The Follicular Lymphoma International Prognostic Index (FLIPI) Is Superior to WHO/REAL Histological Grade for Identifying High-Risk Patients: A Retrospective Review of the MSKCC Experience in 260 patients with Follicular Lymphoma.
Authors: Halaas Jeffrey L. , Teruya-Feldstein Julie , Filippa Daniel A. , Chaya Moskowitz , Naresh Kikkeri N. , Zelenetz Andrew D. 
Published: October 2019

Abstract
Introduction: Follicular lymphoma (FL) is the second most common subtype of non-Hodgkin’s lymphoma (NHL) diagnosed annually in the United States. FL is regarded as an indolent NHL but has a clinically heterogeneous course. Various prognostic systems have been described for follicular lymphoma (e.g. International Prognostic Index (IPI), WHO histological grade, etc.) but none have been satisfactory for identifying patients with high-risk follicular lymphoma. Recently, the FLIPI has been proposed as a useful prognostic index for follicular lymphoma. In this report, we retrospectively analyze patients with follicular lymphoma with respect to the FLIPI and directly compare this prognostic index to the WHO/REAL histological grade.
Methods: We retrospectively identified patients seen at MSKCC who had archived diagnostic or relapsed biopsy specimens available for pathological review. Patients were included if there was sufficient clinical information available and if review of the specimen confirmed follicular lymphoma according to the WHO/REAL classification system. Clinical information was collected for all patients and their archived pathology was reviewed by 2–3 pathologists independently. The WHO/REAL follicular lymphoma grade was assigned by consensus of at least 2 pathologists. Adverse FLIPI risk factors (RF) included age ≥60, stage III/IV, abnormal LDH, >4 nodal sites, hemoglobin < 12 mg/dl. Patients were stratified into low-risk (LR; 0,1 RF), intermediate-risk (IR; 2 RF), high-risk (HR; >2 RF). Survival analysis were performed by Kaplan-Meier and the log-rank method was used to test for signficance.
Results: In all, 260 patients are included in the analysis. The demographics of the patients are as follows: median age at diagnosis was 56 with 38.8% ≥60 years old; 52.3% were male and 47.7% female; 12.3% had a KPS <70; LDH was abnormal in 21.9%; 35.8% had stage I/II and 64.2% had stage III/IV; 15.5% had more than one extranodal site; 12.3% had hemoglobin < 12 mg/dl; and 25.8% had > 4 nodal sites of involvement. Sixty-two percent of biopsies were at diagnosis and 38% at relapse. By FLIPI, 128 patients (49%) had LR disease, 76 (29%) had IR and 56 (22%) had HR disease. LR patients had a median survival and 10 year survival of 16.5 years and 76%, respectively; IR patients, 12.4 years and 52%; and HR patients, 5.4 years and 24% (p<0.0001). By WHO/REAL histological grade, 72 (28%) patients had grade 1, 102 (39%) had grade 2, 68 (26%) had grade 3a and 18 (7%) had grade 3b. The median survival and 10 year surivival of patients with grade 1 was 25.4 years and 62%, respectively; grade 2, 10.3 years and 56%; grade 3a, 18.7 years and 60%; and grade 3b, not-reached and 65% (p =0.41). There was no association between FLIPI risk group and WHO/REAL grade (p=0.88) and no association between grade and survival in FLIPI LR (p=0.50), IR (p=0.33) or HR (p=0.87) groups.
Conclusion: The WHO/REAL grade does not improve upon the abilility of the FLIPI to risk stratify patients with follicular lymphoma. Furthermore, the FLIPI is superior to the WHO/REAL histolgical grade in identfiying patients with high-risk follicular lymphoma.