The optimal treatment strategy in patients with early progressive disease is not well known. In recent years, novel insights into the biology of Follicular Lymphoma (FL), and especially the role of the microenvironment, have resulted in the development of multiple novel treatment modalities. These new agents may ultimately improve the outlook for patients with FL with an unfavorable course, but for the development of the optimal therapeutic strategy, knowledge on the clinical and biological determinants of early refractory FL is needed.

Patients with histologically confirmed follicular lymphoma are registered in the study at the time of the first event after first line treatment. An event is defined as refractory/relapsed disease documented by biopsy, imaging, or clinical evaluation. Registration is based on the locally established histological diagnosis, with exclusion of cases diagnosed on fine needle aspiration cytology, while tru-cut core-needle biopsies are permitted in the study. Registration will be done on-line on a key restricted accessible web-database: the Investigator must complete the on-line registration form after obtaining informed consent dated and signed by the patient.

Investigators are requested to register consecutive cases diagnosed at each participating Institution (all patients satisfying Inclusion criteria without any further selection). A patient number (Patient ID) will be assigned strictly sequentially in ascending order as patient's eligibility is verified. In case a patient's eligibility is not confirmed and the patient is withdrawn from the study, the patient number will not be reused. The assigned number will be used as the identification code for the subject.

Every registered case has to undergo histopathology review by a panel of experts. The reference pathologist will collect and review the pathology material sent by the participating centers, without knowledge of the clinical outcome of the patient. Both material obtained at diagnosis, and at relapse will be reviewed. Classification will be performed according to the World Health Organization recently published.

Inclusion Criteria:

• Patients with initial diagnosis of follicular lymphoma, refractory/relapsed/transformed after first line therapy;
• All stages at the time of relapse;
• Histological grade 1-3a at the time of initial diagnosis;
• Age over 18 years;
• Availability of clinical data, including baseline information, comorbidities, data on disease localization, laboratory parameters at staging, features of treatment adopted and assurance of follow-up updating as requested
• Diagnostic material available for review;
• Written informed consent.

Exclusion Criteria:

• Age < 18 years

Patients with initial diagnosis of follicular lymphoma, refractory/relapsed/transformed after first line therapy.

We plan to share with other involved researchers the minimum information on IPD for publication.

It is responsibility of the Study Coordinators to publish the study results after the completion of the study. It will be ensured that the data from one center are not published before the publication of the whole study. All publications regarding the results of the study will be marked with the sentence "on behalf of the EHA-LyG/Cantera-Lupiae study group". Participating centers and sites will be mentioned according to their overall contribution to the study, while all members of the study group will be included as authors of the manuscripts for their active contribution on the study design and procedures. No publication can occur without agreement of the study sponsor. Study results will be submitted for publication in peer-reviewed journals and for presentation at appropriate scientific meetings and conferences.

Preliminary analysis results will be made available during the study. Final results will be made available 6-12 months after the end of the study.