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Analysis of Prognostic Factors Influencing the Survival of Patients with
Relapsed Follicular Lymphoma
Presented by:Dr.Zaw Htet
Scientific supervisors:Prof.Dr.B.I.Polikov, Dr.D.A.Bykov
Moscow,2010
M.V.LOMONOSOV MOSCOW STATE UNIVERSITYFAULTY OF BASIC MEDICINE
Introduction
• Follicular lymphoma(FL) – formerly called follicle center lymphoma (centrocytes and centroblasts)
• 2nd most common Non-Hodgkin’s lymphoma
• 20 % of all NHLs
• Mostly presented in middle age and elderly
• Male : Female = 1:1.7
Prognosis
• Is determined by FLIPI scoring system-that include: age of patient, stage, no: of involved nodal areas, serum lactate dehydrogenase and haemoglobin level.
• Also depends on tumor grading
Purpose of Study
• To indentify the important clinical factors that influence the prognosis of disease and also predict the survival of the patients with follicular lymphoma at relapse.
Main Tasks of Study
1. To establish the important clinical factors that influence the survival after progression (SFP) of patients with follicular lymphoma.
2. To indentify the cause-specific SFP of patients with follicular lymphoma.
Patients and Methods• Retrospective study
151
69 (46%) 60 (40%) 21 (14%)
32 (47%) 37 (64%)
69
Complete Response Partial Response Undetermined
Disease Progression(median follow up: 4.5 yrs)
Median age: 56 yrs, 36 males, 33 females
Main Characteristics of Patients at diagnosis and at relapse (n=69)
Prognostic factors for survival from progression(SFP) in patients with follicular lymphoma at relapse : Results of univariate analysis (n=69)
Variable No. of Patients Mortality (%) 5-year SFP P value
Stage at diagnosis I-II III-IVAge <60 years ≥60 yearsBulky disease No YesECOG 0-1 ≥2Serum LDH <450 U/L ≥450 U/LBone marrow involvement No Yes
1161
4230
567
578
3810
1815
1453
4154
3589
3790
2767
1753
8242
6028
5422
5311
5644
8123
0.02
0.07
0.007
0.0002
0.015
0.002
Variable No. of patients Mortality (%) 5-year SFP P value
Stage at relapse I-II III-IVIPI Low Inter/High Duration of response <2 years ≥2 yearsTransformation No YesInitial Response CR PRResponse to salavage therapy CR PR NR
2244
3828
4131
287
3138
262215
2651
2566
5536
3333
4449
264890
6834
7213
3363
6362
4448
57590
0.003
<0.0001
0.012
NS
NS
<0.0001
Continued:
Multivariate analysis
• For that analysis, variables with prognostic significance in univariate study ( P value <0.1) and with a sufficient number of assessable cases were selected.
• LDH level, bone marrow involvement were not included
• Response to initial treatment (CR versus PR) was included
Survival from progression(SFP) according to the duration of response (RD) to first-line therapy
5-years SFP according to response duration(RD) to first line therapy
5-years SFP according to performance status (ECOG) and response duration(RD)
5-years SFP according to performance status(ECOG) and response duration (RD)
Cause-specific SFP
• 30 of 69 patients died from lymphoma
• 2 patients died from non-lymphoma related causes
Cause-specific survival from progression
Discussion• The natural history of follicular lymphoma is characterized by
continuous relapses that become progressively less sensitive to chemotherapy.
• Older age, poor performance status, advanced stage, bulky disease, leukaemic expression, high serum LDH level and high risk according to IPI have consistently been found to be associated with a poor outcome.
• Although patients with relapsed follicullar lymphoma often still respond to further therapy.
• Duration of response becomes shorter after each relapse and most patients die due to the disease.
• New therapeutic approaches, such as purine analogs alone or in combination, monoclonal antibodies, stem cell transplantation and biological response modifiers, are being developed.
Conclusion• In univariate analysis, clinical characteristics at progression;
age at relapse, stage of disease, performance status, international prognostics index, bone marrow involvement, serum LDH level , as well as the duration of response to first-line therapy , are the clinical factors that influence the survival of patients with follicular lymphoma at relapse.
• In multivariate analysis, response duration(RD) emerged as an important prognostic factor, with a 5-years SFP ranging from 33% (RD <2 years) to 63%(RD ≥2 years).
• Performance status at relapse emerged as the most important factor to predict cause-specific SFP.