1. Ematologia, Ospedali Riuniti, Bergamo
Reduced-toxicity conditioning with Busulfan and Fludarabine and allogeneic stem cell transplant: chimerism evaluation and global outcome of 26 consecutive patients
Alessandra Algarotti
Ematologia, Ospedali Riuniti, Bergamo
Senigallia, 24 Ottobre 2008

2. Reduced intensity or reduced toxicity conditioning regimens?
RIC regimens have been used to offer an allogeneic transplant to otherwise inelegible patients
RIC regimens are often associated with an increased proportion of disease relapse
We investigated a reduced toxicity conditioning regimen with Busulfan and Fludarabine and we evaluated the outcome and the toxicity

3. Alyea EA: et al.: Blood, 2005, Vol. 105, 1810-1814
Comparative outcome of nonmyeloablative and myeloablative allogeneic hematopoietic cell transplantation for patients older than 50 years of age
Alyea EA: et al.: Blood, 2005, Vol. 105,
Conditioning regimens
“Nonmyeloablative”
Fludarabine (30 mg/m2/d for 4 days)
Busulfan (0.8 mg/kg/d iv for 4 days) on days -6, -5, -4, and -3.
Myeloablative
Cyclophosphamide (1800 mg/m2 for 2 days) and fTBI; 1400 cGy in 7 fractions over 4 days)
Busulfan (16 mg/kg po divided over 4 days) and Cyclophosphamide a
152 patients: 71 nonmyeloablative and 81 myeloablative

4. Overall survival Event Free Survival
Once Daily i.v. Busulfan and Fludarabine (i.v. Bu-Flu) Compares Favorably with i.v. Busulfan and Cyclophosphamide (i.v. BuCy2) as Pretransplant Conditioning Therapy in AML/MDS
OS: Bu-Flu patients survived significantly longer (but shorter follow-up time). EFS: Bu-Flu patients had a longer EFS compared with the BuCy2 group (19,1 months versus 8,4 months)
Overall survival Event Free Survival
Andersson BS et al.: Biology of Blood and Marrow Transplantation 14: (2008)

6. Clinical findings Patients 26 Sex, M/F 15/11
Age,median (range) 53 (23-66)
Diagnosis (n)
AML 12
ALL 1
MDS 1
MM 7
HD 3
NHL 2
Disease status at transplant
CR 9 (5 AML, 1 ALL, 2 NHL, 1 HD)
GPR 7 (MM)
PR 1 (HD)
active disease 9 (7 AML, 1 MDS, 1 HD)

7. Transplantation Sibling/MUD 14/12 BM/PB 3/23 TNC x 10^8/Kg
median (range) ( )
CD34 x 10^6/Kg
median (range) ( )
CD3 x 10^6/Kg
median (range) ( )
Engraftment day, median (range)
N > 500/mmc (13-21)
PLT > /mmc 14 (11-39)

8. BM
BM Chimerism

9. PB Chimerism (CD 15, CD 3) P

10. Immunologic Reconstitution - CD3
p <
Days from transplant

11. Immunologic Reconstitution - CD 4
p <
Days from transplant

12. GVHD Acute GVHD 14/26 (54%) grade I 4 (15%) grade II-IV 10 (38%)
Chronic GVHD 12/23 (52)
mild 7 (30)
extensive 5 (22)

13. Main transplantation outcomes
Alive at last follow up 18
Alive in CR 15
Alive with active disease 3
Relapse/progression 4/6
Mortality
NRM/RRM 1/7

14. Overall and Event Free Survival
OS = 60%
EFS = 55%

15. TRM and Risk to Relapse
RRD = 40%
TRM = 4%
Competing risk analysis

16. Conclusion
In our hands the FLU-Bu regimen confirms its remarkable tolerability and a significant antineoplastic activity
Despite a low Fludarabine dosage, the chimerism full donor was obtained in most patients at 100 days after transplant
Randomized clinical trials are needed to confirm these preliminary results

17. Studio AIFA per la ricerca indipendente 2006