AUTOLOGOUS PBSC TRANSPLANTATION FOR

REFRACTORY OR RELAPSED DBLCL REPORT OF THE « CNGMO, TUNIS»

9ème Congrès Magrébin d’Hématologie Dr Torjemane L

25/05/2012

Introduction • High dose chemotherapy (HDC) followed by

autologous peripheral stem cell transplantation (APSCT) is indicated in case of relapsed or refractory NHL.

• From June 2000 to December 2011, a total of 28 autologous PSCT were performed at the « CNGMO » for DLCBCL in second line

Patients & Methods(1)Number Carateristics at

diagnosis40 years (range; 18-54 years)

20/8 (2,5)

Median ageSexe ratio (M/F)

262

Histological subtype Diffuse LBCL Richter

622

Stage I-II III-IV

919

IPIaa 0-1 2-3

123

Bulky diseaseBM involvement

Number Treatments & Responses

9 (4) 154

Initial Treatment regimen CHOP (± radiotherapy) ACVBP Others

1117

12 months (2-84)

Response for first line therapy Refractory Relapsed NHL Median time of relapse (range)

225 &1

18 2

Salvage therapy (Heterogenous) 1 line 2 to 3 lines + Rituximab + Radiotherapy

Number Caracteristics of

patients

at transplant

18 ( 64%)

10 (39%)

2 (7%)

Disease Status

Complete Remission (CR

+ Cru)

Partial remission

Resistant disease

5 Bulky (Tumor size >7cm)

34 days (21-120)

21 months (5-

122)

Median time, (range)

Last chemotherapy –

ASCT

Diagnosis- ASCT

Transplant procedure• Conditioning regimen consisted in BEAM

regimen (BICNU, Etoposid, Cytarabin, Melphalan)

• Adjustment of dose of Melphalan (50%) to renal function: 2 patients

• PBSC : 6,03 x106 CD34+/kg (range; 1,44- 13 x106).

(PBSC + Bone marrow : 2 patients)

Results Hematopoietic

Engraftment • The medians numbers of days to reach:

-Granulocytes > 500/mm3: 10 days ( range:

9 - 35)

- Platelets ≥ 20 000/mm3: 15 days

( range; 12- 62)

• Transfusion Requirements

- RBC : 4 Units (range: 0- 19)

- PCA: 6 Units (range: 2- 19)

Transplant-related toxicity

o Stomatitis grade 3-4: 85%

o Infectious complication: 100%

- A median of 2 febrile neutropenia (range;1-4)

- Pneumonia : n= 6, Abdominal pain

- Septicemia (19%) : Gram + (n=6)

Gram- (n=4)

, Candida parapsilosis

(n=2)

Transplant-related toxicity

o Renal toxicity (grade 1-2): n= 6 (21%)

o Hepatic toxicity/VOD : n=1 (3,5%)

o Cytomegalovirus Infections: n=4 (14%)

o Treatment related Mortality: n=2 (7%)

( Interstitiel Pneumonia + Septic choc)

Therapeutic results • At 3 months after Transplants:

- Complete Remission : 15/26 ( 58%)

- Partial Remission: 8/26 (30%)

- Resistant disease: 3/26 (12 %)

• Complementary radiotherapy (2 resistant diseases)

:

- 1 Complete Remission / negative TEP scanner

- 1 Stable Partial Remission

Therapeutic results • Relapse rate: 10/26 (38%)

• Median delai of relapse: 6 months (range; 3- 20)

• After a median time of follow-up of 24 months, (range : 8- 120 months) 16 ( 57%) patients were alive and well.

Overall survival, Cumulative

Incidence of relapse and Event

Free Survival

0 20 40 60 80 100 120 1400

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0 20 40 60 80 100 120 1400

0.10.20.30.40.50.60.70.80.9

1

5

0 20 40 60 80 100 120 1400

0.2

0.4

0.6

0.8

1

Temps1

OS at 3 years 50% CI Relapse 42%

EFS at 3 years 53%

EFS curves according prior Rituximab

treatment and disease statuts at

transplant

0 20 40 60 80 100 120 1400

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1

0 1

Temps1

Rituxi;ab +

Rituxi;ab - p= 0,026

0 10 20 30 40 50 60 70 80 900

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1

1 0

Temps1

RC+RCu

P= 0,2RP

Conclusion • The present results demonstrate the

efficacy and moderate toxicity of the HDC followed by autologous stem cell support in refractory or relapsed high-risk DLBCL

• Addition of Rituximab significantly reduce the risk of relapse.

• 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