Prognostic Value of BCL2 Determination in Follicular NHL Patients Treated with Alkylating Containing Regimen Alone or in Combination with Rituximab.
Authors: Laszlo Daniele , Rabascio Cristina , Andreola Giovanna , Corsini Chiara , Peccatori Fedro , Vanazzi Anna , Balzano Rosaria , Bertolini Francesco , Martinelli Giovanni 
Published: October 2019

Abstract
BCL2 over-expression is detected in follicular NHL patients in approximately 60%–80% at diagnosis. The prognostic value of the persistence of such molecular abnormality after treatment is still controversial: its presence could be associated with a shorter time to relapse and poorer survival, but there is no general agreement on that.
Here we report clinical data retrospectively collected (1997 to 2001) on 60 newly diagnosed follicular NHL patients (39 female and 21 male) treated with two different schedules: 35 patients received alkylating containing regimen (CLB + PDN) as standard therapy, while 25 patients received Rituximab alone or in combination with CLB as first line treatment according to investigational studies.
Median age was 55 years (range 28–76); 5 patients were considered in stage I, 14 in stage II, 15 in stage III and 26 patients in stage IV, according to Ann Arbor.
The two groups of patients had similar clinical characteristics and prognostic factors.
BCL2 determination was performed in 42/60 patients on bone marrow or peripheral blood, using PCR qualitative method. 25/42 patients (60%) were considered positive for BCL2 over-expression at diagnosis: 12/25 were in the group treated with chemotherapy and 13/25 in the Rituximab +/− chemotherapy arm.
All patients were re-evaluated at the end of treatment both clinically and with molecular evaluation. Among patients who received CLB plus PDN, 24/35 (68%) achieved CR and 10/35 (28%) achieved PR. 7/12 (58%) BCL2 positive patients at diagnosis still presented positivity at the end of chemotherapy. With a median follow up of 36 months (range 6–134) 14 out 24 (58%) CR patients have relapsed. Among them only one was BCL2 positive at the end of therapy. Three additional relapsed patients were BCL2 negative after treatment.
17/25 (68%) patients receiving Rituximab +/− chemotherapy achieved CR and 5/25 (20%) achieved PR. Only one patient out of 13 BCL2 positive at diagnosis presented BCL2 persistence at the end of therapy. With a median follow up of 36 months (6–71) only one BCL2 negative patient out of 17 CR has relapsed.
In our experience no differences in terms of ORR was observed between the two groups of patients who received CT or Rituximab +/− chemotherapy.
The higher rate of disappearance of BCL2 observed after Rituximab (98%) versus that recorded in patients receiving CT (48%) seems to confirm its more relevant clinical activity in disease eradication, and could be related to the lower incidence of relapse observed. However, the high degree of relapse observed in BCL2 negative patients after therapy could suggest no relationship between BCL2 persistence and the risk of subsequent relapse. The relatively short reported follow-up in the two groups of patients with such indolent disease, doesn’t allow at present time any definitive conclusion about the prognostic value of BCL2 over-expression.