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MOLECULAR ACTIVITY IN FOLLICULAR LYMPHOMA MONITORED BY BCL2/IGH IN THE PERIPHERAL BLOOD. THE OLD STORY IN A NEW LIGHT?
Author(s): ,
Andrea Janikova
Affiliations:
Dept of Hematology and Oncology,University Hospital Brno,Brno,Czech Republic
,
Eva Miculkova
Affiliations:
Dept of Hematology and Oncology,University Hospital Brno,Brno,Czech Republic
,
Andrea Mareckova
Affiliations:
Dept of Hematology and Oncology,University Hospital Brno,Brno,Czech Republic
,
Natasa Kopalova
Affiliations:
Dept of Hematology and Oncology,University Hospital Brno,Brno,Czech Republic
,
Jozef Michalka
Affiliations:
Dept of Hematology and Oncology,University Hospital Brno,Brno,Czech Republic
,
David Salek
Affiliations:
Dept of Hematology and Oncology,University Hospital Brno,Brno,Czech Republic
,
Dana Dvorakova
Affiliations:
Dept of Hematology and Oncology,University Hospital Brno,Brno,Czech Republic
,
Leos Kren
Affiliations:
Dept of Pathology,University Hospital Brno,Brno,Czech Republic
,
Ivo Hanke
Affiliations:
Dept of Surgery,University Hospital Brno,Brno,Czech Republic
,
Sarka Pospisilova
Affiliations:
Dept of Hematology and Oncology,University Hospital Brno,Brno,Czech Republic
Jiri Mayer
Affiliations:
Dept of Hematology and Oncology,University Hospital Brno,Brno,Czech Republic
(Abstract release date: 05/19/16) EHA Library. Miculkova E. 06/09/16; 132705; E1156
Dr. Eva Miculkova
Dr. Eva Miculkova
Contributions
Abstract
Abstract: E1156

Type: Eposter Presentation

Background
Follicular lymphoma (FL) is highly associated with the molecular rearrangement BCL2/IGH. Although BCL2/IGH has been studied many times, its real clinical value remains still matter of debates.

Aims
In our work, we focused on the mutual relationship between molecular levels of BCL2/IGH measured in peripheral blood (PB) and clinical course of FL. 

Methods
We performed qualitative and quantitative testing of BCL2/IGH by nested and real-time PCR in FL patients (grade 1-3B). PB samples were tested before the start of therapy (or watch and wait period, 12.8% cases), during treatment and during follow up at the time of routine clinical controls. According to mutual correlation of clinical course FL and molecular activity in PB, we divided patients into five groups (A, B, C, D, E): Group A included patients in a long-term molecular and clinical remission. Group B was defined by long-term remission with sporadic molecular activity. Group C included patients with concordant clinical and molecular remission and progression. Group D included patients with discordant clinical and molecular activity; there are two subgroups: 1) DM defined as evident molecular positivity in lasting clinical remission, and 2) DR defined by a clinically evident relapse in lasting molecular remission (Figure 1). Group E includes non-evaluable patients with the initial molecular negativity in PB, patients without treatment (watch and wait) and patients with lack of samples. Groups A and B with lasting molecular and clinical remissions brought no correlation information, the only informative population is represented by subgroups C and D.

Results
Totally, 187 patients with initial BCL2/IGH positivity were included, median of molecular follow up was 4.7 ys (range 1.1-14.8 ys) and median clinical follow up 5.3 ys (range 0.4-18.4ys); systemic treatment (chemotherapy or immunochemotherapy) was administered in 173/187 (92.5%) cases. There were 83 men (44%) with median age of 57 ys (range 28-79 ys), clinical stage III-IV was determined in 144/187 (77%) patients. Median number of PCR samples per patient was 15 (range 3-67).There were 60 (32.2%) patients in group A, 16 (8.7%) pts in group B, 39 (20.8%) pts in group C, 26 pts (13.9%) in group D and 46 (24.6%) pts in group E. Groups C and D (65 pts) gave a relevant correlation information only; the proportion of discordant cases was 26/65 (40%) pts. As mentioned, group D was divided into two subgroups: DR group (clinical relapse in molecular remission) with 19 (10.2%) patients, 17/19 (89.5%) patients remain alive with median overall survival (OS) of 8.5 ys. DM subgroup (molecular activity in lasting clinical remission) consisting of 7 pts, all of them remain alive with median OS of 12.1 ys. Interestingly, 10/39 (25.6%) patients subscribed into group C died (median OS 4.5 ys; 7 cases with confirmed death due to FL progression), compared to 2/26 died patients from group D (7.7%, 1 died probably due to progression only) with median OS of 8.8 ys (p 0.067).

