1. 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

2. 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.

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

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

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

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

7. GvHD

8. 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

9. 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

10. 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

11. 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)

12. 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)

13. 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.

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