Abstract

In vivo T-cell depletion with alemtuzumab has been used to reduce acute and chronic GVHD. In order to evaluate its overall effect on transplant outcomes in AML and MDS we compared 90 pts who received fludarabine/melphalan/alemtuzumab (FMA) conditioning and post-transplant tacrolimus at the University of Chicago, with 112 who received fludarabine/melphalan (FM) and post-transplant tacrolimus/methotrexate at MD Anderson Cancer Center. Pt and transplant characteristics were well balanced except for a higher proportion of MDS in the FM group. Median age, proportion unrelated donor tx and proportion high/intermediate and low risk by ASBMT criteria were balanced between the groups. With median follow up of 28 months in both groups, one year progression free survival and overall survival are identical. TRM is significantly higher after FM, but relapse is higher in FMA. 19/103 d 28 survivors after FM vs 7/84 after FMA developed gr III–IV acute GVHD (p=0.04). 46/77 d100 survivors after FM developed ext cGVHD vs 7/63 after FMA (p=0.0000). 43 patients remain alive after FM and 27 have ext cGVHD. 41 remain alive after FMA and 1 has ext cGVHD. Alemtuzumab results in a considerable reduction in acute and particularly chronic GVHD. TRM is reduced compared with standard GVHD prophylaxis. Low incidence of chronic GVHD and reduced TRM may be the major benefit of this strategy. Relapse rates are increased, because of reduced GVL effects or because of improved early survival of high risk patients. Other approaches are necessary for improving long term outcomes.

Patient Characteristics and Outcome

FMAFMP-value
90 102  
Age (range) 54 (22–74) 51 (17–77) 0.6 
AML/MDS 13/77 29/83 0.04 
MUD/related 42/48 59/63 0.5 
High./Intermediate/LowRisk 48/13/28 76/10/26 0.12 
Median Follow up mths (range) 28 (3–89) 28 (1–66) 0.07 
TRM@ 100 days 13% + 7% 24% + 8% 0.04 
TRM@ 1 year 30% + 12% 42% + 10% 0.04 
Relapse @ 1 year 40% + 12% 26% + 10% 0.01 
PFS @ 2 years 33% + 11% 37% + 9% 0.9 
OS @ 2 year 42% + 11% 44% + 9% 0.5 
AGVD gr III–IV 7/84 19/103 0.04 
Ext cGVHD 7/63 46/77 0.0000 
Ext cGVHD in survivors 1/41 27/43 0.0000 
FMAFMP-value
90 102  
Age (range) 54 (22–74) 51 (17–77) 0.6 
AML/MDS 13/77 29/83 0.04 
MUD/related 42/48 59/63 0.5 
High./Intermediate/LowRisk 48/13/28 76/10/26 0.12 
Median Follow up mths (range) 28 (3–89) 28 (1–66) 0.07 
TRM@ 100 days 13% + 7% 24% + 8% 0.04 
TRM@ 1 year 30% + 12% 42% + 10% 0.04 
Relapse @ 1 year 40% + 12% 26% + 10% 0.01 
PFS @ 2 years 33% + 11% 37% + 9% 0.9 
OS @ 2 year 42% + 11% 44% + 9% 0.5 
AGVD gr III–IV 7/84 19/103 0.04 
Ext cGVHD 7/63 46/77 0.0000 
Ext cGVHD in survivors 1/41 27/43 0.0000 

Author notes

Disclosure:Research Funding: Funding from Berlex Pharmaceuticals.