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ANALYSIS OF PERCENT IDENTITY OF IGHV MUTATION AS PROGNOSTIC FACTOR IN CLL PATIENTS TREATED WITH FLUDARABINE, CYCLOFOSFAMIDE AND RITUXIMAB: A SINGLE CENTRE EXPERIENCE
Author(s): ,
Annamaria Giordano
Affiliations:
haematology,university,bari,Italy
,
Paola Curci
Affiliations:
haematology,university,bari,Italy
,
Rita Rizzi
Affiliations:
haematology,university,bari,Italy
,
Mario Delia
Affiliations:
haematology,university,bari,Italy
,
Tommasina Perrone
Affiliations:
haematology,university,bari,Italy
,
Marina Aurora Urbano
Affiliations:
haematology,university,bari,Italy
,
Sonia Mallano
Affiliations:
haematology,university,bari,Italy
,
Vera Carluccio
Affiliations:
haematology,university,bari,Italy
,
Anna Mestice
Affiliations:
haematology,university,bari,Italy
,
Ezio Minervini
Affiliations:
haematology,university,bari,Italy
,
Francesco Albano
Affiliations:
haematology,university,bari,Italy
Giorgina Specchia
Affiliations:
haematology,university,bari,Italy
(Abstract release date: 05/17/18) EHA Library. giordano A. 06/14/18; 216280; PB1883
Dr. Annamaria giordano
Dr. Annamaria giordano
Contributions
Abstract

Abstract: PB1883

Type: Publication Only

Background

The mutation status of the immunoglobulin heavy chain variable region gene (IGHV) is an established prognostic factor in patients with chronic lymphocytic leukaemia (CLL).

The degree of somatic hypermutation, determined as percent sequence identity to germline in IGHV (IGHV%)  is analyzed in clinical practice. Currently CLL with <98% IGVH  identity  are considered “mutated” and CLL patients with > 98% IGHV identity  are considered “unmutated. ” Recent data have assessed  the prognostic role of IGHV% as a continuous variable in CLL patients treated with fludarabine, cyclophosphamide and rituximab (FCR).

Aims

In our  study we investigated  the prognostic significance of absolute percent identity of somatic of IGHV mutation on Progression Free Survival (PFS) and Overall Survival (OS)  in unmutated CLL patients (pts)  treated  with  frontline FCR  in our Institution.

Methods

We retrospectively evaluated 73 pts with CLL treated with frontline FCR at the University Hospital of Bari (Italy) with a median of 5 years follow-up. The mutational status of the IGHV  was studied in all pts and the degree of somatic hypermutation of IGHV  was determined as percent identity from the germline sequence. Pts were divided in mutated and unmutated using a cut-off of 98% sequence identity. Among unmutated pts (identity sequence > 98%) we selected two groups: the first one between 98% and 99%  (IGHV 98-99%) and the second one with identity range between 99% and 100% (IGHV 99-100%), respectively. PFS and OS were calculate and compared between the two groups.

Results

Among the 73 CLL pts treated with frontline FCR 48 pts (65%) with unmutated IGHV CLL were identified; among them, 20 pts (41%) and 28 (59%) belonged to IGHV 98-99% and IGHV 99-100% group, respectively. No significant differences were observed (p = ns) in terms of PFS and OS between the two groups.

Conclusion

In our study no difference in terms of survival was observed in unmutated IGHV CLL pts on the basis of the percent identity of IGHV mutation for  distinguishing  two classes of risk. Further studies and more consistent cohorts of pts are warranted to confirm these data.

Session topic: 6. Chronic lymphocytic leukemia and related disorders - Clinical

Keyword(s): Chronic Lymphocytic Leukemia, IgH rearrangment, Survival

Abstract: PB1883

Type: Publication Only

Background

The mutation status of the immunoglobulin heavy chain variable region gene (IGHV) is an established prognostic factor in patients with chronic lymphocytic leukaemia (CLL).

The degree of somatic hypermutation, determined as percent sequence identity to germline in IGHV (IGHV%)  is analyzed in clinical practice. Currently CLL with <98% IGVH  identity  are considered “mutated” and CLL patients with > 98% IGHV identity  are considered “unmutated. ” Recent data have assessed  the prognostic role of IGHV% as a continuous variable in CLL patients treated with fludarabine, cyclophosphamide and rituximab (FCR).

Aims

In our  study we investigated  the prognostic significance of absolute percent identity of somatic of IGHV mutation on Progression Free Survival (PFS) and Overall Survival (OS)  in unmutated CLL patients (pts)  treated  with  frontline FCR  in our Institution.

Methods

We retrospectively evaluated 73 pts with CLL treated with frontline FCR at the University Hospital of Bari (Italy) with a median of 5 years follow-up. The mutational status of the IGHV  was studied in all pts and the degree of somatic hypermutation of IGHV  was determined as percent identity from the germline sequence. Pts were divided in mutated and unmutated using a cut-off of 98% sequence identity. Among unmutated pts (identity sequence > 98%) we selected two groups: the first one between 98% and 99%  (IGHV 98-99%) and the second one with identity range between 99% and 100% (IGHV 99-100%), respectively. PFS and OS were calculate and compared between the two groups.

Results

Among the 73 CLL pts treated with frontline FCR 48 pts (65%) with unmutated IGHV CLL were identified; among them, 20 pts (41%) and 28 (59%) belonged to IGHV 98-99% and IGHV 99-100% group, respectively. No significant differences were observed (p = ns) in terms of PFS and OS between the two groups.

Conclusion

In our study no difference in terms of survival was observed in unmutated IGHV CLL pts on the basis of the percent identity of IGHV mutation for  distinguishing  two classes of risk. Further studies and more consistent cohorts of pts are warranted to confirm these data.

Session topic: 6. Chronic lymphocytic leukemia and related disorders - Clinical

Keyword(s): Chronic Lymphocytic Leukemia, IgH rearrangment, Survival

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