AUTOLOGOUS PERIPHERAL STEM CELL TRANSPLANTATION FOR

DIFFUSE LARGE B CELL LYMPHOMA (DLBCL) IN FIRST LINE:

REPORT OF THE "CNGMO "  DE TUNIS

9ème Congrès Magrébin d’Hématologie

Dr Torjemane L25/05/2012

High dose chemotherapy (HDC) followed by autologous peripheral stem cell transplantation (APSCT) is a part of therapeutic strategy:

National GELT 2002-2008 Protocol (Group 2B):

A subset of adult patients (aged of 16-60 years) with high risk (IPI≥2) DLBCL.

Introduction

From June 2000 to December 2011, a total of 122 autologous PSCT were performed at the CNGMO for NHL.

A total of 72 patients , with DLBCL ( IPI=2-3 ), were intensified in first line (partial or complete remission)

Induction regimen: 4 ACVBP ± Rituximab + 2MTX

Patients & Methods (1)

Caracteristics of patients

at diagnosis

Number)%(

Mean age (range)

Sexe ratio (M/F)

36 years (17- 59

years)

32/30 ( 1,06)

Ann Arbor stage

II- IIE

III- IV

Bulky

BM involvement

3 (4%)

69 (96%)

47 (65%)

8 (11%)

Caracteristics of patients

before transplant

Number (%)

Induction regimen +

Rituximab

Radiotherapy (CNS,

epiduritis)

51 (70%)

4 (5%)

Disease status

Complete remission (CR +

CRu)

Partial Remission (PR)

Resistant disease

53 (73,5 %)

18 (25 %)

1 (1,5%)

LDH>N

HVB or HVC+

Atrophic gastritis HP+

22 (30%)

8 (11%)

4/8 ( Gastric LNH)

Conditioning regimen: BEAM

The mean number of CD34+ cells : 6,15 x10 6 /kg (range; 1,9- 19,8)

( + Bone Marrow in one patient)

The mean time [Induction - ASCT ] : 112 days (range; 74 - 158)

The mean time [the 2nd MTX-ASCT]: 38 days (range; 20-107)

Methods (2)

ResultsHematopoietic Engraftment

The mean numbers of days to reach:

-Granulocytes > 500/mm3: 11 days ( range:

9 - 28)

- Platelets ≥ 20 000/mm3: 12 days ( range;

9- 38)

Transfusion Requirements :

- RBC : 2 Units (range: 0- 10)

- PCA : 3 Units (range: 0- 19)

Transplant-related toxicity

Stomatitis grade 3-4: 50%

Infectious complications:

- A mean of 1,58 febrile neutropenia (range; 0-4)

- Pneumonia : (n= 5) , Cellulitis: (n=5)

- Septicemia ( 14%) : Gram + (n=8)

Gram – (n= 8)

Candida parapsilosis

(n=1)

Transplant-related toxicity

Renal toxicity (grade 1-2) : n= 3 (4%)

Liver toxicity (grade 1-2): n=3 (4%)

Cytomegalovirus Infections: n=3 (4%)

Treatment related Mortality : 0

At 3 months after APSCT, Overall Response : 67/72 ( 93%)

- Complete Remission (RC+Rcu) : 53/72 ( 73,5 %)

- Partial Remission : 14/72 (19,5%)

- Progressive disease : 5/72 ( 7%)

Consolidative radiotherapy (CNS, residual mass): n=7

Therapeutic Results (1)

Relapse rate : 11/72 (15%)

- Median delai of 6 months (range; 1- 30 months) - Prior Rituximab: 5/11 (45%)

After a median follow-up of 48 months (range; 10- 118 months), 61 (85%) patients were alive and well.

Preserved Fertility : age <35 years ( 5 pregnancy)

Therapeutic Results (2)

Overall survival, Cumulative Incidence of relapse Event Free

Survivall ( Kaplan-Meier)

OS at 5 years =85%

EFS at 5 years=82%

Parameter (N)EFS at % years

P (Log-rank)

Bulky Yes ( n=47) No (n=25)

84%80

0,84

Prior Rituximab Yes (n=51) No (n=21)

89%68%

0,042

Status before transplant RC+Rcu (n=53) RP+P (n=19)

94%51%

<0,001

Prognosis Factors

EFS curves according Prognosis Factors

RC+Rcu

RP

p<0,001

The present results demonstrate the efficacy and low toxicity of the HDC followed by autologous stem cell support in high-risk DLBCL

Achievement of Complete Remission is the main prognostic factor.

Addition of Rituximab significantly reduce the risk of relapse.

Conclusion

Equipe d’Hhématologie de l’Hôpital Hédi Chaker, Sfax Equipe de Carcinologie Médicale de l’hôpital Hédi Chaker, Sfax Equipe d’Hématologie de l’hôpital Farhat Hached, Sousse Equipe de Carcinologie Médicale de l’hôpital Farhat Hached,

Sousse Equipe d’Hématologie de l’Hôpital de Monastir Equipe d’Hématologie de l’Hôpital Aziza Othmana, Tunis Equipe d’Hématologie de l’Hôpital Militaire de Tunis Equipe de Carcinologie Médicale de l’Institut Salah Azaiez de

Tunis Médecins Hématologues et Oncologues du Privé (Tunis, Sousse,

Sfax)

THANKS