Conclusion
Based on our results, molecular activity of BCL2/IGH in blood does not correlate sufficiently with clinical activity of FL in about 40% cases. However, patients with correlating molecular activity in their clinical relapses seem to have a tendency to a worse prognosis with more deaths related to FL and shorter overall survival. We can speculate, that release bcl2/IGH+ cells into PB mirrors the real aggressiveness of FL.

Session topic: E-poster

Keyword(s): BCL2, Follicular lymphoma, Molecular markers, Prognosis
Abstract: E1156

Type: Eposter Presentation

Background
Follicular lymphoma (FL) is highly associated with the molecular rearrangement BCL2/IGH. Although BCL2/IGH has been studied many times, its real clinical value remains still matter of debates.

Aims
In our work, we focused on the mutual relationship between molecular levels of BCL2/IGH measured in peripheral blood (PB) and clinical course of FL. 

Methods
We performed qualitative and quantitative testing of BCL2/IGH by nested and real-time PCR in FL patients (grade 1-3B). PB samples were tested before the start of therapy (or watch and wait period, 12.8% cases), during treatment and during follow up at the time of routine clinical controls. According to mutual correlation of clinical course FL and molecular activity in PB, we divided patients into five groups (A, B, C, D, E): Group A included patients in a long-term molecular and clinical remission. Group B was defined by long-term remission with sporadic molecular activity. Group C included patients with concordant clinical and molecular remission and progression. Group D included patients with discordant clinical and molecular activity; there are two subgroups: 1) DM defined as evident molecular positivity in lasting clinical remission, and 2) DR defined by a clinically evident relapse in lasting molecular remission (Figure 1). Group E includes non-evaluable patients with the initial molecular negativity in PB, patients without treatment (watch and wait) and patients with lack of samples. Groups A and B with lasting molecular and clinical remissions brought no correlation information, the only informative population is represented by subgroups C and D.

Results
Totally, 187 patients with initial BCL2/IGH positivity were included, median of molecular follow up was 4.7 ys (range 1.1-14.8 ys) and median clinical follow up 5.3 ys (range 0.4-18.4ys); systemic treatment (chemotherapy or immunochemotherapy) was administered in 173/187 (92.5%) cases. There were 83 men (44%) with median age of 57 ys (range 28-79 ys), clinical stage III-IV was determined in 144/187 (77%) patients. Median number of PCR samples per patient was 15 (range 3-67).There were 60 (32.2%) patients in group A, 16 (8.7%) pts in group B, 39 (20.8%) pts in group C, 26 pts (13.9%) in group D and 46 (24.6%) pts in group E. Groups C and D (65 pts) gave a relevant correlation information only; the proportion of discordant cases was 26/65 (40%) pts. As mentioned, group D was divided into two subgroups: DR group (clinical relapse in molecular remission) with 19 (10.2%) patients, 17/19 (89.5%) patients remain alive with median overall survival (OS) of 8.5 ys. DM subgroup (molecular activity in lasting clinical remission) consisting of 7 pts, all of them remain alive with median OS of 12.1 ys. Interestingly, 10/39 (25.6%) patients subscribed into group C died (median OS 4.5 ys; 7 cases with confirmed death due to FL progression), compared to 2/26 died patients from group D (7.7%, 1 died probably due to progression only) with median OS of 8.8 ys (p 0.067).

Conclusion
Based on our results, molecular activity of BCL2/IGH in blood does not correlate sufficiently with clinical activity of FL in about 40% cases. However, patients with correlating molecular activity in their clinical relapses seem to have a tendency to a worse prognosis with more deaths related to FL and shorter overall survival. We can speculate, that release bcl2/IGH+ cells into PB mirrors the real aggressiveness of FL.

Session topic: E-poster

Keyword(s): BCL2, Follicular lymphoma, Molecular markers, Prognosis

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