MANAGEMENT OF MANTLE CELL LYMPHOMA IN TUNISIA

R BEN LAKHAL , L KAMMOUN , K ZAHRA , S KEFI

Sousse 25 MAY 2012

MCL uncommon lymphoma

Armitage JO, et al. J Clin Oncol. 1998;16:2780-2795.

Diffuse large B cell: 31%

Follicular: 22%Marginal zone, extranodal: 8%

Peripheral T cell: 7%

Small lymphocytic/CLL: 7%

Mantle cell: 6%

Mediastinal large B cell: 2%

Anaplastic large cell: 2%

Burkitt: 2%

Marginal zone, nodal: 2%

T lymphoblastic: 2%

Other: 9%

Introduction

Mantel Cell Lymphoma (MCL) :

Aggressive B-cell Malignancy.

Complex pathophysiology : t(11, 14) aberrant

expression of cylcin D1.

Advanced non-bulky disease.

Diagnosed at age 60 to 65 years.

Short median survival (3 years) despite intensive

therapy.

OBJECTIVE

Retrospective Tunisian multicenter study :

Analyze epidemiological,clinical and biological features of tunisian MCL patients.

Evaluate the response to treatement according to classical prognostic factors.

Analyze the event free survival (EFS) and the overal survival (OS) according to prognostic factors

32 patients : 2000-2011

3 centers :

Tunis : 20 patients

Sousse : 7 patients

Sfax : 5 patients

PATIENTS

Epidémiologic Features

0

1

2

3

4

5

6

7

8

9

2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011

Annual incidence of MCL

Epidémiologic Features Median age : 62 years ( 30-84 years)

23 males ( 72%) Sex-ratio : 2.55

Clinical and biological features

N Pencentage

B symptoms

No 20 62.5%

Yes 12 37.5%

PS

2 23 72%

>2 9 28%

Stage

Early 5 18%

Advanced 27 84%

LDH

>Nle 21 66%

<Nle 11 34%

Bone Marrow involvement

Yes 19 60%

No 13 40%

Prognosis of patients

N Percentage

IPI

0-1 12 38

2-3 20 62

MIPI (16 cases)

Low risk 3 19

Intermediate 5 31

High risk 8 50

Methods

STATISTIC STUDY STATISTIC STUDY

1- Predictives response factors :

( Chi-square test, p < 0.05 )

2 - The EFS «event free survival» and the OS «overall survival» :

(Kaplan-Meier method and Log-Rank test)

- Univariate study

- Multivariate study

Treatment Features

30 patients treated (1death, 1 lost to follow-up) 25/30 patients received Rituximab (83%)

2 patients treated on 20013 patients > 75 years (Mini-CEOP)

Chemotherapy : CHOP/DHAP = 12 patients ( 40%) CHOP = 13 patients ( 43.3%)Velcade – CHP = 2 patients (6.6%) Mini-CEOP = 3 patients ( 10%)

Autologous stem cell transplantation = 5 patients (13pts<60 years)

Allogeneic stem cell transplantation : 1 patient

Response of Treatment

30 patients treated

4 lost to follow-up (13 %)

26 evaluables patients

CR11 patients

(42%)

PR07 patients

(27%)

Failure/progression 08 patients

(31%)

ORR = 69% 6 Deaths (4 toxic deaths)

Gender : ORR P

Male 68.4% 0.88 NS

Female 71.4%

Stage :

Early 100% 0.13 NS

Advanced 61.9%

LDH:

N 72.7% 0.94 NS

>N 71.4%

PS :

2 70% 0.84 NS

>2 75%

Response according to prognostic factors

ORR P

IPI :

0-1 72.7% 0.85 NS

2-3 69.2%

Auto :

Yes 100% 0.2 NS

No 65%

Rituximab :

Yes 72.7% 0.37 NS

No 50%

DHAP:

Yes 81.8% 0.23 NS

No 60%

Response according to prognostic factors

OVERALL SURVIVAL (OS)

Recul en mois

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OS : 60% (5years)

OS according to prognostic factors

One significant adverse

prognostic factor :

failure to treatement

Recul en mois

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Réponse

3+4+5

0+1+2

p < 0,001

OR

Failure

Event free survival (EFS)

Recul en mois

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EFS(5years) : 52%

DEATHS : 8 patients

1 death before treatement 5 toxic deaths 2 deaths progression

RELAPSES

One relapse Late relapse (5 years) Post ASCT

DISCUSSION

Epidemiological , clinical and biological characteristics of Tunisian patients are comparables to littérature data.

annual incidence increasing ?

or

improvement of diagnosis tools ?

DISCUSSION

There is no generally established prognostic

index for patients with MCL.

For our patients :

IPI>2 (High risk patients) : 20 (62%)

MIPI evaluated in 16 patients

High risk patients : 8 (50%)

PROGNOSIS

MIPI > FLIPI > IPI

Biologic MIPI = MIPI +

proliferation marker Ki-67

DISCUSSION

Aggressive therapies including chemo-immunotherapy or high dose chemotherapy followed by autologous stem cell transplant have been shown to improve outcome BUT

no standard therapy offers the potential for cure.

Our patients :

Immunotherapy : all younger patients

RCHOP/RDHAP : 12 patients

ASCT : only 5 patients (13 pts < 60 yrs)

ORR : 69% (DHAP : ORR at 80%)

OS : 60%

EFS : 52%

TREATMENT

Role of cytarabine (Ara-C)

Role of ASCT

CONCLUSION Epidemiological , clinical and biological characteristics of Tunisian

patients are comparables to littérature data.

Therapeutic results must be improved +++

Younger patients (< 60 yrs) : HD Arac + ASCT

Patients <40yrs : allogeneic transplantation

Older patients : RCHOP +/- Rituximab maintenance

Salvage therapy +++

Better management of toxicity