PREDICTIVE FACTORS AFFECTING THE OUTCOME OF ALLOGENEIC STEM CELL TRANSPLANTATION USING RIC REGIMENS: EXPERIENCE FROM A SINGLE CENTRE Dott.ssa M. Medeot.

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Presentation transcript:

PREDICTIVE FACTORS AFFECTING THE OUTCOME OF ALLOGENEIC STEM CELL TRANSPLANTATION USING RIC REGIMENS: EXPERIENCE FROM A SINGLE CENTRE Dott.ssa M. Medeot Clinica Ematologica e Centro Trapianti “Carlo Melzi” Azienda Ospedaliero-Universitaria di Udine Senigallia, October 23th, 2008

OBJECTIVES To assess the impact of patient- and transplant-related variables on the outcome (TRM, DFS and OS) after RIC HSCT for hematological malignancies. Retrospective analysis on 116 patients treated from January 2002 to June 2007 in our centre.

PATIENTS’ CHARACTERISTICS: total 116 Sex (male/female): 64/52 Median age, years (range): 56 (19-69) Diagnosis, n (%): Acute leukemia 28 (25%) Aggressive NHL 22 (19%) Indolent NHL 18 (15%) Hodgkin lymphoma 19 (16%) Multiple myeloma 21 (18%) Idiopathic myelofibrosis 8 (7%) Previous treatments, n (%): 1 CHT line 29 (25%) 2 CHT lines 37 (32%) ≥3 CHT lines 50 (43%) Autologous SCT 50 (43%) HCT - Comorbidity Index, n (%): 0 59 (52%) 1 27 (23%) 2 18 (7%) 3 19 (16%) >3 3 (2%) Pre-HSCT disease status, n (%): CR 41 (35%) PR 26 (22%) SD/PD 49 (43%)

TRANSPLANT PROCEDURES’ CHARACTERISTICS CONDITIONING REGIMEN, n (%): Thiotepa-CTX ± fludarabine 83 (72%) TBI 200 + fludarabine ± melphalan 18 (15%) Melphalan or busulfan + fludarabine 15 (13%) GvHD PROPHYLAXIS, n (%): Cyclosporin + MTX 49 (42%) Cyclosporin + MTX + ATG 48 (41%) Cyclosporin + MMF or alemtuzumab 19 (17%) DONORS, n (%): Sibling HLA-matched 53 (46%) Unrelated 63 (54%) HSC SOURCE, n (%): Bone marrow 19 (16%) Peripheral blood 97 (84%)

OUTCOMES Engraftment 107 (92%) Autologous recovery 5 (4%) Engraftment not evaluable 4 (4%) Median time BMT- last follow-up: 11 months (1-71)

TRM CAUSES GvHD 11 (42%) Infections 10 (38%) Ictus cerebri 3 (12%) Microangiopathy 1 (4%) Car accident 1 (4%)

GvHD

CUMULATIVE INCIDENCE OF TRM % probability 100 75 TRM: 13% at 1 year 28% at 3 years 50 25 20 40 60 80 Months from transplant

KAPLAN-MEIER ANALYSIS OF OVERALL SURVIVAL AND DISEASE-FREE SURVIVAL % probability 100 75 OS: 66% at 1 year 52% at 3 years 50 DFS: 50% at 1 year 38% at 3 years 25 20 40 60 80 Months from transplant

VARIABLES EXAMINED PATIENT-RELATED VARIABLES: Age (continuous variable) Sex (male vs female) Diagnosis: acute leukemia vs aggressive NHL vs indolent NHL vs Hodgkin lymphoma vs multiple myeloma vs idiopathic myelofibrosis Previous autologous SCT: yes vs no Previous treatment: < 3 chemotherapic lines vs ≥ 3 Disease status before SCT: CR vs PR vs resistance/progression Sorror comorbidity index: 0 vs ≥1 TRANSPLANT-RELATED VARIABLES: Conditioninig regimen: thiotepa + CTX ± fluda vs TBI + fluda vs alkylating agents + fluda GVHD prophylaxis : no serum vs ATG vs alemtuzumab HLA-matching: full-matched vs mismatched Donor: sibling vs unrelated Number of CD34+ infused (continuous variable) Stem cell source: bone marrow vs peripheral blood Acute GVHD: grade 0-I vs grade II-IV Chronic GVHD: yes vs no Proven/probable mycotic infection: yes vs no CMV reactivations: 0 vs ≥1

VARIABLES that significantly increase HR UNIVARIATE ANALYSIS VARIABLES that significantly increase HR TRM HR (p) DFS OS Age (as continuous variable) 1.06 (0.013) 1.01 (0.498) 1.04(0.014) HCT - CI ≥ 1 1.25 (0.073) 1.19 (0.046) 1.23 (0.037) Disease status pre-SCT: resistance/progression 1.84 (0.164) 2.19 (0.006) 2.15 (0.023) GvHD prophylaxis: use of alemtuzumab 3.078 (0.044) 1.56 (0.241) 2.18 (0.061) N° CD 34+ cells infused 1.12 (0.033) 1.03 (0.457) 1.08(0.102) Grade II-IV acute GvHD 3.00 (0.010) 1.08 (0.759) 1.21 (0.551) Probable/proven mycoses 3.77(0.001) 2.60 (0.001) 2.59 (0.003)

MULTIVARIATE ANALYSIS VARIABLES that significantly increase HR TRM HR (p) DFS OS Age (as continuous variable) n.s. 1.05 (0.007) HCT - CI ≥ 1 1.20 (0.040) Disease status pre-SCT: resistance/progression 2.19 (0.009) N° CD 34+ cells reinfused 1.14 (0.049) GvHD prophylaxis: use of alemtuzumab 5.98 (0.005) Grade II-IV acute GvHD 4.44 (0.002) Probable/proven mycoses 2.08 (0.011) 2.59 (0.004)

CONCLUSIONS Our data confirm the feasibility of RIC transplant in a setting of “unfit” and heavily pre-treated patients, with a TRM around 20%. Despite the application of RIC regimens, advanced age and presence of comorbidities significantly affect the outcome of transplant. Development of fungal infections showed to be one of the principal predictive factors for outcome in RIC transplants.

THANKS TO… Team Trapianti: Francesca Patriarca Prof. Renato Fanin Marta Battista Alessandra Sperotto Michela Cerno Antonella Geromin