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.