We investigated the safety and efficacy of administering rituximab in combination with a standard myeloablative conditioning regimen of cyclophosphamide (Cy, 60 mg/kg daily x 2 doses) and total body irradiation (TBI, 12 Gy in four daily fractions) with allogeneic SCT in adult patients (pts) with ALL. Pts were eligible if their disease expressed CD20 in >20% blasts by flow cytometry. Rituximab was administered at 375 mg/m2 on days 6, −1, +7 and +14 following stem cell infusion. 24 pts were entered on study. The results were retrospectively compared with those of a historical control group of 31 pts receiving the same preparative regimen without rituximab. The two treatment groups had similar numbers of matched sibling and unrelated donor grafts. Pt and donor characteristics are detailed in Table 1. GVHD prophylaxis consisted of tacrolimus and methotrexate for nearly all pts in both study and control groups; 4 pts in the control group and 1 pt in the study group received pentostatin in addition to tacrolimus and methotrexate. Preliminary data suggests that pentostatin reduces the incidence of acute GVHD (

de Lima et al. Blood 2004;104:727a
). The cumulative incidence of non-relapse mortality (NRM) at 2 years was 18% for the study group and 33% for the controls. There was no delay in engraftment or increased incidence of infection in pts treated with rituximab. Despite the greater use of pentostatin in the control group, the incidence of grade II–IV acute GVHD tended to be lower in pts treated with rituximab as compared to controls: 17% vs. 39%, p=0.07. The incidence of chronic extensive GVHD was not significantly different between the two groups: 37% vs. 34%, p=0.7. OS at 2 years was 45% for the study group and 38% for the controls, p=0.5. PFS at 2 years was 31% for the study group and 38% for the control group, p=0.8. Treatment outcomes are summarized in Table 1. In conclusion, our results demonstrate that the addition of rituximab to standard Cy/TBI conditioning for allogeneic SCT in ALL is associated with a relatively low rate of acute GVHD and NRM. Differences in pt characteristics preclude direct comparison. However, there is no apparent benefit for the addition of rituximab on disease relapse.

Table 1.

Patient, Donor Characteristics, and Outcomes

Cy/TBI/rituximab No. ptsCy/TBI No. ptsP-value
1. Donor age missing for 1 pt in each treatment group. 
Total Pts 24 31  
Median Recipient Age, yrs (range 30 (18–54) 35 (18–53)  
Median Pt Age, yrs (range)1 38 (15–53) 36 (14–54)  
Donor Type (%)    
Matched related 15 (62) 21 (68)  
Matched unrelated 9 (38) 10 (32) 0.7 
Stem Cell Source (%)    
BM 9 (38) 17 (55)  
PB 15 (62) 14 (45) 0.2 
Sex donor/pt mismatch (%) 8 (33) 12 (40) 0.7 
CMV donor/pt mismatch (%) 10 (43) 12 (40) 0.8 
ABO donor/pt mismatch (%) 14 (58) 10 (33) 0.05 
Graft Composition, median (range)    
Total nucleated cells (x108/kg) 4 (1–14) 4 (1–9) 0.6 
CD34+(x106/kg) 5 (1–9) 5 (2–8) 0.9 
CD3+ (x106/kg) 110 (8–370) 37 (5–286) 0.2 
Disease Status at SCT (%)    
CR1 6 (25) 17 (54)  
Remission, beyond CR1 13 (54) 7 (23)  
Not in Remission 5 (21) 7 (23) 0.03 
Acute GVHD II–IV 17% 39% 0.07 
Chronic Extensive GVHD 37% 34% 0.7 
OS, 2 yrs 45% 37% 0.5 
PFS, 2 yrs 31% 38% 0.8 
Cy/TBI/rituximab No. ptsCy/TBI No. ptsP-value
1. Donor age missing for 1 pt in each treatment group. 
Total Pts 24 31  
Median Recipient Age, yrs (range 30 (18–54) 35 (18–53)  
Median Pt Age, yrs (range)1 38 (15–53) 36 (14–54)  
Donor Type (%)    
Matched related 15 (62) 21 (68)  
Matched unrelated 9 (38) 10 (32) 0.7 
Stem Cell Source (%)    
BM 9 (38) 17 (55)  
PB 15 (62) 14 (45) 0.2 
Sex donor/pt mismatch (%) 8 (33) 12 (40) 0.7 
CMV donor/pt mismatch (%) 10 (43) 12 (40) 0.8 
ABO donor/pt mismatch (%) 14 (58) 10 (33) 0.05 
Graft Composition, median (range)    
Total nucleated cells (x108/kg) 4 (1–14) 4 (1–9) 0.6 
CD34+(x106/kg) 5 (1–9) 5 (2–8) 0.9 
CD3+ (x106/kg) 110 (8–370) 37 (5–286) 0.2 
Disease Status at SCT (%)    
CR1 6 (25) 17 (54)  
Remission, beyond CR1 13 (54) 7 (23)  
Not in Remission 5 (21) 7 (23) 0.03 
Acute GVHD II–IV 17% 39% 0.07 
Chronic Extensive GVHD 37% 34% 0.7 
OS, 2 yrs 45% 37% 0.5 
PFS, 2 yrs 31% 38% 0.8 
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Topics:
acute lymphocytic leukemia, allogeneic stem cell transplant, graft-versus-host disease, graft-versus-host disease, acute, rituximab, brachial plexus neuritis, pentostatin, disease remission, methotrexate, tacrolimus

Author notes

Corresponding author

2005, The American Society of Hematology
2005
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