm.


CONCLUSIONS
These results show that MC can predict outcome of FL patients and that rituximab is able to circumvent the unfavorable outcome associated with high MC.
Canioni
Danielle
D
Department of Pathology, Assistance Publique-Hopitaux de Paris, Hôpital Necker-Enfants Malades, Université Paris-Descartes, 149 rue de Sèvres, 75015, Paris, France. danielle.canioni@nck.ap-hop-paris.fr
Salles
Gilles
G
Mounier
Nicolas
N
Brousse
Nicole
N
Keuppens
Marie
M
Morchhauser
Frank
F
Lamy
Thierry
T
Sonet
Anne
A
Rousselet
Marie-Christine
MC
Foussard
Charles
C
Xerri
Luc
L
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D058846:Antibodies, Monoclonal, Murine-Derived; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000627:therapeutic use; D004317:Doxorubicin / Q000627:therapeutic use; D005260:Female; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use; D008224:Lymphoma, Follicular / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D008264:Macrophages / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011241:Prednisone / Q000627:therapeutic use; D011379:Prognosis; D011446:Prospective Studies; D000069283:Rituximab; D015996:Survival Rate; D013713:Teniposide / Q000627:therapeutic use; D016896:Treatment Outcome; D000097382:CD68 Molecule
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D003520:Cyclophosphamide; D004317:Doxorubicin; D016898:Interferon-alpha; D011241:Prednisone; D000069283:Rituximab; D013713:Teniposide; C067980:CD68 antigen, human; D000097382:CD68 Molecule