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) Carateristics at diagnosis Median age Sexe ratio (M/F) Number 40 years (range; 18-54 years) 20/8 (2,5) Histological subtype Diffuse LBCL Richter 26 2 Stage I-II III-IV 6 22 IPIaa 9 19 12 3 0-1 2-3 Bulky disease BM involvement Treatments & Responses Initial Treatment regimen CHOP (± radiotherapy) ACVBP Others Number 9 (4) 15 4 Response for first line therapy Refractory Relapsed NHL Median time of relapse (range) 11 17 12 months (2-84) Salvage therapy (Heterogenous) 1 line 2 to 3 lines + Rituximab + Radiotherapy 22 5&1 18 2 Caracteristics of patients Number at transplant Disease Status Complete Remission (CR + Cru) 18 ( 64%) Partial remission 10 (39%) Resistant disease 2 (7%) Bulky (Tumor size >7cm) 5 Median time, (range) Last chemotherapy –ASCT Diagnosis- ASCT 34 days (21-120) 21 months (5-122) 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 • Transfusion Requirements - RBC : 4 Units (range: 0- 19) - PCA: 6 Units (range: 2- 19) ( range; 12- 62) 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 1 0.8 OS at 3 years 50% 0.8 0.7 0.6 0.6 CI Relapse 42% 0.5 0.4 0.4 0.3 0.2 0.2 0.1 0 0 20 40 60 80 100 120 0 140 0 Temps1 20 40 60 80 1 0.8 EFS at 3 years 53% 0.6 0.4 0.2 0 0 20 40 60 5 80 100 120 140 100 120 140 EFS curves according prior Rituximab treatment and disease statuts at transplant 1 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0 1 0.9 0.8 Rituxi;ab + 0.7 0.6 0.5 Rituxi;ab - 0.4 p= 0,026 0.3 0.2 0.1 0 0 20 40 60 80 120 140 P= 0,2 RP 0 20 40 60 Temps1 Temps1 0 100 RC+RCu 1 1 0 80 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. THANKS • 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)