Request for modifications from the ANSM of the initial protocol before the start of the study (the main modification was to precise the principal objective paragraph).

• "GELARC" replaced by "LYSARC”; “GELA" replaced by "LYSA" reflecting change to names of these organizations; • Suppression of certain evaluations and extension of the deadline for carrying out certain evaluations: vital signs before day 1 of each cycle and each evaluation, and complete blood cells count at Day 7 and 10 of each cycle • Addition of a new rule for SAE reporting: SAE linked to scheduled hospitalizations before patient randomization into the study should not be reported • Addition of a jugal epithelial cells sample for genomic study

• This amendment follows the letter from the ANSM dated October 17, 2012, concerning a case of progressive multifocal leukoencephalopathy (PML) reported in a patient who was treated with GA101 (GA101). • Patients with a history of PML will not be included in the study. The exclusion criterion "Prior history of Progressive Multifocal Leukoencephalopathy (PML)" is added. • A neurological examination must be carried out during each clinical examination, during the treatment phase as well as during the follow-up phase, in order to detect any neurological signs suggestive of potential PML. • Information on what to do in case of suspected PML: symptoms, diagnosis, what to do with the administration of anti CD20. In the event of symptoms suggestive of PML, investigations must be carried out: consultation with a neurologist, brain MRI, search for the JC virus in the cerebrospinal fluid, etc. Treatment with Rituximab or GA101 should be suspended during investigations, and definitively stopped if the diagnosis of PML is confirmed.

Change of tubes used for biological studies. Analysis of samples collected for the first patients included revealed that the stability of blood cells in EDTA tubes was not compatible with the achievement of standardized NFP. It was decided to keep the number of tubes taken per patient, i.e. 4 tubes, but to distribute these tubes as follows: - 2 EDTA tubes for genetic study - 2 heparin tubes for standardized NFP.

Following the shortage of vindesine, possibility of replacing vindesine by vincristine for patients treated with ACVBP chemotherapy. In this study, the centers use CHOP or ACVBP as chemotherapy, according to their habits. This choice is valid for all patients in the same center and cannot be modified, the randomization being stratified on the choice of chemotherapy. Vindesine, a component of ACVBP, was out of stock worldwide (laboratory release dated June 7, 2013). This substitution should only take place in the event of a complete shortage of the stock of vindesine (dosage: D1 and D5 vincristine 0.7 mg / m2 without exceeding 1 mg total dose by injection, which makes a total dose of 1.4mg / m2 per cycle of ACVBP without exceeding 2 mg total dose).

• Recommendations have been put in place to alert investigators on the increased toxicity of GA101 and the potential risks of severe infection: contraception until 18 months after last dose of GA101 instead of 12 months, changes in management of hematological toxicities, GA101 dose adjustments. • Addition and modification of blood and bone marrow samples for further biological analyzes.

Following the announcement by the ANSM, on November 24, 2014, of the global shortage of BCNU (Carmustine), a drug forming part of the BEAM multidrug therapy (Carmustine, Etoposide, Cytarabine, Melphalan), proposal for 2 alternative conditioning regimes: - Benda-EAM polychemotherapy (Bendamustine, Etoposide, Cytarabine, Melphalan) - BAM polychemotherapy (Busulfan, Cytarabine, Melphalan

Modification of the schedule of intermediate and final analyzes. Intermediate analysis n°3 after treatment phase of all patients and final analysis performed after the onset of 345 events